Prediabetes and diabetes prevalence in the Workers’ Oral Health Study

Abstract

Objective

To examine the association between periodontitis, diabetes, and prediabetes, assessed by fasting plasma glucose (FPG).

Materials and methods

Workers' Oral Health Study is a cross-sectional survey conducted on a representative sample of the Spanish employed population including 5154 participants (59.5% men, aged 16–65). Examination of periodontal status assessed Community Periodontal Index (CPI) and clinical attachment levels (CAL). Biochemical determinations included fasting plasma glucose (FPG), triglycerides, and total cholesterol. Logistic regression analysis with adjustment for potential confounders was used to evaluate the association between periodontitis and abnormal glucose regulation.

Results

Ninety-five participants (2.2%) of the study population had diabetes, while 373 (8.8%) presented prediabetes. Prediabetes was not associated with CPI or CAL in fully adjusted multivariate logistic regressions models. Diabetes was significantly associated with subjects having a CPI 4 after adjustment for potential confounders (odds ratio OR = 1.9, 95% confidence interval (CI) 1.1–3.1). This association was stronger in subjects < 45 years (OR = 4.0, 95% CI 1.2–12.7).

Conclusion

Periodontitis was associated with diabetes mellitus, but not with prediabetes, in a representative sample of the Spanish employed population. The association was stronger for younger subjects, which emphasizes the need for early detection of diabetes in younger patients affected by periodontitis, particularly because periodontal therapy may help to improve glycemic control.

Clinical relevance

Periodontitis is associated with diabetes mellitus, having at the same time a negative effect on glycemic control. It is important to develop proper early diagnosis strategies for both conditions, particularly in young male adults.

https://ift.tt/2NB02Nh

Transcatheter mitral valve therapies

Abstract

Dr.O.P. Yadava, Editor-in-Chief, IJTC and Dr. V Bapat, Assistant Professor at Columbia University, New York, discuss issues related to slow development and uptake of transcatheter mitral valve replacement. Dr. Bapat stresses on the basic difference between transcatheter aortic and mitral valve interventions. He laments that issues related to mitral valve repair versus replacement and role of percutaneous MitraClip are still being hotly debated. He, however, is hopeful that technology shall evolve to make percutaneous options for secondary mitral regurgitation a viable proposition.

https://ift.tt/2H9nLmo

Opportunities and challenges for thoracic organ transplantation in government institutions

Abstract

The first successful heart transplant in India was performed by Panangipalli Venugopal on 3 August 1994 at the All India Institute of Medical Sciences, New Delhi. Twenty-five years later, only seven government institutions are performing heart transplants and only one government hospital has an established heart transplant program in India. Only one lung transplant has been performed in a government institution all over the country. This article reviews the history and current status of thoracic organ transplant in India. The authors discuss the factors responsible for the dismal progress of thoracic organ transplant in government hospitals, opportunities available in government institutions for widening the scope of transplant program, and the steps taken by the Government of India to improve healthcare in the country.

https://ift.tt/2tKARyx

Effect of temperature on thermal, mechanical and morphological properties of polypropylene foams prepared by single step and two step batch foaming process

Abstract

This study reports the influence of foaming temperature on morphological and thermo-mechanical characteristics of polypropylene (PP) foams prepared using two different methods of batch foaming at low saturation pressures. In the first method, involving single-step pressure-induced-foaming (PIF), the solid specimen was heated to different temperatures in a high-pressure vessel, and then saturated CO₂ under pressure. Depressurization then led to foaming. In the second method, involving a two-step temperature-induced-foaming (TIF), the solid specimen was saturated with pressurized CO₂ at room temperature for a specific period of time and then the CO₂ laden specimen was immersed in hot glycerol bath at different temperatures for foaming. SEM micrographs of the fractured foamed specimens were employed for measurement of cell-size distribution. The average cell sizes ranged between 3 and 310 μm in specimens obtained using PIF, while in case of foams prepared by TIF, the cell sizes ranged between 30 and 70 μm. The cell sizes achieved in TIF are significantly smaller and more uniform as compared to those in PIF foams. The density (0.393–0.186 g cm⁻³) of PIF foams was seen to decrease with increasing foaming temperature; in contrast, in case of TIF the density remained more or less unchanged around 0.43–0.47 g cm⁻³ with changes in foaming temperature. The foamed specimens were characterized in uniaxial compression; the stiffness (elastic and collapse moduli) and compressive strengths of both the PIF and TIF foams were seen to decrease with increase in cell-size. The magnitude of plateau-regime stresses within the compressive stress-strain response showed strong correlation with the foam cell-wall thickness. The crystallinity of the foamed specimens was observed to decrease with increase in foaming temperatures. The thermal stability of both PIF and TIF foams in general showed improvement compared with the PP matrix.

https://ift.tt/2GQU3n5

Natural woodlands hold more diverse, abundant, and unique biota than novel anthropogenic forests: a multi-group assessment

Abstract

Biodiversity sustained by natural ecosystems, particularly forests, provides ecosystem services essential to human well-being. However, many forests have been severely transformed, notably via monospecific plantations and the spread of invasive species. Given the extension of these novel anthropogenic forests (plantations and invasive copses), it is critical to know how they can support forest biodiversity, particularly in highly humanized biodiversity hotspots as the southwest Mediterranean Europe. Because the effects likely vary across taxonomic groups, such assessments require an integrative multi-group approach. Here, we evaluated the abundance, richness, and composition of shrubs, herbs, macrofungi, ground and flying arthropods, birds, small mammals, carnivores, and bats across the four most common forest types in Central Portugal, namely: natural oak woodlands (dominated by Quercus faginea Lam.) and anthropogenic forests, invasive Acacia dealbata Link copses, Pinus pinaster Aiton plantations (native), and Eucalyptus globulus Labill. plantations (exotic). Oak woodlands sustained higher abundance, diversity, and a unique species composition compared to the other forests, especially those dominated by exotic species. The greatest changes in biodiversity occurred in herbs and birds. Contrary to our expectations, species richness and composition of macrofungi and carnivores in acacia copses were similar to those of oak woodlands, revealing that groups respond differently to forest changes. The large-scale replacement of natural forests by novel anthropogenic forests has significant negative impacts in most, but not all groups, which should be actively considered for integrative conservation strategies.

https://ift.tt/2EoaR0N

Carnosic Acid Inhibits CXCR3 Ligands Production in IL-27-Stimulated Human Oral Epithelial Cells

Abstract

Carnosic acid, which is a bioactive compound isolated from rosemary, has various pharmacological effects. However, the anti-inflammatory effect of carnosic acid on periodontitis is still unknown. The aim of this study was to investigate the effect of carnosic acid on CXC chemokine receptor 3 (CXCR3) ligands, which are involved in Th1 cells migration and accumulation, production in interleukin (IL)-27-stimulated human oral epithelial cells (TR146 cells). Carnosic acid decreased CXC chemokine ligand (CXCL)9, CXCL10, and CXCL11 production in IL-27-stimulated TR146 cells in a dose-dependent fashion. Moreover, we disclosed that carnosic acid could suppress signal transducer and activator of transcription (STAT)1, STAT3, and protein kinase B (Akt) phosphorylation in IL-27-stimulated TR146 cells. Furthermore, STAT1, STAT3, and Akt inhibitors could suppress CXCR3 ligands production in IL-27-treated TR146 cells. In summary, carnosic acid could reduce CXCR3 ligands production in human oral epithelial cell by inhibiting STAT1, STAT3, and Akt activation.

https://ift.tt/2VryKeQ

Regulatory T Cells Could Improve Intestinal Barrier Dysfunction in Heatstroke

Abstract

Intestinal barrier dysfunction plays a pivotal role in multiorgan dysfunction during heatstroke (HS). Neutrophils are involved in intestinal inflammation and thus dampen the mucosal integrity. Regulatory T cells (Tregs) have been shown to orchestrate neutrophils and thus sustain mucosal integrity in miscellaneous inflammation-related diseases. However, whether Tregs are involved in HS-induced intestinal barrier dysfunction remains unknown. Thus, we investigated whether Tregs could alleviate intestinal barrier dysfunction in mice. We found that HS could induce intestinal injury and mucosal barrier dysfunction 0, 24, and 72 h after heat stress. Flow cytometry revealed an increase of neutrophil infiltration and a decrease of Treg frequencies in the small intestinal epithelium 72 h after heat stress. Treg depletion starting 2 days before HS exacerbated intestinal damage and mucosal barrier dysfunction. Adoptive transfer of Tregs at 0 h improved intestinal injury and mucosal barrier dysfunction at 72 h. The manipulation of Tregs affected the neutrophil frequencies in the small intestinal epithelium 72 h after heat stress. Our study demonstrated that Tregs could improve HS-induced intestinal barrier dysfunction, probably via modulation of neutrophils in the intestine of mice during HS.

https://ift.tt/2EFEwEm

Diagnosis and Treatment Patterns in Celiac Disease

Abstract

Celiac disease (CD) is an immune-mediated gastrointestinal (GI) disorder driven by innate and adaptive immune responses to gluten. Presentation of CD has changed over time, with non-GI symptoms, such as anemia and osteoporosis, presenting more commonly. With improved screening and diagnostic methods, the reported prevalence of CD has increased globally, and there is considerable global variation in diagnostic and treatment practices. The objective of this study was to describe the current state of CD diagnosis and treatment patterns. A targeted review of literature from MEDLINE, Embase, the Cochrane Library, and screening of relevant conference abstracts was performed. The generally recommended diagnostic approach is GI endoscopy with small bowel biopsy; however, in selected patients, biopsy may be avoided and diagnosis based on positive serology and clinical symptoms. Diagnosis often is delayed; the average diagnostic delay after symptom onset is highly variable and can last up to 12 years. Barriers to accurate and timely diagnosis include atypical presentation, lack of physician awareness about current diagnostic criteria, misdiagnosis, and limited access to specialists. Currently, strict adherence to a gluten-free diet (GFD) is the only recommended treatment, which is not successful in all patients. Only one-third of patients are monitored regularly following diagnosis. Unmet needs for CD include improvements in the accuracy and timeliness of diagnosis, and the development of treatments for both refractory CD and GFD nonresponsive CD. Further research should investigate the impact of education about gluten-free eating and the availability of gluten-free foods support adherence and improve outcomes in patients with CD.

https://ift.tt/2Sv4UV3

The effect of severe and moderate hypoxia on exercise at a fixed level of perceived exertion

Abstract

Purpose

The purpose of this study was to determine the primary cues regulating perceived effort and exercise performance using a fixed-RPE protocol in severe and moderate hypoxia.

Methods

Eight male participants (26 ± 6 years, 76.3 ± 8.6 kg, 178.5 ± 3.6 cm, 51.4 ± 8.0 mL kg^− 1 min^− 1 \(\dot {V}\) O_2max) completed three exercise trials in environmental conditions of severe hypoxia (F_IO₂ 0.114), moderate hypoxia (F_IO₂ 0.152), and normoxia (F_IO₂ 0.202). They were instructed to continually adjust their power output to maintain a perceived effort (RPE) of 16, exercising until power output declined to 80% of the peak 30-s power output achieved.

Results

Exercise time was reduced (severe hypoxia 428 ± 210 s; moderate hypoxia 1044 ± 384 s; normoxia 1550 ± 590 s) according to a reduction in F_IO₂ (P < 0.05). The rate of oxygen desaturation during the first 3 min of exercise was accelerated in severe hypoxia (− 5.3 ± 2.8% min^− 1) relative to moderate hypoxia (− 2.5 ± 1.0% min^− 1) and normoxia (− 0.7 ± 0.3% min^− 1). Muscle tissue oxygenation did not differ between conditions (P > 0.05). Minute ventilation increased at a faster rate according to a decrease in F_IO₂ (severe hypoxia 27.6 ± 6.6; moderate hypoxia 21.8 ± 3.9; normoxia 17.3 ± 3.9 L min^− 1). Moderate-to-strong correlations were identified between breathing frequency (r = − 0.718, P < 0.001), blood oxygen saturation (r = 0.611, P = 0.002), and exercise performance.

Conclusions

The primary cues for determining perceived effort relate to progressive arterial hypoxemia and increases in ventilation.

https://ift.tt/2XsKpfi

Bioaugmentation and Biostimulation of Total Petroleum Hydrocarbon Degradation in a Petroleum-contaminated Soil with Fungi Isolated from Olive Oil Effluent

Abstract

In degradation of total petroleum hydrocarbon, 35 isolates belonging to 11 genera were sanitized and 3 isolates as well as their consortium were initiated to be able to raise in association with petroleum hydrocarbon as sole source of carbon under in vitro circumstances. The isolated strains were grounded on internal transcribed spacer (ITS) rDNA sequence analysis. The fungal strains with the utmost potentiality to reduce petroleum hydrocarbon without emerging antagonistic activities were Aspergillus niger, Penicillium ochrochloron, and Trichodema viride. For fungal growth on petroleum hydrocarbon, P. ochrocholon gained weight of 44%, A. niger 49%, and T. viride 39% within the first 30–40 days. As compared to the controls, these fungi accumulated significantly higher biomass, produced extracellular enzymes, and degraded total petroleum hydrocarbon and A. niger strongly degraded total petroleum hydrocarbon with a degradation of about 71.19%. These observations with GC-MS data confirm that these isolates displayed rapid total petroleum hydrocarbon biodegradation within a period of 60 days and the half-life showed that A. niger was the shortest with t1/2 = 21.280 day⁻¹ corresponding to the highest percent degradation of 71.19% and first-order kinetic fitted into the present study. By multivariate analysis, five main factors were identified by factor analysis (FA). The first factor (F1) of the fungi species accounts for 20.0% which signifies that fungi species controls the degradation of petroleum variability and hierarchical cluster analysis (HCA) as a dendrogram with five observations and three variables shows two predominant clusters order cluster 1 > 2.

https://ift.tt/2GP5JXv

IJMS, Vol. 20, Pages 1059: Role and Functional Differences of HKT1-Type Transporters in Plants under Salt Stress

IJMS, Vol. 20, Pages 1059: Role and Functional Differences of HKT1-Type Transporters in Plants under Salt Stress

International Journal of Molecular Sciences doi: 10.3390/ijms20051059

Authors: Akhtar Ali Albino Maggio Ray A. Bressan Dae-Jin Yun

Abiotic stresses generally cause a series of morphological, biochemical and molecular changes that unfavorably affect plant growth and productivity. Among these stresses, soil salinity is a major threat that can seriously impair crop yield. To cope with the effects of high salinity on plants, it is important to understand the mechanisms that plants use to deal with it, including those activated in response to disturbed Na+ and K+ homeostasis at cellular and molecular levels. HKT1-type transporters are key determinants of Na+ and K+ homeostasis under salt stress and they contribute to reduce Na+-specific toxicity in plants. In this review, we provide a brief overview of the function of HKT1-type transporters and their importance in different plant species under salt stress. Comparison between HKT1 homologs in different plant species will shed light on different approaches plants may use to cope with salinity.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader https://ift.tt/2EkZgjm

Alu element insertion in the MLH1 exon 6 coding sequence as a mutation predisposing to Lynch syndrome

Abstract

Lynch syndrome (LS) is the most frequent cause of hereditary colorectal cancer. A subset of patients with a history of LS shows no causal germline pathogenic alteration and are identified as having Lynch‐like syndrome (LLS). Alu retrotransposons are the most abundant mobile DNA sequences in the human genome and have been associated with numerous human cancers by either disrupting coding regions or altering epigenetic modifications or splicing signals. We report a family first classified as having LLS by Sanger sequencing analysis. Next‐generation sequencing (NGS) analysis identified an AluY5a insertion in MLH1 exon 6 that led to exon skipping. This splicing alteration inducing a pathogenic frameshift was found in patients who developed colorectal adenocarcinomas. Retroelement insertion might thus be an important but underestimated mechanism of cancer genetics that could be systematically tested in patients with a phenotype suggesting LS to accurately assess family risk and surveillance approaches.

This article is protected by copyright. All rights reserved.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader https://ift.tt/2T8aUbz

RECQL5: another DNA helicase potentially involved in hereditary breast cancer susceptibility

Abstract

There is still around 50% of the familial breast cancer (BC) cases with an undefined genetic cause, here we have used Next Generation Sequencing (NGS) technology in order to identify new BC susceptibility genes. This approach has led to the identification of RECQL5, a member of RECQL‐helicases family as a new BC susceptibility candidate, which deserves further study. We have used a combination of Whole Exome Sequencing (WES) in a family negative for mutations in BRCA1/2 throughout (BRCAX), in which we found a probably deleterious variant in RECQL5, and targeted NGS of the complete coding regions and exon‐intron boundaries of the candidate gene in 699 BC Spanish BRCAX families and 665 controls. Functional characterization and in silico inference of pathogenicity were performed to evaluate deleterious effect of detected variants. We found at least seven deleterious or likely deleterious variants among the cases and only one in controls. These results prompt us to propose RECQL5 as a gene that would be worth to analyze in larger studies to explore its possible implication in BC susceptibility.

This article is protected by copyright. All rights reserved.

from ! Human Diseases via Alexandros G.Sfakianakis on Inoreader https://ift.tt/2EjQ7ra

SLC35A2‐CDG: Functional Characterization, Expanded Molecular, Clinical, and Biochemical Phenotypes of 30 Unreported Individuals

Abstract

Pathogenic de novo variants in the X‐linked gene SLC35A2 encoding the major Golgi‐localized UDP‐galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2‐CDG (formerly CDG‐IIm). To date, twenty‐nine unique de novo variants from thirty‐two unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N‐glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2‐CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2‐dependent UDP‐galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild‐type to mutant alleles in fibroblasts from affected individuals.

This article is protected by copyright. All rights reserved.

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A new in silico approach to investigate molecular aspects of Factor IX (F9) missense causative mutations and their impact on the Hemophilia B severity

Abstract

Factor IX (encoded by F9) is a protein in the coagulation process, where its lack or deficiency leads to hemophilia B. This condition has been much less studied than hemophilia A, especially in Latin America. We analyzed the structural and functional impact of 54 missense mutations (18 reported by us previously, and 36 other mutations from the Factor IX database) through molecular modeling approaches. To accomplish this task, we examine the electrostatic patterns, hydrophobicity/hydrophily, disulfide and H‐bond differences of the Factor IX structures harboring the missense mutations found, correlating them with their clinical effects. The 54 mutated sequences were modeled and their physicochemical features were determined and used as input in clusterization tools. The electrostatic pattern seems to influence in disease severity, especially for mutations investigated in EGF1/2 domains. The combined use of all physicochemical information improved the clustering of structures associated to similar phenotypes, especially for mutations from GLA and EGF1‐2 domains. The effect of mutations in the disease phenotype severity seems to be a complex interplay of molecular features, each one contributing to different impacts. This highlights that previous studies and tools analyzing individually single features for single mutations are missing elements that fulfill the whole picture.

This article is protected by copyright. All rights reserved.

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When Does Intelligence Peak?

Maybe that's not even the right question.

-- Read more on ScientificAmerican.com

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Regional morphometric abnormalities and clinical relevance in Wilson's disease

Abstract

Background

Morphology builds Wilson's disease's clincal basis.

Objectives

To detect and quantify regional morphometric abnormalities, in terms of both volume and shape, in patients with Wilson's disease.

Methods

Twenty‐seven Wilson's disease patients and 24 healthy controls were enrolled. Specific brain structures, including the bilateral caudate, putamen, globus pallidus, thalamus, amygdala, hippocampus, red nucleus, and substantia nigra (SN), were automatically extracted from each participant's T₁‐weighted image. Volume abnormalities and correlations with the modified Young scale were investigated. Furthermore, vertex‐based shape analysis was performed to explore region‐specific morphometric abnormalities.

Results

Significant global volume atrophy and local shape abnormalities were detected and quantified in the bilateral caudate, putamen, globus pallidus, thalamus, amygdala, red nucleus, and SN. Morphometric abnormalities of the caudate, putamen, and thalamus were strong, whereas those of the globus pallidus, amygdala, red nucleus, and SN were weaker. No hippocampal abnormalities were observed. The modified Young scale was found to correlate significantly with the volumes of the bilateral putamen and the right globus pallidus. Shape analysis revealed subregion‐specific atrophy of the bilateral caudate and putamen. They were concentrated in the subregions that project to the limbic and executive cortices. Significant region‐specific atrophy was also detected in the bilateral thalamic subregions that project to the primary motor, sensory, and premotor cortices.

Conclusions

We found significant morphometric abnormalities of specific structures of interest in patients with Wilson's disease, both globally and locally. These morphometric abnormalities may serve as useful imaging biomarkers for Wilson's disease. © 2019 International Parkinson and Movement Disorder Society

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Molecular basis of cullin-3 (Cul3) ubiquitin ligase subversion by vaccinia virus protein A55 [Microbiology]

BTB-Kelch proteins are substrate-specific adaptors for cullin-3 (Cul3) RING-box–based E3 ubiquitin ligases, mediating protein ubiquitylation for subsequent proteasomal degradation. Vaccinia virus encodes three BTB-Kelch proteins: A55, C2, and F3. Viruses lacking A55 or C2 have altered cytopathic effects in cultured cells and altered pathology in vivo. Previous studies have shown that the ectromelia virus orthologue of A55 interacts with Cul3 in cells. We report that the N-terminal BTB-BACK (BB) domain of A55 binds directly to the Cul3 N-terminal domain (Cul3-NTD), forming a 2:2 complex in solution. We solved the structure of an A55BB/Cul3-NTD complex from anisotropic crystals diffracting to 2.3/3.7 Å resolution in the best/worst direction, revealing that the overall interaction and binding interface closely resembles the structures of cellular BTB/Cul3-NTD complexes, despite low sequence identity between A55 and cellular BTB domains. Surprisingly, despite this structural similarity, the affinity of Cul3-NTD for A55BB was stronger than for cellular BTB proteins. Glutamate substitution of A55 residue Ile 48, adjacent to the canonical ϕ-X-D/E Cul3-binding motif, reduced affinity of A55BB for Cul3-NTD by at least two orders of magnitude. Moreover, Ile 48 and the ϕ-X-D/E motif are conserved in A55 orthologs from other poxviruses, but not in the vaccinia virus proteins C2 or F3. The high-affinity interaction between A55BB and Cul3-NTD suggests that, in addition to directing the Cul3–RING E3 ligase complex to degrade cellular/viral target proteins that are normally unaffected, A55 may also sequester Cul3 from cellular adaptor proteins, thereby protecting substrates of these cellular adaptors from ubiquitylation and degradation.

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The disordered plant dehydrin Lti30 protects the membrane during water-related stress by cross-linking lipids [Molecular Biophysics]

Dehydrins are intrinsically disordered proteins, generally expressed in plants as a response to embryogenesis and water-related stress. Their suggested functions are in membrane stabilization and cell protection. All dehydrins contain at least one copy of the highly conserved K-segment, proposed to be a membrane binding motif. The dehydrin Lti30 (Arabidopsis thaliana) is upregulated during cold and drought stress conditions and comprises six K-segments, each with two adjacent histidines. Lti30 interacts with the membrane electrostatically via pH dependent protonation of the histidines. In this work, we seek a molecular understanding of the membrane interaction mechanism of Lti30 by determining the diffusion and molecular organization of Lti30 on model membrane systems by Imaging Total Internal Reflection Fluorescence Correlation Spectroscopy (ITIR-FCS) and molecular dynamics (MD) simulations. The dependence of the diffusion coefficient explored by ITIR-FCS together with MD simulations yield insights into Lti30 binding, domain partitioning and aggregation. The effect of Lti30 on membrane lipid diffusion was studied on fluorescently labelled supported lipid bilayers of different lipid compositions at mechanistically important pH conditions. In parallel, we compared the mode of diffusion for short individual K-segment peptides. The results indicate that Lti30 binds the lipid bilayer via electrostatics, which restricts the mobility of lipids and bound protein molecules. At low pH, Lti30 binding induced lipid micro-domain formation as well as protein aggregation, which could be correlated with one other. Moreover, at physiological pH, Lti30 forms nanoscale aggregates when proximal to the membrane suggesting that Lti30 may protect the cell by "cross-linking" the membrane lipids.

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2D gel electrophoresis reveals dynamics of t-loop formation during the cell cycle and t-loop in maintenance regulated by heterochromatin state [DNA and Chromosomes]

Linear chromosome ends are capped by telomeres that have been previously reported to adopt a t-loop structure. The lack of simple methods for detecting t-loops has hindered progress in understanding the dynamics of t-loop formation and its function in protecting chromosome ends. Here, we employed a classical two-dimensional agarose gel method (2D gel method) to innovatively apply to t-loop detection. Briefly, restriction fragments of genomic DNA were separated in a 2D gel, and the telomere sequence was detected by in-gel hybridization with telomeric probe. Using this method, we found that t-loops are present throughout the cell cycle and t-loop formation tightly couples to telomere replication. We also observed that t-loop abundance positively correlates with chromatin condensation, i.e. cells with less compact telomeric chromatin (ALT cells and trichostatin A [TSA]-TSA treated HeLa cells) exhibited fewer t-loops. Moreover, we observed that telomere dysfunction-induced foci (TIFs), ALT-associated PML bodies (APBs), and telomere sister chromatid exchanges (T-SCEs) are activated upon TSA-induced loss of t-loops. These findings confirm the importance of the t-loop in protecting linear chromosomes from damage or illegitimate recombination.

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Unraveling the subtleties of {beta}-(1->3)-glucan phosphorylase specificity in the GH94, GH149 and GH161 glycoside hydrolase families [Glycobiology and Extracellular Matrices]

Glycoside phosphorylases (GPs) catalyze the phosphorolysis of glycans into the corresponding sugar 1-phosphates and shortened glycan chains. Given the diversity of natural β-(1→3)-glucans and their wide range of biotechnological applications, the identification of enzymatic tools that can act on β-(1→3)-glucooligosaccharides is an attractive area of research. GP activities acting on β-(1→3)-glucooligosaccharides have been described in bacteria, the photosynthetic excavate Euglena gracilis, and the heterokont Ochromonas spp. Previously, we characterized β-(1→3)-glucan GPs from bacteria and E. gracilis, leading to their classification in glycoside hydrolase family GH149. Here, we characterized GPs from Gram-positive bacteria and heterokont algae acting on β-(1→3)-glucooligosaccharides. We identified a phosphorylase sequence from Ochromonas spp. (OcP1) together with its orthologs from other species, leading us to propose the establishment of a new GH family, designated GH161. To establish the activity of GH161 members, we recombinantly expressed a bacterial GH161 gene sequence (PapP) from the Gram-positive bacterium Paenibacillus polymyxa ATCC 842 in Escherichia coli. We found that PapP acts on β-(1→3)-glucooligosaccharide acceptors with degree of polymerization (DP) ≥ 2. This activity was distinct from that of characterized GH149 β-(1→3)-glucan phosphorylases, which operate on acceptors with DP ≥ 1. We also found that bacterial GH161 genes co-localize with genes encoding β-glucosidases and ABC transporters, highlighting a probable involvement of GH161 enzymes in carbohydrate degradation. Importantly, in some species, GH161 and GH94 genes were present in tandem, providing evidence that GPs from different CAZy families may work sequentially to degrade oligosaccharides.

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Trout myomaker contains 14 minisatellites and two sequence extensions, but retains fusogenic function [Developmental Biology]

The formation of new myofibers in vertebrates occurs by myoblast fusion and requires fusogenic activity of the muscle-specific membrane protein myomaker. Here, using in silico (BLAST) genome analyses, we show that the myomaker gene from trout includes 14 minisatellites, indicating that it has an unusual structure compared with those of other animal species. We found that the trout myomaker gene encodes a 434-aa protein, in accordance with its apparent molecular weight (~40kDa) observed by immunoblotting. The first half of the trout myomaker protein (1-220 aa) is similar to the 221-aa mouse myomaker protein, whereas the second half (222-234 aa) does not correspond to any known motifs and arises from two protein extensions. The first extension (~70 aa) apparently appeared with the radiation of the bony fish clade Euteleostei, whereas the second extension (up to 236 aa) is restricted to the superorder Protacanthopterygii (containing salmonids and pike) and corresponds to the insertion of minisatellites having a length of 30 nucleotides. According to gene expression analyses, trout myomaker expression is consistently associated with the formation of new myofibers during embryonic development, postlarval growth, and muscle regeneration. Using cell-mixing experiments, we observed that trout myomaker has retained the ability to drive the fusion of mouse fibroblasts with C2C12 myoblasts. Our work reveals that trout myomaker has fusogenic function despite containing two protein extensions.

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Comparative study on long-term stability in mandibular sagittal split ramus osteotomy: hydroxyapatite/poly- l -lactide mesh versus titanium miniplate

Abstract

Background

Resorbable devices have recently been adopted in the field of orthognathic surgery with controversies about their postoperative skeletal stability. Hence, we determined the long-term skeletal stability of unsintered hydroxyapatite/poly-l-lactic acid (HA/PLLA) mesh for osteofixation of mandibular sagittal split ramus osteotomy (SSRO), and compared it with that of titanium miniplate.

Methods

Patients were divided into resorbable mesh and titanium miniplate fixation groups. A comparative study of the change in the mandibular position was performed with preoperative, 1-day, 6-month, and 2-year postoperative lateral cephalograms.

Results

At postoperative 6 months—compared with postoperative 1 day, point B (supra-mentale) was significantly displaced anteriorly in the titanium-fixation group. Moreover, at postoperative 2 years—compared with postoperative 6 months, point B was significantly displaced inferiorly in the titanium-fixation. However, the HA/PLLA mesh-fixation group did not show any significant change with respect to point B postoperatively.

Conclusions

The HA/PLLA mesh-fixation group demonstrated superior long-term skeletal stability with respect to the position of mandible, when compared with the titanium-fixation group.

https://ift.tt/2EjKQzP

[ASAP] Superlocalized Three-Dimensional Live Imaging of Mitochondrial Dynamics in Neurons Using Plasmonic Nanohole Arrays

ACS Nano

DOI: 10.1021/acsnano.8b08178

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[ASAP] Patterning Multicolor Hybrid Perovskite Films Top-Down Lithography

ACS Nano

DOI: 10.1021/acsnano.8b09592

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Extrapolation of Oligonucleotide Dose Levels Used in Nonclinical Toxicity Studies to Selection of Safe Starting Dose Levels in Human Clinical Trials

Nucleic Acid Therapeutics, Ahead of Print.


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IONIS-PKKRx a Novel Antisense Inhibitor of Prekallikrein and Bradykinin Production

Nucleic Acid Therapeutics, Ahead of Print.


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The Use of OJIP Fluorescence Transients to Monitor the Effect of Elevated Ozone on Biomass of Canola Plants

Abstract

The effects of elevated ozone (O₃) levels (80 ppb and 120 ppb) on photosynthetic efficiency and growth of canola plants were studied in open-top chambers. The chlorophyll a polyphasic fluorescence rise kinetics OJIP, stomatal conductance and Chlorophyll Content Index (CCI) were measured after 15 and 30 days of O₃ fumigation, as well as in control plants; biomass measurements were done only after 30 days with and without fumigation. Analysis of the OJIP kinetics by the JIP-test led to the calculation of several photosynthetic parameters and the total Performance Index (PI_total). The decline of PI_total under the 80 ppb O₃ treatment was due to a lower density of reaction centres (RC/ABS), while the notable decline under the 120 ppb treatment was found to be due both to a further decline of RC/ABS and to a pronounced lowering of the efficiency with which an electron can move from the reduced intersystem electron acceptors to the PSI end acceptors (δ_Ro). Stomatal conductance was affected by both treatments. Biomass was found to be affected by O₃ fumigation (for 30 days), decreasing by 40% at 80 ppb and by more than 70% under 120 ppb. Our findings indicate that biomass decline is due both to the lowering of CCI and the lowering of photosynthetic efficiency parameters. They thus suggest that two simple, non-invasive and rapid methods, namely, the analysis of OJIP fluorescence transients and the measurement of CCI, can be used to screen the effect of elevated O₃ on biomass of canola plants.

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The Blocking Mechanism of the Vertical Feeding System of Roadside Support Body Material for Backfilling Gob-Side Entry Retaining

Reliable operation of the feeding system plays a crucial role in ensuring the safe and efficient production of the working face of backfilling gob-side entry retaining (GER). In the process of vertical feeding of the roadside support body material, the problem of blocking of the feeding shaft has occurred to the test mine, which seriously affects the production safety in mines. In this paper, based on the theoretical analysis, a fluid-solid coupling numerical model was established. The change rules of the speed of sacked gangue, pressure of air below it, and speed vector distribution with different vent diameters were obtained. The blocking mechanism of the feeding system was revealed. The results show that if the exhaust vent of the stock bin was shut, the speed of gangue in the mine increased and then decreased and finally blocked in the feeding shaft. If the exhaust vent of the stock bin was opened for pressure discharge, with the increase of diameter of the exhaust vent, the maximum speed and ending speed of sacked gangue increased, pressure differential reduced, and speed vector was uniformly distributed. The energy criterion of blocking of the feeding shaft was further obtained. Based on the engineering conditions of the test mine, when the feeding shaft is blocked, the critical value of diameter of the exhaust vent is 30 mm. The research results provide basis for the design of key parameters of the vertical feeding system, ensuring the safe and efficient production of gob-backfilled GER working face.

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[Correspondence] Leishmaniasis

Sakib Burza and colleagues1 infer that no autochtonous cases of visceral leishmaniasis have been reported in Thailand. Several cases of visceral leishmaniasis, however, have been recorded in this country in the past few years.2 All these cases were caused by Leishmania (Mundinia) martiniquensis except one, which was caused by L (Mundinia) siamensis.2 A new autochtonous species causing cutaneous leishmaniasis, L (Mundinia) orientalis, has also been described in Thailand in 2018,3 so three species of Leishmania are now known to cause leishmaniasis in this country.

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[Correspondence] Leishmaniasis

Sakib Burza and colleagues1 adeptly reviewed different aspects of visceral leishmaniasis and cutaneous leishmaniasis.

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[Correspondence] Leishmaniasis – Authors' reply

We share the concern raised by Suman Saurabh about duration of contraception when miltefosine is used as a treatment for leishmaniasis, since it is a major gap in clinical practice.

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[Editorial] Health and wellbeing in adolescence and early adulthood

That young people are less healthy in the UK than in similar high-income countries is the headline finding of a major report published last week. International comparisons of health and wellbeing in adolescence and early adulthood, published by the Nuffield Trust and the Association for Young People's Health, examines 17 indicators of health and wellbeing in young people aged 10–24 years in 19 similar high-income countries within and outside Europe.

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[Clinical Picture] Rogue “stem cell clinic” leads to Mycobacterium abscessus infection

A 58-year-old man was admitted to our hospital with a 2-week history of persistent fever and pancytopenia. Physical examination showed no other abnormal findings. However, a septic screen isolated Mycobacterium abscessus from his blood and bone marrow. An 18fluorodeoxyglucose PET/CT scan showed an area of increased uptake in the patient's prostate (figure). Prostate specific antigen was 8·06 ng/mL—previously, it had been measured and reported to be 0·8 ng/mL. A transrectal biopsy of his prostate showed granulomatous inflammation.

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[Department of Error] Department of Error

Yoong J, Alonso S, Ching WC, et al. Investing in gender equity in health and biomedical research: a Singapore perspective. Lancet 2019; 393: e21–22—In this Correspondence, the competing interests statement has been updated to specify that some authors are current members of the Women in Science and Healthcare Executive Council. This correction has been made to the online version as of Feb 28, 2019.

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[Department of Error] Department of Error

Seifalian A, Osborne A, Gurung B. Improving foundations for future global health practitioners. Lancet 2019; 393: 641–42—The webappendix of this Correspondence has been corrected as of Feb 28, 2019.

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[World Report] Constitution: al-Sisi's presidency could to be expanded

An amendment could open the door to al-Sisi's presidency to be extended until 2034. Meanwhile, health and human rights in the country are under pressure. Sharmila Devi reports.

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[Comment] Glomerular podocytes in kidney health and disease

Chronic kidney disease affects more than 10% of the world's population.1 90% of all cases are attributed to glomerular diseases.2 Therefore, understanding the underpinnings of glomerular structure, physiology, and pathophysiology is of priority in overcoming the clinical, societal, and economic consequences of chronic kidney disease.1

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[Obituary] Adeniran Olubukola Fawole

Clinician and researcher who fought to improve perinatal health. He was born in Jebba, Nigeria, on July 4, 1960, and died in Ibadan, Nigeria, on Jan 9, 2019, aged 58 years.

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[Department of Error] Department of Error

Adepoju P. Nigeria's unending war with Lassa fever. Lancet 2018; 393: 627–628—In this World Report, an image's credit line was wrongly attributed to Pius Utomi Ekpei/Getty Images. The credit line should have been 'Paul Adepoju/The Lancet'. This correction has been made to the online version as of Feb 28, 2019.

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[World Report] Death of Ugandan man tests country's preparedness

The death of a man in the DR Congo whose body was transported to Uganda by family triggered fears of an Ebola virus contamination crossing the border. Esther Nakkazi reports.

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[Comment] Offline: UK citizens are losing the right to health—who cares?

If and when Brexit takes place, 66 million people living in the UK will lose their legally enshrined right to health care. The loss of this fundamental right has been almost totally missed in the debate about the UK's departure from the European Union (EU). Yet the forfeiture of this legal right to health care is the most important setback ever seen in the country's quest to protect and advance the health of its people. How has this calamity come about? The European Convention on Human Rights came into force in 1953.

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[Perspectives] Seven circles of antimicrobial hell

It started out as a winter holiday, climbing the Egyptian pyramids of Giza and descending into the dark tombs of Luxor's Valley of the Kings. Steffanie Strathdee and Tom Patterson, a married pair of HIV/AIDS researchers, had enjoyed many excursions of discovery all over the world. A trek to the age of Rameses seemed the perfect holiday. That is, until Strathdee realised her husband's sudden fever wasn't trivial. And Patterson, bouncing in and out of delirium in a small Luxor clinic, thought, "I can feel the world collapsing now, from the inside out".

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[World Report] Australia reports on audit of silicosis for stonecutters

Poorly managed working practices, including poor provision of education to artificial stonecutters, has led to what has been called an epidemic of silicosis. Tony Kirby reports.

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[Perspectives] Physician burnout in the modern era

The Library of the Royal College of Surgeons of England is home to a meticulously kept archive of the lives of medical students who attended Sir James Paget's anatomy lectures at St Bartholomew's Hospital in London, UK, between 1839 and 1859. Published in 1869, "What Becomes of Medical Students" is Paget's personal appraisal of his apprentices' achievements, ranging from "distinguished success" to "scandalous misconduct". Although many went on to differentiate themselves, of the 1226 students under his tutelage, five died by suicide—a rate roughly 25 times higher than the male suicide mortality rate during that period.

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[World Report] Germany's Global Health hub

Germany's Global Health Hub is aimed at improving Germany's global health infrastructure, although uncertainty remains over the remit of this initiative. Andrew Green reports from Berlin.

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[Correspondence] Leishmaniasis

I congratulate Sakib Burza and colleagues (Sept 15, 2018, p 951)1 for their comprehensive Seminar on leishmaniasis.

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[Perspectives] The anatomy professors

Anatomists and artists have long enjoyed a close, at times symbiotic, relationship. Past anatomists often employed artists to record their handiwork with an accuracy and a delicacy that could not be supplied by any other means before the arrival of photography. The 18th-century surgeon and anatomist John Hunter had a succession of live-in artists at his bidding. Both disciplines were united by the impulse to see and record life in its myriad forms as a route to advancing knowledge and understanding the human condition.

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Testing a priming account of the contingent-capture effect

Abstract

In the contingent-capture protocol, singleton cues that have a target's searched-for feature capture attention, but cues that do not have the target's searched-for feature do not, a result labeled the contingent-capture effect. The contingent-capture effect is usually regarded as evidence for the observers' ability to establish search settings for certain nonspatial features in a top-down manner. However, in recent years it has become increasingly clear that selection history is also a powerful mediator of attentional capture. In this vein, it has been suggested that contingent-capture effects could emerge as a result of (intertrial) priming: The idea is that features that have been encountered previously in the target are primed, so that cues that have these features automatically capture attention in a subsequent encounter. Here we tested a strong version of the priming account of the contingent-capture effect. We wanted to know whether cues that had target features would capture attention when the corresponding features were not part of the instructions (i.e., when the corresponding features were task-irrelevant). The results suggested that a strong version of the priming account of contingent capture is not supported. In five experiments, we found little evidence that the contingent-capture effect could be explained by (intertrial) priming of task-irrelevant features alone. These results show that processes beyond priming through task-irrelevant features are critical for contingent-capture effects.

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The dephosphorylated S8A and S18A mutants of (oat) phytochrome A comprise its two species, phyA' and phyA'', suggesting that autophosphorylation at these sites is not involved in the phyA differentiation

Photochem. Photobiol. Sci., 2019, Accepted Manuscript
DOI: 10.1039/C8PP00574E, Paper

Vitaly Alexey Sineshchekov, Larissa Koppel, Jeong-Il Kim
Phytochrome A (phyA) is represented in plants by two species, phyA′ and phyA″, with different properties and modes of action (Sineshchekov, Funct. Plant Biol., 2019)1. They differ by the modification...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Novel application of Macrolampis sp2 firefly luciferase for intracellular pH-biosensing in mammalian cells

Photochem. Photobiol. Sci., 2019, Accepted Manuscript
DOI: 10.1039/C8PP00573G, Paper

Gabriele Verônica de Mello Gabriel, Rie Yasuno, Yasuo Mitani, Yoshihiro Ohmiya, Vadim Viviani
Bioluminescence is widely used in biosensors. Firefly luciferase-based bioluminescent sensors are among the most popular ones. Firefly luciferases are pH-sensitive, displaying a large red shift at acidic pH, a property...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Stromal Cell-Derived Factor 1 Promotes Cell Migration to Enhance Bone Regeneration After Hypoxic Preconditioning

Tissue Engineering Part A, Ahead of Print.


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[ASAP] Mapping Hot Spots at Heterogeneities of Few-Layer Ti3C2 MXene Sheets

ACS Nano

DOI: 10.1021/acsnano.8b09103

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iCAD partners with Swedish team on AI for breast cancer

Computer-aided detection (CAD) developer iCAD will collaborate with researchers...

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Related Reading:

iCAD to highlight AI for tomosynthesis at ECR

iCAD highlights study results of DBT software

iCAD gets CE Mark for PowerLook Tomo

iCAD system treats 1st patient in Australia

iCAD launches DBT computer-aided detection package

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COCIR restates need to replace old imaging equipment

The European Coordination Committee of the Radiological, Electromedical, and...

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Related Reading:

COCIR endorses proposed EHR exchange format

COCIR applauds new data storage rules

COCIR revises code of conduct

COCIR appoints new president

COCIR publishes advice on new device regulation

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Philips unveils Incisive CT at ECR 2019

Royal Philips, parent company of Philips Healthcare, is showing its new Incisive...

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Related Reading:

Philips to launch IntelliSpace Portal upgrade at ECR

Philips partners with Microsoft on AR for imaging

Philips launches new Zenition mobile C-arm

Philips launches new Epiq Elite ultrasound family

IGT, ultrasound sales growth propel Philips sales in Q4

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Video from ECR 2019: Nicola Strickland on Brexit & radiology

VIENNA - The planned withdrawal of the U.K. from the European Union is due...

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Related Reading:

Brexit dilemma: Do I stay or do I go?

Countdown to Brexit: Impact on radiology

New study sheds light on U.K. doctors' views on Brexit

Health warning: Experts spell out Brexit risks

Video from ECR 2018: Bernd Hamm on Brexit, AI, and the big chill

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Metabolic cross-talk between human bronchial epithelial cells and internalized Staphylococcus aureus as a driver for infection [Research]

Staphylococcus aureus is infamous for causing recurrent infections of the human respiratory tract. This is a consequence of its ability to adapt to different niches, including the intracellular milieu of lung epithelial cells. To understand the dynamic interplay between epithelial cells and the intracellular pathogen, we dissected their interactions over four days by mass spectrometry. Additionally, we investigated the dynamics of infection through live cell imaging, immunofluorescence and electron microscopy. The results highlight a major role of often overlooked temporal changes in the bacterial and host metabolism, triggered by fierce competition over limited resources. Remarkably, replicating bacteria reside predominantly within membrane-enclosed compartments and induce apoptosis of the host within ~24 hours post infection. Surviving infected host cells carry a subpopulation of non-replicating bacteria in the cytoplasm that persists. Altogether, we conclude that, besides the production of virulence factors by bacteria, it is the way in which intracellular resources are used, and how host and intracellular bacteria subsequently adapt to each other that determines the ultimate outcome of the infectious process.

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Spatiotemporal changes of the phagosomal proteome in dendritic cells in response to LPS stimulation [Research]

Dendritic cells (DCs) are professional phagocytes that use innate sensing and phagocytosis to internalize and degrade self as well as foreign material, such as pathogenic bacteria, within phagosomes. These intracellular compartments are equipped to generate antigenic peptides that serve as source for antigen presentation to T cells initiating adaptive immune responses. The phagosomal proteome of DCs is only partially studied, in particular in response to inflammatory cues, and is highly dynamic as it changes during phagosome maturation, when phagosomes sequentially interact with endosomes and lysosomes. In addition, the activation status of the phagocyte can modulate the phagosomal composition and is able to shape phagosomal functions.

In this study, we determined spatiotemporal changes of the proteome of DC phagosomes during their maturation and compared resting and lipopolysaccharide (LPS)-stimulated bone marrow-derived DCs by label-free, quantitative mass spectrometry. Ovalbumin-coupled latex beads were used as phagocytosis model system and revealed that LPS-treated DCs show decreased recruitment of proteins involved in phagosome maturation, such as subunits of the vacuolar proton ATPase, cathepsin B, D, S and RAB7. In contrast, those phagosomes were characterized by an increased recruitment of proteins involved in antigen cross-presentation, e.g. different subunits of MHC I molecules, the proteasome and tapasin, confirming the observed increase in cross-presentation efficacy in those cells. Furthermore, several proteins were identified that were not previously associated with phagosomal functions. Hierarchical clustering of phagosomal proteins demonstrated that their acquisition to DC phagosomes is not only dependent on the duration of phagosome maturation but also on the activation state of DCs. Thus, our study provides a comprehensive overview of how DCs alter their phagosome composition in response to LPS, which has profound impact on the initiation of efficient immune responses.

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Dorsal Augmentation with Diced Conchal Cartilage Wrapped in Retroauricular Fascia

Abstract

Background

Dorsal augmentation is of primary importance to shape an ideal nose. Although costal cartilage is still used for this purpose, diced cartilage grafts wrapped in autogenous fascia became more and more popular in recent decades. In this paper, the authors report their experience with a new combination made by diced conchal cartilage wrapped in retroauricular fascia in primary and secondary cases.

Methods

The clinical records of the first 19 patients to undergo dorsal augmentation with this technique were reviewed. The entire concha has been harvested and, once diced, wrapped in a sleeve of retroauricular fascia obtained using the same incision. Quilting reabsorbable sutures closed the mastoid dead space and prevented the risk of hematoma. The graft has been used in all the cases through a closed approach.

Conclusion

The use of diced cartilage is nowadays considered one of the best options among the available procedures for dorsal augmentation. Diced conchal cartilage wrapped in posterior auricular fascial graft is a new, simple and safe procedure that eliminates the necessity of a secondary donor site (temple or thorax), speeds up the operation and leaves a well-concealed scar behind the ear. Its main disadvantages toward costal diced cartilage wrapped in rectus abdominis fascia are the minor quantity of cartilage that can be obtained, even in case of bilateral harvest, and compared to temporal fascia a longer postoperative swelling (6–8 weeks).

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

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Interleukin 21 collaborates with interferon-γ for the optimal expression of interferon-stimulated genes and enhances protection against enteric microbial infection

by Shahram Solaymani-Mohammadi, Jay A. Berzofsky

The mucosal surface of the intestinal tract represents a major entry route for many microbes. Despite recent progress in the understanding of the IL-21/IL-21R signaling axis in the generation of germinal center B cells, the roles played by this signaling pathway in the context of enteric microbial infections is not well-understood. Here, we demonstrate that Il21r^-/- mice are more susceptible to colonic microbial infection, and in the process discovered that the IL-21/IL-21R signaling axis surprisingly collaborate with the IFN-γ/IFN-γR signaling pathway to enhance the expression of interferon-stimulated genes (ISGs) required for protection, via amplifying activation of STAT1 in mucosal CD4⁺ T cells in a murine model of Citrobacter rodentium colitis. As expected, conditional deletion of STAT3 in CD4⁺ T cells indicated that STAT3 also contributed importantly to host defense against C. rodentium infection in the colon. However, the collaboration between IL-21 and IFN-γ to enhance the phosphorylation of STAT1 and upregulate ISGs was independent of STAT3. Unveiling this previously unreported crosstalk between these two cytokine networks and their downstream genes induced will provide insight into the development of novel therapeutic targets for colonic infections, inflammatory bowel disease, and promotion of mucosal vaccine efficacy.

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Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation

by Sonia Assil, Nicolas Futsch, Elodie Décembre, Sandrine Alais, Antoine Gessain, François-Loïc Cosset, Renaud Mahieux, Marlène Dreux, Hélène Dutartre

Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs. Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal β-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs. Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity.

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High-risk human papillomavirus oncogenes disrupt the Fanconi anemia DNA repair pathway by impairing localization and de-ubiquitination of FancD2

by Sujita Khanal, Denise A. Galloway

Persistent expression of high-risk HPV oncogenes is necessary for the development of anogenital and oropharyngeal cancers. Here, we show that E6/E7 expressing cells are hypersensitive to DNA crosslinking agent cisplatin and have defects in repairing DNA interstrand crosslinks (ICL). Importantly, we elucidate how E6/E7 attenuate the Fanconi anemia (FA) DNA crosslink repair pathway. Though E6/E7 activated the pathway by increasing FancD2 monoubiquitination and foci formation, they inhibited the completion of the repair by multiple mechanisms. E6/E7 impaired FancD2 colocalization with double-strand breaks (DSB), which subsequently hindered the recruitment of the downstream protein Rad51 to DSB in E6 cells. Further, E6 expression caused delayed FancD2 de-ubiquitination, an important process for effective ICL repair. Delayed FancD2 de-ubiquitination was associated with the increased chromatin retention of FancD2 hindering USP1 de-ubiquitinating activity, and persistently activated ATR/CHK-1/pS565 FancI signaling. E6 mediated p53 degradation did not hamper the cell cycle specific process of FancD2 modifications but abrogated repair by disrupting FancD2 de-ubiquitination. Further, E6 reduced the expression and foci formation of Palb2, which is a repair protein downstream of FancD2. These findings uncover unique mechanisms by which HPV oncogenes contribute to genomic instability and the response to cisplatin therapies.

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Complete protection of the BALB/c and C57BL/6J mice against Ebola and Marburg virus lethal challenges by pan-filovirus T-cell epigraph vaccine

by Md Niaz Rahim, Edmund G. Wee, Shihua He, Jonathan Audet, Kevin Tierney, Nathifa Moyo, Zara Hannoun, Alison Crook, Andrea Baines, Bette Korber, Xiangguo Qiu, Tomáš Hanke

There are a number of vaccine candidates under development against a small number of the most common outbreak filoviruses all employing the virus glycoprotein (GP) as the vaccine immunogen. However, antibodies induced by such GP vaccines are typically autologous and limited to the other members of the same species. In contrast, T-cell vaccines offer a possibility to design a single pan-filovirus vaccine protecting against all known and even likely existing, but as yet unencountered members of the family. Here, we used a cross-filovirus immunogen based on conserved regions of the filovirus nucleoprotein, matrix and polymerase to construct simian adenovirus- and poxvirus MVA-vectored vaccines, and in a proof-of-concept study demonstrated a protection of the BALB/c and C57BL/6J mice against high, lethal challenges with Ebola and Marburg viruses, two distant members of the family, by vaccine-elicited T cells in the absence of GP antibodies.

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Colonization of the tsetse fly midgut with commensal Kosakonia cowanii Zambiae inhibits trypanosome infection establishment

by Brian L. Weiss, Michele A. Maltz, Aurélien Vigneron, Yineng Wu, Katharine S. Walter, Michelle B. O'Neill, Jingwen Wang, Serap Aksoy

Tsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infected animals and reducing tsetse population densities. However, relevant programs are costly, labor intensive and difficult to sustain. As such, novel strategies aimed at reducing tsetse vector competence require development. Herein we investigated whether Kosakonia cowanii Zambiae (Kco_Z), which confers Anopheles gambiae with resistance to Plasmodium, is able to colonize tsetse and induce a trypanosome refractory phenotype in the fly. Kco_Z established stable infections in tsetse's gut and exhibited no adverse effect on the fly's survival. Flies with established Kco_Z infections in their gut were significantly more refractory to infection with two distinct trypanosome species (T. congolense, 6% infection; T. brucei, 32% infection) than were age-matched flies that did not house the exogenous bacterium (T. congolense, 36% infected; T. brucei, 70% infected). Additionally, 52% of Kco_Z colonized tsetse survived infection with entomopathogenic Serratia marcescens, compared with only 9% of their wild-type counterparts. These parasite and pathogen refractory phenotypes result from the fact that Kco_Z acidifies tsetse's midgut environment, which inhibits trypanosome and Serratia growth and thus infection establishment. Finally, we determined that Kco_Z infection does not impact the fecundity of male or female tsetse, nor the ability of male flies to compete with their wild-type counterparts for mates. We propose that Kco_Z could be used as one component of an integrated strategy aimed at reducing the ability of tsetse to transmit pathogenic trypanosomes.

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Killing two birds with one stone: How the respiratory syncytial virus polymerase initiates transcription and replication

by Sarah L. Noton, Chadene Z. Tremaglio, Rachel Fearns

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The selective autophagy receptors Optineurin and p62 are both required for zebrafish host resistance to mycobacterial infection

by Rui Zhang, Monica Varela, Wies Vallentgoed, Gabriel Forn-Cuni, Michiel van der Vaart, Annemarie H. Meijer

Mycobacterial pathogens are the causative agents of chronic infectious diseases like tuberculosis and leprosy. Autophagy has recently emerged as an innate mechanism for defense against these intracellular pathogens. In vitro studies have shown that mycobacteria escaping from phagosomes into the cytosol are ubiquitinated and targeted by selective autophagy receptors. However, there is currently no in vivo evidence for the role of selective autophagy receptors in defense against mycobacteria, and the importance of autophagy in control of mycobacterial diseases remains controversial. Here we have used Mycobacterium marinum (Mm), which causes a tuberculosis-like disease in zebrafish, to investigate the function of two selective autophagy receptors, Optineurin (Optn) and SQSTM1 (p62), in host defense against a mycobacterial pathogen. To visualize the autophagy response to Mm in vivo, optn and p62 zebrafish mutant lines were generated in the background of a GFP-Lc3 autophagy reporter line. We found that loss-of-function mutation of optn or p62 reduces autophagic targeting of Mm, and increases susceptibility of the zebrafish host to Mm infection. Transient knockdown studies confirmed the requirement of both selective autophagy receptors for host resistance against Mm infection. For gain-of-function analysis, we overexpressed optn or p62 by mRNA injection and found this to increase the levels of GFP-Lc3 puncta in association with Mm and to reduce the Mm infection burden. Taken together, our results demonstrate that both Optn and p62 are required for autophagic host defense against mycobacterial infection and support that protection against tuberculosis disease may be achieved by therapeutic strategies that enhance selective autophagy.

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Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes

by Aria Ronsmans, Maxime Wery, Ugo Szachnowski, Camille Gautier, Marc Descrimes, Evelyne Dubois, Antonin Morillon, Isabelle Georis

GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes.

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Draft Genome of Burkholderia cenocepacia TAtl-371, a Strain from the Burkholderia cepacia Complex Retains Antagonism in Different Carbon and Nitrogen Sources

Abstract

Burkholderia cenocepacia TAtl-371 was isolated from the rhizosphere of a tomato plant growing in Atlatlahucan, Morelos, Mexico. This strain exhibited a broad antimicrobial spectrum against bacteria, yeast, and fungi. Here, we report and describe the improved, high-quality permanent draft genome of B. cenocepacia TAtl-371, which was sequenced using a combination of PacBio RS and PacBio RS II sequencing methods. The 7,496,106 bp genome of the TAtl-371 strain is arranged in three scaffolds, contains 6722 protein-coding genes, and 99 RNA only-encoding genes. Genome analysis revealed genes related to biosynthesis of antimicrobials such as non-ribosomal peptides, siderophores, chitinases, and bacteriocins. Moreover, analysis of bacterial growth on different carbon and nitrogen sources shows that the strain retains its antimicrobial ability.

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Outside in

by Jonathan Flint

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Correction: TOR-autophagy branch signaling via Imp1 dictates plant-microbe biotrophic interface longevity

by Guangchao Sun, Christian Elowsky, Gang Li, Richard A. Wilson

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Making room for opinions

by Gregory P. Copenhaver, Gregory S. Barsh

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Two isoforms of the RAC-specific guanine nucleotide exchange factor TIAM2 act oppositely on transmission ratio distortion by the mouse t-haplotype

by Yves Charron, Jürgen Willert, Bettina Lipkowitz, Barica Kusecek, Bernhard G. Herrmann, Hermann Bauer

Transmission ratio distortion (TRD) by the mouse t-haplotype, a variant region on chromosome 17, is a well-studied model of non-Mendelian inheritance. It is characterized by the high transmission ratio (up to 99%) of the t-haplotype from t/+ males to their offspring. TRD is achieved by the exquisite ability of the responder (Tcr) to trigger non-Mendelian inheritance of homologous chromosomes. Several distorters (Tcd1-Tcd4), which act cumulatively, together promote the high transmission ratio of Tcr and the t-haplotype. Molecularly, TRD is brought about by deregulation of Rho signaling pathways via the distorter products, which impair sperm motility, and the t-sperm specific rescue of sperm motility by the responder. The t-sperm thus can reach the egg cells faster than +-sperm and fertilize them. Previously we have shown that the responder function is accomplished by a dominant negative form of sperm motility kinase (SMOK^TCR), while the distorter functions are accomplished by the Rho G protein regulators TAGAP, FGD2 and NME3 proposed to function in two oppositely acting pathways. Here we identify the RAC1-specific guanine nucleotide exchange factor TIAM2 as modifier of t-haplotype TRD. Tiam2 is expressed in two isoforms, the full-length (Tiam2l) and a short transcript (Tiam2s). Tiam2s expression from the t-allele is strongly increased compared to the wild-type allele. By transgenic approaches we show that Tiam2s enhances t-haplotype transmission, while Tiam2l has the opposite effect. Our data show that a single modifier locus can encode different gene products exerting opposite effects on a trait. They also suggest that the expression ratio of the isoforms determines if the outcome is an enhancing or a suppressive effect on the trait.

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Genotype-phenotype correlations in ataxia telangiectasia patients with ATM c.3576G>A and c.8147T>C mutations

Background

Ataxia telangiectasia (A-T) is a neurodegenerative disorder. While patients with classic A-T generally die in their 20s, some patients with variant A-T, who have residual ataxia-telangiectasia mutated (ATM) kinase activity, have a milder phenotype. We noticed two commonly occurring ATM mutations that appeared to be associated with prolonged survival and decided to study patients carrying one of these mutations.

Methods

Data were retrospectively collected from the Dutch, Italian, German and French A-T cohorts. To supplement these data, we searched the literature for patients with identical genotypes.

Results

This study included 35 patients who were homozygous or compound heterozygous for the ATM c.3576G>A; p.(Ser1135_Lys1192del58) mutation and 24 patients who were compound heterozygous for the ATM c.8147T>C; p.(Val2716Ala) mutation. Compared with 51 patients with classic A-T from the Dutch cohort, patients with ATM c.3576G>A had a longer survival and were less likely to develop cancer, respiratory disease or immunodeficiency. This was also true for patients with ATM c.8147T>C, who additionally became wheelchair users later in life and had fewer telangiectasias. The oldest patient with A-T reported so far was a 78-year-old patient who was compound heterozygous for ATM c.8147T>C. ATM kinase activity was demonstrated in cells from all patients tested with the ATM c.8147T>C mutant protein and only at a low level in some patients with ATM c.3576G>A.

Conclusion

Compared with classic A-T, the presence of ATM c.3576G>A results in a milder classic phenotype. Patients with ATM c.8147T>C have a variant phenotype with prolonged survival, which in exceptional cases may approach a near-normal lifespan.

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Antihypertensive effects of the hydro-ethanol extract of Senecio serratuloides DC in rats

Senecio serratuloides DC is used in folk medicine for treating hypertension, skin disorders, internal and external sores, rashes, burns and wounds. This study aimed at investigating the antihypertensive effects o...

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Cardiopulmonary resuscitation (CPR) complications encountered in forensic autopsy cases

Cardiopulmonary resuscitation (CPR) provides a significant increase in survival rate, even if performed by bystanders. However, bystanders may refrain from performing CPR for fear of eventual malpractice litig...

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Pre-referral stabilization and compliance with WHO guidelines for trauma care among adult patients referred to an urban emergency department of a tertiary referral hospital in Tanzania

The outcomes of trauma are considered to be time dependent. Efficient and timely pre-referral stabilization of trauma patients has been shown to impact survival. Tanzania has no formal pre-hospital or trauma s...

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Respiratory compromise in children presenting to an urban emergency department of a tertiary hospital in Tanzania: a descriptive cohort study

Respiratory compromise is the leading cause of cardiac arrest and death among paediatric patients. Emergency medicine is a new field in low-income countries (LICs); the presentation, treatment and outcomes of ...

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Effects of Cigarette Smoke on Fat Graft Survival in an Experimental Rat Model

Abstract

Introduction

A fat graft is the closest thing to being the ideal soft tissue filler. Although it has many advantages, reliability of late-term survival is a never-ending debate. Although there are observational studies that research the effect of cigarette smoke on fat graft take in clinical setting, there has not been an objective experimental animal study on the affect of smoking on fat graft survival. The aim of our study is to search if smoking has an affect on fat grafts.

Materials and Methods

Twenty-two Sprague-Dawley type rats were used. Exposure was maintained via a passive smoke exposure system. Rats were divided into three groups regarding their exposure period. At the end of the study, transferred fat grafts were extracted and weighed with a precision scale, an arterial blood sample was taken for biochemical analysis, and grafts were sent to the pathology laboratory for immunohistochemical assessment.

Results

There were meaningful differences between the control group and the other two groups in graft weight loss, serum cotinine, tissue MDA, adipose tissue/fibrosis ratio, stem cell counts, perilipin positive cell density and inflammation density. Furthermore, we detected meaningful correlations between serum cotinine, tissue MDA and graft weight loss.

Conclusion

Fat graft takes with the same mechanisms as a wound heals. So like wound healing, cigarette smoke has a negative affect on fat graft survival. A fat graft is by its nature an elective procedure so to improve our late-term success, cigarette smoke exposure should be kept to a minimum for increased reliability.

No Level Assigned

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

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[ASAP] Plasmon-Induced Direct Hot-Carrier Transfer at Metal–Acceptor Interfaces

ACS Nano

DOI: 10.1021/acsnano.8b08703

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[ASAP] Engineering Graphene Flakes for Wearable Textile Sensors Highly Scalable and Ultrafast Yarn Dyeing Technique

ACS Nano

DOI: 10.1021/acsnano.9b00319

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Anti-Vaxxers Are Here to Stay

So what can officials do to protect the public's health?

-- Read more on ScientificAmerican.com

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