bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated HIV Prevalence and Correlates of PrEP Use Among a Community Sample of Black Men Who Have Sex With Men
Authors: Eaton Lisa A. , Matthews Derrick D. , Bukowski Leigh A. , Friedman M. Ruvel , Chandler Cristian J. , Whitfield Darren L. , Sang Jordan M. , Stall Ron D. ,   The POWER Study Team
Published: August 2018

Background:
The HIV epidemic among black men who have sex with men (BMSM) demands urgent public health attention. Pre-exposure prophylaxis (PrEP) is a highly efficacious option for preventing HIV, but characteristics of PrEP use among community samples of BMSM are not well-understood.

Methods:
A serial cross-sectional survey assessment (N = 4184 BMSM reporting HIV-negative/unsure status) and HIV testing were conducted at Black Gay Pride events in 6 US cities in 2014, 2015, 2016, and 2017.

Results:
HIV prevalence was higher among BMSM self-reporting current PrEP use (1 of 3 participants) than BMSM not self-reporting current PrEP use (1 of 5 participants) [32.3%, N = 103/319 vs. 20.0%, N = 639/3,193, adjusted odds ratio (aOR) = 1.68, 95% confidence interval (CI): 1.31 to 2.15]. BMSM reporting current PrEP use (N = 380) were more likely to report having a greater number of male sex partners (aOR = 1.02, 95% CI: 1.01 to 1.03), a sexually transmitted infection diagnosis (aOR = 2.44, 95% CI: 1.88 to 3.16), and stimulant drug use (aOR = 2.05, 95% CI, 1.21 to 3.47) when compared with BMSM not reporting current PrEP use (N = 3804). PrEP use increased from 4.7% (2014) to 15.5% (2017) (aOR = 1.19, 95% CI: 1.13 to 1.25). Among PrEP users, inability to afford health care coverage was associated with testing HIV-positive (aOR = 2.10, 95% CI: 1.24 to 3.56).

Conclusions:
The high prevalence of HIV infection among BMSM reporting PrEP use is concerning. It does not, however, challenge the efficacy of PrEP itself but rather the uptake of the surrounding preventative package including behavioral risk reduction support, sexually transmitted infection treatment, and medication adherence counseling. Further research to understand barriers to fully effective PrEP is needed to guide operational and behavioral interventions that close the gap on incident infection.
Partial Deletion of Tie2 Affects Microvascular Endothelial Responses to Critical Illness in A Vascular Bed and Organ-Specific Way
Authors: Jongman Rianne M. , Zwiers Peter J. , van de Sluis Bart , van der Laan Marleen , Moser Jill , Zijlstra Jan G. , Dekker Daphne , Huijkman Nicolette , Moorlag Henk E. , Popa Eliane R. , Molema Grietje , van Meurs Matijs 
Published: August 2018

ABSTRACT
Tyrosine kinase receptor (Tie2) is mainly expressed by endothelial cells. In animal models mimicking critical illness, Tie2 levels in organs are temporarily reduced. Functional consequences of these reduced Tie2 levels on microvascular endothelial behavior are unknown. We investigated the effect of partial deletion of Tie2 on the inflammatory status of endothelial cells in different organs. Newly generated heterozygous Tie2 knockout mice (exon 9 deletion, ΔE9/Tie2+/−) exhibiting 50% reduction in Tie2 mRNA and protein, and wild-type littermate controls (Tie2+/+), were subjected to hemorrhagic shock and resuscitation (HS + R), or challenged with i.p. lipopolysaccharide (LPS). Kidney, liver, lung, heart, brain, and intestine were analyzed for mRNA levels of adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular cell adhesion molecule 1 (ICAM-1), and CD45. Exposure to HS + R did not result in different expression responses of these molecules between organs from Tie2+/− or Tie2+/+ mice and sham-operated mice. In contrast, the LPS-induced mRNA expression levels of E-selectin, VCAM-1, and ICAM-1, and CD45 in organs were attenuated in Tie2+/− mice when compared with Tie2+/+ mice in kidney and liver, but not in the other organs studied. Furthermore, reduced expression of E-selectin and VCAM-1 protein, and reduced influx of CD45+ cells upon LPS exposure, was visible in a microvascular bed-specific pattern in kidney and liver of Tie2+/− mice compared with controls. In contrast to the hypothesis that a disbalance in the Ang/Tie2 system leads to increased microvascular inflammation, heterozygous deletion of Tie2 is associated with an organ-restricted, microvascular bed-specific attenuation of endothelial inflammatory response to LPS.
Does Surgical Margin Impact Recurrence in Noninvasive Intraductal Papillary Mucinous Neoplasms?
Authors: Dhar Vikrom K. , Merchant Nipun B. , Patel Sameer H. , Edwards Michael J. , Wima Koffi , Imbus Joseph , Abbott Daniel E. , Weber Sharon M. , Louie Raphael , Kim Hong J. , Martin Robert C. G. , Scoggins Charles R. , Bentrem David J. , LeCompte Michael T. , Idrees Kamran , Lopez-Aguiar Alexandra G. , Maithel Shishir K. , Kooby David A. , Franco Daniel A. , Yakoub Danny , Ahmad Syed A. 
Published: August 2018

Objective:
The relevance of margin positivity on recurrence after resection of intraductal papillary mucinous neoplasms (IPMNs) is poorly defined and represents one reason controversy remains regarding optimal surveillance recommendations.

Methods:
Patients undergoing surgery for noninvasive IPMN at 8 academic medical centers from the Central Pancreas Consortium were analyzed. A positive margin was defined as presence of IPMN or pancreatic intraepithelial neoplasia.

Results:
Five hundred two patients underwent surgery for IPMN; 330 (66%) did not have invasive cancer on final pathology and form the study cohort. Of these, 20% harbored high grade dysplasia. A positive margin was found in 20% of cases and was associated with multifocal disease (P = 0.02). The majority of positive margins were associated with low grade dysplasia. At a median follow-up of 36 months, 34 (10.3%) patients recurred, with 6.7% developing recurrent cystic disease and 3.6% developing invasive cancer. On multivariate analysis, margin positivity was not associated with recurrence of either IPMN or invasive cancer (P > 0.05). No association between margin status and development of recurrence at the margin was found. Only 6% of recurrences developed at the resection margin and median time to recurrence was 22 months. Of note, 18% of recurrences occurred > 5 years following surgery.

Conclusion:
Margin positivity after resection for noninvasive IPMNs is primarily due to low grade dysplasia and is not associated with developing recurrence in the remnant pancreas or at the resection margin. Long-term surveillance is required for all patients, as a significant number of recurrences developed over 5 years after the index operation.
Synthetic metabolic pathways for photobiological conversion of CO2 into hydrocarbon fuel
Authors: Yunus Ian Sofian , Wichmann Julian , Wördenweber Robin , Lauersen Kyle J. , Kruse Olaf , Jones Patrik R. 
Published: August 2018

ABSTRACTLiquid fuels sourced from fossil sources are the dominant energy form for mobile transport today. The consumption of fossil fuels is still increasing, resulting in a continued search for more sustainable methods to renew our supply of liquid fuel. Photosynthetic microorganisms naturally accumulate hydrocarbons that could serve as a replacement for fossil fuel, however productivities remain low. We report successful introduction of five synthetic metabolic pathways in two green cell factories, prokaryotic cyanobacteria and eukaryotic algae. Heterologous thioesterase expression enabled high-yield conversion of native acyl-ACP into free fatty acids (FFA) in Synechocystis sp. PCC 6803 but not in Chlamydomonas reinhardtii where the polar lipid fraction instead was enhanced. Despite no increase in measurable FFA in Chlamydomonas, genetic recoding and over-production of the native fatty acid photodecarboxylase (FAP) resulted in increased accumulation of 7-heptadecene. Implementation of a carboxylic acid reductase (CAR) and aldehyde deformylating oxygenase (ADO) dependent synthetic pathway in Synechocystis resulted in the accumulation of fatty alcohols and a decrease in the native saturated alkanes. In contrast, the replacement of CAR and ADO with Pseudomonas mendocina UndB (so named as it is responsible for 1-undecene biosynthesis in Pseudomonas) or Chlorella variabilis FAP resulted in high-yield conversion of thioesterase-liberated FFAs into corresponding alkenes and alkanes, respectively. At best, the engineering resulted in an increase in hydrocarbon accumulation of 8- (from 1 to 8.5 mg/g dell dry weight) and 19-fold (from 4 to 77 mg/g cell dry weight) for Chlamydomonas and Synechocystis, respectively. In conclusion, reconstitution of the eukaryotic algae pathway in the prokaryotic cyanobacteria host generated the most effective system, highlighting opportunities for mix-and-match synthetic metabolism. These studies describe functioning synthetic metabolic pathways for hydrocarbon fuel synthesis in photosynthetic microorganisms for the first time, moving us closer to the commercial implementation of photobiocatalytic systems that directly convert CO2 into infrastructure-compatible fuels.HighlightsSynthetic metabolic pathways for hydrocarbon fuels were engineered in algaeFree fatty acids were effectively converted into alkenes and alkanesTransfer of algal pathway into cyanobacteria was the most effectiveAlkane yield was enhanced 19-fold in Synechocystis spp. PCC 6803Alkene yield was enhanced 8-fold in Chlamydomonas reinhardtii
An Ishihara-style test of animal colour vision
Authors: Cheney Karen L. , Green Naomi F. , Vibert Alexander P. , Vorobyev Misha , Marshall N. Justin , Osorio Daniel C. , Endler John A. 
Published: August 2018

AbstractColour vision mediates ecologically relevant tasks for many animals, such as mate choice, foraging and predator avoidance. However, our understanding of animal colour perception is largely derived from human psychophysics, even though animal visual systems differ from our own. Behavioural tests of non-human animals are required to understand how colour signals are perceived by them.Here we introduce a novel test of colour vision in animals inspired by the Ishihara colour charts, which are widely used to identify human colour deficiencies. These charts consist of dots that vary in colour, brightness and size, and are designed so that a numeral or letter is distinguishable from distractor dots for humans with normal colour vision. In our method, distractor dots have a fixed chromaticity (hue and saturation) but vary in luminance. Animals can be trained to find single target dots that differ from distractor dots in chromaticity. We provide Matlab code for creating these stimuli, which can be modified for use with different animals.We demonstrate the success of this method with triggerfìsh, Rhinecanthus aculeatus, and highlight behavioural parameters that can be measured, including success of finding the target dot, time to detect dot and error rate. Triggerfìsh quickly learnt to select target dots that differed from distractors dots regardless of the particular hue or saturation, and proved to use acute colour vision. We measured discrimination thresholds by testing the detection of target colours that were of increasing colour distances (ΔS) from distractor dots in different directions of colour space. At least for some colours, thresholds indicated better discrimination than expected from the Receptor Noise Limited (RNL) model assuming 5% Weber fraction for the long-wavelength cone.This methodology seems to be highly effective because it resembles natural foraging behavior for the triggerfìsh and may well be adaptable to a range of other animals, including mammals, birds, bees and freshwater fish. Other questions may be addressed using this methodology, including luminance thresholds, sensory bias, effects of sensory noise in detection tasks, colour categorization and saliency.
Characterizing Activity and Thermostability of GH5 Cellulase Chimeras from Mesophilic and Thermophilic Parents
Authors: Zheng Fei , Vermaas Josh V. , Zheng Jie , Wang Yuan , Tu Tao , Wang Xiaoyu , Xie Xiangming , Yao Bin , Beckham Gregg T. , Luo Huiying 
Published: August 2018

ABSTRACTCellulases from glycoside hydrolase (GH) family 5 are key enzymes in the degradation of diverse polysaccharide substrates and are used in industrial enzyme cocktails to break down biomass. The GH5 family shares a canonical (βα)8-barrel structure, where each (βα) module is essential for the enzyme stability and activity. Despite their shared topology, the thermostability of GH5 enzymes can vary significantly, and highly thermostable variants are often sought for industrial applications. Based on a previously characterized thermophilic GH5 cellulase from Talaromyces emersonii (TeEgl5A, with an optimal temperature of 90°C), we created ten hybrid enzymes with the mesophilic cellulase from Prosthecium opalus (PoCel5) to determine which elements are responsible for enhanced thermostability. Five of the expressed hybrid enzymes exhibit enzyme activity. Two of these hybrids exhibited pronounced increases in the temperature optima (10 and 20°C), T50 (15 and 19°C), Tm (16.5 and 22.9°C), and extended half life, t1/2 (~240- and 650-fold at 55°C) relative to the mesophilic parent enzyme, and demonstrated improved catalytic efficiency on selected substrates. The successful hybridization strategies were validated experimentally in another GH5 cellulase from Aspergillus nidulans (AnCel5), which demonstrated a similar increase in thermostability. Based on molecular dynamics simulations (MD) of both PoCel5 and TeEgl5A parent enzymes as well as their hybrids, we hypothesize that improved hydrophobic packing of the interface between α2 and α3 is the primary mechanism by which the hybrid enzymes increase their thermostability relative to the mesophilic parent PoCel5.IMPORTANCEThermal stability is an essential property of enzymes in many industrial biotechnological applications, as high temperatures improve bioreactor throughput. Many protein engineering approaches, such as rational design and directed evolution, have been employed to improve the thermal properties of mesophilic enzymes. Structure-based recombination has also been used to fuse TIM-barrel fragments and even fragments from unrelated folds, to generate new structures. However, there are not many research on GH5 cellulases. In this study, two GH5 cellulases, which showed TIM-barrel structure, PoCel5 and TeEgl5A with different thermal properties were hybridized to study the roles of different (βα) motifs. This work illustrates the role that structure guided recombination can play in helping to identify sequence function relationships within GH5 enzymes by supplementing natural diversity with synthetic diversity.
Magnetic resonance spectroscopy analysis of intramyocellular lipid composition in lipodystrophic patients and athletes
Authors: Savage David B , Watson Laura , Carr Katie , Adams Claire , Brage Soren , Chatterjee Krishna K , Hodson Leanne , Boesch Chris , Kemp Graham J , Sleigh Alison 
Published: August 2018

AbstractContextParadoxically, intramyocellular lipid (IMCL) accumulation has been linked to both insulin-resistant and to insulin-sensitive (athletes) states. The composition of this lipid store is unknown in these states.Design and MethodsWe used a recently validated and potentially widely applicable 1H magnetic resonance spectroscopy method to compare the compositional saturation index (CH2:CH3 ratio) and concentration independent of composition (CH3) of intramyocellular lipid in the soleus and tibialis anterior muscles of 16 female insulin-resistant lipodystrophic patients with that of age- and gender-matched athletes (n=14) and healthy controls (n = 41).Main OutcomeIMCL compositional saturation index (CH2:CH3 ratio).ResultsThe IMCL CH2:CH3 ratio was significantly higher in both muscles of the lipodystrophic patients compared with age- and gender-matched controls but not compared to athletes. IMCL CH2:CH3 was dependent on IMCL concentration in the controls and after adjusting the composition index for quantity (CH2:CH3adj) was able to distinguish patients from athletes. With groups pooled, this CH2:CH3adj marker had the strongest relation to insulin resistance (HOMA-IR) compared to other measures of lipid concentration and composition, especially in the soleus muscle. Contrary to the ‘athlete’s paradox’, IMCL in athletes was similar in tibialis anterior (p>0.05) and significantly lower in the soleus (p < 0.004) compared to both controls and patients.ConclusionsThe IMCL saturation index adjusted for quantity, which likely reflects accumulation of saturated IMCL, is more closely associated with insulin resistance than concentration alone.
Measuring “Intolerance to Mutation” in Human Genetics
Authors: Fuller Zachary L. , Berg Jeremy J. , Mostafavi Hakhamanesh , Sella Guy , Przeworski Molly 
Published: August 2018

AbstractIn numerous applications, from working with animal models to mapping the genetic basis of human disease susceptibility, it is useful to know whether a single disrupting mutation in a gene is likely to be deleterious1–4. With this goal in mind, a number of measures have been developed to identify genes in which protein-truncating variants (PTVs), or other types of mutations, are absent or kept at very low frequency in large population samples—genes that appear “intolerant to mutation”3,5–9. One measure in particular, pLI, has been widely adopted7. By contrasting the observed versus expected number of PTVs, it aims to classify genes into three categories, labelled “null”, “recessive” and “haploinsufficient”7. Such population genetic approaches can be useful in many applications. As we clarify, however, these measures reflect the strength of selection acting on heterozygotes, and not dominance for fitness or haploinsufficiency for other phenotypes.
Cell type-specific structural plasticity of the ciliary transition zone inC. elegans
Authors: Akella Jyothi S. , Silva Malan , Morsci Natalia S. , Nguyen Ken C. , Rice William J. , Hall David H. , Barr Maureen M. 
Published: August 2018

AbstractBackground informationThe current consensus on cilia development posits that the ciliary transition zone (TZ) is formed via extension of nine centrosomal microtubules. In this model, TZ structure remains unchanged in microtubule number throughout the cilium life cycle. This model does not however explain structural variations of TZ structure seen in nature, and could also lend itself to the misinterpretation that deviations from nine-doublet microtubule ultrastructure represent an abnormal phenotype. Thus, a better understanding of events that occur at the TZin vivoduring metazoan development is required.ResultsTo address this issue, we characterized ultrastructure of two types of sensory cilia in developingCaenorhabditis elegans. We discovered that, in cephalic male (CEM) and inner labial quadrant (IL2Q) sensory neurons, ciliary TZs are structurally plastic and remodel from one structure to another during animal larval development. The number of microtubules doublets forming the TZ can be increased or decreased over time, depending on cilia type. Both cases result in structural TZ intermediates different from TZ in adult cilia. In CEM cilia, axonemal extension and maturation occurs concurrently with TZ structural maturation.Conclusions and SignificanceOur work extends the current model to include the structural plasticity of metazoan transition zone, which can be structurally delayed, maintained or remodeled in cell type-specific manner.
A molecular inversion probe and sequencing-based microsatellite instability assay for high throughput cancer diagnostics and Lynch syndrome screening
Authors: Gallon Richard , Hayes Christine , Redford Lisa , Alhilal Ghanim , O’Brien Ottie , Waltham Amanda , Needham Stephanie , Arends Mark , Oniscu Anca , Alonso Angel Miguel , Laguna Sira Moreno , Sheth Harsh , Santibanez-Koref Mauro , Jackson Michael S , Burn John 
Published: August 2018

AbstractBackgroundClinical guidelines recommend microsatellite instability (MSI) and BRAF V600E testing of all colorectal cancers (CRCs) to screen for Lynch syndrome (LS), a hereditary predisposition to cancer. MSI is also associated with response to immunotherapy. However, uptake of MSI testing is poor and current assays are not suitable for high throughput diagnostics.We aimed to develop a cheap and scalable sequencing assay for MSI classification, which is robust to variables in clinical samples and simultaneously tests for BRAF V600E to streamline the LS screening pipeline.Methods24 short (7-12bp) microsatellites and the BRAF V600E locus were amplified in multiplex using single molecule molecular inversion probes (smMIPs) and sequenced using the Illumina MiSeq platform. Reads were aligned to reference genome hg19. An MSI classifier was trained from 98 CRCs and validated in 99 independent CRCs collected in pathology laboratories in Edinburgh, Spain and Newcastle.ResultsThe smMIP-based MSI assay has 100% accuracy for MSI status relative to MSI Analysis System (Promega). MSI classification is reproducible (100% concordance) and is robust to sample variables, detecting less than 5% MSI-high content in template DNA and giving reliable classification from sequencing only 75 DNA molecules per marker. BRAF V600E was detected with mutant allele frequencies down to 1.7%.ConclusionsOur short microsatellite, smMIP-based, MSI assay provides a cheap and fully automatable assessment of MSI status and BRAF mutation. It is readily scalable to high throughput cancer diagnostics, and is suitable both as a companion diagnostic for immunotherapy and for streamlined LS screening.
Liquid droplet germ granules require assembly and localized regulators for mRNA repression
Authors: Aoki Scott Takeo , Lynch Tina R , Crittenden Sarah L , Bingman Craig A , Wickens Marvin , Kimble Judith 
Published: August 2018

SummaryCytoplasmic RNA-protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P-granules are paradigmatic liquid droplet granules and central to germ cell development. Here we analyze a key P-granule scaffolding protein, called PGL, to investigate the functional relationship between P-granule assembly and function. Using a protein-RNA tethering assay, we find that reporter mRNA expression is repressed when recruited to PGL granules. We determine the crystal structure of the PGL N-terminal region to 1.5 Å, discover its dimerization and identify key residues at the dimer interface.In vivomutations of those interface residues prevent P-granule assembly, de-repress PGL-tethered mRNA and reduce fertility. Therefore, PGL dimerization lies at the heart of both P-granule assembly and function. Finally, we identify the P-granule-associated Argonaute WAGO-1 as crucial for repression of PGL-tethered mRNA. We conclude that P-granule function requires both assembly and localized regulators.