bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sural Nerve Splitting in Reverse Sural Artery Perforator Flap: Anatomical Study in 40 Cadaver Legs
Authors: Kim Hyeonwoo , Hu Julong , Chang Hak , Kim Byung Jun 
Published: July 2017

Background:
The reverse sural artery perforator flap has been widely used in reconstruction of the lower extremity. However, along with the high rate of flap necrosis, sural nerve injury is one of the most frequent complications. This cadaveric study investigated a simple sural nerve preservation technique during reverse sural artery perforator flap surgery.

Methods:
Cadaver dissection was performed on 40 cadaver lower legs, to investigate the pattern of sural nerve distribution. The points where the lateral and medial sural cutaneous nerves penetrate the deep fascia were measured. The converging point of these nerves into the sural nerve was also recorded. Furthermore, the sural nerve was split until no tethering was observed, to simulate the sural nerve–sparing reverse sural artery perforator flap.

Results:
Twenty-nine legs (72.5 percent) showed the lateral and medial sural cutaneous nerves converging to become the sural nerve (combined pattern); seven (17.5 percent) and four legs (10.0 percent) demonstrated the diminished and parallel types, respectively. The distances between the lateral malleolus and the fascia-penetrating point of the lateral and medial sural cutaneous nerves were 29.9 ± 3.3 cm and 18.8 ± 5.6 cm, respectively. In the combined type, the point of convergence was 13.6 ± 4.2 cm from the lateral malleolus. Nerve splitting was successfully performed in all combined cases, without injuring the nerve fascicles.

Conclusions:
The medial sural cutaneous nerve enters the deep fascia significantly more distally than does the lateral sural cutaneous nerve. Furthermore, using nerve splitting, the medial sural cutaneous nerve can be kept intact during reverse sural artery perforator flap surgery.
Factors Associated With Prevalent HIV Infection Among Kenyan MSM: The Anza Mapema Study
Authors: Kunzweiler Colin P. , Bailey Robert C. , Okall Duncan O. , Graham Susan M. , Mehta Supriya D. , Otieno Fredrick O. 
Published: July 2017

Background:
To inform future HIV treatment and care programs for men who have sex with men (MSM), we assessed the prevalence of and factors associated with previously diagnosed HIV-positive and out-of-care (PDOC) or newly diagnosed HIV-positive and out-of-care (NDOC) HIV infection among MSM enrolled in the prospective Anza Mapema cohort study.

Methods:
Participants were aged 18 years and older, reported oral or anal sex with a man in the past 6 months and were not already in HIV care or taking antiretroviral therapy in the past 3 months. At enrollment, men were tested for HIV infection and completed questionnaires through audio computer–assisted self-interview. Multinomial logistic regression was used to identify associations with PDOC or NDOC HIV infection, relative to HIV-negative status.

Results:
Among 711 enrolled men, 75 (10.5%) were seropositive including 21 PDOC and 54 NDOC men. In multivariable modeling, PDOC status was more likely than HIV-negative status among men who had experienced upsetting sexual experiences during childhood, had recently experienced MSM trauma, and did not report harmful alcohol use. NDOC infection status was more common among men aged 30 years and older and who had completed ≤8 years of education, relative to HIV-negative status.

Conclusions:
Most HIV-positive men were unaware of their infection, indicating that HIV testing and counseling services tailored to this population are needed. To improve linkage to and retention in care, HIV testing and care services for MSM should screen and provide support for those with hazardous alcohol use and those who have experienced childhood sexual abuse or MSM trauma.
Examining Chronic Disease, Pain-Related Impairment, and Physical Activity Among Middle-Aged and Older Adults in Canada
Authors: Meisner Brad A. , Linton Vanessa , Séguin Ariane , Spassiani Natasha A. 
Published: July 2017

Purpose:
With high levels of chronic disease and pain-related functional impairment and low levels of physical activity (PA) among middle-aged and older adults, it is important to investigate ways to design age- and health condition–appropriate PA interventions.

Methods:
Using Canadian Community Health Survey data, relationships among chronic disease, pain-related functional impairment, covariates, and PA were examined in mid- (40-59 y; n = 36 288) and later- (60 y+, n = 44 890) life.

Results/Conclusions:
Physical activity levels varied between middle-aged and older groups according to chronic disease and pain-related functional impairment status. Results are useful for developing targeted and tailored PA interventions to support the health of current and future populations.
Langevin Dynamics Simulation of AKAP-PKA Complex: Re-Envisioning the Local Concentration Mechanism for Directing PKA Phosphorylation
Authors: Rigatti Marc , Michalski Paul J. , Dodge-Kafka Kimberly L. , Moraru Ion I. 
Published: July 2017

AbstractThe second messenger cAMP and its effector cAMP-dependent protein kinase A (PKA) constitute a ubiquitous cell signaling system. In its inactive state PKA is composed of two regulatory subunits that dimerize, and two catalytic subunits that are inhibited by the regulatory subunits. Activation of the catalytic subunits occurs upon binding of two molecules of cAMP to each regulatory subunit. Although many receptor types existing within the same cell may use this signaling system, compartmentation of signaling is thought to occur due to A-Kinase Anchoring Proteins (AKAPs), which act to co-localize PKA with specific substrates. However, the molecular mechanism allowing AKAPs to direct PKA phosphorylation to a particular substrate remained elusive, as prior evidence suggested that the catalytic subunit, which is highly diffusible, is released after cAMP binding to the regulatory subunit. Recent evidence from Smith et al. suggests that in the cell, the catalytic subunit may in fact not be released from the AKAP complex [1, 2]. They further demonstrated that alterations in the structure of the PKA regulatory subunit tether affect substrate phosphorylation. We use a novel computational software based on Langevin dynamics, SpringSaLaD, to simulate the AKAP-PKA complex in order to determine a molecular mechanism for the changes in phosphorylation seen with alteration in tether length and flexibility, and to demonstrate whether or not AKAPs can effectively direct PKA phosphorylation to a particular substrate upon release of the catalytic subunit from the complex. We find that short and flexible tethers contribute to a decrease in the average characteristic time of binding, allowing the catalytic subunit to spend more time in a bound state with the substrate, which yields faster characteristic times of phosphorylation. We further demonstrate that release of the catalytic subunit from the AKAP complex abrogates the effect of tethering, with characteristic times of phosphorylation similar to non-AKAP bound PKA. The data demonstrates that AKAPs likely do not release the catalytic subunit in directing PKA phosphorylation to AKAP bound substrates. In combination with the changes in characteristic time of phosphorylation which are driven by tether structure, this work indicates that the purpose of AKAPs may be to increase the efficiency of phosphorylation of particular AKAP substrates.
Cytosine methylation within marine sediment microbial communities: potential epigenetic adaptation to the environment
Authors: Rambo Ian M. , Marsh Adam , Biddle Jennifer F. 
Published: July 2017

AbstractMarine sediments harbor a vast amount of Earth’s microbial biomass, yet little is understood regarding how cells subsist in this low-energy, presumably slow-growth environment. Cells in marine sediments may require additional methods for genetic regulation, such as epigenetic modification via DNA methylation. We investigated this potential phenomenon within a shallow estuary sediment core spanning 100 years of age across its depth. Here we provide evidence of dynamic community m5-cytosine methylation within estuarine sediment metagenomes using a methylation-sensitive Illumina assay. The methylation states of individual CpG sites were reconstructed and quantified across three depths within the sediment core. A total of 6254 CpG sites were aligned for direct comparison of methylation states between samples, with 4235 sites mapped to taxa and genes. Our results demonstrate the presence of differential methylation within environmental CpG sites across an age/depth gradient of sediment. We show that epigenetic modification can be detected within complex environmental communities. The change in methylation state of environmentally relevant genes across depths may indicate a dynamic role of DNA methylation in biogeochemical processes.
Repositioning the Sm-binding site inS. cerevisiaetelomerase RNA reveals RNP organizational flexibility and Sm-directed 3′-end formation
Authors: Hass Evan P. , Zappulla David C. 
Published: July 2017

ABSTRACTTelomerase RNA contains a template for synthesizing telomeric DNA by reverse transcription and has been proposed to act as a flexible scaffold for holoenzyme protein subunits in the RNP. InSaccharomyces cerevisiae, the telomerase subunits Est1 and Ku bind to the telomerase RNA, TLC1, and it has been shown that these proteins still function when their binding sites are repositioned within the RNA. TLC1 is also bound by the Sm7protein complex, which is required for stabilization of the predominant, non-polyadenylated (poly(A)–) TLC1 isoform. Here, we first show that Sm7can perform this function even when its binding site is repositioned via circular permutation to several different positions within TLC1, further supporting the conclusion that the telomerase holoenzyme is organizationally flexible. Next, we tested the hypothesis that the location of the Sm7-binding site relative to the 3′ end is contrastingly important. When we moved the Sm site to locations 5′ of its native position, we observed that this stabilized shorter forms of poly(A)– TLC1 in a manner precisely corresponding to how far upstream the Sm site was moved. This provides strong evidence that the location of Sm7binding to TLC1 controls where the mature poly(A)– 3′ end is formed. In summary, our results show that Sm7and the 3′ end of yeast telomerase RNA comprise an organizationally flexible module within the telomerase RNP and provide insights into the mechanistic role of Sm7in telomerase RNA biogenesis.
Sonic Kayaks: Environmental monitoring and experimental music by citizens
Authors: Griffiths Amber GF , Kemp Kirsty M , Matthews Kaffe , Garrett Joanne K , Griffiths David J 
Published: July 2017

AbstractThe Sonic Kayak is a musical instrument with which to investigate nature, developed during open hacklab events. Kayaks rigged with underwater environmental sensors allow paddlers to hear real-time water temperature sonifications and underwater sounds, generating live music from the marine world. Sensor data is also logged every second with GPS, time and date, allowing fine scale mapping of water temperatures and underwater noise that was previously unattainable using standard research equipment. The system provides the paddler with an extra dimension of senses with which to explore the underwater climate, while enabling citizens to gather data for scientific research. The system can be used as a citizen-science data-collection device, research equipment for professional scientists, or a sound-art installation in its own right, and has been implemented in a public setting at the British Science Festival 2016, demonstrating the considerable advantages of adopting transdisciplinary approaches during project development. Here we present instructions for building the open-hardware and open-source software, tests of the sensors used, and preliminary data demonstrating applications for the Sonic Kayak in marine climate and noise-pollution research.
A Biomaterial Screening Approach Reveals Microenvironmental Mechanisms of Drug Resistance
Authors: Schwartz Alyssa D. , Barney Lauren E. , Jansen Lauren E. , Nguyen Thuy V. , Hall Christopher L. , Meyer Aaron S. , Peyton Shelly R. 
Published: July 2017

TOC FigureDrug response screening, gene expression, and kinome signaling were combined across biomaterial platforms to combat adaptive resistance to sorafenib.Insight BoxWe combined biomaterial platforms, drug screening, and systems biology to identify mechanisms of extracellular matrix-mediated adaptive resistance to RTK-targeted cancer therapies. Drug response was significantly varied across biomaterials with altered stiffness, dimensionality, and cell-cell contacts, and kinome reprogramming was responsible for these differences in drug sensitivity. Screening across many platforms and applying a systems biology analysis were necessary to identify MEK phosphorylation as the key factor associated with variation in drug response. This method uncovered the combination therapy of sorafenib with a MEK inhibitor, which decreased viability on and within biomaterialsin vitro, but was not captured by screening on tissue culture plastic alone. This combination therapy also reduced tumor burdenin vivo,and revealed a promising approach for combating adaptive drug resistance.AbstractTraditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment. We developed an approach to screen drug responses in cells cultured on 2D and in 3D biomaterial environments to explore how key features of ECM mediate drug response. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between thesein vitromodels and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistancein vitroand reducedin vivotumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments.
A large kinome in a large cell:Stentor coeruleuspossesses highly expanded kinase families and novel domain architectures
Authors: Reiff Sarah B. , Marshall Wallace F. 
Published: July 2017

AbstractBackgroundStentor coeruleusis a large ciliated protist, about 1mm in length, with the extraordinary ability to fully regenerate each fragment after being cut into pieces, perfectly restoring cell polarity and morphology. Single-cell regeneration inStentorremains one of the greatest long-standing mysteries of biology, but the recently publishedStentorgenome now enables studies on this organism at the molecular and genetic levels. Here we characterize the complete complement of kinases, or kinome, ofStentor, in order to begin to understand the signaling capacities that underlieStentor’s unique biology.ResultsThe genome ofS. coeruleuscontains over 2000 kinases, representing 6% of the predicted proteome. Classification of the kinase genes reveals large expansions in several kinase families, particularly in the CDPKs, the DYRKs, and in several mitotic kinase families including the PLKs, NEKs, and Auroras. The large expansion of the CDPK and DYRK kinase families is an unusual feature of theStentorkinome compared to other ciliates with sequenced genomes. The DYRK family inStentor, notably, contains only a single pseudokinase which may suggest an important role inStentorgrowth and survival, while the smaller PEK family contains a novel pseudokinase subfamily. TheStentorkinome also has examples of new domain architectures that have not been previously observed in other organisms.ConclusionOur analysis provides the first gene-level view into the signaling capabilities ofStentorand will lay the foundation for unraveling how this organism can coordinate processes as complex as regeneration throughout a giant cell.
Flexible, multi-use, PCR-based nucleic acid integrity assays based on the ubiquitin C gene
Authors: Van Poucke Mario , Peelman Luc J. 
Published: July 2017

ABSTRACTNucleic acid integrity assessment is an important aspect of quality control for many applications in molecular biology. A number of methods exist (electrophoresis- or PCR-based), but they are not universally applicable. Some of them need huge amounts of input, process certain amount of samples, require expensive equipment, only work specifically on (c)DNA, (m)RNA, certain species or certain tissues, or produce fragments covering a small length range. We investigated if the ubiquitin C gene (UBC) could be used to develop flexible, multi-use PCR-based (deoxy)ribonucleic acid integrity assays. UBC gene analysis (in human, mouse, pig, cow, horse, sheep, dog and cat) shows that UBC is a highly conserved and ubiquitously expressed gene (reference gene in RT-qPCR), that encodes a polyubiquitin precursor (containing tandem repeats of at least 5 ubiquitin monomers of 228 bp) in a single exon. On average, ubiquitin monomers show a nucleic acid sequence identity of 96% at intraspecies level and 93% at interspecies level. Based on a multiple alignment of all monomer ubiquitin sequences of all investigated species, we could design a single degenerated primer pair generating PCR amplicons of 137, 365, 593 and 821 bp on low amounts of high quality DNA of all investigated species (down to 10 pg) and on cDNA reverse transcribed from high quality RNA from different tissues (e.g. heart, liver, brain, kidney). Increasing levels of nucleic acid degradation resulted in a decrease of amplification products starting with the longer amplicons. We conclude that UBC is suited to develop a single, cheap, universal assay to estimate the presence, integrity and amplificability of native mammalian nucleic acids. In addition, we used the same strategy to design a similar assay to check the quality of bisulfite treated mammalian DNA.
Convergent evolution as an indicator for selection during acute HIV-1 infection
Authors: Bertels Frederic , Metzner Karin J. , Regoes Roland 
Published: July 2017

AbstractConvergent evolution describes the process of different populations acquiring similar phenotypes or genotypes. Complex organisms with large genomes only rarely and only under very strong selection converge to the same genotype. In contrast, independent virus populations with very small genomes often acquire identical mutations. Here we test the hypothesis of whether convergence in early HIV-1 infection is common enough to serve as an indicator for selection. To this end, we measure the number of convergent mutations in a well-studied dataset of full-length HIV-1envgenes sampled from HIV-1 infected individuals during early infection. We compare this data to a neutral model and find an excess of convergent mutations. Convergent mutations are not evenly distributed across the env gene, but more likely to occur in gp41, which suggests that convergent mutations provide a selective advantage and hence are positively selected. In contrast, mutations that are only found in an HIV-1 population of a single individual are significantly affected by purifying selection. Our analysis suggests that comparisons between convergent and private mutations with neutral models allow us to identify positive and negative selection in small viral genomes. Our results also show that selection significantly shapes HIV-1 populations even before the onset of the adaptive immune system.
Remodeling of ER-exit sites initiates a membrane supply pathway for autophagosome biogenesis
Authors: Ge Liang , Zhang Min , Kenny Samuel J , Liu Dawei , Maeda Miharu , Saito Kota , Mathur Anandita , Xu Ke , Schekman Randy 
Published: July 2017

AbstractAutophagosomes are double-membrane vesicles generated during autophagy. Biogenesis of the autophagosome requires membrane acquisition from intracellular compartments, the mechanisms of which are unclear. We previously found that a relocation of COPII machinery to the ER-Golgi intermediate compartment (ERGIC) generates ERGIC-derived COPII vesicles which serve as a membrane precursor for the lipidation of LC3, a key membrane component of the autophagosome. Here we employed super-resolution microscopy to show that starvation induces the enlargement of ER-exit sites (ERES) positive for the COPII activator, SEC12, and the remodeled ERES patches along the ERGIC. A SEC12 binding protein, CTAGE5, is required for the enlargement of ERES, SEC12 relocation to the ERGIC, and modulates autophagosome biogenesis. Moreover, FIP200, a subunit of the ULK protein kinase complex, facilitates the starvation-induced enlargement of ERES independent of the other subunits of this complex and associates via its C-terminal domain with SEC12. Our data indicate a pathway wherein FIP200 and CTAGE5 facilitate starvation-induced remodeling of the ERES, a prerequisite for the production of COPII vesicles budded from the ERGIC that contribute to autophagosome formation.
Corrosion behavior of carbon steel in chloride contaminated simulated concrete pore solution with carboxylate of benzoic acid and dimethylethanolamine
Authors: Liu J.Z. , Cai Jing Shun , Shi L. , Zhao D. , Chen C.C. , Jiang Q. , Sha J.F. 
Published: July 2017

PurposeThe purpose of this study is to investigate the inhibition efficiency and mechanism of a specific carboxylate corrosion inhibitor which consists of benzoic acid and dimethylethanolamine on steel surface.Design/methodology/approachThe performance of carbon steel influenced by this organic inhibitor under different concentration of Cl−and immersion time was studied by linear polarization resistance and electrochemical impedance spectroscopy in a simulated concrete pore (SCP) solution. The surface morphology and composition of steel was also analyzed by optical microscopy, SEM and EDS to investigate the effect of inhibitor on the pattern of the steel surface after long-term immersion.FindingsCarboxylate of benzoic acid and dimethylethanolamine can increase the chloride threshold level and decrease the corrosion area of carbon steel in SCP solution with 0.6 mol/L Cl−even after 120 days exposure. The inhibition mechanism of inhibitor lies in quick adsorption and buffering effect at initial time then formed deposited layer on steel surface after long-term immersion in chloride-rich environment.Originality/valueIt demonstrated that the carboxylate corrosion inhibitor not only can improve the chloride threshold level for carbon steel but also effectively decrease the corrosion rate even in chloride-rich SCP solution after long-term immersion, which is different form the conventional amino alcohol.