bluuebunny/crossref_metadata_2025 huggingface dataset:
Posttransplant Cyclophosphamide for HLA-haploidentical Transplantation in Patients With Mucopolysaccharidosis
Authors: Yue Yan , Song Zeliang , Li Junhui , Feng Shunqiao , Liu Rong , Shi Xiaodong
Published: April 2018

We successfully used a haploidentical transplantation protocol with posttransplant cyclophosphamide (CY) (50 mg/kg/d on days +3 and +4) for in vivo T-cell depletion in patients with mucopolysaccharidosis using reduced-intensive conditioning regimens, followed by a busulfan-based conditioning regimen, which included busulfan (12 to 16 mg/kg) and fludarabine(150 to 200 mg/m2)+rabbit antihuman thymocyte globulin (7.5 to 10 mg/kg) as a conditioning regimen. Cyclosporine or tacrolimus, methotrexate, mycophenolate mofetil, and methylprednisolone were administered to prevent graft-versus-host disease (GVHD). After follow-up for a median period of 1.5 years, all 8 patients without preexisting severe comorbidities and early transplant referrals are alive, with 100% donor chimerism and excellent performance status. Only 1 patient developed chronic GVHD(II). We conclude that posttransplant CY is effective in vivo for T-cell depletion to promote full donor engraftment in patients with mucopolysaccharidosis. In addition, with posttransplant CY, the procedure reduced the rate of GVHD and the cost of transplant and improved the patients’ quality of life.
Clostridium difficile infection: a review
Authors: Kouhsari Ebrahim , Abbasian Sara , Sedighi Mansour , Yaseri Hashem F. , Nazari Shahram , Bialvaei Abed Z. , Dahim Parisa , Mirzaei Elnaze Z. , Rahbar Mohammad
Published: April 2018

Clostridium difficile, as one of the main bacterial causes of diarrhea, is an important healthcare-associated pathogen. It is also the main causative agent of antibiotic-associated diarrhea and pseudomembranous colitis. The C. difficile infection is a life threatening disease, and there is an urgent need to control its spread in healthcare centers. This review summarizes the most recent work on epidemiology and interactions between host and C. difficile.
Ovarian Sertoli-Leydig Cell Tumor With Heterologous Hepatocytes and a Hepatocellular Carcinomatous Element
Authors: Yamamoto Sohei , Sakai Yu
Published: April 2018

Sertoli-Leydig cell tumors are a group of tumors composed of variable proportions of Sertoli cells, Leydig cells, and sometimes heterologous elements. We describe the case of a 68-yr-old woman who presented with abdominal distention. A computed tomographic scan revealed a large right adnexal mass without evidence of intrahepatic tumors, and a complete cytoreductive surgery was performed. Pathologic examination revealed a moderately differentiated Sertoli-Leydig cell tumor with various heterologous elements, including gastrointestinal-type glands, insular carcinoid, and aggregations of hepatocytes without significant cytologic atypia. Moreover, adjacent to these hepatocytes, extensive overgrowth of highly atypical hepatocyte-like cells, providing a striking morphologic similarity to hepatocellular carcinoma of the liver, was identified. Both the heterologous hepatocytes and hepatocellular carcinomatous tumor cells were immunohistochemically positive for alpha-fetoprotein, hepatocyte paraffin 1, and arginase-1. Some Sertoli cells adjacent to the heterologous hepatocytes were also positive for alpha-fetoprotein and hepatocyte paraffin 1. The present case showed that a tumor morphologically and immunohistochemically analogous to hepatocellular carcinoma of the liver can arise in the ovary, in association with Sertoli-Leydig cell tumors.
Inflammatory Myofibroblastic Tumor Arising in the Cul-De-Sac, Mimicking Ectopic Decidua
Authors: Ioannidis Ioannis , Huang Jui-Han
Published: April 2018

Extra-ovarian neoplasms incidentally discovered during cesarean section are very rare. Here we report a case of inflammatory myofibroblastic tumor found during cesarean section of a 30-year-old, full-term woman, forming a mass in her cul-de-sac. Histology revealed an extensively decidualized spindle cell process, positive for anaplastic large cell lymphoma kinase (ALK) through immunohistochemistry and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first presentation of inflammatory myofibroblastic tumor in this location without concurrent intrauterine component, that additionally demonstrates this degree of decidualization, mimicking ectopic decidua.
Unique Autonomic Responses to Pain in Yoga Practitioners
Authors: Cotton Valerie A. , Low Lucie A. , Villemure Chantal , Bushnell M. Catherine
Published: April 2018

Objective

Autonomic nervous system activity is associated with neurobehavioral aspects of pain. Yogis use breathing, relaxation, and mindfulness to tolerate pain, which could influence autonomic responses. To evaluate how the link between autonomic responses and pain is altered by other factors, we compared perceptual and autonomic responses to pain between yogis and controls.

Methods

Nineteen yogis and 15 controls rated warm and painfully hot stimuli (1-cm2 thermode on calf), with visual anticipatory cues indicating certainly painful, certainly nonpainful, or uncertainly either painful or nonpainful. Heart rate, skin conductance, respiration, and blood pressure were measured.

Results

At baseline, yogis breathed slower and deeper than did controls, with no differences in other autonomic measures. During the task, perceptual ratings did not differ between groups in either the certain or uncertain conditions. Nevertheless, yogis had higher phasic skin conductance responses in anticipation of and response to all stimuli, but particularly during painful heat in uncertain contexts (uncertain: 0.46 [0.34] μS; certain: 0.37 [0.28] μS; t(18) = 3.962, p = .001). Furthermore, controls showed a decrease in heart rate to warm (−2.51 [2.17] beats/min) versus painful stimuli (0.83 [1.63] beats/min; t(13) = 5.212, p < .001) and lower respiratory sinus arrhythmia during pain compared with warm trials, whereas yogis had similar reactions to painful and nonpainful stimuli.

Conclusions

Autonomic responses to pain differed in yogis and healthy volunteers, despite similar pain ratings. Thus, autonomic reactivity to pain may be altered by environmental and psychological factors throughout an individual's life.
A Multicenter Collaboration for Simulation-Based Assessment of ACGME Milestones in Emergency Medicine
Authors: Salzman David H. , Watts Hannah , Williamson Kelly , Sergel Michelle , Dobiesz Valerie , DeGarmo Noah , Vora Samreen , Sharp Louis J. , Wang Ernest E. , Gisondi Michael A.
Published: April 2018

Summary Statement

In 2014, the six allopathic emergency medicine (EM) residency programs in Chicago established an annual, citywide, simulation-based assessment of all postgraduate year 2 EM residents. The cases and corresponding assessment tools were designed by the simulation directors from each of the participating sites. All assessment tools include critical actions that map directly to numerous EM milestones in 11 different subcompetencies. The 2-hour assessments provide opportunities for residents to lead resuscitations of critically ill patients and demonstrate procedural skills, using mannequins and task trainers respectively. More than 80 residents participate annually and their assessment experiences are essentially identical across testing sites. The assessments are completed electronically and comparative performance data are immediately available to program directors.
Learners' Perceptions During Simulation-Based Training
Authors: Duch Christensen Margrethe , Oestergaard Doris , Dieckmann Peter , Watterson Leonie
Published: April 2018

Introduction

Remotely facilitated simulation-based training (RF-SBT) is less positively appraised than face-to-face, locally facilitated simulation-based training (LF-SBT), despite being considered as an acceptable alternative. This study compared the perceptions of learners after RF-SBT and LF-SBT to explain differences between the two and identify relevant theories that would guide future practice.

Methods

Telephone interviews were conducted with 21 newly graduated doctors and nurses who completed a standardized simulation course delivered in both RF-SBT and LF-SBT formats.

Results

Participants reported that both SBT formats to be highly beneficial, however, were less positive about RF-SBT. They described a range of psychosocial and cognitive responses that explained their positive and negative attitudes to different aspects of the training. These perceptions, occurring across both formats, included a sense of the following: belonging to instructor and group, surveillance, responsibility, realism, contextual understanding, conscious mental effort, control of attention, and engagement with task. Participants associated these perceptions and ensuing attitudes to SBT with factors arising during, and/or existing before, the SBT as if in an input-output process model. The former ‘enabling’ factors related to human interaction, technology, and instructional design, whereas the latter ‘precursor’ factors reflected pre-existing attributes of the participants and instructors. These findings are supported by several theoretical models of which the technology acceptance model is arguably the best fit.

Conclusions

Locally facilitated simulation-based training is easier to use and experience than RF-SBT; however, the latter's negative impact may be concealed by SBT's overarching very high perceived value. The technology acceptance model is an appropriate conceptual model to explain these processes.
Reduced Access to Liver Transplantation in Women: Role of Height, MELD Exception Scores, and Renal Function Underestimation
Authors: Allen Alina M. , Heimbach Julie K. , Larson Joseph J. , Mara Kristin C. , Kim W. Ray , Kamath Patrick S. , Therneau Terry M.
Published: April 2018

Background

Sex-based disparities in liver transplantation (LT) are incompletely understood. We assessed the role of height, Model for End-Stage Liver Disease (MELD), MELD-Na, and exception points in the disparate access to LT.

Methods

Adults waitlisted for LT at Organ Procurement and Transplantation Network between 2002 and 2013 were included. Covariates associated with likelihood of LT were analyzed by Cox proportional model. In a separate cohort of waitlisted adults with glomerular filtration rate measurement by iothalamate clearance (n = 611), we determined the number of creatinine-derived MELD points in men versus women, across all ranges of glomerular filtration rate. The impact of correcting the MELD score deficit in women on LT was modeled.

Results

Among 90 720 Organ Procurement and Transplantation Network registrants, women had higher mortality than men (4 years after listing: 22% vs 18%, P < 0.0001), and lower likelihood of LT (49% vs 58%, P < 0.0001); women were 20% less likely to be transplanted (hazard ratio, 0.80; 95% confidence interval, 0.78-0.81). Differences in height and MELD exception scores accounted for most of the LT deficit in women (hazard ratio, 0.91; 95% confidence interval, 0.89-0.94). Women received between 1 and 2.4 fewer creatinine-derived MELD points than men with similar renal dysfunction. MELD-Na worsened the gender disparity. Addition of 1 or 2 MELD points to women significantly impacted LT access.

Conclusions

Differences in height and MELD exception points explained most of the sex-based disparity in LT. Additionally, MELD score underestimated disease severity in women by up to 2.4 points and MELD Na exacerbated this disparity. The degree of underestimation based on MELD had significant impact on allocation.
Pancreas Transplantation From Pediatric Donors: A Single-Center Experience
Authors: Spaggiari Mario , Di Bella Caterina , Di Cocco Pierpaolo , Campara Maya , Galen Kelly , Gheza Federico , Oberholzer Jose , Benedetti Enrico , Tzvetanov Ivo
Published: April 2018

Background

Pancreas allografts from pediatric donors are considered less suitable due to the increased risk of surgical complications and reduced islet cell mass that may compromise function.

Methods

All pancreatic transplants, procured from donors younger than 18 years, between January 2007 and March 2017, were included in the analysis. The grafts were subdivided into 3 groups by donor's weight: less than 30 kg, 30 to 60 kg, greater than 60 kg. Analysis of patient and graft survival was done between the groups, and subsequently between the pediatric cohort and the adult-donor control group.

Results

Sixty-three pediatric-donor pancreas transplants were performed. The mean donor age and weight were of 12.10 ± 4.13 years and 47.8 ± 21.3 kg. Excellent metabolic control was achieved in 59 (93.65%) patients at the time of discharge and at a mean 5 year follow up, with the average hemoglobin A1c of 5.30 ± 0.61% and blood glucose level of 102.75 ± 20.70 mg/dL in those with a functioning graft. Nine graft losses were registered, of which one (1.6%) was due to arterial thrombosis. Eight (12.7%) patients experienced rejection. Overall graft survival and patient survival were of 85.7% and 92.1%, respectively, at a median follow-up of 37.07 months (minimum, 0.19 to maximum, 119.57). No differences among the 3 groups were identified. Long-term patient and allograft survival was comparable to that of the adult-donor pancreatic transplants.

Conclusions

Pediatric-donor pancreas demonstrated excellent short-term outcomes with no surgical complications and promising long-term outcomes despite the smaller islet mass. Pancreata from pediatric donors should not be marginalized and can offset worsening organ shortage.
Extreme diversity in the songs of Spitsbergen's bowhead whales
Authors: Stafford K. M. , Lydersen C. , Wiig Ø. , Kovacs K. M.
Published: April 2018

Almost all mammals communicate using sound, but few species produce complex songs. Two baleen whales sing complex songs that change annually, though only the humpback whale (
Megaptera novaeangliae
) has received much research attention. This study focuses on the other baleen whale singer, the bowhead whale (
Balaena mysticetus
). Members of the Spitsbergen bowhead whale population produced 184 different song types over a 3-year period, based on duty-cycled recordings from a site in Fram Strait in the northeast Atlantic. Distinct song types were recorded over short periods, lasting at most some months. This song diversity could be the result of population expansion, or immigration of animals from other populations that are no longer isolated from each other by heavy sea ice. However, this explanation does not account for the within season and annual shifting of song types. Other possible explanations for the extraordinary diversity in songs could be that it results either from weak selection pressure for interspecific identification or for maintenance of song characteristics or, alternatively, from strong pressure for novelty in a small population.
Opportunities and obstacles for deep learning in biology and medicine
Authors: Ching Travers , Himmelstein Daniel S. , Beaulieu-Jones Brett K. , Kalinin Alexandr A. , Do Brian T. , Way Gregory P. , Ferrero Enrico , Agapow Paul-Michael , Zietz Michael , Hoffman Michael M. , Xie Wei , Rosen Gail L. , Lengerich Benjamin J. , Israeli Johnny , Lanchantin Jack , Woloszynek Stephen , Carpenter Anne E. , Shrikumar Avanti , Xu Jinbo , Cofer Evan M. , Lavender Christopher A. , Turaga Srinivas C. , Alexandari Amr M. , Lu Zhiyong , Harris David J. , DeCaprio Dave , Qi Yanjun , Kundaje Anshul , Peng Yifan , Wiley Laura K. , Segler Marwin H. S. , Boca Simina M. , Swamidass S. Joshua , Huang Austin , Gitter Anthony , Greene Casey S.
Published: April 2018

Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes and treatment of patients—and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine.
Evolution and mechanics of mixed phospholipid fibrinogen monolayers
Authors: Williams Ian , Squires Todd M.
Published: April 2018

All mammals depend on lung surfactant (LS) to reduce surface tension at the alveolar interface and facilitate respiration. The inactivation of LS in acute respiratory distress syndrome (ARDS) is generally accompanied by elevated levels of fibrinogen and other blood plasma proteins in the alveolar space. Motivated by the mechanical role fibrinogen may play in LS inactivation, we measure the interfacial rheology of mixed monolayers of fibrinogen and dipalmitoylphosphatidylcholine (DPPC), the main constituent of LS, and compare these to the single species monolayers. We find DPPC to be ineffective at displacing preadsorbed fibrinogen, which gives the resulting mixed monolayer a strongly elastic shear response. By contrast, how effectively a pre-existing DPPC monolayer prevents fibrinogen adsorption depends upon its surface pressure. At low DPPC surface pressures, fibrinogen penetrates DPPC monolayers, imparting a mixed viscoelastic shear response. At higher initial DPPC surface pressures, this response becomes increasingly viscous-dominated, and the monolayer retains a more fluid, DPPC-like character. Fluorescence microscopy reveals that the mixed monolayers exhibit qualitatively different morphologies. Fibrinogen has a strong, albeit preparation-dependent, mechanical effect on phospholipid monolayers, which may contribute to LS inactivation and disorders such as ARDS.
Circadian protein regulation in the green lineage I. A phospho-dawn of protein modification anticipates light onset in the picoeukaryoteO. tauri
Authors: Noordally Zeenat B. , Hindle Matthew M. , Martin Sarah F. , Seaton Daniel D. , Simpson T. Ian , Bihan Thierry Le , Millar Andrew J.
Published: April 2018

Diel regulation of protein levels and protein modification had been less studied than transcript rhythms. Here, we compare transcriptome data under light-dark cycles to partial proteome and phosphoproteome data, assayed using shotgun mass-spectrometry, from the algaOstreococcus tauri, the smallest free-living eukaryote. 10% of quantified proteins but two-thirds of phosphoproteins were rhythmic. Mathematical modelling showed that light-stimulated protein synthesis can account for the observed clustering of protein peaks in the daytime. Prompted by night-peaking and apparently dark-stable proteins, we also tested cultures under prolonged darkness, where the proteome changed less than under the diel cycle. The dark-stable, prasinophyte-specific proteins were also reported to accumulate whenO. tauriformed lipid droplets. In the phosphoproteome, 39% of rhythmic phospho-sites reached peak levels just before dawn. This anticipatory phosphorylation suggests that a clock-regulated phospho-dawn prepares green cells for daytime functions. Acid-directed and proline-directed protein phosphorylation sites were regulated in antiphase, implicating the clock-related, casein kinases 1 and 2 in phase-specific regulation, alternating with the CMGC protein kinase family. Understanding the dynamic phosphoprotein network should be facilitated by the minimal kinome and proteome ofO. tauri. The data are available from ProteomeXchange, with identifiers PXD001734, PXD001735 and PXD002909. This submission updates a previous version, posted on bioRxiv on 4th April 2018, ashttps://www.biorxiv.org/content/10.1101/287862v1

Highlight

The phosphorylation of most protein sites was rhythmic under light-dark cycles, and suggested circadian control by particular kinases. Day-peaking, rhythmic proteins likely reflect light-stimulated protein synthesis in this microalga.
Primate immunodeficiency virus Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex
Authors: Yurkovetskiy Leonid , Guney Mehmet Hakan , Kim Kyusik , Goh Shih Lin , McCauley Sean , Dauphin Ann , Diehl William , Luban Jeremy
Published: April 2018

Drugs that inhibit HIV-1 replication and prevent progression to AIDS do not eliminate HIV-1 proviruses from the chromosomes of long-lived CD4+memory T cells. To escape eradication by these antiviral drugs, or by the host immune system, HIV-1 exploits poorly defined host factors that silence provirus transcription. These same factors, though, must be overcome by all retroviruses, including HIV-1 and other primate immunodeficiency viruses, in order to activate provirus transcription and produce new virus. Here we show that Vpx and Vpr, proteins from a wide range of primate immunodeficiency viruses, activate provirus transcription in human CD4+T cells. Provirus activation required the DCAF1 adaptor that links Vpx and Vpr to the CUL4A/B ubiquitin ligase complex, but did not require degradation of SAMHD1, a well-characterized target of Vpx and Vpr. A loss-of-function screen for transcription silencing factors that mimic the effect of Vpx on provirus silencing identified all components of the Human Silencing Hub (HUSH) complex, FAM208A (TASOR/RAP140), MPHOSPH8 (MPP8), PPHLN1 (PERIPHILIN), and MORC2. Vpx associated with the HUSH complex components and decreased steady-state levels of these proteins in a DCAF-dependent manner. Finally,vpxand FAM208A knockdown accelerated HIV-1 and SIVMACreplication kinetics in CD4+T cells to a similar extent, and HIV-2 replication required eithervpxor FAM208A disruption. These results demonstrate that the HUSH complex restricts transcription of primate immunodeficiency viruses and thereby contributes to provirus latency. To counteract this restriction and activate provirus expression, primate immunodeficiency viruses encode Vpx and Vpr proteins that degrade HUSH complex components.
Pre-saccadic remapping relies on dynamics of spatial attention
Authors: Szinte Martin , Jonikaitis Donatas , Rangelov Dragan , Deubel Heiner
Published: April 2018

Each eye movement shifts the projections of the visual scene on the retina. It has been proposed that the receptive fields of neurons in oculomotor areas are remapped pre-saccadically to account for these shifts. While remapping of the whole visual scene seems prohibitively complex, selection by visual attention may limit these processes to a subset of attended locations. Because attentional selection consumes time, remapping of attended locations should evolve in time, too. In our study, we cued a spatial location by presenting an attention capturing cue at different times before a saccade and constructed detailed maps of attentional allocation across the visual field. We observed no remapping when the cue appeared shortly before saccade. In contrast, when the cue appeared sufficiently early before saccade, attentional resources were reallocated to the remapped location. Our results suggest that pre-saccadic remapping is an attentional process relying on the spatial and temporal dynamics of visual attention.
The Influence Of Social Behavior On Competition Between Virulent Pathogen Strains
Authors: Pharaon Joe , Bauch Chris T.
Published: April 2018

1

Infectious disease interventions like contact precautions and vaccination have proven effective in disease control and elimination. The priority given to interventions can depend strongly on how virulent the pathogen is, and interventions may also depend partly for their success on social processes that respond adaptively to disease dynamics. However, mathematical models of competition between pathogen strains with differing natural history profiles typically assume that human behaviour is fixed. Here, our objective is to model the influence of social behaviour on the competition between pathogen strains with differing virulence. We couple a compartmental Susceptible-Infectious-Recovered model for a resident pathogen strain and a mutant strain with higher virulence, with a differential equation of a population where individuals learn to adopt protective behaviour from others according to the prevalence of infection of the two strains and the perceived severity of the respective strains in the population. We perform invasion analysis, time series analysis and phase plane analysis to show that perceived severities of pathogen strains and the efficacy of infection control against them can greatly impact the invasion of more virulent strain. We demonstrate that adaptive social behaviour enables invasion of the mutant strain under plausible epidemiological scenarios, even when the mutant strain has a lower basic reproductive number than the resident strain. Surprisingly, in some situations, increasing the perceived severity of the resident strain can facilitate invasion of the more virulent mutant strain. Our results demonstrate that for certain applications, it may be necessary to include adaptive social behaviour in models of the emergence of virulent pathogens, so that the models can better assist public health efforts to control infectious diseases.
Predicting humoral alloimmunity from differences in donor-recipient HLA surface electrostatic potential
Authors: Mallon Dermot H , Kling Christiane , Robb Matthew , Ellinghaus Eva , Bradley J Andrew , Taylor Craig J , Kabelitz Dieter , Kosmoliaptsis Vasilis
Published: April 2018

In transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesised that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared to recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level (electrostatic mismatch score-three dimensional; EMS-3D). We then examined humoral alloimmune responses in healthy females subjected to a standardised injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.
The solvent-excluded surfaces of water-soluble proteins
Authors: Wang Lincong
Published: April 2018

The solvent-excluded surface (SES) of a protein is determined by and in turn affects protein-solvent interaction and consequently plays important roles in its solvation, folding and function. However, accurate quantitative relationships between them remain largely unknown at present. To evaluate SES’s contribution to protein-solvent interaction we have applied our accurate and robust SES computation algorithm to various sets of proteins and ligand-protein interfaces. Our results show that each of the analyzed water-soluble proteins has a negative net charge on its SES. In addition we have identified a list of SES-defined physical and geometrical properties that likely pertain to protein solvation and folding based on their characteristic changes with protein size, their differences between folded and extended conformations, and their correlations with known hydrophobicity scales and with experimentally-determined protein solubility. The relevance of the list of SES-defined properties to protein structure and function is supported by their differences between water-soluble proteins and transmembrane proteins and between solvent-accessible regions and ligand-binding interfaces. Taken together our analyses reveal the importance of SES for protein solvation, folding and function. In particular the universal enrichment of negative charge and the larger than average SES area for a polar atom on the surface of a water-soluble protein suggest that from a protein-solvent interaction perspective to fold into a native state is to optimize the electrostatic and hydrogen-bonding interactions between solvent molecules and the surface polar atoms of a protein rather than to only minimize its apolar surface area.
An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence
Authors: Saitou Marie , Lizardo Darleny Y. , Taskent Recep Ozgur , Millner Alec , Atilla-Gokcumen Gunes Ekin , Gokcumen Omer
Published: April 2018

Cellular senescence, the irreversible ceasing of cell division, has been associated with organismal aging, prevention of cancerogenesis, and developmental processes. As such, the evolutionary basis and biological features of cellular senescence remain a fascinating area of research. In this study, we conducted comparative RNAseq experiments to detect genes associated with replicative senescence in two different human cell lines and at different time points. We identified 841 and 900 genes (core senescence-associated genes) that are significantly up- and downregulated in senescent cells, respectively, in both cell lines. Our functional enrichment analysis showed that downregulated core genes are primarily involved in cell cycle processes while upregulated core gene enrichment indicated various lipid-related processes. We further demonstrated that downregulated genes are significantly more conserved than upregulated genes. Using both transcriptomics and genetic variation data, we identified one of the upregulated, lipid metabolism gene, CD36 as an outlier. We found that overexpression of CD36 induces a senescence-like phenotype and, further, the media of CD36-overexpressing cells alone can induce a senescence-like phenotype in proliferating young cells. Moreover, we used a targeted lipidomics approach and showed that phosphatidylcholines accumulate during senescence in these cells, suggesting that upregulation of CD36 could contribute to membrane remodeling during senescence. Overall, these results contribute to the understanding of evolution and biology of cellular senescence and identify several targets and questions for future studies.
Plants with purple abaxial leaves: A repository of metrics from stomata distribution
Authors: de Almeida filho Humberto Antunes , Bruno Odemir Martinez
Published: April 2018

Plants with purple abaxial leaves are very common in nature but the ecophysiological aspects of this phenotype are not well known. We observed here that the purple color of the abaxial tegument in extant plants make stomata completely visible. Based in it we measured the relations between stomatic density and distance between stomata pairs and observed a general log-normal trend line between density and interstomatic distance. These data shows that measures of stomatic distances at purple abaxial leaves are able to be a sensor to environmental changes of living purple plants. In future ecophysiological inferences will be established from the information brought by the measurements of the distance between stomata in purple plants.
Fitness effects of altering gene expression noise inSaccharomyces cerevisiae
Authors: Duveau Fabien , Hodgins-Davis Andrea , Metzger Brian P.H. , Yang Bing , Tryban Stephen , Walker Elizabeth A. , Lybrook Patricia , Wittkopp Patricia J.
Published: April 2018

Gene expression noise is an evolvable property of biological systems that describes differences in gene expression among genetically identical cells in the same environment. Prior work has shown that expression noise is heritable and can be shaped by natural selection, but the impact of variation in expression noise on organismal fitness has proven difficult to measure. Here, we quantify the fitness effects of altering expression noise for theTDH3gene inSaccharomyces cerevisiae. We show that increases in expression noise can be deleterious or beneficial depending on the difference between the average expression level of a genotype and the expression level maximizing fitness. We also show that a simple model relating single-cell expression levels to population growth produces patterns that are consistent with our empirical data. We use this model to explore a broad range of average expression levels and expression noise, providing additional insight into the fitness effects of variation in expression noise.
Myosin-II mediated traction forces evoke localized Piezo1 Ca2+ flickers
Authors: Ellefsen Kyle L. , Holt Jesse R. , Chang Alice , Nourse Jamison L. , Arulmoli Janahan , Mekhdjian Armen , Abuwarda Hamid , Tombola Francesco , Flanagan Lisa A. , Dunn Alexander R. , Parker Ian , Pathak Medha M.
Published: April 2018

Piezo channels transduce mechanical stimuli into electrical and chemical signals, and in doing so, powerfully influence development, tissue homeostasis, and regeneration. While much is known about how Piezo1 responds to external forces, its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that actomyosin-based cellular traction forces generate spatially-restricted Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched in regions proximal to force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that diffusion allows channel molecules to efficiently respond to transient, local mechanical stimuli.
metamicrobiomeR: an R package for analysis of microbiome relative abundance data using zero-inflated beta GAMLSS and meta-analysis across studies using random effect models
Authors: Ho Nhan Thi , Li Fan
Published: April 2018

Background

The rapid growth of high-throughput sequencing-based microbiome profiling has yielded tremendous insights into human health and physiology. Data generated from high-throughput sequencing of 16S rRNA gene amplicons are often preprocessed into composition or relative abundance. However, reproducibility has been lacking due to the myriad of different experimental and computational approaches taken in these studies. Microbiome studies may report varying results on the same topic, therefore, meta-analyses examining different microbiome studies to provide robust results are important. So far, there is still a lack of implemented methods to properly examine differential relative abundances of microbial taxonomies and to perform meta-analysis examining the heterogeneity and overall effects across microbiome studies.

Results

We developed an R package ‘metamicrobiomeR’ that applies Generalized Additive Models for Location, Scale and Shape (GAMLSS) with a zero-inflated beta (BEZI) family (GAMLSS-BEZI) for analysis of microbiome relative abundance datasets. Both simulation studies and application to real microbiome data demonstrate that GAMLSS-BEZI well performs in testing differential relative abundances of microbial taxonomies. Importantly, the estimates from GAMLSS-BEZI are log(odds ratio) of relative abundances between groups and thus are comparable between microbiome studies. As such, we also apply random effects meta-analysis models to pool estimates and their standard errors across microbiome studies. We demonstrate the meta-analysis workflow and highlight the utility of our package on four studies comparing gut microbiomes between male and female infants in the first six months of life.

Conclusions

GAMLSS-BEZI allows proper examination of microbiome relative abundance data. Random effects meta-analysis models can be directly applied to pool comparable estimates and their standard errors to evaluate the heterogeneity and overall effects across microbiome studies. The examples and workflow using our metamicrobiomeR package are reproducible and applicable for the analyses and meta-analyses of other microbiome studies.
Physiological Characteristics of Viable-but-nonculturableVibrio parahaemolyticusupon Prolonged Exposure to the Refrigerator Temperature
Authors: Yoon Jae-Hyun , Lee Sun-Young
Published: April 2018

Although it has been reported thatviable-but-nonculturable (VBNC) cells ofVibrio parahaemolyticuscan be developed by a prolonged duration of cold-starvation there are restricted cellular characteristics available on understanding the exact mechanisms governing the entry of pathogens into the VBNC state. Therefore, this research was aimed at determining the cellular profile of VBNC cells ofV. parahaemolyticusupon exposure to the refrigerator temperature. Strains ofV. parahaemolyticuswere incubated in artificial sea water (ASW) microcosms (pH 6) added with different amounts of NaCl at 4°C until these pathogens entered into such a dormant state. At a regular time-interval, both culturability and viability of these bacteria were enumerated, and then cellular profiling were carried out in terms of cellular membrane permeability, enzymatic activity, hydrophobicity, fatty acid composition, and morphological changes after cells ofV. parahaemolyticusbecame the VBNC state. Three strains ofV. parahaemolyticusused in this study showed that VBNC cells retained the strong virulent properties to Vero and CACO-2 cell lines, re-gained the cytotoxicity even after resuscitation, became permeabilized in terms of the outer membrane, showed lower levels of enzymatic (catalase and glutathione-S-transferase) activities, exerted the increasing hydrophobicity, and then exhibited increasing amounts of saturated fatty acids.

IMPORTANCE

To the current best knowledge, there are restricted information available on understanding the physiological characterization of viable-but-nonculturable cells. Most previous studies are still making a degree of efforts in discovering the causative effector causing microorganisms to be induced into the VBNC state. Herein, the present study showed that pathogenicV. parahaemolyticuscan enter into the VBNC state when challenged by a certain environmental stress where higher amounts of NaCl combined with acidic pHs was artificially controlled. Importantly, it was indicated that VBNCV. parahaemolyticusmaintained peculiarly different physiological characteristics. Furthermore, this study proposed a novel approach on the transient/stepwise conversion of the bacteria into the VBNC state. Specific alternative tools for measuring and controlling the incidence of VBNC pathogens on food are not established until now. In this aspect, results obtained from this study will used to provide an effective insight in determining physiological properties of viable-but-nonculturableV. parahaemolyticus.
Manganese oxide biomineralization is a social trait protecting against nitrite toxicity
Authors: Zerfaß Christian , Christie-Oleza Joseph A. , Soyer Orkun S.
Published: April 2018

Manganese bio-mineralization by oxidation is a costly but, still, widespread process among bacteria and fungi. While certain potential advantages of manganese oxidation have been suggested, to date there is no conclusive experimental evidence for, how and if this process impacts microbial fitness in the environment. Here we show how a model organism for manganese oxidation,Roseobacter sp.AzwK-3b, is growth-inhibited by nitrite, and that this inhibition is mitigated when manganese is added to the culture medium. We show that manganese-mediated mitigation of nitrite-inhibition is dependent on the culture inoculum size, with larger inocula being able to withstand higher concentrations of nitrite stress. Furthermore, the bio-mineralized manganese oxide (MnOX) forms granular precipitates in the culture, rather than sheaths around individual cells. These findings support the notion that MnOXis a shared community product that improves the cultures’ survival against nitrite-stress. We show that the mechanistic basis of the MnOXeffect involves both its ability to catalyze nitrite oxidation into (non-toxic) nitrate under physiological conditions, and its potential role in influencing redox chemistry around reactive oxygen species (ROS). Taken together, these results provide for the first direct evidence of improved microbial fitness byMnOXdeposition in an ecological setting, i.e. mitigation of nitrite toxicity, and point to a key role of MnOXin handling stresses arising from ROS. These findings could be of generalrelevance for all organisms oxidizing manganese, allowing them to offset costs associated with extracellular bio-mineralization.
Equity financing constraints and R&D investments: evidence from an IPO suspension in China
Authors: Cui Binxi , Yang Chaojun
Published: April 2018

Purpose

The purpose of this paper is to exploit the effect of equity financing constraints on the firm’s investment in research and development (R&D) by utilizing a quasi-experiment in China.

Design/methodology/approach

A difference-in-difference identification strategy is employed to test the treatment effect of the IPO suspension in China. For robustness testing, the authors incorporate cross-sectional variation in external financial dependence to identify the different influences an IPO suspension has on R&D investments for firms across multiple industries through the difference-in-difference-in-difference approach and the authors also adopt a matching approach to check the parallel trend assumption. Moreover, the authors introduce a placebo test to further verify the empirical results.

Findings

Through the empirical analysis, the authors find that the firms subjecting to the IPO suspension are more likely to reduce their investments in R&D than those not affected by the IPO suspension. Besides, the negative effect of equity financing constraints on R&D investments is concentrated on external financial dependent industries. The firms in industries with larger external financial dependence tend to decrease more in their R&D expenditures when they experience the equity financing constraints.

Research limitations/implications

This paper provides a new negative evidence on equity financing constraints on R&D investments link so that contributes to the debate about the effect of the financing constraints on R&D investments.

Practical implications

The study provides a meaningful suggestion for governments to diminish the frictions in the financial market and to improve enterprises’ public financing circumstances by finding that equity financing constraints have negative impacts on firms’ R&D investments.

Originality/value

There are some apprehensions around previous empirical studies investigating the impact of financing constraints on R&D investments as the existing literature is unable to provide an unambiguous method to exactly distinguish and measure the degree of financing constraints the firms confronting with. This paper solves this problem by first utilizing an IPO suspension in China as a quasi-experiment to examine the effect of equity financing constraints. Therefore, it gives insight to solve the problem of measuring financing constraints in future researches.
Balancing of life cycle carbon and cost appraisal on alternative wall and roof design verification for residential building
Authors: Tighnavard Balasbaneh Ali , Bin Marsono Abdul Kadir , Kasra Kermanshahi Emad
Published: April 2018

Purpose

The purpose of this study is to describe life cycle cost (LCC) and life cycle assessment (LCA) evaluation for single story building house in Malaysia. Two objective functions, namely, LCA and LCC, were evaluated for each design and a total of 20 alternatives were analyzed. Two wall schemes that have been adopted from two different recent studies toward mitigation of climate change require clarification in both life cycle objectives.

Design/methodology/approach

For this strategic life cycle assessment, Simapro 8.3 tool has been chosen over a 50-year life span. LCC analysis was also used to determine not only the most energy-efficient strategy, but also the most economically feasible one. A present value (PV)-based economic analysis takes LCC into account.

Findings

The results will appear in present value and LC carbon footprint saving, both individually and in combination with each other. Result of life cycle management shows that timber wall−wooden post and beam covered by steel stud (W5) and wood truss with concrete roof tiles (R1) released less carbon emission to atmosphere and have lower life cycle cost over their life span. W5R1 releases 35 per cent less CO2 emission than the second best choice and costs 25 per cent less.

Originality/value

The indicator assessed was global warming, and as the focus was on GHG emissions, the focus of this study was mainly in the context of Malaysian construction, although the principles apply universally. The result would support the adoption of sustainable building for building sector.