bluuebunny/crossref_metadata_2025 huggingface dataset:
Process evaluation of a community-based diabetes prevention program in China: the Pathway to Health (PATH)
Authors: Strand Mark A , He Meizi , Johnson Ryan , Perry Judith , Yin Zenong
Published: July 2019

High prevalence of diabetes and prediabetes has emerged as a concern in China. The Pathway to Health Program was designed to prevent type 2 diabetes onset in prediabetic women in a north China urban community. This process evaluation of a randomized controlled trial analysed participant surveys at the 6- and 12-month assessment times, participant weekly logs, class attendance records and post-study participant focus group results. The reported levels of participant engagement in physical activity (PA)-related behaviors were higher than diet-related behaviors at the 6-month assessment. The engagement in both PA- and diet-related behaviors declined during the 6-month follow-up period. Step counts from the participants’ pedometers indicated an increase in PA in the first 6 months of the intervention. Study participants expressed high levels of satisfaction with the intervention and increased their scores on diabetes-related knowledge. Conflicts with work and family responsibilities were the main barriers for missing health lessons, likely contributing to minimal weight loss. There was good fidelity in program implementation. Intensive lifestyle modification programs are difficult to sustain once the program is complete. A more structured 6-month follow-up phase may have provided needed support to enable participants to maintain their lifestyle changes.
Patients’ preimplantation genetic testing decision-making experience: an opinion on related psychological frameworks
Authors: Pastore L M , Cordeiro Mitchell C N , Rubin L R , Nicoloro-SantaBarbara J , Genoff Garzon M C , Lobel M
Published: July 2019

The process of deciding whether to pursue preimplantation genetic testing (PGT) of an embryo is highly stressful for individuals and couples and has adverse emotional consequences (e.g. distress and uncertainty). PGT influences patients’ lives in both positive and negative ways and is experienced at an individual level, as a dyadic unit, as a family member and as part of the society. Here, we argue that providing a conceptual framework with which to understand the `experience of decision making’ about PGT for monogenic disease (PGT-M) testing specifically, as well as the factors contributing to `decisional distress’ and `uncertainty’ that patients endure as a result—apart from what decision they make—is crucial to optimizing patient counseling, satisfaction and outcomes in the field of ART. Derived from psychological theory, the framework proposed here identifies three categories of contributing factors to decisional distress and uncertainty in considering PGT-M; namely, ‘intraindividual’, ‘interpersonal’ and ‘situational’ factors. We reviewed evidence from the PGT literature to inform our framework. Well-accepted theories of stress and health decision making were also reviewed for their relevance to PGT-M decision making, focusing on potential distress and uncertainty. Our novel conceptual framework can be used to inform clinical practice, to advance research and to aid the development of interventions for individuals and couples who are deciding whether or not to use PGT-M. Alleviating emotional distress and uncertainty can improve patients’ well-being during their reproductive journey.
Environmental Microbial Factors Determine the Pattern of Inflammatory Lesions in a Murine Model of Crohn’s Disease–Like Inflammation
Authors: Stolzer Iris , Kaden-Volynets Valentina , Ruder Barbara , Letizia Marilena , Bittel Miriam , Rausch Philipp , Basic Marijana , Bleich André , Baines John F , Neurath Markus F , Wirtz Stefan , Weidinger Carl , Bischoff Stephan C , Becker Christoph , Günther Claudia
Published: July 2019

Here we provide compelling evidence that inflammation in a murine model of Crohn’s disease–like inflammation is characterized by an immune reaction presumably directed at a disease-relevant microflora in a genetically susceptible host with impaired mucosal barrier function and bacterial clearance.
Planned right ventricular support for combined heart–liver transplantation
Authors: Barac Yaron D , McCartney Sharon L , Sudan Debra , Schroder Jacob N
Published: July 2019

Right ventricular dysfunction post heart transplantation (HTx) is a common problem and its likelihood to occur after combined heart–liver transplantation is even higher. The placement of an extracorporeal planned right ventricular assist device following the HTx during liver transplantation may assist in preventing this complication.
Piecewise Linear Sheaves
Authors: Kashiwara Masaki , Schapira Pierre
Published: July 2019

On a finite-dimensional real vector space, we give a microlocal characterization of (derived) piecewise linear sheaves (PL sheaves) and prove that the triangulated category of such sheaves is generated by sheaves associated with convex polyhedra. We then give a similar theorem for PL $\gamma $-sheaves, that is, PL sheaves associated with the $\gamma $-topology, for a closed convex polyhedral proper cone $\gamma $. Our motivation is that convex polyhedra may be considered as building blocks for higher dimensional barcodes.
Inhibition of p53 inhibitors: progress, challenges and perspectives
Authors: Sanz Gema , Singh Madhurendra , Peuget Sylvain , Selivanova Galina
Published: July 2019

p53 is the major tumor suppressor and the most frequently inactivated gene in cancer. p53 could be disabled either by mutations or by upstream negative regulators, including, but not limited to MDM2 and MDMX. p53 activity is required for the prevention as well as for the eradication of cancers. Restoration of p53 activity in mouse models leads to the suppression of established tumors of different origin. These findings provide a strong support to the anti-cancer strategy aimed for p53 reactivation. In this review, we summarize recent progress in the development of small molecules, which restore the tumor suppressor function of wild-type p53 and discuss their clinical advance. We discuss different aspects of p53-mediated response, which contribute to suppression of tumors, including non-canonical p53 activities, such as regulation of immune response. While targeting p53 inhibitors is a very promising approach, there are certain limitations and concerns that the intensive research and clinical evaluation of compounds will hopefully help to overcome.
Mother and Father Controlling Feeding Behaviors and Associations With Observed Mealtime Family Functioning
Authors: Westen Sarah C , Mitchell Tarrah B , Mayer-Brown Sarah , Resmini Rawlinson Alana , Ding Ke , Janicke David M
Published: July 2019

Objective

Mealtime family functioning is important in shaping health behaviors associated with overweight/obesity, particularly for preschool-aged children. Parental controlling feeding behaviors (i.e., restriction and pressure to eat), may impact mealtime family functioning and thus be targets of prevention and intervention efforts. The current study aimed to address literature gaps by examining both mother and father self-reports of controlling feeding behaviors, and the discrepancies between parents’ reports. Further, the study examined the associations among controlling feeding behaviors and objective mealtime family functioning in a community sample of preschool-aged children.

Methods

The sample included 27 children between 2 and 6 years of age and their immediate family members. Two mealtimes were videotaped for each family and coded for family functioning using the Mealtime Interaction Coding System, and self-reports of feeding practices were collected using the Child Feeding Questionnaire.

Results

Mother controlling feeding behaviors were not significantly related to any mealtime family functioning domain. Father controlling feeding behaviors were only significantly related to interpersonal involvement. However, discrepancies in the use of controlling feeding behaviors accounted for nearly one fourth of the variance in overall family functioning and affect management, with greater discrepancies being related to poorer family functioning.

Conclusions

Interventions may be designed to reduce parental discrepancies in the use of controlling feeding behaviors. Future research should consider longitudinal design, using larger, more representative samples, to better understand the impact of parental controlling feeding behaviors, particularly the impact of parental discrepancies in these areas, on mealtime family functioning and subsequent health outcomes.
A deeper look at the dust attenuation law of star-forming galaxies at high redshift
Authors: Tress M , Ferreras I , Pérez-González P G , Bressan A , Barro G , Domínguez-Sánchez H , Eliche-Moral C
Published: July 2019

A diverse range of dust attenuation laws is found in star-forming galaxies. In particular, Tress et al. (2018) studied the SHARDS survey to constrain the NUV bump strength (B) and the total-to-selective ratio (RV) of 1753 star-forming galaxies in the GOODS-N field at 1.5 < z < 3. We revisit here this sample to assess the implications and possible causes of the correlation found between RV and B. The UVJ bicolour plot and main sequence of star formation are scrutinized to look for clues into the observed trend. The standard boundary between quiescent and star-forming galaxies is preserved when taking into account the wide range of attenuation parameters. However, an additional degeneracy – regarding the effective attenuation law – is added to the standard loci of star-forming galaxies in the UVJ diagram. A simple phenomenological model with an age-dependent extinction (at fixed dust composition) is compatible with the observed trend between RV and B, whereby the opacity decreases with the age of the populations, resulting in a weaker NUV bump when the overall attenuation is shallower (greyer). In addition, we compare the constraints obtained by the SHARDS sample with dust models from the literature, supporting a scenario where geometry could potentially drive the correlation between RV and B.
Star formation in CALIFA early-type galaxies: a matter of discs
Authors: Méndez-Abreu J , Sánchez S F , de Lorenzo-Cáceres A
Published: July 2019

The star formation main sequence (SFMS) is a tight relation between the galaxy star formation rate (SFR) and its total stellar mass (M⋆). Early-type galaxies (ETGs) are often considered as low-SFR outliers of this relation. We study, for the first time, the separated distribution in the SFR versus M⋆ of bulges and discs of 49 ETGs from the CALIFA survey. This is achieved using c2d, a new code to perform spectrophotometric decompositions of integral field spectroscopy data cubes. Our results reflect that: (i) star formation always occurs in the disc component and not in bulges; (ii) star-forming discs in our ETGs are compatible with the SFMS defined by star-forming galaxies at z ∼ 0; (iii) the star formation is not confined to the outskirts of discs, but it is present at all radii (even where the bulge dominates the light); (iv) for a given mass, bulges exhibit lower sSFR than discs at all radii; and (v) we do not find a deficit of molecular gas in bulges with respect to discs for a given mass in our ETGs. We speculate our results favour a morphological quenching scenario for ETGs.
Structural intermediates of a DNA–ligase complex illuminate the role of the catalytic metal ion and mechanism of phosphodiester bond formation
Authors: Williamson Adele , Leiros Hanna-Kirsti S
Published: July 2019

DNA ligases join adjacent 5′ phosphate (5′P) and 3′ hydroxyl (3′OH) termini of double-stranded DNA via a three-step mechanism requiring a nucleotide cofactor and divalent metal ion. Although considerable structural detail is available for the first two steps, less is known about step 3 where the DNA-backbone is joined or about the cation role at this step. We have captured high-resolution structures of an adenosine triphosphate (ATP)-dependent DNA ligase from Prochlorococcus marinus including a Mn-bound pre-ternary ligase–DNA complex poised for phosphodiester bond formation, and a post-ternary intermediate retaining product DNA and partially occupied AMP in the active site. The pre-ternary structure unambiguously identifies the binding site of the catalytic metal ion and confirms both its role in activating the 3′OH terminus for nucleophilic attack on the 5′P group and stabilizing the pentavalent transition state. The post-ternary structure indicates that DNA distortion and most enzyme-AMP contacts remain after phosphodiester bond formation, implying loss of covalent linkage to the DNA drives release of AMP, rather than active site rearrangement. Additionally, comparisons of this cyanobacterial DNA ligase with homologs from bacteria and bacteriophage pose interesting questions about the structural origin of double-strand break joining activity and the evolution of these ATP-dependent DNA ligase enzymes.
Phosphorylation orchestrates the structural ensemble of the intrinsically disordered protein HMGA1a and modulates its DNA binding to the NFκB promoter
Authors: Kohl Bastian , Zhong Xueyin , Herrmann Christian , Stoll Raphael
Published: July 2019

High Mobility Group Protein A1a (HMGA1a) is a highly abundant nuclear protein, which plays a crucial role during embryogenesis, cell differentiation, and neoplasia. Here, we present the first ever NMR-based structural ensemble of full length HMGA1a. Our results show that the protein is not completely random coil but adopts a compact structure consisting of transient long-range contacts, which is regulated by post-translational phosphorylation. The CK2-, cdc2- and cdc2/CK2-phosphorylated forms of HMGA1a each exhibit a different binding affinity towards the PRD2 element of the NFκB promoter. Our study identifies connected regions between phosphorylation sites in the wildtype ensemble that change considerably upon phosphorylation, indicating that these posttranslational modifications sites are part of an electrostatic contact network that alters the structural ensemble by shifting the conformational equilibrium. Moreover, ITC data reveal that the CK2-phosphorylated HMGA1a exhibits a different DNA promoter binding affinity for the PRD2 element. Furthermore, we present the first structural model for AT-hook 1 of HMGA1a that can adopt a transient α-helical structure, which might serve as an additional regulatory mechanism in HMAG1a. Our findings will help to develop new therapeutic strategies against HMGA1a-associated cancers by taking posttranslational modifications into consideration.
Dietary satisfaction and quality of life in chronic kidney disease patients on low-protein diets: a multicentre study with long-term outcome data (TOrino-Pisa study)
Authors: Piccoli Giorgina Barbara , Di Iorio Biagio Raffaele , Chatrenet Antoine , D’Alessandro Claudia , Nazha Marta , Capizzi Irene , Vigotti Federica Neve , Fois Antioco , Maxia Stefania , Saulnier Patrick , Cabiddu Gianfranca , Cupisti Adamasco
Published: July 2019

Background

Concerns about adherence and quality of life (QoL) limit the diffusion of low-protein diets (LPDs) as a way to slow chronic kidney disease (CKD) progression and postpone dialysis. The aim of this multicentre study is to assess dietary satisfaction in stable CKD patients.

Methods

This was a multicentre cross-sectional study with long-term follow-up data. Prevalent patients on LPD for at least 6 months were selected in four Italian centres. QoL was assessed using the World Health Organization Quality of Life questionnaire, and diet satisfaction with the Modification of Diet in Renal Disease satisfaction questionnaire. Comorbidity was assessed by Charlson Comorbidity Index, estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation and protein intake by Maroni–Mitch formula. Survival was analysed with Kaplan–Meier curves and Cox Proportional Hazard Model.

Results

Four hundred and twenty-two CKD Stages 3–5 patients were enrolled. Over 95% were on moderately restricted diets (0.6 g/kg/day). Compliance was good (protein intake: 0.59 g/kg/day at baseline, 0.72 at the end of follow-up). Median dietary satisfaction was 4 on a 1–5 scale. QoL was not affected by the type of diet, but was influenced by age, comorbidity and setting of care. Two years later, at the end of follow-up, 66.6% of the patients were still on a diet; the main causes of discontinuation were dialysis and death. The dropout rate was low (5.5%); in Cox analysis, patient and renal survival were influenced by age and eGFR, but not by QoL, setting of care or type of diet.

Conclusions

LPDs are compatible with high dietary satisfaction and minimal dropout, at least in patients who are able to follow such a diet for at least 6 months.
Serum bicarbonate and cardiovascular events in hypertensive adults: results from the Systolic Blood Pressure Intervention Trial
Authors: Dobre Mirela , Pajewski Nicholas M , Beddhu Srinivasan , Chonchol Michel , Hostetter Thomas H , Li Ping , Rahman Mahboob , Servilla Karen , Weiner Daniel E , Wright Jackson T , Raphael Kalani L ,   for the SPRINT Research Group
Published: July 2019

Background

Low serum bicarbonate level is associated with increased mortality, but its role as a predictor of cardiovascular disease (CVD) is unclear. This study evaluates the association between serum bicarbonate concentration and CVD and whether the effect of intensive blood pressure (BP) lowering on CVD outcomes is modified by serum bicarbonate level.

Methods

The Systolic Blood Pressure Intervention Trial (SPRINT) randomized participants to a systolic BP target <120 mmHg (intensive treatment) or <140 mmHg (standard treatment). The primary CVD outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure and CVD death. Cox proportional hazards models adjusted for demographic, clinical and laboratory characteristics were used to evaluate the association of interest in 9334 SPRINT participants (ClinicalTrials.gov: NCT01206062).

Results

Over a median follow-up of 3.33 years (interquartile range 2.87–3.87 years), 618 (6.6%) participants experienced a primary CVD outcome. Participants with serum bicarbonate <22 mEq/L had a significantly higher risk of the primary CVD outcome (hazard ratio 1.54; 95% confidence interval 1.11–2.14, P = 0.01), compared with participants with bicarbonate 22–26 mEq/L. The magnitude of the CVD risk reduction with intensive BP lowering was similar across bicarbonate strata (P-value for interaction = 0.97).

Conclusions

In hypertensive individuals, serum bicarbonate level <22 mEq/L was associated with an increased CVD risk. The effect of intensive BP lowering on CVD outcomes was not modified by the serum bicarbonate level.
Systemic air embolism as a complication of gastroscopy
Authors: Emir Tulumović , Denijal Tulumović
Published: July 2019

Gastroscopy is a common medical procedure with a low complication rate. Most complications are related to respiratory or cardiovascular incidents, especially in sedated patients. Systemic air embolism secondary to gastroscopy is one of the most serious complications, which has been described in few case reports. We describe an interesting case of gastroscopy-related systemic air embolism in a 73-year-old patient.
Prey preference, environmental tolerances and ichthyotoxicity by the red-tide dinoflagellate Noctiluca scintillans cultured from Tasmanian waters
Authors: Hallegraeff Gustaaf M , Albinsson Maria E , Dowdney Jo , Holmes Angela K , Mansour Maged P , Seger Andreas
Published: July 2019

The large phagotrophic dinoflagellate Noctiluca has become a prominent red tide organism in southeast Australian waters since the 2000s, raising concerns for beach tourism, grazing impacts as well as ichthyotoxicity for finfish aquaculture. Satisfactory culture growth rates (0.23–0.56 per day) were obtained by feeding with small Thalassiosira diatom and Tetraselmis flagellate diets, while optimal growth rates sustained for up to 8 months (0.69 per day) were achieved by feeding in a plankton wheel with the large chain-forming dinoflagellate Gymnodinium catenatum. Noctiluca was highly tolerant towards salinities from 20 to 35 and growth was stimulated by temperatures increasing from 10 to 23°C, which in combination with the key factor of prey abundance explains the incidence in southeast Australia of predominantly summer and spring but occasionally also winter blooms. Fatty acid biomarkers suggest that Tasmanian field populations indiscriminately feed on available diatom and dinoflagellate mixtures. Noctiluca exhibited very limited ichthyotoxicity, and only at the highest cell concentrations of 2 000 000/L (50% reduction in RTgill W1 cell viability). Only the densest red tide surface slicks contained acutely toxic levels of unionized ammonia of 242 to 510 μg/L while inshore slicks generated oxygen concentrations as low as 0–1.5 ppm. Lipid phycotoxins (eicosapentaenoic acid, docosahexaenoic acid) did not appear to contribute to Noctiluca ichthyotoxicity. The fatty acid 20:0 eicosanoic acid may serve as a potential Noctiluca biomarker in marine food webs and sediments.
Top down or bottom up? An observational investigation of improvement in fibromyalgia symptoms following hip and knee replacement
Authors: Schrepf Andrew , Moser Stephanie , Harte Steven E , Basu Neil , Kaplan Chelsea , Kolarik Ellen , Tsodikov Alexander , Brummett Chad M , Clauw Daniel J
Published: July 2019

Objectives

Many patients with osteoarthritis have comorbid symptoms of FM, but it is unknown how these symptoms respond to surgical procedures that address nociceptive input in the periphery, such as total joint replacement. Here we explore differences in clinical characteristics between patients whose FM symptoms do and do not improve following total hip or knee replacement.

Methods

Participants were 150 patients undergoing knee or hip replacement who had a minimum FM survey score of 4 or greater prior to surgery. The top tertile of patients experiencing the most improvement in FM symptoms at month 6 were categorized as ‘Improve’ (n = 48) while the bottom two tertiles were categorized as ‘Worsen/Same’ (n = 102). Baseline symptom characteristics were compared between groups, as well as improvement in overall pain severity, surgical pain severity and physical function at 6 months.

Results

The Worsen/Same group had higher levels of fatigue, depression and surgical site pain at baseline (all P < 0.05). Additionally, they improved less on overall pain severity and physical functioning 6 months after surgery (both P < 0.05).

Conclusion

Most patients derive significant benefit in improvement of comorbid FM symptoms following total joint replacement, but a substantial proportion do not. Understanding the neurobiological basis for these different trajectories may help inform clinical judgment and improve patient care.
Molecular Epidemiology of Ralstonia solanacearum Species Complex Strains Causing Bacterial Wilt of Potato in Uganda
Authors: Abdurahman Abdulwahab , Parker Monica L. , Kreuze Jan , Elphinstone John G. , Struik Paul C. , Kigundu Andrew , Arengo Esther , Sharma Kalpana
Published: July 2019

Bacterial wilt (BW) caused by the Ralstonia solanacearum species complex (RSSC) is a serious threat to potato production in Uganda. However, little is known about the extent of the disease and the type of the pathogen strains involved. A nationwide survey was conducted to study BW prevalence and incidence in potato, and potato tuber and stem samples of potential alternative hosts were collected for pathogen isolation. DNA was extracted from pure cultures for genetic diversity studies. The pathogen was phylotyped by multiplex PCR; then, a subset of isolates was typed at sequevar level. Isolates of the same sequevar were then haplotyped using multilocus tandem repeat sequence typing (TRST) schemes. BW prevalence and incidence in potato farms were 81.4 and 1.7%, respectively. Three RSSC phylotypes were identified, with the majority of the strains belonging to Phylotype II (80%) followed by Phylotype I (18.5%) and III (1.5%). Phylotype I strains belonged to Sequevar 31, and Phylotype II strains belonged to Sequevar 1. Potato-associated Phylotype II Sequevar 1 strains were more diverse (27 TRST haplotypes) than nonpotato Phylotype I (5 TRST haplotypes). Mapping of TRST haplotypes revealed that three TRST haplotypes of Phylotype II Sequevar 1 strains play an important epidemiological role in BW of potato in Uganda being disseminated via latently infected seed.

[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
PALM-Seq: integrated sequencing of cell-free long RNA and small RNA
Authors: Yang Xi , Wang Taifu , Zhu Sujun , Zeng Juan , Xing Yanru , Zhou Qing , Liu Zhongzhen , Chen Haixiao , Sun Jinghua , Li Liqiang , Xu Jinjin , Geng Chunyu , Xu Xun , Wang Jian , Yang Huanming , Zhu Shida , Chen Fang , Wang Wen-Jing
Published: July 2019

Cell-free RNA, including both long RNA and small RNA, has been considered important for its biological functions and potential clinical usage, but the major challenge is to effectively sequence them at the same time. Here we present PolyAdenylation Ligation Mediated-Seq (PALM-Seq), an integrated sequencing method for cell-free long and small RNA. Through terminal modification and addition of 3’ polyadenylation and 5’ adaptor, we could get mRNA, long non-coding RNA, microRNA, tRNA, piRNA and other RNAs in a single library. With target RNA depletion, all these RNAs could be sequenced with relatively low depth. Using PALM-Seq, we identified pregnant-related mRNAs, long non-coding RNAs and microRNAs in female plasma. We also applied PALM-Seq to sequence RNA from amniotic fluids, leukocytes and placentas, and could find RNA signatures associated with specific sample type. PALM-Seq provides an integrated, cost-effective and simple method to characterize the landscape of cell-free RNA, and can stimulate further progress in cell-free RNA study and usage.
Genetic evidence suggests relationship between contemporary Bulgarian population and Iron Age steppe dwellers from Pontic-Caspian steppe
Authors: Stamov Svetoslav , Chobanov Todor
Published: July 2019

Ancient DNA analysis on the ancestry of European populations conducted in the last decade came to the puzzling conclusion that while all contemporary European populations can be best represented as an admixture of 3 ancestral populations –Early European Neolithic farmers (ENF), Western Hunter-Gatherers (WHG) and Ancestral North Eurasians (ANE), contemporary Bulgarians and few other SEE populations can also be represented as an admixture of two groups only – Early European Neolithic farmers and contemporary Caucasian people equally well.

If modeled as an admixture of two groups only, the ANE component presented in contemporary Bulgarians would have arrived on the Balkans with hypothetical ANE (Ancestral North Eurasians)-rich Caucasian population.

In this paper, we test the hypothesis that increased Caucasian component in contemporary SE Europeans, has been introduced on the Balkans by migrating Iron Age steppe dwellers from Pontic-Caspian steppe. We analyze available DNA datasets from both ancient and contemporary samples and identify a Caucasian signal, carried to Balkan populations by the nomadic dwellers of Early Medieval Saltovo-Mayaki Culture, located on the northern slope of Caucasus Mountains and adjacent steppe regions. We also identify two additional sources of Caucasian admixture in SEE populations, which are not specific to Bulgarian population only. Based on the results from our population genetic analysis we suggest that contemporary Bulgarians are an admixture of ancestral Slavonic groups, rich on locally absorbed EEF DNA and Proto Bulgarians, rich on Caucasian DNA and genetically related to the bearers of the Saltovo-Mayaki Culture from 8-10 century AD.
Activation of Smad 2/3 signaling by low shear stress mediates artery inward remodeling
Authors: Min Elizabeth , Baeyens Nicolas , Hu Rui , Zhuang Zhenwu , Chen Minghao , Huang Billy , Zarkada Georgia , Acheampong Angela , McEntee Kathleen , Simons Michael , Eichmann Anne , Schwartz Martin A.
Published: July 2019

Rationale

Blood vessel remodeling in response to changes in tissue demand is an important aspect of fitness and is often compromised in vascular disease. Endothelial cell (EC) sensing of fluid shear stress (FSS) governs vessel remodeling to maintain FSS at a specific magnitude or set point in healthy vessels.

Objective

The purpose of this study was to understand how shear stress-regulated Smad 2/3 contributes to artery remodeling.

Methods and Results

We found that shear stress induces Smad 2/3 phosphorylation, nuclear translocation, and gene expression in ECs. Nuclear translocation and gene expression are maximal at low and decrease at high FSS. Reducing flow in the mouse carotid by ligation of branch vessels induces Smad2 nuclear localization in vivo. Activation of Smad 2/3 by FSS requires the Type I TGFβ family receptor Alk5 and the transmembrane protein Neuropilin-1. Flow activation of Smad 2/3 is mediated by increased sensitivity to BMP9 but not BMP10 or TGFβ. By contrast, flow activation of Smad 1/5 is maximal at physiological FSS and requires BMP9 or 10 binding to Alk1 and Endoglin. EC-specific deletion of Alk5 in mice blocks low flow-induced inward remodeling after carotid ligation.

Conclusions

Together, these data elucidate a novel pathway that mediates low flow-induced inward artery remodeling. These results may be relevant to inward remodeling in diseased vessels where Smad 2/3 is activated by pathological stimuli.
A molecular logic of sensory coding revealed by optical tagging of physiologically-defined neuronal types
Authors: Lee Donghoon , Kume Maiko , Holy Timothy E
Published: July 2019

Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. Here, we report physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression-profiling cells based on their functional properties. We demonstrate that PhOTseq is capable of selecting rare cell types and enriching them by nearly one hundred-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among vomeronasal pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands, and revealed that the primary sequence of a chemoreceptor was an unexpectedly strong predictor of functional similarity.
A machine learning approach predicts essential genes and pharmacological targets in cancer
Authors: Gilvary Coryandar , Madhukar Neel S. , Gayvert Kaitlyn , Foronda Miguel , Perez Alexendar , Leslie Christina S. , Dow Lukas , Pandey Gaurav , Elemento Olivier
Published: July 2019

Loss-of-function (LoF) screenings have the potential to reveal novel cancer-specific vulnerabilities, prioritize drug treatments, and inform precision medicine therapeutics. These screenings were traditionally done using shRNAs, but with the recent emergence of CRISPR technology there has been a shift in methodology. However, recent analyses have found large inconsistencies between CRISPR and shRNA essentiality results. Here, we examined the DepMap project, the largest cancer LoF effort undertaken to date, and find a lack of correlation between CRISPR and shRNA LoF results; we further characterized differences between genes found to be essential by either platform. We then introduce ECLIPSE, a machine learning approach, which combines genomic, cell line, and experimental design features to predict essential genes and platform specific essential genes in specific cancer cell lines. We applied ECLIPSE to known drug targets and found that our approach strongly differentiated drugs approved for cancer versus those that have not, and can thus be leveraged to identify potential cancer repurposing opportunities. Overall, ECLIPSE allows for a more comprehensive analysis of gene essentiality and drug development; which neither platform can achieve alone.
Deep Learning For Denoising Hi-C Chromosomal Contact Data
Authors: Highsmith Max , Oluwadare Oluwatosin , Cheng Jianlin
Published: July 2019

Motivation

The three-dimensional (3D) organization of an organism’s genome and chromosomes plays a significant role in many biological processes. Currently, methods exist for modeling chromosomal 3D structure using contact matrices generated via chromosome conformation capture (3C) techniques such as Hi-C. However, the effectiveness of these methods is inherently bottlenecked by the quality of the Hi-C data, which may be corrupted by experimental noise. Consequently, it is valuable to develop methods for eliminating the impact of noise on the quality of reconstructed structures.

Results

We develop unsupervised and semi-supervised deep learning algorithms (i.e. deep convolutional autoencoders) to denoise Hi-C contact matrix data and improve the quality of chromosome structure predictions. When applied to noisy synthetic contact matrices of the yeast genome, our network demonstrates consistent improvement across metrics for contact matrix similarity including: Pearson Correlation, Spearman Correlation and Signal-to-Noise Ratio. Positive improvement across these metrics is seen consistently across a wide space of parameters to both gaussian and poisson noise functions.

Contact

mrh8x5@mail.missouri.edu and chengji@missouri.edu
Bordetella Colonization Factor A (BcfA) elicits protective immunity againstBordetella bronchisepticain the absence of an additional adjuvant
Authors: Yount Kacy S. , Jennings-Gee Jamie , Caution Kyle , Fullen Audra R. , Corps Kara N. , Quataert Sally , Deora Rajendar , Dubey Purnima
Published: July 2019

Bordetella bronchiseptica (B. bronchiseptica)is an etiologic agent of respiratory diseases in animals and humans. Despite widespread use of veterinaryB. bronchisepticavaccines, there is limited information on their composition, relative efficacy, and the immune responses they elicit. Furthermore, humanB. bronchisepticavaccines are not available. We leveraged the dual antigenic and adjuvant functions of BcfA to develop acellularB. bronchisepticavaccines in the absence of an additional adjuvant. Balb/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA and theBordetellaantigens FHA and Prn were equally protected against challenge with a prototypeB. bronchisepticastrain. The trivalent vaccine protected mice significantly better than the canine vaccine Bronchicine®and provided protection against aB. bronchisepticastrain isolated from a dog with kennel cough. Th1/17-polarized immune responses correlate with long-lasting protection againstBordetellaeand other respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by FHA/Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed Balb/c mice. Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a single component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and durability of vaccines againstBordetellaeand other pathogens.
Slow cortico-cortical connectivity (2-5Hz) is a new robust signature of conscious states
Authors: Bourdillon Pierre , Hermann Bertrand , Guénot Marc , Bastuji Hélène , Isnard Jean , King Jean-Rémi , Sitt Jacobo , Naccache Lionel
Published: July 2019

While long-range cortico-cortical functional connectivity has been reported by several studies as a necessary condition of conscious state, precise empirical evidence is still scarce. In the present work we provide such a direct and conclusive evidence in a set of three experiments. In the two first experiments intracranial-EEG was recorded during four distinct states in the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We discovered that long-range FC, computed by the weighted Symbolic-Mutual-Information (wSMI) in the 2-5Hz frequency band was a specific marker of conscious states that could discriminate CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients by revealing that wSMI in the 2-5 Hz range was also able to accurately discriminate patients in the vegetative state (or unresponsive wakefulness syndrome) from patients in the minimally conscious state. Taken together the present results suggest that 2-5Hz FC is a new and robust signature of conscious states.
Does human P-glycoprotein efflux involve transmembrane alpha helix breakage?
Authors: Bonito Cátia A. , Ferreira Maria-José U. , Ferreira Ricardo J. , dos Santos Daniel J. V. A.
Published: July 2019

The occluded conformation suggested in a recent article that revealed a new inward-facing conformation for the human P-glycoprotein may not represent the closing of a gate region but instead an artifact derived from lateral compression in a too small sized nanodisc, used to stabilize the transmembrane domains of the transporter.
Analysis of housekeeping genes in the peripheral blood of retinoblastoma patients
Authors: Martínez-Sánchez Mayra , Hernandez-Monge Jesús , Moctezuma-Dávila Mariana , Rangel-Charqueño Martha , Olivares-Illana Vanesa
Published: July 2019

Retinoblastoma is a pediatric neoplasia with a high incidence in non-developed countries. Nowadays the diagnosis is clinical and unfortunately in advanced stages of the diseases, which puts the child’s life risk. The search for molecular diagnosis on retinoblastoma is necessary. Due to their location and tendency to migrate, biopsies of retinoblastoma are not recommended then, peripheral blood samples can be a good source for the search of biomarker. RT qPCR is a sensitive method for gene expression quantification; in order to achieve optimal results, a crucial step is the reference gene choice that cannot be neglected under any circumstance. Six of the most commonly used housekeeping genes; GAPDH, HPRT1, B2M, TBP, RPL13a and 18S, were tested in the blood samples of patients diagnosed with retinoblastoma and healthy controls. The HPRT and TBP were found the most reliable genes whereas GAPDH, that is one of the most commonly used genes for normalisation, together with B2M, RPL13a and 18S have to be avoided. Using the selected reference genes, the Rb mRNA showed significant differences between patients and healthy children whereas no differences were found using to control groups. In the present study, we validate blood samples of patients with retinoblastoma.
Comparative genome analysis of a multidrug-resistant Pseudomonas aeruginosa sequence type 277 clone that harbours two copies of the blaSPM-1 gene and multiple single nucleotide polymorphisms in other resistance-associated genes
Authors: do Nascimento Ana Paula Barbosa , Filho Fernando Medeiros , Sousa Hério , Senger Hermes , Albano Rodolpho Mattos , dos Santos Marcelo Trindade , Carvalho-Assef Ana Paula D’Alincourt , da Silva Fabrício Alves Barbosa
Published: July 2019

Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of blaSPM-1 gene, encoding a metallo-beta-lactamase, in addition to other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify physiological key aspects that may lead to the exposure of new targets for therapy. This study was designed to characterize the genome of Pseudomonas aeruginosa CCBH4851 through the detection of genomic features and genome comparison with other Pseudomonas aeruginosa strains. The CCBH4851 closed genome showed features that were consistent with data reported for the specie. However, comparative genomics revealed the absence of genes important for pathogenesis. On the other hand, CCBH4851 genome contained acquired genomic islands that carry additional virulence and antimicrobial resistance-related genes. The presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations could influence the multidrug-resistant behavior of CCBH4851. Overall, the characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed several features that could directly impact the profile of virulence and antibiotic resistance of this pathogen in infectious outbreaks.
HERV-K and HERV-W transcriptional activity in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome
Authors: Rodrigues Lucas S , Nali Luiz H da Silva , Leal Cibele O D , Sabino Ester C , Lacerda Eliana M , Kingdon Caroline C , Nacul Luis , Romano Camila M
Published: July 2019

Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS / MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases. Here the expression of Endogenous retroviruses K and W (HERV–K and HERV–W) was determined in blood from moderately and severely affected ME/CFS patients. HERV-K was overexpressed only in moderately affected individuals and HERV-W showed no difference. This is the first report about HERV-K differential expression in moderate ME/CFS.
Correcting for sparsity and non-independence in glycomic data through a systems biology framework
Authors: Bao Bokan , Kellman Benjamin P. , Chiang Austin W.T. , York Austin K. , Mohammad Mahmoud A. , Haymond Morey W. , Bode Lars , Lewis Nathan E.
Published: July 2019

Glycans are fundamental cellular building blocks, involved in many organismal functions. Advances in glycomics are elucidating the roles of glycans, but it remains challenging to properly analyze large glycomics datasets, since the data are sparse (each sample often has only a few measured glycans) and detected glycans are non-independent (sharing many intermediate biosynthetic steps). We address these challenges with GlyCompare, a glycomic data analysis approach that leverages shared biosynthetic pathway intermediates to correct for sparsity and non-independence in glycomics. Specifically, quantities of measured glycans are propagated to intermediate glycan substructures, which enables direct comparison of different glycoprofiles and increases statistical power. Using GlyCompare, we studied diverse N-glycan profiles from glycoengineered erythropoietin. We obtained biologically meaningful clustering of mutant cell glycoprofiles and identified knockout-specific effects of fucosyltransferase mutants on tetra-antennary structures. We further analyzed human milk oligosaccharide profiles and identified novel impacts that the mother’s secretor-status on fucosylation and sialylation. Our substructure-oriented approach will enable researchers to take full advantage of the growing power and size of glycomics data.
A Combinatorial Approach for Single-cell Variant Detection via Phylogenetic Inference
Authors: Edrisi Mohammadamin , Zafar Hamim , Nakhleh Luay
Published: July 2019

Single-cell sequencing provides a powerful approach for elucidating intratumor heterogeneity by resolving cell-to-cell variability. However, it also poses additional challenges including elevated error rates, allelic dropout and non-uniform coverage. A recently introduced single-cell-specific mutation detection algorithm leverages the evolutionary relationship between cells for denoising the data. However, due to its probabilistic nature, this method does not scale well with the number of cells. Here, we develop a novel combinatorial approach for utilizing the genealogical relationship of cells in detecting mutations from noisy single-cell sequencing data. Our method, called scVILP, jointly detects mutations in individual cells and reconstructs a perfect phylogeny among these cells. We employ a novel Integer Linear Program algorithm for deterministically and efficiently solving the joint inference problem. We show that scVILP achieves similar or better accuracy but significantly better runtime over existing methods on simulated data. We also applied scVILP to an empirical human cancer dataset from a high grade serous ovarian cancer patient.
Association of the gut microbiota with colorectal cancer in a South Asian cohort of patients
Authors: Sahankumari AGP , Gamage Bawantha D. , Malavige Gathsaurie Neelika
Published: July 2019

Background

As the gut microbiome is thought to play a role in the pathogenesis of colorectal carcinoma (CRC) and affected by the diet and the genetic composition, we sought to investigate the patterns of gut microbiota that associate with CRC in a South Asian cohort of patients with CRC.

Methodology

The relative abundance of 45 types of gut microbial species were determined in faecal samples of CRC patients (n=24), DM (n=20) and healthy age matched controls (n=44), using a PCR array. Data was analyzed using the specific software for analysis of bacterial DNA quantification.

Results

The species Bacteroides fragilis (23.9-fold), Bacteroides thetaiotaomicron (8-fold) and Akkermansia muciniphila (5.9 fold) were several-fold over expressed in patients with CRC compared to healthy individuals, whereas bacterial species of the Phylum Proteobactria were under expressed. There was no difference in the abundance of these 3 species of bacteria with tumour stage or gender and age of patients. Aeromonas species, Enterococcus faecium and Shigella dysenteriae (Proteobacteria) were over 100-fold over abundant in those with DM compared to healthy individuals. Although 70.83% of those with CRC also had diabetes, the relative abundance of microbiota in CRC patients were different to those who had diabetes and no CRC.

Conclusions

Patients with CRC and DM harbor a markedly different gut microbiota patterns compared to their healthy counterparts. Similar patterns of gut microbial dysbiosis that associate with CRC and DM appear be seen in South Asian populations, compared to Western countries, despite differences in the diet and ethnicity.
Differentiating electrophysiological indices of internal and external performance monitoring: Relationship with perfectionism and locus of control
Authors: Muir Alexandra M. , Carbine Kaylie A. , Goodwin Jayden , Hedges-Muncy Ariana , Endrass Tanja , Larson Michael J.
Published: July 2019

The impact of individual differences on performance monitoring and psychopathology is a question of active debate. Personality traits associated with psychopathology may be related to poor internal performance monitoring (as measured by the error-related negativity [ERN]) but intact external performance monitoring (as measured by the reward positivity [RewP]), suggesting that there are underlying neural differences between internal and external performance monitoring processes. We tested the relationships between individual difference measures of perfectionism, locus of control, and ERN, Pe, and RewP component difference amplitude in a healthy undergraduate sample. A total of 128 participants (69 female, M(SD)age= 20.6(2.0) years) completed two tasks: a modified version of the Eriksen Flanker and a doors gambling task along with the Frost Multidimensional Perfectionism scale, the Rotter Locus of Control scale, and the Levenson Multidimensional Locus of Control scale to quantify perfectionism and locus of control traits, respectively. Linear regressions adjusting for age and gender showed that neither ΔERN nor ΔRewP amplitude were significantly moderated by perfectionism or locus of control scores. Findings suggest that, in psychiatrically-healthy individuals, there is not a strong link between perfectionism, locus of control, and ERN or RewP amplitude. Future research on individual difference measures in people with psychopathology may provide further insight into how these personality traits affect performance monitoring.