bluuebunny/crossref_metadata_2025 huggingface dataset:
Authority and Plurality in Muslim Legal Traditions: The Case of Ismaili Law†
Authors: Jamal Arif A
Published: November 2019

Thoughtful commentators on Islamic law often point out that Islamic law exhibits great interpretational diversity. Typically, this plurality is evidenced by the range of opinions or articulations of the rule in the face of any question or issue. At the level of sources, accounts of Islamic law have often emphasized the reliance on a set of major sources or roots of law, with other lesser sources. Scholarly works have acknowledged that matters are more complex than this and that different Muslim traditions may employ a different range of sources. Nonetheless, source plurality, and in particular how this source plurality is expressed in minority traditions, is underexplored. Focusing on the case of contemporary Nizari Ismaili law this Article will help to demonstrate the expression of source plurality in Islamic law. In so doing, this discussion aims to enrich the understanding of plurality in Islamic law to include not only the plurality of answers or rules on different issues but also the plurality of sources.
The role of haematological traits in risk of ischaemic stroke and its subtypes
Authors: Harshfield Eric L , Sims Matthew C , Traylor Matthew , Ouwehand Willem H , Markus Hugh S
Published: November 2019

Thrombosis and platelet activation play a central role in stroke pathogenesis, and antiplatelet and anticoagulant therapies are central to stroke prevention. However, whether haematological traits contribute equally to all ischaemic stroke subtypes is uncertain. Furthermore, identification of associations with new traits may offer novel treatment opportunities. The aim of this research was to ascertain causal relationships between a wide range of haematological traits and ischaemic stroke and its subtypes. We obtained summary statistics from 27 published genome-wide association studies of haematological traits involving over 375 000 individuals, and genetic associations with stroke from the MEGASTROKE Consortium (n = 67 000 stroke cases). Using two-sample Mendelian randomization we analysed the association of genetically elevated levels of 36 blood cell traits (platelets, mature/immature red cells, and myeloid/lymphoid/compound white cells) and 49 haemostasis traits (including clotting cascade factors and markers of platelet function) with risk of developing ischaemic (AIS), cardioembolic (CES), large artery (LAS), and small vessel stroke (SVS). Several factors on the intrinsic clotting pathway were significantly associated (P < 3.85 × 10−4) with CES and LAS, but not with SVS (e.g. reduced factor VIII activity with AIS/CES/LAS; raised factor VIII antigen with AIS/CES; and increased factor XI activity with AIS/CES). On the common pathway, increased gamma (γ′) fibrinogen was significantly associated with AIS/CES. Furthermore, elevated plateletcrit was significantly associated with AIS/CES, eosinophil percentage of white cells with LAS, and thrombin-activatable fibrinolysis inhibitor activation peptide antigen with AIS. We also conducted a follow-up analysis in UK Biobank, which showed that amongst individuals with atrial fibrillation, those with genetically lower levels of factor XI are at reduced risk of AIS compared to those with normal levels of factor XI. These results implicate components of the intrinsic and common pathways of the clotting cascade, as well as several other haematological traits, in the pathogenesis of CES and possibly LAS, but not SVS. The lack of associations with SVS suggests thrombosis may be less important for this stroke subtype. Plateletcrit and factor XI are potentially tractable new targets for secondary prevention of ischaemic stroke, while factor VIII and γ′ fibrinogen require further population-based studies to ascertain their possible aetiological roles.
A Review of Asymptomatic and Subclinical Middle East Respiratory Syndrome Coronavirus Infections
Authors: Grant Rebecca , Malik Mamunur Rahman , Elkholy Amgad , Van Kerkhove Maria D
Published: November 2019

The epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) since 2012 has been largely characterized by recurrent zoonotic spillover from dromedary camels followed by limited human-to-human transmission, predominantly in health-care settings. The full extent of infection of MERS-CoV is not clear, nor is the extent and/or role of asymptomatic infections in transmission. We conducted a review of molecular and serological investigations through PubMed and EMBASE from September 2012 to November 15, 2018, to measure subclinical or asymptomatic MERS-CoV infection within and outside of health-care settings. We performed retrospective analysis of laboratory-confirmed MERS-CoV infections reported to the World Health Organization to November 27, 2018, to summarize what is known about asymptomatic infections identified through national surveillance systems. We identified 23 studies reporting evidence of MERS-CoV infection outside of health-care settings, mainly of camel workers, with seroprevalence ranges of 0%–67% depending on the study location. We identified 20 studies in health-care settings of health-care worker (HCW) and family contacts, of which 11 documented molecular evidence of MERS-CoV infection among asymptomatic contacts. Since 2012, 298 laboratory-confirmed cases were reported as asymptomatic to the World Health Organization, 164 of whom were HCWs. The potential to transmit MERS-CoV to others has been demonstrated in viral-shedding studies of asymptomatic MERS infections. Our results highlight the possibility for onward transmission of MERS-CoV from asymptomatic individuals. Screening of HCW contacts of patients with confirmed MERS-CoV is currently recommended, but systematic screening of non-HCW contacts outside of health-care facilities should be encouraged.
Parenthood and Couples’ Relative Earnings in Norway
Authors: Bergsvik Janna , Kitterød Ragni Hege , Wiik Kenneth Aarskaug
Published: November 2019

With the advance of the gender revolution, income dynamics in couples are changing. Nonetheless, in most Western societies, parenthood still promotes specialized gender roles. Utilizing Norwegian register data on all married and cohabiting couples born 1946–1989, we investigate possible changes in the associations between parenthood and within-couple inequality in earnings in the years 2005–2014. Precisely, using interactions and fixed effects models, we compare the development of within-couple gender gaps in earnings over time between childless couples and couples with children of different ages, and within couples before and after childbirth. Results showed that the gender gap in earnings in couples increased with the number of children and was most distinct among couples with children below 6 years. However, the association between parenthood and within-couple inequality in earnings was reduced across the study period, a development partly driven by a decreasing fatherhood premium evident from 2009 onwards. Not only women’s but also men’s income development is now negatively affected by having young children in the household. Our findings, thus, indicate important changes in how men and women prioritize paid labour after a childbirth.
Stress Is Associated With Neurocognitive Function in Hispanic/Latino Adults: Results From HCHS/SOL Socio-Cultural Ancillary Study
Authors: Muñoz Elizabeth , Gallo Linda C , Hua Simin , Sliwinski Martin J , Kaplan Robert , Lipton Richard B , González Hector M , Penedo Frank J , Tarraf Wassim , Daviglus Martha L , Llabre Maria M , Isasi Carmen R
Published: November 2019

Objectives

The purpose of this study was to evaluate the hypothesis that chronic and acculturative stress would be negatively associated with neurocognitive function among middle aged to older Hispanics/Latinos.

Method

Our analytic sample consisted of 3,265 participants (mean age = 56.7 (±0.24)) from the Hispanic Community Health Study/Study of Latinos who participated in its Sociocultural Ancillary Study. During the baseline phase of this project, participants were assessed on multiple domains of neurocognitive function, and completed self-report measures of chronic and acculturative stress.

Results

Each standard deviation increase in chronic stress was associated with lower performance in a verbal learning task (B = −.17, 95% CI [−.32, −.01]); this association was no longer significant after adjusting for mental and physical health symptoms, including depression and anxiety symptoms, and cardiovascular health. A standard deviation increase in acculturative stress was associated with poorer performance in all cognitive measures (Bs range = −.13 to −1.03). Associations of acculturation stress with psychomotor speed, verbal learning, and word fluency remained significant after adjusting for mental and physical health symptoms.

Discussion

Our results suggest that mental and physical health may help explain some cross-sectional associations between stress and cognition and highlight the need to examine culture-specific psychosocial stressors to better understand the context of psychosocial risk factors for neurocognitive performance.
Sharing interoperable workflow provenance: A review of best practices and their practical application in CWLProv
Authors: Khan Farah Zaib , Soiland-Reyes Stian , Sinnott Richard O , Lonie Andrew , Goble Carole , Crusoe Michael R
Published: November 2019

Background

The automation of data analysis in the form of scientific workflows has become a widely adopted practice in many fields of research. Computationally driven data-intensive experiments using workflows enable automation, scaling, adaptation, and provenance support. However, there are still several challenges associated with the effective sharing, publication, and reproducibility of such workflows due to the incomplete capture of provenance and lack of interoperability between different technical (software) platforms.

Results

Based on best-practice recommendations identified from the literature on workflow design, sharing, and publishing, we define a hierarchical provenance framework to achieve uniformity in provenance and support comprehensive and fully re-executable workflows equipped with domain-specific information. To realize this framework, we present CWLProv, a standard-based format to represent any workflow-based computational analysis to produce workflow output artefacts that satisfy the various levels of provenance. We use open source community-driven standards, interoperable workflow definitions in Common Workflow Language (CWL), structured provenance representation using the W3C PROV model, and resource aggregation and sharing as workflow-centric research objects generated along with the final outputs of a given workflow enactment. We demonstrate the utility of this approach through a practical implementation of CWLProv and evaluation using real-life genomic workflows developed by independent groups.

Conclusions

The underlying principles of the standards utilized by CWLProv enable semantically rich and executable research objects that capture computational workflows with retrospective provenance such that any platform supporting CWL will be able to understand the analysis, reuse the methods for partial reruns, or reproduce the analysis to validate the published findings.
Stigma and Disclosure in Patients With Inflammatory Bowel Disease
Authors: Guo Ling , Rohde Jacob , Farraye Francis A
Published: November 2019

Stigma in patients suffering from chronic disease is associated with worse clinical outcomes and secondary medical issues such as depression, anxiety, and decreased quality of life. We believe various forms of stigma can have different clinical significance in patients with inflammatory bowel disease (IBD). With further insight and research, we suggest that these forms of stigma could be identified and targeted by researchers or clinicians to lessen the psychological disease burden in patients and to potentially improve their physical well-being. In the current review, we discuss public perceptions, knowledge, and stigmatization of IBD, the prevalence of various forms of IBD stigma, and the impact of such stigma on patient outcomes. We also discuss IBD disclosure, its association with stigma, and the tendencies and effects of such disclosures among youth and adult patient populations. We finish the review by highlighting possible modalities and research areas for future IBD interventions.
Balanced Activation of Striatal Output Pathways by Faster Off-Rate PDE10A Inhibitors Elicits Not Only Antipsychotic-Like Effects But Also Procognitive Effects in Rodents
Authors: Harada Akina , Kaushal Nidhi , Suzuki Kazunori , Nakatani Atsushi , Bobkov Konstantin , Vekich John A , Doyle Joseph P , Kimura Haruhide
Published: November 2019

Background

Faster off-rate competitive enzyme inhibitors are generally more sensitive than slower off-rate ones to binding inhibition by enzyme substrates. We previously reported that the cyclic adenosine monophosphate concentration in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) may be higher than that in D2-MSNs. Consequently, compared with slower off-rate phosphodiesterase 10A inhibitors, faster off-rate ones comparably activated D2-MSNs but partially activated D1-MSNs. We further investigated the pharmacological profiles of phosphodiesterase 10A inhibitors with different off-rates.

Methods

Phosphodiesterase 10A inhibitors with slower (T-609) and faster (T-773) off-rates were used. D1- and D2-MSN activation was assessed by substance P and enkephalin mRNA induction, respectively, in rodents. Antipsychotic-like effects were evaluated by MK-801- and methamphetamine-induced hyperactivity and prepulse inhibition in rodents. Cognition was assessed by novel object recognition task and radial arm maze in rats. Prefrontal cortex activation was evaluated by c-Fos immunohistochemistry in rats. Gene translations in D1- and D2-MSNs were evaluated by translating ribosome affinity purification and RNA sequencing in mice.

Results

Compared with T-609, T-773 comparably activated D2-MSNs but partially activated D1-MSNs. Haloperidol (a D2 antagonist) and T-773, but not T-609, produced antipsychotic-like effects in all paradigms. T-773, but not T-609 or haloperidol, activated the prefrontal cortex and improved cognition. Overall gene translation patterns in D2-MSNs by all drugs and those in D1-MSNs by T-773 and T-609 were qualitatively similar.

Conclusions

Differential pharmacological profiles among those drugs could be attributable to activation balance of D1- and D2-MSNs. The “balanced activation” of MSNs by faster off-rate phosphodiesterase 10A inhibitors may be favorable to treat schizophrenia.
The Complex Orthogonal Gelfand–Zeitlin System
Authors: Colarusso Mark , Evens Sam
Published: November 2019

In this paper, we use the theory of algebraic groups to prove a number of new and fundamental results about the orthogonal Gelfand–Zeitlin system. We show that the moment map (orthogonal Kostant–Wallach map) is surjective and simplify criteria of Kostant and Wallach for an element to be strongly regular. We further prove the integrability of the orthogonal Gelfand–Zeitlin system on regular adjoint orbits and describe the generic flows of the integrable system. We also study the nilfibre of the moment map and show that in contrast to the general linear case it contains no strongly regular elements. This extends results of Kostant, Wallach, and Colarusso from the general linear case to the orthogonal case.
Cosmological constrains on minimally and non-minimally coupled scalar field models
Authors: Davari Zahra , Marra Valerio , Malekjani Mohammad
Published: November 2019

We study the minimally and non-minimally coupled scalar field models as possible alternatives for dark energy, the mysterious energy component that is driving the accelerated expansion of the universe. After discussing the dynamics at both the background and perturbation level, we confront the two models with the latest cosmological data. After obtaining updated constraints on their parameters we perform model selection using the basic information criteria. We found that the ΛCDM model is strongly favored when the local determination of the Hubble constant is not considered and that this statement is weakened once local H0 is included in the analysis. We calculate the parameter combination $S_8=\sigma _8\sqrt{\Omega _{m}/0.3}$ and show the decrement of the tension with respect to the Planck results in the case of minimally and non-minimally coupled scalar field models. Finally, for the coupling constant between DE and gravity, we obtain the constraint $\xi \simeq -0.06^{+0.19}_{-0.19}$, approaching the one from solar system tests |ξ| ≲ 10−2 and comparable to the conformal value ξ = 1/6 at 1σ uncertainty.
Structural insights into target DNA recognition by R2R3-MYB transcription factors
Authors: Wang Baihui , Luo Qiang , Li Yingping , Yin Liufan , Zhou Nana , Li Xiangnan , Gan Jianhua , Dong Aiwu
Published: November 2019

As the largest group of MYB family transcription factors, R2R3-MYB proteins play essential roles during plant growth and development. However, the structural basis underlying how R2R3-MYBs recognize the target DNA remains elusive. Here, we report the crystal structure of Arabidopsis WEREWOLF (WER), an R2R3-MYB protein, in complex with its target DNA. Structural analysis showed that the third α-helices in both the R2 and R3 repeats of WER fit in the major groove of the DNA, specifically recognizing the DNA motif 5′-AACNGC-3′. In combination with mutagenesis, in vitro binding and in vivo luciferase assays, we showed that K55, N106, K109 and N110 are critical for the function of WER. Although L59 of WER is not involved in DNA binding in the structure, ITC analysis suggested that L59 plays an important role in sensing DNA methylation at the fifth position of cytosine (5mC). Like 5mC, methylation at the sixth position of adenine (6mA) in the AAC element also inhibits the interaction between WER and its target DNA. Our study not only unravels the molecular basis of how WER recognizes its target DNA, but also suggests that 5mC and 6mA modifications may block the interaction between R2R3-MYB transcription factors and their target genes.
TFregulomeR reveals transcription factors’ context-specific features and functions
Authors: Lin Quy Xiao Xuan , Thieffry Denis , Jha Sudhakar , Benoukraf Touati
Published: November 2019

Transcription factors (TFs) are sequence-specific DNA binding proteins, fine-tuning spatiotemporal gene expression. Since genomic occupancy of a TF is highly dynamic, it is crucial to study TF binding sites (TFBSs) in a cell-specific context. To date, thousands of ChIP-seq datasets have portrayed the genomic binding landscapes of numerous TFs in different cell types. Although these datasets can be browsed via several platforms, tools that can operate on that data flow are still lacking. Here, we introduce TFregulomeR (https://github.com/benoukraflab/TFregulomeR), an R-library linked to an up-to-date compendium of cistrome and methylome datasets, implemented with functionalities that facilitate integrative analyses. In particular, TFregulomeR enables the characterization of TF binding partners and cell-specific TFBSs, along with the study of TF’s functions in the context of different partnerships and DNA methylation levels. We demonstrated that TFs’ target gene ontologies can differ notably depending on their partners and, by re-analyzing well characterized TFs, we brought to light that numerous leucine zipper TFBSs derived from ChIP-seq experiments documented in current databases were inadequately characterized, due to the fact that their position weight matrices were assembled using a mixture of homodimer and heterodimer binding sites. Altogether, analyses of context-specific transcription regulation with TFregulomeR foster our understanding of regulatory network-dependent TF functions.
Risk factors of damage in early diagnosed systemic lupus erythematosus: results of the Italian multicentre Early Lupus Project inception cohort
Authors: Piga Matteo , Floris Alberto , Sebastiani Gian Domenico , Prevete Imma , Iannone Florenzo , Coladonato Laura , Govoni Marcello , Bortoluzzi Alessandra , Mosca Marta , Tani Chiara , Doria Andrea , Iaccarino Luca , Franceschini Franco , Fredi Micaela , Conti Fabrizio , Spinelli Francesca Romana , Galeazzi Mauro , Bellisai Francesca , Zanetti Anna , Carrara Greta , Scirè Carlo Alberto , Mathieu Alessandro
Published: November 2019

Objective

To investigate risk factors for damage development in a prospective inception cohort of early diagnosed SLE patients.

Methods

The Early Lupus Project recruited an inception cohort of patients within 12 months of SLE classification (1997 ACR criteria). At enrolment and every 6 months thereafter, the SLICC/ACR Damage Index was recorded. The contribution of baseline and time-varying covariates to the development of damage, defined as any SLICC/ACR Damage Index increase from 0 to ≥1, was assessed using univariate analysis. Forward-backward Cox regression models were fitted with covariates with P < 0.05 to identify factors independently associated with the risk of damage development.

Results

Overall, 230 patients with a mean (s.d.) age of 36.5 (14.4) years were eligible for this study; the mean number of visits per patient was 5.3 (2.7). There were 51 (22.2%) patients with SLICC/ACR Damage Index ≥1 after 12 months, 59 (25.6%) after 24 months and 67 (29.1%) after 36 months. Dyslipidaemia [P = 0.001; hazard ratio (HR) 2.9; 95% CI 1.5, 5.6], older age (P = 0.001; HR 3.0; 95% CI 1.6, 5.5), number of organs/systems involved (P = 0.002; HR 1.4; 95% CI 1.1, 1.8) and cardiorespiratory involvement (P = 0.041; HR 1.9; 95% CI 1.0, 3.7) were independently associated with an increased risk of developing damage. Risk profiles for damage development differed for glucocorticoid-related and -unrelated damage. HCQ use (P = 0.005; HR 0.4; 95% CI 0.2, 0.8) reduced the risk of glucocorticoid-unrelated damage.

Conclusion

We identified risk factors of damage development, but little effect of glucocorticoids, in this early SLE cohort. Addressing modifiable risk factors from the time of SLE diagnosis might improve patient outcomes.
Transparency and openness in behavioral medicine research
Authors: McVay Megan A , Conroy David E
Published: November 2019

Open science practices have potential to enhance the rigor, reproducibility, and reach of the work being conducted in behavioral medicine.
Eight in one: morphological and molecular analyses reveal cryptic diversity in Amazonian alopoglossid lizards (Squamata: Gymnophthalmoidea)
Authors: Ribeiro-Júnior Marco Antonio , Choueri Erik , Lobos Simon , Venegas Pablo , Torres-Carvajal Omar , Werneck Fernanda
Published: November 2019

Among the currently recognized species of Alopoglossus, the Amazonian Alopoglossus angulatus has the widest distribution. We here analyse variation in scutellation and morphometrics of A. angulatus by examining 785 specimens of Alopoglossus. We also analyse intra- and interspecific genetic structure and differentiation using two mitochondrial (Cytb and ND4) and two nuclear (SNCAIP and PRLR) genes from 97 samples. Both morphological and molecular analyses are based on specimens and samples from Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru and Suriname. Our results reveal A. angulatus as a monophyletic group composed of eight independently evolved lineages: A. angulatus s.s. plus three revalidated species plus two newly described species plus two putative species. We provide descriptions of all taxa, except for the putative species, including the first description of the neotype of A. angulatus and redescriptions of resurrected junior synonyms. Illustrations, diagnoses and geographical distribution maps are provided. Gene and species trees are also provided. The two new taxa recognized in this paper, along with the revalidation of three taxa, increase the total number of known species of Alopoglossus from nine to 14.
Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D3 and parathyroid hormone‐induced osteoclastogenesis
Authors: Conaway H. Herschel , Henning Petra , Lie Antia , Tuckermann Jan , Lerner Ulf H.
Published: November 2019

Glucocorticoid (GC) therapy decreases bone mass and increases the risk of fractures. We investigated interactions between the GC dexamethasone (DEX) and the bone resorptive agents 1, 25(OH)2‐vitamin D3 (D3) and parathyroid hormone (PTH) on osteoclastogenesis. We observed a synergistic potentiation of osteoclast progenitor cell differentiation and formation of osteoclasts when DEX was added to either D3‐ or PTH‐treated mouse bone marrow cell (BMC) cultures. Cotreatment of DEX with D3 or PTH increased gene encoding calcitonin receptor (Calcr), acid phosphatase 5, tartrate resistant (Acp5), cathepsin K (Ctsk), and TNF superfamily member 11 (Tnfsf11) mRNA, receptor activator of NF‐κB ligand protein (RANKL), numbers of osteoclasts on plastic, and pit formation and release of C‐terminal fragment of type I collagen from cells cultured on bone slices. Enhanced RANKL protein expression caused by D3 and DEX was absent in BMC from mice in which the GC receptor (GR) was deleted in stromal cells/osteoblasts. Synergistic interactions between DEX and D3 on RANKL and osteoclast formation were present in BMC from mice with attenuated GR dimerization. These data demonstrate that the GR cooperates with D3 and PTH signaling, causing massive osteoclastogenesis, which may explain the rapid bone loss observed with high dosages of GC treatment.—Conaway, H. H., Henning, P., Lie, A., Tuckermann, J., Lerner, U. H. Glucocorticoids employ the monomeric glucocorticoid receptor to potentiate vitamin D3 and parathyroid hormone‐induced osteoclastogenesis. FASEB J. 33, 14394‐14409 (2019). www.fasebj.org
Acute myocarditis complicated with permanent complete atrioventricular block caused by Escherichia coli bacteremia
Authors: Hsu Ching-Tsai , Hsiao Po-Jen , Liu Ching-Han , Chou Yen-Lien , Chen Bo-Hau , Liou Jun-Ting
Published: November 2019

Rationale:

Acute myocarditis complicated with complete atrioventricular block (CAVB) is rare in clinical scenario. We report an uncommon case of myocarditis complicated with permanent CAVB caused by Escherichia coli (E coli) bacteremia.

Patient concerns:

A 77-year-old woman presented at the emergency department with chest pain, dizziness, nausea, and cold sweats of 1-day duration. She had histories of type 2 diabetes mellitus, hyperlipidemia, and chronic kidney disease with regular medical therapy.

Diagnosis:

Both blood and urine cultures were positive for E coli. Regional inferior wall motion abnormalities on echocardiography, unexplained life-threatening arrhythmias, newly abnormal electrocardiogram, elevated cardiac troponins, and healthy coronary arteries on angiography were consistent with E coli-induced myocarditis.

Interventions:

The patient received implantation of a dual-chamber pacemaker because of irreversible CAVB.

Outcomes:

The patient was discharged on day 8 and remained asymptomatic at 15 months of follow-up, with ST-segment normalization and normal left ventricular function.

Lessons:

This extremely rare case of E coli-induced myocarditis masquerading as acute STEMI and with permanent CAVB sequelae, highlights the importance of sensitivity to non-ischemia etiologies of ST-segment elevation and the potential impact of E coli sepsis on the cardiac conduction system.
18F-NaF Uptake in Retroperitoneal Neurofibroma and Uterine Leiomyoma Calcifications
Authors: Liu Huipan , Chen Yue , Yang Ling , Fu Wenhui
Published: November 2019

A 48-year-old woman with intermittent lower back pain for 9 months and known retroperitoneal neurofibroma underwent 18F-NaF PET/CT scan to assess possible bony lesions causing the pain. Incidentally, the images showed elevated NaF activity in the retroperitoneal neurofibroma. In addition, uterine leiomyoma with heterogeneous calcifications revealed increased NaF activity.
Effects of Fibroblast Growth Factor-2 Combined With a Collagen/Gelatin Sponge for Adipogenesis in the Mouse Subcutis
Authors: Kakudo Natsuko , Morimoto Naoki , Ogawa Takeshi , Kusumoto Kenji
Published: November 2019

Introduction

A collagen/gelatin sponge (CGS) is a new scaffold that promotes wound healing by slowly releasing fibroblast growth factor (FGF)-2. FGF-2 induces mitogenesis, angiogenesis, and adipogenesis. In this study, the adipogenesis-inducing effects of CGS combined with FGF-2 in the subcutis of mice were evaluated.

Methods

Collagens/gelatin sponges (10 × 5 mm) were impregnated with 50 μL of FGF-2 solution (10 or 100 μg/mL). A CGS (Gunze Corp, Osaka, Japan) combined with FGF-2 was implanted subcutaneously into the thoracic region of mice. At 1, 2, 3, and 4 weeks, samples were collected for hematoxylin and eosin staining, von Willebrand factor immunostaining, and perilipin immunostaining to examine adipose tissue localization and angiogenesis. A CGS with only saline solution was prepared as a control.

Results

Adipocytes in the collagen fibers appeared at 3 weeks, and a zonal fat layer was noted under the panniculus carnosus at 4 weeks in the FGF-2–combined CGS groups. The fat layer was significantly thicker in the FGF-2 (100 μg/mL) group than in the FGF-2 (10 μg/mL) group. In the control group, no fat pad was newly formed. The number of newly formed vessels in the FGF (10 μg/mL) and (100 μg/mL) groups was significantly greater in the FGF-2 group than in the control group.

Conclusion

This study presents a promising method to enhance adipogenic effects in the murine subcutis using CGS combined with FGF-2, representing a potential technique for soft tissue reconstruction.
Gryllotalpicola protaetiae sp. nov., isolated from insect Protaetia brevitarsis seulensis, and emended descriptions of the genus Gryllotalpicola and the species Gryllotalpicola soli
Authors: Cho Hayoung , Heo Jun , Hamada Moriyuki , Tamura Tomohiko , Saitou Satomi , Kim Jeong-Seon , Hong Seung-Beom , Kim Soo-Jin , Kwon Soon-Wo
Published: November 2019

A bacterial strain, designated 2DFW10M-5T, was isolated from gut of the larva of Protaetia brevitarsis seulensis collected in the Republic of Korea. Cells of the strain were Gram-stain-positive, non-motile and rod-shaped. The strain grew at the range of 10–37 °C (optimum, 28–30 °C) and pH 4.0–8.0 (optimum, pH 7.0) and tolerated up to 1 % NaCl (w/v; optimum, 0 %) on Reasoner's 2A medium. It was catalase-positive and oxidase-negative. The 16S rRNA gene sequence of strain 2DFW10M-5T showed the highest similarity to

Gryllotalpicola daejeonensis

RU-04T (98.4 %),

Gryllotalpicola soli

KIS12-7T (98.2 %),

Gryllotalpicola kribbensis

PU-02T (97.5 %),

Gryllotalpicola koreensis

RU-16T (97.4 %) and

Gryllotalpicola reticulitermitis

TS-56T (97.2 %). The phylogenetic tree based on the 16S rRNA gene sequence revealed that strain 2DFW10M-5T fell into the radius of the genus

Gryllotalpicola

. The predominant fatty acid was ω-cyclohexyl-C17:0. The polar lipids of strain 2DFW10M-5T were diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and two unidentified lipids. The detected isoprenoid quinones were MK-11 (61.0 %), MK-10 (33.7 %) and MK-12 (5.3 %). The peptidoglycan contained d- and l-alanine, d-glutamic acid, glycine, l-serine and d-lysine with l-lysine as the diamino acid. The DNA G+C content calculated from the genome sequence of strain 2DFW10M-5T was 69.2 mol%. On the basis of its genomic, phylogenetic and phenotypic properties and distinctiveness, strain 2DFW10M-5T represents a novel species of the genus

Gryllotalpicola

, for which the name Gryllotalpicola protaetiae sp. nov. is proposed. The type strain is 2DFW10M-5T (=KACC 19316T=NBRC 113049T).
Paracoccus liaowanqingii sp. nov., isolated from Tibetan antelope (Pantholops hodgsonii)
Authors: Li Junqin , Lu Shan , Jin Dong , Yang Jing , Lai Xin-He , Huang Yuyuan , Tian Zhi , Dong Kui , Zhang Sihui , Lei Wenjing , Pu Ji , Zhang Gui , Wu Xiaomin , Huang Ying , Ren Zhihong , Wang Suping , Xu Jianguo
Published: November 2019

Two strains, designated 2251T and 3058, that were aerobic, Gram-stain-negative, non-motile, coccoid or short rod-shaped bacilli, have recently been isolated from Tibetan antelopes on the Qinghai-Tibet Plateau. The results of phylogenetic analyses of 16S rRNA gene sequences indicated that strains 2251T and 3058 represent a new species within the genus

Paracoccus

and are most similar to ‘

Paracoccus gahaiensis

’ CUG00006T (98.9 and 99.3 %),

Paracoccus nototheniae

I-41R45T (98.3 and 98.7 %) and

Paracoccus hibiscisoli

THG-T2.31T (97.6 and 97.8 %). Results of genomic sequence-based phylogenomic analysis agreed with those from 16S rRNA gene sequence analysis. Optimal growth was achieved at pH 7.0–7.5 and 28 °C with marine medium. Cells contained C18 : 1
ω7c as the major cellular fatty acid and ubiquinone-10 as the predominant menaquinone. The polar lipids comprised phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phospholipid, glycolipid and an unidentified lipid. The cell-wall peptidoglycan amino acids were meso-2,6-diaminopimelic acid, alanine and glutamic acid; the major cell-wall sugar was galactose. The G+C content of strain 2251T was 66.5 mol%. Both strains (2251T and 3058) had DNA–DNA relatedness values less than 50 % with all available genomes of the genus

Paracoccus

in the ncbi database. Differential genotypic inferences, together with phenotypic and biochemical characteristics, demonstrated that strains 2251T and 3058 should be classified as a novel species of the genus

Paracoccus

, for which the name Paracoccus liaowanqingii sp. nov. is suggested. The type strain is 2251T (=CGMCC 1.16490T=DSM 106269T).
Streptomyces paludis sp. nov., isolated from an alpine wetland soil
Authors: Zhao Jiarong , Tang Xinke , Li Kaiqin , Guo Yihui , Feng Meichang , Gao Jian
Published: November 2019

A Gram-stain-positive actinobacterium, designated strain GSSD-12T, was isolated from an alpine wetland soil. blast search of the full-length 16S rRNA gene sequence of GSSD-12T indicated it represented a member of the genus

Streptomyces

, and displayed highest similarity with

Streptomyces scopuliridis

NRRL B-24574T (99.2 %) and less than 98.6 % similarity with other species of the genus

Streptomyces

with validly published names. Phylogenetic analysis based on 16S rRNA gene sequences indicated that GSSD-12T was closely related to

S. scopuliridis

NRRL B-24574T,

Streptomyces odonnellii

NRRL B-24891T and

Streptomyces lushanensis

NRRL B-24994T. However, the digital DNA–DNA hybridization value, the average nucleotide identity value and the multilocus sequence analysis evolutionary distance between this strain and its closest relatives indicated that it represented a distinct species. Furthermore, GSSD-12T was also distinctly differentiated from them by morphological, physiological and biochemical characteristics. Therefore, strain GSSD-12T(=CICC 11051T=JCM 33019T) represents a novel species of the genus

Streptomyces

, for which the name Streptomyces paludis sp. nov. is proposed.
Glycocaulis profundi sp. nov., a marine bacterium isolated from seawater of the Mariana Trench
Authors: Sun Hao , Hu Yuyao , Zhou Shun , Zheng Yanfen , Zhang Xiao-Hua
Published: November 2019

A Gram-stain-negative, strictly aerobic, rod-shaped bacterium, without flagellum and designated ZYF765T, was isolated from seawater sampled at a depth of 4000 m in the Mariana Trench. Strain ZYF765T grew with 1–15 % (w/v) NaCl (optimum, 4 %), at 16–37 °C (28 °C) and at pH 6.0–10.0 (pH 7.0–8.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain ZYF765T formed a lineage within the family

Hyphomonadaceae

, and was distinct from the most closely related species

Glycocaulis abyssi

,

Glycocaulis albus

and

Glycocaulis alkaliphilus

with 16S rRNA gene sequences similarities ranging from 98.42 to 98.63 %. The major respiratory quinone was ubiquinone-10 (Q-10). The polar lipids comprised three unidentified glycolipids, one unidentified aminophospholipid, one unidentified phospholipid and one unidentified aminolipid. The predominant fatty acids (more than 10 % of total fatty acids) were C18 : 1ω7c (46.2 %) and C18 : 0 (14.1 %). The DNA G+C content was 67.7 mol%. On the basis of the results of polyphasic taxonomic analysis, strain ZYF765T is considered to represent a novel species within the genus

Glycocaulis

, for which the name Glycocaulis profundi sp. nov. is proposed. The type strain is ZYF765T (=JCM 33028T=MCCC 1K03554T).
AncientYersinia pestisgenomes provide no evidence for the origins or spread of the Justinianic Plague
Authors: Keller Marcel , Spyrou Maria A. , McCormick Michael , Bos Kirsten I. , Herbig Alexander , Krause Johannes
Published: November 2019

Along with the publication of 137 ancient human genomes retrieved from archaeological remains of the Eurasian steppe, Damgaard et al., 2018 identified two individuals infected withYersinia pestis, yielding one genome with 0.24x average coverage (DA147, 6th–9thc. AD) and another with 8.7x (DA101, 2nd–3rdc. AD). A phylogenetic analysis performed on the latter placed it in a position ancestral to a 6th-century Justinianic genome from Aschheim, Germany. These results are used to fuel an argument that the Justinianic Plague (541–544 AD) “was brought to Europe towards the end of the Hunnic period through the Silk Road along the southern fringes of the steppes” in contrast to the leading hypothesis of introduction via the Red Sea that is supported by historical accounts. In our reanalysis, we question the contested historical context of the presented genomes with the Justinianic Plague and show that the lower coverage genome might be rather related to the Black Death (1346–1353 AD).
SVants – A long-read based method for structural variation detection in bacterial genomes
Authors: Hanson BM , Johnson JS , Leopold SR , Sodergren E , Weinstock GM
Published: November 2019

Motivation

Mobile genetic elements (MGEs) are genetic material that can transfer between bacterial cells and move to new locations within a single bacterial genome. These elements range from several hundred to tens of thousands of bases, and are often bordered by repeat regions, which makes resolving these elements difficult with short-read sequencing data. The development and availability of long-read sequencing technologies has opened up new opportunities in the study of structural variation but there is a lack of bioinformatics tools designed to take advantage of these longer reads.

Results

We present an assembly-free method for identifying the location of these MGEs when compared to any reference genome (including draft genomes). Using an artificially constructed Escherichia coli genome containing single and tandem-repeats of a Tn9 transposon, we demonstrate the ability of SVants to accurately identify multiple insertion sites as well as count the number of repeats of this MGE. Additionally, we show that SVants accurately identifies the transposon of interest, Tn9, but does not erroneously identify existing IS1 regions present within the chromosome of the E. coli artificial reference.

Availability and Implementation

SVants is available as open-source software at https://github.com/EpiBlake/SVants
A cryo-tomography-based volumetric model of the actin core of mouse vestibular hair cell stereocilia lacking plastin 1
Authors: Song Junha , Patterson Roma , Krey Jocelyn F. , Hao Samantha , Wang Linshanshan , Ng Brian , Sazzed Salim , Kovacs Julio , Wriggers Willy , He Jing , Barr-Gillespie Peter G. , Auer Manfred
Published: November 2019

Electron cryo-tomography allows for high-resolution imaging of stereocilia in their native state. Because their actin filaments have a higher degree of order, we imaged stereocilia from mice lacking the actin crosslinker plastin 1 (PLS1). We found that while stereocilia actin filaments run 13 nm apart in parallel for long distances, there were gaps of significant size that were stochastically distributed throughout the actin core. Actin crosslinkers were distributed through the stereocilium, but did not occupy all possible binding sites. At stereocilia tips, protein density extended beyond actin filaments, especially on the side of the tip where a tip link should anchor. Along the shaft, repeating density was observed that corresponds to actin-to-membrane connectors. In the taper region, most actin filaments terminated near the plasma membrane. The remaining filaments twisted together to make a tighter bundle than was present in the shaft region; the spacing between them decreased from 13 nm to 9 nm. Our models illustrate detailed features of distinct structural domains that are present within the stereocilium.
A generalized machine-learning aided method for targeted identification of industrial enzymes from metagenome: a xylanase temperature dependence case study
Authors: Shahraki Mehdi Foroozandeh , Farhadyar Kiana , Kavousi Kaveh , Azarabad Mohammad Hadi , Boroomand Amin , Ariaeenejad Shohreh , Salekdeh Ghasem Hosseini
Published: November 2019

Growing industrial utilization of enzymes, and the increasing availability of metagenomic data highlights the demand for effective methods of targeted identification and verification of novel enzymes from various environmental microbiota. Xylanases are a class of enzymes with numerous industrial applications and are involved in the degradation of xylose, a component of lignocellulose. Optimum temperature of enzymes are essential factors to be considered when choosing appropriate biocatalysts for a particular purpose. Therefore, in-silico prediction of this attribute is a significant cost and time-effective step in the effort to characterize novel enzymes. The objective of this study was to develop a computational method to predict the thermal dependence of xylanases. This tool was then implemented for targeted screening of putative xylanases with specific thermal dependencies from metagenomic data and resulted in identification of three novel xylanases from sheep and cow rumen microbiota. Here we present TAXyl (Thermal Activity Prediction for Xylanase), a new sequence-based machine learning method that has been trained using a selected combination of various protein features. This random forest classifier discriminates non-thermophilic, thermophilic, and hyper-thermophilic xylanases. Model’s performance was evaluated through multiple iterations of six-fold cross-validations, and it exhibited a mean accuracy of ∼0.79. TAXyl is freely accessible as a web-service.
A geostatistical approach to modelling human Holocene migrations in Europe using ancient DNA
Authors: Racimo Fernando , Woodbridge Jessie , Fyfe Ralph M. , Sikora Martin , Sjögren Karl-Göran , Kristiansen Kristian , Linden Marc Vander
Published: November 2019

The European continent was subject to two major migrations of peoples during the Holocene: the northwestward movement of Anatolian farmer populations during the Neolithic and the westward movement of Yamnaya steppe peoples during the Bronze Age. These movements changed the genetic composition of the continent’s inhabitants, via admixture and population replacement processes. The Holocene was also characterized by major changes in vegetation composition, which altered the environment occupied by the original hunter-gatherer populations. Here, we use a combination of paleogenomics and geostatistical modelling to produce detailed maps of the movement of these populations over time and space, and to understand how these movements impacted the European vegetation landscape. We find that the dilution of hunter-gatherer ancestries and the Yamnaya steppe migration coincided with a reduction in the amount of broad-leaf forest and an increase in the amount of pasture lands in the continent. We also show that climate played a role in these vegetational changes. Additionally, we find that the spread of Neolithic farmer ancestry had a two-pronged wavefront, in agreement with similar findings based on patterns of the cultural spread of farming from radiocarbon-dated archaeological sites. With thousands of ancient genomes publicly available and in production, we foresee that the integration of ancient DNA with geostatistical techniques and large-scale archaeological datasets will revolutionize the study of ancient populations movements, and their effects on local fauna and flora.
TXO: Transcription-Only genetic circuits as a novel cell-free approach for Synthetic Biology
Authors: Millacura Felipe A. , Li Mengxi , Valenzuela-Ortega Marcos , French Christopher E.
Published: November 2019

While synthetic biology represents a promising approach to solve real-world problems, the use of genetically modified organisms is a cause of legal and environmental concerns. Cell-free systems have emerged as a possible solution but much work is needed to optimize their functionality and simplify their usage for Synthetic Biology. Here we present TXO, transcription-only genetic circuits, independent of translation or post-translation maturation. RNA aptamers are used as reaction output allowing the generation of fast, reliable and simple-to-design transcriptional units. TXO cell-free reactions and their possible applications are a promising new tool for fast and simple bench-to-market genetic circuit and biosensor applications.
The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+T cells
Authors: Kwesi-Maliepaard Eliza Mari , Aslam Muhammad Assad , Alemdehy Mir Farshid , van den Brand Teun , McLean Chelsea , Vlaming Hanneke , van Welsem Tibor , Korthout Tessy , Lancini Cesare , Hendriks Sjoerd , Ahrends Tomasz , van Dinther Dieke , den Haan Joke M.M. , Borst Jannie , de Wit Elzo , van Leeuwen Fred , Jacobs Heinz
Published: November 2019

Cytotoxic T-cell differentiation is guided by epigenome adaptations but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8+T cells. T-cell specific ablation ofDot1Lresulted in loss of naïve CD8+T cells and premature differentiation towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Without DOT1L, the memory-like CD8+cells fail to acquire full effector functionsin vitroandin vivo. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. Through our study DOT1L is emerging as a central player in physiology of CD8+T cells, acting as a barrier to prevent premature differentiation and supporting the licensing of the full effector potential of cytotoxic T cells.