bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel evaluation of sevoflurane anesthetic exposure on the testicular germ cells of neonatal male mice
Authors: Ebrahim Soltani Ali Raza , Kajbafzadeh Abdolmohammad , Ezzati Maryam , Ebrahim Soltani Zahra , Hosseinifar Navid , Maleki Anahid , Nezhad Sistani Maryam 
Published: October 2019

AbstractBackground: Inhalatory anesthetics may impact spermatogenesis and sexual behavior. Comprehensive evaluation should be conducted to screen the effect of inhalatory anesthetics on the sperm and semen quality. This experimental research was organized to assess the impacts of sevoflurane during the period of neonatal spermatogenesis. Materials and methods: Twenty-one pregnant mice were obtained from the Pasteur Institute. After birth, neonates were categorized based on exposure to Monitored Anesthesia Care (MAC) of sevoflurane into three groups: experimental 1, experimental 2 and control. In order to investigate the testicular condition, a histological evaluation, including apoptosis study and immunohistochemistry, was performed. Not only apoptotic target genes such as Bax and Bcl-2, but also microRNA17-92, were investigated in testicular samples via real-time polymerase chain reaction (real-time PCR). Results: The outcomes of this work indicated the effects of sevoflurane on spermatogonial and germ cells in testicular tissue via stimulating apoptotic target genes and microRNA-17-92. The proportion of Bax/Bcl-2 in the experimental group was 8.318699 ± 1.093, and the proportion of Bax/Bcl-2 in the control group was 2.631 ± 0.079. There was a significant (p ≤ 0.002) difference among the control group and both experimental groups. Conclusion: Sequential sevoflurane exposure during the neonatal period may create testicular dysfunction due to the high level of apoptosis in spermatogonial cells. Also, sevoflurane may affect spermatogenesis by influencing other biomarkers, such as microRNA.
The signature of primordial black holes in the dark matter halos of galaxies
Authors: Hawkins M. R. S. 
Published: October 2019

Aims. The aim of this paper is to investigate the claim that stars in the lensing galaxy of a gravitationally lensed quasar system can always account for the observed microlensing of the individual quasar images.
Methods. A small sample of gravitationally lensed quasar systems was chosen where the quasar images appear to lie on the fringe of the stellar distribution of the lensing galaxy. As with most quasar systems, all the individual quasar images were observed to be microlensed. The surface brightness of the lensing galaxy at the positions of the quasar images was measured from Hubble Space Telescope frames, and converted to stellar surface mass density. The surface density of smoothly distributed dark matter at the image positions was obtained from lensing models of the quasar systems and applied to the stellar surface mass density to give the optical depth to microlensing. This was then used to assess the probability that the stars in the lensing galaxy could be responsible for the observed microlensing. The results were supported by microlensing simulations of the star fields around the quasar images combined with values of convergence and shear from the lensing models.
Results. Taken together, the probability that all the observed microlensing is due to stars was found to be ∼3 × 10−4. Errors resulting from the surface brightness measurement, the mass-to-light ratio, and the contribution of the dark matter halo do not significantly affect this result.
Conclusions. It is argued that the most plausible candidates for the microlenses are primordial black holes, either in the dark matter halos of the lensing galaxies, or more generally distributed along the lines of sight to the quasars.
3-Länder-Manifest: Zeitenwende in der Medizin – Patientenversorgung auf dem gefährlichen Weg in die Ökonomisierung und Industrialisierung
Authors: Mann Klaus , Kapitza Thomas , Likar Rudolf , Egger Bernhard 
Published: October 2019

Das 3-Länder-Manifest „Zeitenwende in der Medizin“ ergänzt die bestehenden Eide, Gelöbnisse und Selbstverpflichtungen der Ärzteschaft. Es soll die inhaltliche Lücke zwischen medizinethischen Grundsätzen und den moralischen Herausforderungen des durch Ökonomisierung, Kommerzialisierung und Industrialisierung geprägten ärztlichen Berufsalltags im Gesundheitswesen füllen. Konkrete Vorschläge sollen helfen, bestehende Hindernisse zu überwinden. Der Vorrang der Medizin gegenüber Ökonomie und Technologie ist auf allen Ebenen beruflichen Handelns durch die Ärzteschaft sicherzustellen.Das 3-Länder-Manifest soll den hierfür notwendigen Diskurs innerhalb der Ärzteschaft und in der Gesellschaft anregen und thematisch unterstützen.In diesem Zusammenhang werden die folgenden Forderungen im 3-Länder-Manifest erhoben:Die Verfasser dieses Manifests fordern dazu auf, die ethischen Werte medizinischen Wirkens zu sichern, und rufen alle Beteiligten im Gesundheitswesen auf danach zu handeln, um somit eine Zeitenwende herbeizuführen.
Two-beam interference lattice lightsheet for structured illumination microscopy
Authors: Chang Bo-Jui , Tang Wei-Chun , Liu Yen-Ting , Tsai Yun-Chi , Tsao Chieh , Chen Peilin , Chen Bi-Chang 
Published: October 2019

Abstract
Combining super-resolution structured illumination microscopy (SIM) and lattice lightsheet microscopes (LLSMs) has always been an ideal approach for high spatiotemporal resolution in 3D applications. We propose a simpler method to perform 2D-SIM with three phases, which is 5/3 faster and less sensitive to optical alignment compared to 3D-SIM in LLSM. In this research, we modify the original square lattice lightsheet to become an ideal pattern for the 2D-SIM by filtering the illumination pattern on the back pupil of the excitation objective. We show that the generated lattice pattern is consistent in the experiment and the simulation. We achieved a spatial resolution of 184  ±  28 nm, 244  ±  48 nm and 384  ±  20 nm in the x, y  and z directions, respectively for 2D-SIM in LLSM, with an exposure time of 5 ms for each phase per plane. For biological applications, we perform 2D-SIM in LLSM by imaging the dynamics of actin and membrane ruffling in a U2OS cell, with an exposure time of 20 ms per phase and two colors recorded for 121 optical-sectioning planes per 3D stack.
Depression and Incident HIV in Adolescent Girls and Young Women in HIV Prevention Trials Network 068: Targets for Prevention and Mediating Factors
Authors: Goin Dana E , Pearson Rebecca M , Craske Michelle G , Stein Alan , Pettifor Audrey , Lippman Sheri A , Kahn Kathleen , Neilands Torsten B , Hamilton Erica L , Selin Amanda , MacPhail Catherine , Wagner Ryan G , Gomez-Olive F Xavier , Twine Rhian , Hughes James P , Agyei Yaw , Laeyendecker Oliver , Tollman Stephen , Ahern Jennifer 
Published: October 2019

Abstract
The human immunodeficiency virus (HIV) epidemic among adolescent girls and young women (AGYW) in sub-Saharan Africa is a critical public health problem. We assessed whether depressive symptoms in AGYW were longitudinally associated with incident HIV, and identified potential social and behavioral mediators. Data came from a randomized trial of a cash transfer conditional on school attendance among AGYW (ages 13–21 years) in rural Mpumalanga Province, South Africa, during 2011–2017. We estimated the relationship between depressive symptoms and cumulative HIV incidence using a linear probability model, and we assessed mediation using inverse odds ratio weighting. Inference was calculated using the nonparametric bootstrap. AGYW with depressive symptoms had higher cumulative incidence of HIV compared with those without (risk difference = 3.5, 95% confidence interval (CI): 0.1, 7.0). The strongest individual mediators of this association were parental monitoring and involvement (indirect effect = 1.6, 95% CI: 0.0, 3.3) and reporting a partner would hit her if she asked him to wear a condom (indirect effect = 1.5, 95% CI: –0.3, 3.3). All mediators jointly explained two-thirds (indirect effect = 2.4, 95% CI: 0.2, 4.5) of the association between depressive symptoms and HIV incidence. Interventions addressing mental health might reduce risk of acquiring HIV among AGYW.
Cancer stem cells enrichment with surface markers CD271 and CD44 in human head and neck squamous cell carcinomas
Authors: Elkashty Osama A , Abu Elghanam Ghada , Su Xinyun , Liu Younan , Chauvin Peter J , Tran Simon D 
Published: October 2019

Abstract
Head and neck squamous cell carcinoma (HNSCC) has a poor 5-year survival rate of 50%. One potential reason for treatment failure is the presence of cancer stem cells (CSCs). Several cell markers, particularly CD44, have been used to isolate CSCs. However, isolating a pure population of CSC in HNSCC still remains a challenging task. Recent findings show that normal oral stem cells were isolated using CD271 as a marker. Thus, we investigated the combined use of CD271 and CD44 to isolate an enriched subpopulation of CSCs, followed by their characterization in vitro, in vivo, and in patients’ tissue samples. Fluorescent-activated cell sorting was used to isolate CD44+/CD271+ and CD44+/CD271− from two human HNSCC cell lines. Cell growth and self-renewal were measured with MTT and sphere/colony formation assays. Treatment-resistance was tested against chemotherapy (cisplatin and 5-fluorouracil) and ionizing radiation. Self-renewal, resistance, and stemness-related genes expression were measured with qRT-PCR. In vivo tumorigenicity was tested with an orthotopic immunodeficient mouse model of oral cancer. Finally, we examined the co-localization of CD44+/CD271+ in patients’ tissue samples. We found that CD271+ cells were a subpopulation of CD44+ cells in human HNSCC cell lines and tissues. CD44+/CD271+ cells exhibited higher cell proliferation, sphere/colony formation, chemo- and radio-resistance, upregulation of CSCs-related genes, and in vivo tumorigenicity when compared to CD44+/CD271− or the parental cell line. These cell markers showed increased expression in patients with the increase of the tumor stage. In conclusion, using both CD44 and CD271 allowed the isolation of CSCs from HNSCC. These enriched CSCs will be more relevant in future treatment and HNSCC progression studies.
A comparison of contemporary versus older studies of aspirin for primary prevention
Authors: Moriarty Frank , Ebell Mark H 
Published: October 2019

Abstract

Background
Recent aspirin trials have not shown similar benefits for primary prevention as older studies.

Objective
To compare benefits and harms of aspirin for primary prevention before and after widespread use of statins and colorectal cancer screening.

Methods
We compared studies of aspirin for primary prevention that recruited patients from 2005 onward with previous individual patient data (IPD) meta-analyses that recruited patients from 1978 to 2002. Data for contemporary studies were synthesized using random-effects models. We report vascular [major adverse cardiovascular events (MACE), myocardial infarction (MI) and stroke], bleeding, cancer and mortality outcomes.

Results
The IPD analyses of older studies included 95 456 patients for CV prevention and 25 270 for cancer mortality, while the four newer studies had 61 604 patients. Relative risks for vascular outcomes for older versus newer studies follow: MACE: 0.89 [95% confidence interval (CI) 0.83–0.95] versus 0.93 (0.86–0.99); fatal haemorrhagic stroke: 1.73 (1.11–2.72) versus 1.06 (0.66–1.70); any ischaemic stroke: 0.86 (0.74–1.00) versus 0.86 (0.75–0.98); any MI: 0.84 (0.77–0.92) versus 0.88 (0.77–1.00); and non-fatal MI: 0.79 (0.71–0.88) versus 0.94 (0.83–1.08). Cancer death was not significantly decreased in newer studies (1.11, 0.92–1.34). Major haemorrhage was significantly increased (older studies RR 1.48, 95% CI 1.25–1.76 versus newer studies RR 1.37, 1.24–1.53). There was no effect on all-cause mortality, cardiovascular mortality, fatal stroke or fatal MI.

Conclusions
Per 1200 persons taking aspirin for primary prevention for 5 years, there will be 4 fewer MACEs, 3 fewer ischaemic strokes, 3 more intracranial haemorrhages and 8 more major bleeding events. Aspirin should no longer be recommended for primary prevention.
Key challenges facing data-driven multicellular systems biology
Authors: Macklin Paul 
Published: October 2019

Abstract
Increasingly sophisticated experiments, coupled with large-scale computational models, have the potential to systematically test biological hypotheses to drive our understanding of multicellular systems. In this short review, we explore key challenges that must be overcome to achieve robust, repeatable data-driven multicellular systems biology. If these challenges can be solved, we can grow beyond the current state of isolated tools and datasets to a community-driven ecosystem of interoperable data, software utilities, and computational modeling platforms. Progress is within our grasp, but it will take community (and financial) commitment.
Real- time interaction analysis of Shiga toxins and membrane microdomains of primary human brain microvascular endothelial cells
Authors: Detzner Johanna , Steil Daniel , Pohlentz Gottfried , Legros Nadine , Humpf Hans-Ulrich , Mellmann Alexander , Karch Helge , Müthing Johannes 
Published: October 2019

Abstract
Infections of the human intestinal tract with enterohemorrhagic Escherichia coli (EHEC) result in massive extraintestinal complications due to translocation of EHEC-released Shiga toxins (Stxs) from the gut into the circulation. Stx-mediated damage of the cerebral microvasculature raises serious brain dysfunction being the most frequent cause of acute mortality in patients suffering from severe EHEC infections. Stx2a and Stx2e are associated with heavy and mild course of infection, respectively. Stx2a preferentially binds to globotriaosylceramide (Gb3Cer, Galα1-4Galβ1-4Glcβ1-1Cer), while Stx2e prefers globotetraosylceramide (Gb4Cer, GalNAcβ1-3Galα1-4Galβ1-4Glcβ1-1Cer). Both glycosphingolipids (GSLs) were detected in detergent-resistant membranes (DRMs) of primary human brain microvascular endothelial cells (pHBMECs) resembling microdomains of the plasma membrane. In this study we show that Gb3Cer and Gb4Cer of pHBMECs with saturated C16:0, C22:0, and C24:0 fatty acids dominated in DRMs, corresponding to the liquid-ordered membrane phase, whereas lipoforms carrying unsaturated C24:1 and C24:2 fatty acids prevailed in the nonDRM fractions, which correspond to the liquid-disordered membrane phase. Similarly, a shift of the phospholipids from saturated lipoforms in the DRM to unsaturated species in the nonDRM fractions was observed. Real-time biomolecular interaction analysis using affinity-purified Stx2a and Stx2e, recorded with a surface acoustic wave (SAW) biosensor, evidenced high binding strength of both toxins towards DRMs and failure in interaction with nonDRMs. These results support the hypothesis of preferential binding of Stxs towards microdomains harbouring GSL receptors carrying saturated fatty acids in their lipid anchors. Collectively, unravelling the precise mechanisms of Stx-microdomain interaction may help to develop antiadhesive compounds to combat Stx-mediated cellular injury.
Crystal structure of the complex of the interaction domains of Escherichia coli DnaB helicase and DnaC helicase loader: structural basis implying a distortion-accumulation mechanism for the DnaB ring opening caused by DnaC binding
Authors: Nagata Koji , Okada Akitoshi , Ohtsuka Jun , Ohkuri Takatoshi , Akama Yusuke , Sakiyama Yukari , Miyazaki Erika , Horita Shoichiro , Katayama Tsutomu , Ueda Tadashi , Tanokura Masaru 
Published: October 2019

AbstractLoading the bacterial replicative helicase DnaB onto DNA requires a specific loader protein, DnaC/DnaI, which creates the loading-competent state by opening the DnaB hexameric ring. To understand the molecular mechanism by which DnaC/DnaI opens the DnaB ring, we solved 3.1-Å co-crystal structure of the interaction domains of Escherichia coli DnaB–DnaC. The structure reveals that one N-terminal domain (NTD) of DnaC interacts with both the linker helix of a DnaB molecule and the C-terminal domain (CTD) of the adjacent DnaB molecule by forming a three α-helix bundle, which fixes the relative orientation of the two adjacent DnaB CTDs. The importance of the intermolecular interface in the crystal structure was supported by the mutational data of DnaB and DnaC. Based on the crystal structure and other available information on DnaB–DnaC structures, we constructed a molecular model of the hexameric DnaB CTDs bound by six DnaC NTDs. This model suggested that the binding of a DnaC would cause a distortion in the hexameric ring of DnaB. This distortion of the DnaB ring might accumulate by the binding of up to six DnaC molecules, resulting in the DnaB ring to open.
A novel technique for fabricating antibiotic-coated intramedullary nails using an antibiotic-loaded calcium sulphate hydroxyapatite bio-composite, Cerament-V
Authors: Anugraha Anoop , Hughes Luke D , Pillai Anand 
Published: October 2019

Abstract
Deformity correction in the setting of osteomyelitis is a challenge for any orthopaedic surgeon. Principles of management are well described and include staged debridement, stable fixation and a combination of local and systemic antibiotic therapy. An antibiotic-coated nail (ACN) can prove a useful tool—stabilizing bone, whilst allowing for local antibiotic elution. Typically, the surgeon will prepare these implants in the operating room using materials that are routinely at hand. Most frequently, this will involve the use of antibiotic-loaded poly-methyl methacrylate (PMMA). This method of ACN fabrication has several disadvantages. PMMA is non-degradable and can be difficult to remove surgically. There are limitations with regard to antibiotic suitability, antibiotic release as well as toxicity effects. In this case report, we present a novel technique for the preparation of ACNs for use in hindfoot surgery, using a calcium sulphate/hydroxyapatite-based bio-composite—Cerament-V.
Dodder-transmitted mobile signals prime host plants for enhanced salt tolerance
Authors: Li Shalan , Zhang Jingxiong , Liu Hui , Liu Nian , Shen Guojing , Zhuang Huifu , Wu Jianqiang 
Published: October 2019

Abstract
The dodders (Cuscuta spp.) are a genus of shoot parasites. In nature, a dodder often simultaneously parasitizes two or more neighboring hosts. Salt stress is a common abiotic stress for plants. It is unclear whether dodder transmits physiologically relevant salt stress-induced systemic signals among its hosts and whether these systemic signals affect the hosts’ tolerance to salt stress. Here, we simultaneously parasitized two or more cucumber plants with dodder. We found that salt treatment of one host highly primed the connected host, which showed strong decreases in the extent of leaf withering and cell death in response to subsequent salt stress. Transcriptomic analysis indicated that 24 h after salt treatment of one cucumber, the transcriptome of the other dodder-connected cucumber largely resembled that of the salt-treated one, indicating that inter-plant systemic signals primed these dodder-connected cucumbers at least partly through transcriptomic reconfiguration. Furthermore, salt treatment of one of the cucumbers induced physiological changes, including altered proline contents, stomatal conductance, and photosynthetic rates, in both of the dodder-connected cucumbers. This study reveals a role of dodder in mediating salt-induced inter-plant signaling among dodder-connected hosts and highlights the physiological function of these mobile signals in plant–plant interactions under salt stress.
Signal transduction networks during stress combination
Authors: Zandalinas Sara I , Fritschi Felix B , Mittler Ron 
Published: October 2019

Abstract
Episodes of heat waves combined with drought can have a devastating impact on agricultural production worldwide. These conditions, as well as many other types of stress combinations, impose unique physiological and developmental demands on plants and require the activation of dedicated pathways. Here, we review recent RNA sequencing studies of stress combination in plants, and conduct a meta-analysis of the transcriptome response of plants to different types of stress combination. Our analysis reveals that each different stress combination is accompanied by its own set of stress combination-specific transcripts, and that the response of different transcription factor families is unique to each stress combination. The alarming rate of increase in global temperatures, coupled with the predicted increase in future episodes of extreme weather, highlight an urgent need to develop crop plants with enhanced tolerance to stress combination. The uniqueness and complexity of the physiological and molecular response of plants to each different stress combination, highlighted here, demonstrate the daunting challenge we face in accomplishing this goal. Dedicated efforts combining field experimentation, omics, and network analyses, coupled with advanced phenotyping and breeding methods, will be needed to address specific crops and particular stress combinations relevant to maintaining our future food chain secured.
DNA Methylation Profiles Suggest Intergenerational Transfer of Maternal Effects
Authors: Venney Clare J , Love Oliver P , Drown Ellen Jane , Heath Daniel D 
Published: October 2019

AbstractThe view of maternal effects (nongenetic maternal environmental influence on offspring phenotype) has changed from one of distracting complications in evolutionary genetics to an important evolutionary mechanism for improving offspring fitness. Recent studies have shown that maternal effects act as an adaptive mechanism to prepare offspring for stressful environments. Although research into the magnitude of maternal effects is abundant, the molecular mechanisms of maternal influences on offspring phenotypic variation are not fully understood. Despite recent work identifying DNA methylation as a potential mechanism of nongenetic inheritance, currently proposed links between DNA methylation and parental effects are indirect and primarily involve genomic imprinting. We combined a factorial breeding design and gene-targeted sequencing methods to assess inheritance of methylation during early life stages at 14 genes involved in growth, development, metabolism, stress response, and immune function of Chinook salmon (Oncorhynchus tshawytscha). We found little evidence for additive or nonadditive genetic effects acting on methylation levels during early development; however, we detected significant maternal effects. Consistent with conventional maternal effect data, maternal effects on methylation declined through development and were replaced with nonadditive effects when offspring began exogenous feeding. We mapped methylation at individual CpG sites across the selected candidate genes to test for variation in site-specific methylation profiles and found significant maternal effects at selected CpG sites that also declined with development stage. While intergenerational inheritance of methylated DNA is controversial, we show that CpG-specific methylation may function as an underlying molecular mechanism for maternal effects, with important implications for offspring fitness.