bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary history of dimethylsulfoniopropionate (DMSP) demethylation enzyme DmdA in marine bacteria
Authors: Hernández Laura , Vicens Alberto , Eguiarte Luis Enrique , Souza Valeria , Anda Valerie De , González José M. 
Published: October 2019

ABSTRACTDimethylsulfoniopropionate (DMSP), an osmolyte produced by oceanic phytoplankton, is predominantly degraded by bacteria belonging to theRoseobacterlineage and other marineAlphaproteobacteriavia DMSP-dependent demethylase A protein (DmdA). To date, the evolutionary history of DmdA gene family is unclear. Some studies indicate a common ancestry between DmdA and GcvT gene families and a co-evolution betweenRoseobacterand the DMSP-producing-phytoplankton around 250 million years ago (Mya). In this work, we analyzed the evolution of DmdA under three possible evolutionary scenarios: 1) a recent common ancestor of DmdA and GcvT, 2) a coevolution betweenRoseobacterand the DMSP-producing-phytoplankton, and 3) pre-adapted enzymes to DMSP prior toRoseobacterorigin. Our analyses indicate that DmdA is a new gene family originated from GcvT genes by duplication and functional divergence driven by positive selection before a coevolution betweenRoseobacterand phytoplankton. Our data suggest thatRoseobacteracquireddmdAby horizontal gene transfer prior to exposition to an environment with higher DMSP. Here, we propose that the ancestor that carried the DMSP demethylation pathway genes evolved in the Archean, and was exposed to a higher concentration of DMSP in a sulfur rich atmosphere and anoxic ocean, compared to recentRoseobacterecoparalogs (copies performing the same function under different conditions), which should be adapted to lower concentrations of DMSP.
Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome
Authors: Wagner Felix R. , Dienemann Christian , Wang Haibo , Stützer Alexandra , Tegunov Dimitry , Urlaub Henning , Cramer Patrick 
Published: October 2019

AbstractChromatin remodelling complexes of the SWI/SNF family function in the formation of nucleosome-depleted regions and transcriptionally active promoters in the eukaryote genome. The structure of the Saccharomyces cerevisiae SWI/SNF family member RSC in complex with a nucleosome substrate reveals five protein modules and suggests key features of the remodelling mechanism. A DNA-interacting module grasps extra-nucleosomal DNA and helps to recruit RSC to promoters. The ATPase and arm modules sandwich the nucleosome disc with their ‘SnAC’ and ‘finger’ elements, respectively. The translocase motor engages with the edge of the nucleosome at superhelical location +2 to pump DNA along the nucleosome, resulting in a sliding of the histone octamer along DNA. The results elucidate how nucleosome-depleted regions are formed and provide a basis for understanding human chromatin remodelling complexes of the SWI/SNF family and the consequences of cancer mutations that frequently occur in these complexes.
Malaria parasite immune evasion and adaptation to its mosquito host is influenced by the acquisition of multiple blood meals
Authors: Kwon Hyeogsun , Reynolds Rebekah A. , Simões Maria L. , Dimopoulos George , Smith Ryan C. 
Published: October 2019

AbstractA minimum of two blood meals are required for a mosquito to acquire and transmit malaria, yet Anopheles mosquitoes frequently obtain additional blood meals during their adult lifespan. To determine the impact of subsequent blood-feeding on parasite development in Anopheles gambiae, we examined rodent and human Plasmodium parasite infection with or without an additional non-infected blood meal. We find that an additional blood meal significantly reduces P. berghei immature oocyst numbers, yet does not influence mature oocysts that have already begun sporogony. This is in contrast to experiments performed with the human parasite, P. falciparum, where an additional blood meal does not affect oocyst numbers. These observations are reproduced when mosquitoes were similarly challenged with an artificial protein meal, suggesting that parasite losses are due to the physical distension of the mosquito midgut. We provide evidence that feeding compromises the integrity of the midgut basal lamina, enabling the recognition and lysis of immature P. berghei oocysts by the mosquito complement system. Moreover, we demonstrate that additional feeding promotes P. falciparum oocyst growth, suggesting that human malaria parasites exploit host resources provided with blood-feeding to accelerate their growth. This contrasts experiments with P. berghei, where the size of surviving oocysts is independent of an additional blood meal. Together, these data demonstrate differences in the ability of Plasmodium species to evade immune detection and adapt to utilize host resources at the oocyst stage, representing an additional, yet unexplored component of vectorial capacity that has important implications for transmission of malaria.
Temperature dependence of platelet metabolism
Authors: Jóhannsson F. , Yurkovich J.T. , Guðmundsson S. , Sigurjónsson Ó. E. , Rolfsson Ó. 
Published: October 2019

AbstractTemperature plays a fundamental role in biology, influencing cellular function, affecting chemical reaction rates, molecular structures, and interactions. While the temperature dependence of many biochemical reactions is well definedin vitro, the effect of temperature on metabolic function at the network level is not well understood but remains an important challenge in optimizing the storage of cells and tissues at lower temperatures. Here, we have used time-course metabolomics data and systems biology approaches to characterize the effects of storage temperature on human platelets (PLTs) in platelet additive solution. We observed that changes to the metabolome with storage time do not simply scale with temperature but instead display complex temperature dependence, with only a small subset of metabolites following an Arrhenius-type. Investigation of PLT energy metabolism through integration with computational modeling revealed that oxidative metabolism is more sensitive to temperature changes than is glycolysis. The increased contribution of glycolysis to ATP turnover at lower temperature indicates a stronger glycolytic phenotype with decreasing storage temperature. More broadly, these results demonstrate that the temperature dependence of the PLT metabolic network is not uniform, suggesting that efforts to improve the health of stored PLTs could be targeted at specific pathways.Statement of SignificanceThe temperature dependence of cellular metabolism is difficult to study due to regulatory events that are activated upon deviation from the optimal temperature range. Platelets are blood components used in transfusion medicine but also serve as a model cell to study human energy metabolism in the absence of genetic regulation. We investigated changes in platelet metabolism at temperatures spanning from 4 °C-37 °C using a quantitative metabolic systems biology approach as opposed to assessing individual reactions. We found that energy producing metabolic pathways have different temperature sensitivities. The results define the metabolic response to temperature on the metabolic pathway level and are of importance for understanding the cryopreservation of human platelets and more complex human cells used in cellular therapy.
PRIGSA2: Improved version of Protein Repeat Identification by Graph Spectral Analysis
Authors: Chakrabarty Broto , Parekh Nita 
Published: October 2019

AbstractTandemly repeated structural motifs in proteins form highly stable structural folds and provide multiple binding sites associated with diverse functional roles. The tertiary structure and function of these proteins are determined by the type and copy number of the repeating units. Each repeat type exhibits a unique pattern of intra- and inter-repeat unit interactions that is well-captured by the topological features in the network representation of protein structures. Here we present an improved version of our graph based algorithm, PRIGSA, with structure-based validation and filtering steps incorporated for accurate detection of tandem structural repeats. The algorithm integrates available knowledge on repeat families with de novo prediction to detect repeats in single monomer chains as well as in multimeric protein complexes. Three levels of performance evaluation are presented: comparison with state-of-the-art algorithms on benchmark dataset of repeat and non-repeat proteins, accuracy in the detection of members of 13 known repeat families reported in UniProt and execution on the complete Protein Data Bank to show its ability to identify previously uncharacterized proteins. A ∼3-fold increase in the coverage of the members of 13 known families and 3,408 novel uncharacterized structural repeat proteins are identified on executing it on PDB. URL: http://bioinf.iiit.ac.in/PRIGSA2/.
Nucleotide inhibition of the pancreatic ATP-sensitive K+ channel explored with patch-clamp fluorometry
Authors: Usher Samuel G. , Ashcroft Frances M. , Puljung Michael C. 
Published: October 2019

AbstractPancreatic ATP-sensitive K+ channels (KATP) comprise four inward rectifier subunits (Kir6.2), each associated with a sulphonylurea receptor (SUR1). ATP/ADP binding to Kir6.2 shuts KATP. Mg-nucleotide binding to SUR1 stimulates KATP. In the absence of Mg2+, SUR1 increases the apparent affinity for nucleotide inhibition at Kir6.2 by an unknown mechanism. We simultaneously measured channel currents and nucleotide binding to Kir6.2. Fits to combined data sets suggest that KATPcloses with only one nucleotide molecule bound. A Kir6.2 mutation (C166S) that increases channel activity did not affect nucleotide binding, but greatly perturbed the ability of bound nucleotide to inhibit KATP. Mutations at position K205 in SUR1 affected both nucleotide affinity and the ability of bound nucleotide to inhibit KATP. This suggests a dual role for SUR1 in KATPinhibition, both in directly contributing to nucleotide binding and in stabilising the nucleotide-bound closed state.
NOX4 regulates TGFβ-induced proliferation and self-renewal in glioblastoma stem cells
Authors: García-Gómez P , Dadras M , Bellomo C , Mezheyeuski A , Tzavlaki K , Moren A , Caja L 
Published: October 2019

ABSTRACTGlioblastoma (GBM) is the most aggressive and common glioma subtype with a median survival of 15 months after diagnosis. Current treatments have limited therapeutic efficacy, thus more effective approaches are needed. The glioblastoma tumoral mass is characterized by a small cellular subpopulation, the Glioblastoma stem cells (GSCs), which has been held accountant for initiation, invasion, proliferation, relapse and resistance to chemo- and radiotherapy. Targeted therapies against GSCs are crucial, and so is the understanding of the molecular mechanisms that govern the GSCs. Transforming growth factor β (TGFβ), platelet growth factor (PDGF) signalling and Reactive Oxygen Species (ROS) production govern and regulate cancer-stem cell biology. In this work, we focus on the role of the NADPH oxidase 4 (NOX4) downstream of TGFβ signalling in the GSCs. NOX4 utilises NADPH to generate ROS; TGFβ induces NOX4 expression, thus increasing ROS production. Interestingly, NOX4 itself regulates GSC self-renewal and modulates Since TGFβ regulates PDGFB in GSC, we analysed how PDGFB modulates NOX4 expression and increases ROS production. Both TGFβ and PDGF signalling regulate GSC proliferation in a NOX4/ROS-dependent manner. The transcription factor NRF2, involved in the transcriptional regulation of antioxidant and metabolic responses, is regulated by both TGFβ and NOX4. This results in an antioxidant response, which positively contributes to GSC self-renewal and proliferation. In conclusion, this work functionally establishes NOX4 as a key mediator of GSC biology.
Volumetric fluorescence imaging in a human eye model by oblique scanning laser ophthalmoscope (oSLO): a feasibility study
Authors: Shao Wenjun , Song Weiye , Yi Ji 
Published: October 2019

AbstractFluorescence retinal imaging, such as fluorescein angiography, indocyanine green angiography, and autofluorescence imaging, are valuable tools in ophthalmology and vision science. However, these clinical imaging modalities provideen faceview of the retina, with limited capability to discriminate retinal layers over a large field-of-view (FOV). We recently developed a novel retinal imaging method, oblique scanning laser ophthalmoscopy (oSLO), to provide volumetric retinal fluorescence imaging without any depth sectioning. OSLO breaks the coaxial alignment of the excitation and detection, to produce a cross-sectional view on retina using the natural ocular optics. In this paper, we demonstrated oSLO in a realistic human eye model and showed the feasibility for futurein vivohuman retinal imaging. A new optical design was implemented to significantly simplify our previous oSLO systems. We overcame the limitation by the small numerical aperture (NA) of the human eye, by integrating a pair of cylindrical lens in the remote focusing system. We experimentally showed that the current setup can achieve a FOV of ∼3×6×0.8 mm3, and the transverse and axial resolutions of 7 and 41 µm, respectively. The capability of volumetric fluorescence imaging over a large FOV in the human retina could lead to new clinical imaging paradigms for retinal diseases.
Targeting cardiac myocyte Na+-K+ pump function with β3 adrenergic agonist in rabbits and patients with severe congestive heart failure
Authors: Fry Natasha AS , Liu Chia-Chi , Garcia Alvaro , Hamilton Elisha J , Galougahi Keyvan Karimi , Kim Yeon Jae , Harris Jacqueline L , Nelson Gregory IC , Whalley David W , Bundgaard Henning , Rasmussen Helge H 
Published: October 2019

AbstractBackgroundReported one- and two-year mortality for patients with advanced heart failure (HF) treated medically are ~75% and nearly 100%. In such patients, reversible cellular abnormalities are potential treatment targets and a raised cytosolic Na+ concentration that impairs their myocardial contractility is one potential target. β3 adrenoceptor (β3 AR) agonists stimulate the myocyte Na+-K+ pump.MethodsWe induced severe HF in rabbits by coronary ligation and measured indices of organ congestion after treatment with β3 AR agonists. Na+-K+ pump current was measured in voltage-clamped myocytes isolated from non-infarct myocardium. To assess if β3 ARs might add benefit to optimised guideline-directed medical treatment we report outcomes of giving the β3 AR agonist mirabegron to patients hospitalized with advanced, treatment-refractory stage D HF.ResultsTreatment of rabbits after coronary ligation with β3 AR agonist reversed a decreased myocyte Na+-K+ pump current and significantly reduced organ congestion and prevalence of ascites. Oral treatment with mirabegron rapidly improved signs and symptoms of 9 patients with advanced HF and improvement of ≥1 NYHA Class was maintained early post-discharge with continued treatment. One patient died from HF at 16 months, 4 died from other causes at 2 – 30 months and 4 remain alive at 38 ± 4 months with NYHA Class II symptoms.ConclusionsParallel β3 AR agonist-induced reversal of Na+-K+ pump inhibition and severe HF in rabbits identify pump inhibition as a treatment target, and changed in-hospital clinical trajectory and post-discharge course more favorable than expected suggest efficacy of mirabegron in advanced human HF.
Branched evolution and genomic intratumor heterogeneity in the pathogenesis of cutaneous T-cell lymphoma
Authors: Iyer Aishwarya , Hennessey Dylan , O’Keefe Sandra , Patterson Jordan , Wang Weiwei , Wong Gane Ka-Shu , Gniadecki Robert 
Published: October 2019

AbstractMycosis fungoides (MF) is a slowly progressive cutaneous T-cell lymphoma (CTCL) for which there is no cure. In the early plaque stage the disease is indolent, but development of tumors heralds an increased risk of metastasis and death. Previous research into the genomic landscape of CTCL revealed a complex pattern of >50 driver mutations implicated in more than a dozen of signaling pathways. However, the genomic mechanisms governing disease progression and treatment resistance remain unknown. Building on our previous discovery of the clonotypic heterogeneity of MF, we hypothesized that this lymphoma does not progress in a linear fashion as currently thought, but comprises heterogeneous mutational subclones. We sequenced exomes of 49 cases of MF and identified 28 previously unreported putative driver genes. MF exhibited extensive intratumoral heterogeneity (ITH) of a median of six subclones showing branched pattern of phylogenetic relationships. Stage progression was correlated with an increase in ITH and redistribution of mutations from the stem to the clades. The pattern of clonal driver mutations was highly variable with no consistent mutations between patients. A similar intratumoral heterogeneity was detected in leukemic CTCL (Sézary syndrome). Based on these findings we propose a model of the pathogenesis of MF comprising neutral, divergent evolution of cancer subclones and discuss how ITH impacts the efficacy of targeted drug therapies and immunotherapies of CTCL.
ADHD symptoms and their neurodevelopmental correlates in children born very preterm
Authors: Montagna Anita , Karolis Vjaceslavs , Batalle Dafnis , Counsell Serena , Rutherford Mary , Arulkumaran Sophie , Happe Francesca , Edwards David , Nosarti Chiara 
Published: October 2019

AbstractThis study investigated the association between attention-deficit/hyperactivity disorder (ADHD) symptomatology in preschool-aged children who were born very preterm (<32 weeks) and cognitive outcomes, clinical risk and socio-demographic characteristics. 119 very preterm children who participated in the Evaluation of Preterm Imaging Study at term-equivalent age were assessed at a mean age of 4.5 years. Parents completed the ADHD Rating Scale IV, a norm-referenced checklist that evaluates ADHD symptomatology according to diagnostic criteria, and the Behavior Rating Inventory of Executive Function-Preschool version. Children completed the Wechsler Preschool and Primary Scales of Intelligence and the Forward Digit Span task. Longitudinal data including perinatal clinical, qualitative MRI classification, socio-demographic variables and neurodevelopmental disabilities were investigated in relation to ADHD symptomatology. All results were corrected for multiple comparisons using false discovery rate. Results showed that although the proportion of very preterm children with clinically significant ADHD did not differ from normative data after excluding those with neurodevelopmental disabilities, 32.7% met criteria for subthreshold ADHD inattentive type and 33.6% for combined type, which was higher than the expected 20% in normative samples. Higher ADHD symptom scores (all) were associated with greater executive dysfunction (inhibitory self-control, flexibility, and emergent metacognition, corrected p<0.001 for all tests). Higher inattentive ADHD symptom scores were associated with lower IQ (ρ=-0.241, p=0.036) and higher perinatal clinical risk (more days on mechanical ventilation (ρ=0.206, p=0.025) and more days on parenteral nutrition (ρ=0.223, p=0.015)). Higher hyperactive ADHD symptom scores instead were associated with lower socio-economic status (ρ=0.278, p=0.002). These results highlight the importance of monitoring and supporting the development of very preterm children throughout the school years, as subthreshold ADHD symptoms represent risk factors for psychosocial problems and for receiving a future clinical diagnosis of ADHD.
Intracellular Neutralization of Ricin Toxin by Single Domain Antibodies Targeting the Active Site Pocket
Authors: Rudolph Michael J. , Czajka Timothy F. , Davis Simon A. , Thi Nguyen Chi My , Li Xiao-ping , Tumer Nilgun E. , Vance David J. , Mantis Nicholas J. 
Published: October 2019

AbstractThe extreme potency of the plant toxin, ricin, is due to its enzymatic subunit, RTA, which inactivates mammalian ribosomes with near perfect efficiency. Here we characterized, at the functional and structural levels, seven alpaca single-domain antibodies (VHHs) previously reported to recognize epitopes in proximity to RTA’s active site. Three of the VHHs, V2A11, V8E6 and V2G10, were potent inhibitors of RTAin vitroand protected Vero cells from ricin when expressed as intracellular antibodies (“intrabodies”). Crystal structure analysis revealed that the complementarity-determining region 3 (CDR3) elements of V2A11 and V8E6 penetrate RTA’s active site and interact with key catalytic residues. V2G10, in contrast, sits atop the enzymatic pocket and occludes substrate accessibility. The other four VHHs also penetrated/occluded RTA’s active site, but lacked sufficient binding affinities to outcompete RTA-ribosome interactions. Intracellular delivery of high-affinity, single-domain antibodies may offer a new avenue in the development of countermeasures against ricin toxin.
Identification of continuous-time hybrid “Box–Jenkins” systems with multiple unknown time delays using two-stage parameter estimation algorithm
Authors: Ghoul Yamna 
Published: October 2019

Purpose
This study/paper aims to present a separable identification algorithm for a multiple input single output (MISO) continuous time (CT) hybrid “Box–Jenkins”.

Design/methodology/approach
This paper proposes an optimal method for the identification of MISO CT hybrid “Box–Jenkins” systems with unknown time delays by using the two-stage recursive least-square (TS-RLS) identification algorithm.

Findings
The effectiveness of the proposed scheme is shown with application to a simulation example.

Originality/value
A two-stage recursive least-square identification method is developed for multiple input single output continuous time hybrid “Box–Jenkins” system with multiple unknown time delays from sampled data. The proposed technique allows the division of the global CT hybrid “Box–Jenkins” system into two fictitious subsystems: the first one contains the parameters of the system model, including the multiple unknown time delays, and the second contains the parameters of the noise model. Then the TS-RLS identification algorithm can be applied easily to estimate all the parameters of the studied system.
Emerging destination mobility
Authors: Gbollie Charles , Gong Shaoying 
Published: October 2019

PurposeThe purpose of this paper is to explore the push-pull factors and motivations of African and Asian international students in Chinese universities.Design/methodology/approachConcurrent mixed methods (qualitative and quantitative) design was used. The quantitative component included 537 Africans and Asians from five notable universities, while the qualitative aspect consisted of 30 participants in Wuhan and few other cities in China.FindingsFindings revealed availability of scholarship opportunities, China’s flexibility (visa and program entry) and perception of better education quality as important push-pull factors. It also discovered several new pull factors, including citizens’ attitude and good report, development potential and hospitality and receptiveness, while career development and entertainment were found to be the most and least significant motivational factors, respectively. The study also found a significant relationship between push-pull factors and study abroad motivation (SAM) as well as cross-cultural differences between African and Asian students.Research limitations/implicationsMost of the participants were drawn from Wuhan city. Hence, the findings cannot be outrightly generalized to other contexts.Practical implicationsThis research provides valuable knowledge for policy makers, higher education institutions, international students and other stakeholders in China to inform better student experience.Originality/valueThere was no study found that combines push-pull factors and SAM or comparatively investigates African and international students in China. Knowledge about sojourners push-pull factors and motivations, their relationship and cross-cultural differences is essential for evidence-based interventions.