bluuebunny/crossref_metadata_2025 huggingface dataset:
Maximization of non-nitrogenous metabolite production inE. coliusing population systems biology
Authors: Rajagopal Sreenath , Ghatak Arindam , Mookherjee Debdatto , Hmar Rothangmawi Victoria , Shanbhag Anirudh P. , Katagihallimath Nainesh , Venkataraman Janani , Ramanujan KS , Datta Santanu
Published: December 2019

TheE. colimetabolome is an interconnected set of enzymes that has measurable kinetic parameters ascribed for the production of most of its metabolites. Flux Balance Analysis (FBA) or Ordinary Differential Equation (ODE) models are used to increase product yield using defined media. However, they either give a range (FBA) or exact amount (ODE) of metabolite yield which isn’t true as the transcriptome diversity of individual cells isn’t considered. We formulate the metabolic-behaviour of individual cells by using a POpulation SYstems-Biology ALgorithm (POSYBAL) which predicts multiple-gene knockouts for increasing industrially relevant metabolites. We validate this prediction for producing isobutanol (Heterogenous metabolite) and shikimate (Homogenous metabolite) where, the product-yield was increased by 40 times (~2000 ppm) and 42 times (~3000 ppm) respectively. Also, we introduce a nitrogen-swap in standard media to its low-nitrogen counterpart during post-growth phase to redistribute flux towards non-nitrogenous pathways for increasing overall product-yield. Further, our model shows growth-phase diversity in bacterial population even under normal glucose-uptake, portraying a real-world scenario of diverse and robust environment thus, making it evolutionarily favourable to threats such as anti-bacterial attack.
Computations, optimization and tuning of deep feedforward neural networks
Authors: Rahman Md. Shoaibur
Published: December 2019

This article presents an overview of the generalized formulations of the computations, optimization, and tuning of a deep feedforward neural network. A small network has been used to systematically explain the computing steps, which were then used to establish the generalized forms of the computations in forward and backward propagations for larger networks. Additionally, some of the commonly used cost functions, activation functions, optimization algorithms, and hyper-parameters tuning approaches have been discussed.
Neuropeptide VF neurons promote sleep via the serotonergic raphe
Authors: Lee Daniel A. , Oikonomou Grigorios , Cammidge Tasha , Hong Young , Prober David A.
Published: December 2019

Although several sleep-regulating neurons have been identified, little is known about how they interact with each other for sleep/wake control. We previously identified neuropeptide VF (NPVF) and the hypothalamic neurons that produce it as a sleep-promoting system (Lee et al., 2017). Here we use zebrafish to describe a neural circuit in whichneuropeptide VF(npvf)-expressing neurons control sleep via the serotonergic raphe nuclei (RN), a hindbrain structure that promotes sleep in both diurnal zebrafish and nocturnal mice. Using genetic labeling and calcium imaging, we show thatnpvf-expressing neurons innervate and activate serotonergic RN neurons. We additionally demonstrate that optogenetic stimulation ofnpvf-expressing neurons induces sleep in a manner that requires NPVF and is abolished when the RN are ablated or lack serotonin. Finally, genetic epistasis demonstrates that NPVF acts upstream of serotonin in the RN to maintain normal sleep levels. These findings reveal a novel hypothalamic-hindbrain circuit for sleep/wake control.
Statistical agnostic mapping: a framework in neuroimaging based on concentration inequalities
Authors: Gorriz J.M. ,   SiPBA Group,   Cam Neuroscience Group,   International Initiatives
Published: December 2019

In the 70s a novel branch of statistics emerged focusing its effort in selecting a function in the pattern recognition problem, which fulfils a definite relationship between the quality of the approximation and its complexity. These data-driven approaches are mainly devoted to problems of estimating dependencies with limited sample sizes and comprise all the empirical out-of sample generalization approaches, e.g. cross validation (CV) approaches. Although the latter arenot designed for testing competing hypothesis or comparing different modelsin neuroimaging, there are a number of theoretical developments within this theory which could be employed to derive a Statistical Agnostic (non-parametric) Mapping (SAM) at voxel or multi-voxel level. Moreover, SAMs could relieve i) the problem of instability in limited sample sizes when estimating the actual risk via the CV approaches, e.g. large error bars, and provide ii) an alternative way of Family-wise-error (FWE) corrected p-value maps in inferential statistics for hypothesis testing. In this sense, we propose a novel framework in neuroimaging based on concentration inequalities, which results in (i) a rigorous development for model validation with a small sample/dimension ratio, and (ii) a less-conservative procedure than FWE p-value correction, to determine the brain significance maps from the inferences made using small upper bounds of the actual risk.
CSF1R inhibition by a small molecule inhibitor affects hematopoiesis and the function of macrophages
Authors: Lei Fengyang , Cui Naiwen , Zhou Chengxin , Chodosh James , Vavvas Demetrios G. , Paschalis Eleftherios I.
Published: December 2019

Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a method for microglia depletion, with the assumption that it does not affect peripheral immune cells. Here, we show that CSF1R inhibition by PLX5622 indeed affects the myeloid and lymphoid compartments, causes long-term changes in bone marrow-derived macrophages by suppressing their IL-1β, CD68 and phagocytosis, but not CD208, following exposure to endotoxin, and also reduces the population of tissue resident macrophages of peritoneum, lung, liver, but not spleen. Thus, small molecule CSF1R inhibition is not restricted to microglia only, but rather causes strong effects on circulating and tissue macrophages that perdure long after cessation of the treatment. Given that peripheral monocytes repopulate the CNS after CSF1R inhibition, these changes may have practical implications on relevant experimental data.
Type I interferons act directly on nociceptors to produce pain sensitization: Implications for viral infection-induced pain
Authors: Barragan-Iglesias Paulino , Franco-Enzástiga Úrzula , Jeevakumar Vivekanand , Wangzhou Andi , Granados-Soto Vinicio , Campbell Zachary T. , Dussor Gregory , Price Theodore J.
Published: December 2019

One of the first signs of viral infection is body-wide aches and pain. While this type of pain usually subsides, at the extreme, viral infections can induce painful neuropathies that can last for decades. Neither of these types of pain sensitization are well understood. A key part of the response to viral infection is production of interferons (IFNs), which then activate their specific receptors (IFNRs) resulting in downstream activation of cellular signaling and a variety of physiological responses. We sought to understand how type I IFNs (IFN-α and IFN-β) might act directly on nociceptors in the dorsal root ganglion (DRG) to cause pain sensitization. We demonstrate that type I IFNRs are expressed in small/medium DRG neurons and that their activation produces neuronal hyper-excitability and mechanical pain in mice. Type I IFNs stimulate JAK/STAT signaling in DRG neurons but this does not apparently result in PKR-eIF2α activation that normally induces an anti-viral response by limiting mRNA translation. Rather, type I interferons stimulate MNK-mediated eIF4E phosphorylation in DRG neurons to promote pain hypersensitivity. Endogenous release of type I IFNs with the double stranded RNA mimetic poly(I:C) likewise produces pain hypersensitivity that is blunted in mice lacking MNK-eIF4E signaling. Our findings reveal mechanisms through which type I IFNs cause nociceptor sensitization with implications for understanding how viral infections promote pain and can lead to neuropathies.

SIGNIFICANCE STATEMENT

It is increasingly understood that pathogens interact with nociceptors to alert organisms to infection as well as to mount early host defenses. While specific mechanisms have been discovered for diverse bacteria and fungal pathogens, mechanisms engaged by viruses have remained elusive. Here we show that type 1 interferons, one of the first mediators produced by viral infection, act directly on nociceptors to produce pain sensitization. Type I interferons act via a specific signaling pathway (MNK-eIF4E signaling) that is known to produce nociceptor sensitization in inflammatory and neuropathic pain conditions. Our work reveals a mechanism through which viral infections cause heightened pain sensitivity
Quantitative measurements of hydroxyl radicals generated by irradiated titanium dioxide nanoparticle suspensions
Authors: Coral Jason A. , Kitchens Christopher L.
Published: December 2019

Increased use of titanium dioxide (TiO2) nanoparticles in different applications has increased risk for adverse environmental implications based on an elevated likelihood of organism exposure. Anatase TiO2is photoactive with exposure to ultraviolet light. TiO2nanoparticle exposure to UV-A radiation in aquatic environments generates hydroxyl radical species, which may ultimately be responsible increased organism toxicity. The present research demonstrates that the rate of radical generation heavily depends on exposure conditions, particularly the presence of natural organic matter (NOM). Environmentally relevant concentrations of TiO2nanoparticles were co-exposed to increasing NOM amounts (measured as concentration of dissolved organic carbon (DOC)) and UV-A intensities. Hydroxyl radical generation rate was determined using fluorescence spectroscopy. Radical generation rate was positively correlated to increases in TiO2concentration and UV-A intensity, and negatively correlated to increased DOC concentration. Nanoparticle aggregation over time and decrease in light transmission from NOM had negligible contributions to the generation rate. This suggests the decreased radical generation rate is a result of radical quenching by NOM functionalities.D. magnatoxicity to hydroxyl radicals is also demonstrated to decreased following the addition of DOC. These results correlate with the rate generation data, indicating that DOC provides rate attenuation that is protection to organisms. These conclusions demonstrate the importance considering exposure conditions during TiO2toxicity testing, and during TiO2waste management and regulatory decisions.
Introducing divisive inhibition in the Wilson-Cowan model
Authors: Papasavvas Christoforos A. , Wang Yujiang
Published: December 2019

Abstract

Both subtractive and divisive inhibition has been recorded in cortical circuits and recent findings suggest that different interneuronal populations are responsible for the different types of inhibition. This calls for the formulation and description of these inhibitory mechanisms in computational models of cortical networks. Neural mass and neural field models typically only feature subtractive inhibition. Here, we introduce how divisive inhibition can be incorporated in such models, using the Wilson-Cowan modelling formalism as an example. In addition, we show how the subtractive and divisive modulations can be combined. Including divisive inhibition in neural mass models is a crucial step in understanding its role in shaping oscillatory phenomena in cortical networks.
The Ortholog Conjecture Revisited: the Value of Orthologs and Paralogs in Function Prediction
Authors: Stamboulian Moses , Guerrero Rafael F. , Hahn Matthew W. , Radivojac Predrag
Published: December 2019

The computational prediction of gene function is a key step in making full use of newly sequenced genomes. Function is generally predicted by transferring annotations from homologous genes or proteins for which experimental evidence exists. The “ortholog conjecture” proposes that orthologous genes should be preferred when making such predictions, as they evolve functions more slowly than paralogous genes. Previous research has provided little support for the ortholog conjecture, though the incomplete nature of the data cast doubt on the conclusions. Here we use experimental annotations from over 40,000 proteins, drawn from over 80,000 publications, to revisit the ortholog conjecture in two pairs of species: (i)Homo sapiensandMus musculusand (ii)Saccharomyces cerevisiaeandSchizosaccharomyces pombe. By making a distinction between questions about the evolution of function versus questions about the prediction of function, we find strong evidence against the ortholog conjecture in the context of function prediction, though questions about the evolution of function remain difficult to address. In both pairs of species, we quantify the amount of data that must be ignored if paralogs are discarded, as well as the resulting loss in prediction accuracy. Taken as a whole, our results support the view that the types of homologs used for function transfer are largely irrelevant to the task of function prediction. Aiming to maximize the amount of data used for this task, regardless of whether it comes from orthologs or paralogs, is most likely to lead to higher prediction accuracy.
A Molecular Pathway for Arterial-Specific Association of Vascular Smooth Muscle Cells
Authors: Stratman Amber N. , Burns Margaret C. , Farrelly Olivia M. , Davis Andrew E. , Li Wenling , Pham Van N. , Castranova Daniel , Yano Joseph J. , Goddard Lauren M. , Nguyen Oliver , Galanternik Marina Venero , Bolan Timothy J. , Kahn Mark L. , Mukouyama Yohsuke , Weinstein Brant M.
Published: December 2019

The preferential accumulation of vascular smooth muscle cells on arteries versus veins during early development is a well-described phenomenon, but the molecular pathways underlying this polarization are not well understood. During zebrafish embryogenesis thecxcr4areceptor (mammalian CXCR4) and its ligandcxcl12b(mammalian CXCL12) are both preferentially expressed on arteries at time points consistent with the arrival and differentiation of the first vascular smooth muscle cells (vSMCs). We show that autocrinecxcl12b/cxcr4activity leads to increased production of the vSMC chemoattractant ligandpdgfbby endothelial cellsin vitroand increased expression ofpdgfbby arteriesin vivo. Additionally, we demonstrate that expression of the well-characterized blood flow-regulated transcription factorklf2ain primitive veins negatively regulatescxcr4/cxcl12andpdgfbexpression, restricting vSMC recruitment to the arterial vasculature. Together, this signaling axis leads to the differential acquisition of smooth muscle cells at sites whereklf2aexpression is low and bothcxcr4aandpdgfbare co-expressed, i.e. arteries during early development.
Arrhythmic gut microbiome signatures for risk profiling of Type-2 Diabetes
Authors: Reitmeier Sandra , Kießling Silke , Clavel Thomas , List Markus , Almeida Eduardo L. , Ghosh Tarini S. , Neuhaus Klaus , Grallert Harald , Troll Martina , Rathmann Wolfgang , Linkohr Birgit , Franke Andre , Le Roy Caroline I. , Bell Jordana T. , Spector Tim , Baumbach Jan , O’Toole Peter W. , Peters Annette , Haller Dirk
Published: December 2019

To combat the epidemic increase in Type-2-Diabetes (T2D), risk factors need to be identified. Diet, lifestyle and the gut microbiome are among the most important factors affecting metabolic health. We demonstrate in 1,976 subjects of a prospective population cohort that specific gut microbiota members show diurnal oscillations in their relative abundance and we identified 13 taxa with disrupted rhythmicity in T2D. Prediction models based on this signature classified T2D with an area under the curve of 73%. BMI as microbiota-independent risk marker further improved diagnostic classification of T2D. The validity of this arrhythmic risk signature to predict T2D was confirmed in 699 KORA subjects five years after initial sampling. Shotgun metagenomic analysis linked 26 pathways associated with xenobiotic, amino acid, fatty acid, and taurine metabolism to the diurnal oscillation of gut bacteria. In summary, we determined a cohort-specific risk pattern of arrhythmic taxa which significantly contributes to the classification and prediction of T2D, highlighting the importance of circadian rhythmicity of the microbiome in targeting metabolic human diseases.
Timing and nature of palliative care discussions are patient-specific according to clinicians: a qualitative study
Authors: Tavares Nuno , Wilkinson Tom , Jarrett Nikki , Hunt Katherine
Published: December 2019

Background: Chronic obstructive pulmonary disease (COPD) is associated with an unpredictable and complex disease trajectory. Consequently, most patients are not involved in advance care planning and do not receive palliative care until the end of life.
Aim: To explore clinicians experiences, opinions and recommendations for the timing and nature of palliative care discussions in COPD.
Design: Qualitative interviews with nurses and doctors that provide direct care to COPD patients.
Setting/Participants: 14 clinicians working across primary and secondary care in the UK were interviewed.
Results: Participants suggested that those with the appropriate expertise and an established relationship with patients were best placed to initiate discussions about palliative and future care. Early, gradual and informed palliative and future care discussions were considered best practice, however they uncommon occurrence due to service, patient and clinician-related barriers. The unpredictable disease trajectory and fine balance between providing acute care and discussing palliative care options were suggested as key greatest barriers for discussions. However, damaging patient hope was a concern for clinicians and reduced their inclination to discuss palliative care. Clinicians did not seem to think that patients were ready for discussions, therefore they avoided broaching the subject leading early in the disease trajectory.
Conclusion: Stand-alone conversations about and near the end of life was described as current usual practice by clinicians, however individualised early, regular and gradual discussions with patients about immediate and long-term future plans may make such discussions feel less negative and ordinary for patients and clinicians.
Diet-induced loss of adipose Hexokinase 2 triggers hyperglycemia
Authors: Shimobayashi Mitsugu , Shetty Sunil , Frei Irina C. , Wölnerhanssen Bettina K. , Weissenberger Diana , Dietz Nikolaus , Thomas Amandine , Ritz Danilo , Meyer-Gerspach Anne Christin , Maier Timm , Hay Nissim , Peterli Ralph , Rohner Nicolas , Hall Michael N.
Published: December 2019

Chronically high blood glucose (hyperglycemia) leads to diabetes, fatty liver disease, and cardiovascular disease. Obesity is a major risk factor for hyperglycemia, but the underlying mechanism is unknown. Here we show that a high fat diet (HFD) in mice causes early loss of expression of the glycolytic enzyme Hexokinase 2 (HK2) specifically in adipose tissue. Adipose-specific knockout ofHk2caused enhanced gluconeogenesis and lipogenesis in liver, a condition known as selective insulin resistance, leading to glucose intolerance. Furthermore, we observed reduced hexokinase activity in adipose tissue of obese and diabetic patients, and identified a loss-of-function mutation in thehk2gene of naturally hyperglycemic Mexican cavefish. Mechanistically, HFD in mice led to loss of HK2 by inhibiting translation ofHk2mRNA. Our findings identify adipose HK2 as a critical mediator of systemic glucose homeostasis, and suggest that obesity-induced loss of adipose HK2 is an evolutionarily conserved, non-cell-autonomous mechanism for the development of hyperglycemia.

One Sentence Summary

Loss of the glycolytic enzyme Hexokinase 2 in adipose tissue is a mechanism underlying high blood glucose levels.
An Unconventional Melanin Biosynthetic Pathway inUstilago maydis
Authors: Reyes-Fernández Esmeralda Z. , Shi Yi-Ming , Grün Peter , Bode Helge B. , Bölker Michael
Published: December 2019

Ustilago maydisis a phytopathogenic fungus responsible for corn smut disease. Although it is a very well established model organism for the study of plant-microbe interactions, its biosynthetic potential has not been totally explored. By analyzingU. maydisgenome, we identified a biosynthetic gene cluster whose activation led to the production of a black melanin pigment. Single deletion mutants of the cluster genes revealed that five encoded enzymes are required for the accumulation of the black pigment, including three polyketide synthases (pks3, pks4andpks5), a cytochrome P450 monooxygenase (cyp4) and a protein with similarity to versicolorin B-synthase (vbs1). Moreover, metabolic profiles of the mutants defective forpks3andpks4indicated that the products of these genes catalyze together the first step in the melanin biosynthetic pathway since none of the mutants accumulated any melanin or intermediate products. Mutants deleted forpks5produced orsellinic acid (OA) and triacetic acid lactone (TAL), suggesting that both products are produced by Pks3 and Pks4. It might thus demonstrate that Pks5 plays a role in a reaction downstream of that catalyzed by Pks3 and Pks4. OA and TAL were also found in extracts of acyp4deletion mutant along with several heterodimers of TAL and Pks5-derived orsellinic aldehyde compounds. According to their phenotypes and the intermediate products isolated from these strains, Cyp4 and Vbs1 seem to be involved in reactions downstream of Pks5. Our findings suggest thatU. maydissynthesizes a new melanin based on coumarin and pyran-2-one intermediates, while most fungal melanins are derived from 1,8-dihydroxynaphthalene (DHN) or L-3,4-dihydroxyphenylalanine (L-DOPA). Along with these observations, this work also provides an insight into the mechanisms of polyketide synthases in this filamentous fungus.

IMPORTANCE

Ustilago maydisrepresents one of the major threats for maize plants since it is responsible for corn smut disease, which generates considerable economical losses around the world. Therefore, contributing to a better understanding of the biochemistry of defense mechanisms used byU. maydisto protect itself against harsh environments, as the synthesis of melanin, could provide improved biological tools for tackling the problem and protect the crops. In addition, the fact that this fungus synthesizes melanin in a very unique way, requiring more than one polyketide synthase for producing this secondary metabolite, gives a different perspective on the complexity of these multimodular enzymes and their evolution in the fungal kingdom.
Deep6mA: a deep learning framework for exploring similar patterns in DNA N6-methyladenine sites across different species
Authors: Li Zutan , Jiang Hangjin , Kong Lingpeng , Chen Yuanyuan , Zhang Liangyun , Pian Cong
Published: December 2019

N6-methyladenin(6mA) is an important DNA modification form associated with a wide range of biological processes. Identifying accurately 6mA sites on a genomic scale is crucial for understanding of 6mA’s biological functions. In this paper, we developed, without requiring any prior knowledge of 6mA and manually crafted sequence features, a deep learning framework named Deep6mA to identify DNA 6mA sites, and its performance is superior to other DNA 6mA prediction tools. Specifically, the 5-fold cross-validation on a benchmark dataset of rice gives the sensitivity and specificity of Deep6mA as 92.96% and 95.06%, respectively, and the overall prediction accuracy is 94%. Importantly, we find that the sequences with 6mA sites share similar patterns across different species. The model trained with rice data predicts well the 6mA sites of other three species:Arabidopsis thaliana,Fragaria vesca, andRosa chinensis, with a prediction accuracy over 90%. In addition, we find that (1) 6mA tends to occur at GAGG motifs, which means the sequence near the 6mA site may be conservative; (2) 6mA is enriched in the TATA box of the promoter, which may be the main source of its regulating downstream gene expression.
The voltage-sensing mechanism of the KvAP channel involves breaking of the S4 helix
Authors: Bignucolo Olivier , Bernèche Simon
Published: December 2019

Voltage-gated ion channels allow ion permeation upon changes of the membrane electrostatic potential (Vm). Each subunit of these tetrameric channels is composed of six transmembrane helices, of which the anti-parallel helix bundle S1-S4 constitutes the voltage-sensor domain (VSD) and S5-S6 forms the pore domain. Here, using molecular dynamics (MD) simulations, we report novel responses of the archaebacterial potassium channel KvAP to cell polarization. We show that the S4 helix, which is straight in the experimental crystal structure solved under depolarized conditions (Vm ∼ 0), breaks into two segments when the cell is polarized (Vm << 0), and reversibly forms a single straight helix following depolarization of the cell (Vm =0). The outermost segment of S4 translates along the normal to the membrane, bringing new perspective to previously paradoxical accessibility experiments that were initially thought to imply the displacement of the whole VSD across the membrane. Our simulations of KvAP reveal that the breaking of S4 under polarization is not a feature unique to hyperpolarization activated channel, as might be suggested by recent cryo-EM structures and MD simulations of the HCN channel.
Major QTLs for seedling traits in barley using a DArT-based linkage map
Authors: Capo-chich Ludovic , Eldridge Sharla , Elakhdar Ammar , Kumamaru Toshihiro , Anyia Anthony O.
Published: December 2019

Seed vigor is considered as the most critical stage for barley production, and cultivar with high early seedling vigour (ESV) allow plants to form a canopy more quickly. In this study, the QTLs of seedling vigour related-traits were investigated using 185 RILs derived from Xena and H94061120 using DArT approach. In total, 46 significant QTLs for ESV related-traits were detected. The total map length was 1075.1 cM with an average adjacent-marker distance of 3.28 cM. Fourteen QTLs for BY were found on all chromosomes, two of them co-located with QTLs on 1H for GY. The related-traits; LL1, LL2, LA1 and LDW1 had high heritability (>60%). Meanwhile, a significant correlation was observed between GY and BY, which provide the clear image of these traits in the selection process. Our results demonstrate that a pleiotropic QTL related to SLA2, BY, and GY was linked to to the DArT markers bPb-9280 and bPb-9108 on 1H, which could be used to significantly improve the seed vigor by marker-assisted selection and possible future map-based cloning of the gene of intrest.
Discovery of new mitochondrial DNA segregation machinery components inTrypanosoma brucei: a comparison of three approaches
Authors: Baudouin Hélène Clémentine Margareta , Pfeiffer Laura , Ochsenreiter Torsten
Published: December 2019

Trypanosoma bruceiis a single celled eukaryotic parasite and the causative agent of human African sleeping sickness and Nagana in cattle. Aside from its medical relevanceT. bruceihas also been key to the discovery of several general biological principles including GPI-anchoring, RNA-editing and trans-splicing. The parasite contains a single mitochondrial organelle with a singular genome. Recent studies have identified several molecular components of the mitochondrial genome segregation machinery (tripartite attachment complex, TAC), which connects the basal body of the flagellum to the mitochondrial DNA ofT. brucei. The TAC component in closest proximity to the mitochondrial DNA is TAC102. Here we apply and compare three different approaches (proximity labeling, Immunoprecipitation and yeast two-hybrid) to identify novel interactors of TAC102 and subsequently verify their localisation. Furthermore, we establish the direct interaction of TAC102 and p166 in the unilateral filaments of the TAC.

Subject area

biochemistry, molecular biology, cellular biology
Influence Of Urbanization On Ecological Status Of River In Amhara Region, Ethiopia 2019
Authors: Alie Melsew Setegn
Published: December 2019

Introduction

Urbanization is one of the main causes for environmental problems due to the introduction of pollutants into water bodies. Lahi is crossing fintoselam. This river has long been used for a variety of purposes including source of public water supply, small scale irrigation, bathing, washing, animal watering, sand and stone dredging and recreation.

Objective

To assess the influence of Finoteselam town on ecological status of Lahi river

Methods

The assessment were assessed using physicochemical parameters, physical habitat assessment, biotic indices /metrics, human activity by observation as well as macroinvertabretes samples from eleven sampling sites coded S1 to S11 along the river using the standard procedures. The assessments were involved in-situ measurements and collection of water samples in April 2019 then, analyzed the water samples in laboratory.

Results

The biological analysis reveals a notable reduction of the diversity macroinvertabrates in the downstream direction where the minimum was at midstream sites. Upstream has significantly better macroinvertabrates assemblage than midstream (p-value<0.05). Physical habitat evaluation scores varied from 43 at S8 to 173 at S1 and relatively lower score were recorded at midstream sites. Low % of Ephemeroptera, Plecoptera and Trichoptera with high family biotic index and high % of Diptera with low biological monitoring working party also indicated water ecology deteriorated mainly at midstream sites. Multivariate analysis of classical analysis, canonical correspondence analysis and none metric multidimensional scaling also indicated ecological deterioration at midstream sites mainly at S5, S6, S7 and S8.

Conclusion

Midstream was relatively more polluted than upstream due to influence of pollutant from Finoteselam town. The ecological status of upstream segments of the river is very good with slight organic pollutions, and at midstream is poor and significant degree of organic pollutions; whereas the status of the downstream is fair with fairly substantial water pollution showing moderate ecological disturbance. In general, midstream the sampling stations show the deterioration in water ecology and thus necessitated a need for mitigation measure to save the Lahi.
Characterization of human-iPSCs derived spinal motor neurons by single-cell RNA sequencing
Authors: Thiry Louise , Hamel Regan , Pluchino Stefano , Durcan Thomas , Stifani Stefano
Published: December 2019

Human induced pluripotent stem cells (iPSCs) offer the opportunity to generate specific cell types from healthy and diseased individuals, allowing the study of mechanisms of early human development, modelling a variety of human diseases, and facilitating the development of new therapeutics. Human iPSC-based applications are often limited by the variability among iPSC lines originating from a single donor, as well as the heterogeneity among specific cell types that can be derived from iPSCs. The ability to deeply phenotype different iPSC-derived cell types is therefore of primary importance to the successful and informative application of this technology. Here we describe a combination of motor neuron (MN) derivation and single-cell RNA sequencing approaches to generate and characterize specific MN subtypes obtained from human iPSCs. Our studies provide evidence for rapid and robust generation of MN progenitor cells that can give rise to a heterogenous population of brainstem and spinal cord MNs. Approximately 58% of human iPSC-derived MNs display molecular characteristics of lateral motor column MNs, ∼19% of induced MNs resemble hypaxial motor column MNs, while ∼6% of induced MNs have features of medial motor column MNs. The present study has the potential to improve our understanding of iPSC-derived MN subtype function and dysfunction, possibly leading to improved iPSC-based applications for the study of human MN biology and diseases.
Increased variability but intact integration during visual navigation in Autism Spectrum Disorder
Authors: Noel Jean-Paul , Lakshminarasimhan Kaushik J. , Park Hyeshin , Angelaki Dora E.
Published: December 2019

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disturbance afflicting a variety of functions from perception to cognition. The recent computational focus suggesting aberrant Bayesian inference in ASD has yielded promising but conflicting results in attempting to explain a wide variety of phenotypes by canonical computations. Here we used a naturalistic visual path integration task that combines continuous action with active sensing and allows tracking of subjects’ dynamic belief states. Both groups showed a previously documented bias pattern, by overshooting the radial distance and angular eccentricity of targets. For both control and ASD groups, these errors were driven by misestimated velocity signals due to a non-uniform speed prior, rather than imperfect integration. We tracked participant’s beliefs and found no difference in the speed prior, but heightened variability in the ASD group. Both end-point variance and trajectory irregularities correlated with ASD symptom severity. With feedback, variance was reduced and ASD performance approached that of controls. These findings highlight the need for both more naturalistic tasks and a broader computational perspective to understand the ASD phenotype and pathology.
Replication timing maintains the global epigenetic state in human cells
Authors: Klein Kyle N. , Zhao Peiyao A. , Lyu Xiaowen , Bartlett Daniel A. , Singh Amar , Tasan Ipek , Watts Lotte P. , Hiraga Shin-ichiro , Natsume Toyoaki , Zhou Xuemeng , Leung Danny , Kanemaki Masato T. , Donaldson Anne D. , Zhao Huimin , Dalton Stephen , Corces Victor G. , Gilbert David M.
Published: December 2019

DNA is replicated in a defined temporal order termed the replication timing (RT) program. RT is spatially segregated in the nucleus with early/late replication corresponding to Hi-C A/B chromatin compartments, respectively. Early replication is also associated with active histone modifications and transcriptional permissiveness. However, the mechanistic interplay between RT, chromatin state, and genome compartmentalization is largely unknown. Here we report that RT is central to epigenome maintenance and compartmentalization in both human embryonic stem cells (hESCs) and cancer cell line HCT116. Knockout (KO) of the conserved RT control factor RIF1, rather than causing discrete RT switches as previously suspected, lead to dramatically increased cell to cell heterogeneity of RT genome wide, despite RIF1’s enrichment in late replicating chromatin. RIF1 KO hESCs have a nearly random RT program, unlike all prior RIF1 KO cells, including HCT116, which show localized alterations. Regions that retain RT, which are prevalent in HCT116 but rare in hESCs, consist of large H3K9me3 domains revealing two independent mechanisms of RT regulation that are used to different extents in different cell types. RIF1 KO results in a striking genome wide downregulation of H3K27ac peaks and enrichment of H3K9me3 at large domains that remain late replicating, while H3K27me3 and H3K4me3 are re-distributed genome wide in a cell type specific manner. These histone modification changes coincided with global reorganization of genome compartments, transcription changes and a genome wide strengthening of TAD structures. Inducible degradation of RIF1 revealed that disruption of RT is upstream of genome compartmentalization changes. Our findings demonstrate that disruption of RT leads to widespread epigenetic mis-regulation, supporting previously speculative models in which the timing of chromatin assembly at the replication fork plays a key role in maintaining the global epigenetic state, which in turn drives genome architecture.
An ultrasound absorbing inflorescence zone enhances echo-acoustic contrast of bat-pollinated cactus flowers
Authors: Simon Ralph , Matt Felix , Santillan Vinicio , Tschapka Marco , Tuttle Merlin , Halfwerk Wouter
Published: December 2019

Flowering plants have evolved an extraordinary variety of signaling traits to attract and guide their pollinators. Most flowers rely on visual and chemical signals, but some bat-pollinated plants have evolved reflective surfaces to acoustically guide echolocating bats. All known acoustic flower signals rely on the same principle of increased sonar reflectivity. Here we describe a novel mechanism through which plants can make flowers acoustically conspicuous, a principle that relies on increased absorption of the area surrounding the flower. In a bat-pollinated columnar cactus (Espostoa frutescens) we found a hairy inflorescence zone, a so called cephalium. Flowers solely emerge out of this zone. We measured the ultrasound echoes of cephalia, flowers and unspecialized column surfaces and recorded echolocation calls of approaching bats. We found that the cephalium acts as strong ultrasound absorber, attenuating the sound by −14 dB compared to other parts of the column. The absorption was highest around the echolocation call frequencies of approaching bats. Our results indicate that, instead of making flowers more reflective, plants can also evolve structures to attenuate the background echo, thereby enhancing the acoustic contrast with the target. Similar sound absorbing mechanisms may be found in other species that interact with bats across a wide range of ecological contexts.
Biotinylating Antibodies Using Biotin Polyethylene Oxide (PEO) Iodoacetamide
Authors: Berg Eric A. , Fishman Jordan B.
Published: January 2020

There are several techniques for biotinylating antibodies, from the most basic (using NHS-ester biotin to label primary amines) to more complex experiments (modifying sulfhydryls and carbohydrates). Biotinylation of free sulfhydryls, described here, can be effectively mediated using haloacetyl biotin derivatives. To modify an antibody using this reagent, sulfhydryls must be available. Digestion of antibodies by the enzyme pepsin produces F(ab′)2 fragments, which can be separated by mild reduction into two sulfhydryl-containing, univalent Fab′ fragments. Alternatively, thiol groups can be added by modifying amines with an appropriate cross-linker.
Synthesis of Single-Stranded RNA Probes by In Vitro Transcription
Authors: Green Michael R. , Sambrook Joseph
Published: January 2020

In this protocol, we describe procedures for synthesizing RNA probes of high specific activity from DNA templates containing promoters for bacteriophage-encoded RNA polymerases. The DNA fragment to be transcribed should have previously been cloned into one of the commercially available plasmids containing bacteriophage RNA polymerase promoters. Alternatively, DNA templates can be synthesized in polymerase chain reactions (PCRs) using gene-specific primers whose 5′ ends encode synthetic promoters for bacteriophage-encoded RNA polymerases.
Scandals and reforms: combating police corruption in Taiwan
Authors: Ko Ernie
Published: January 2020

Purpose

The purpose of this paper is to analyze the causes of police corruption in Taiwan and identify those factors which can enhance the status of police.

Design/methodology/approach

A literature review and eight in-depth interviews of informants are employed to support the arguments of environment, education, governance and culture and to formulate a typology of police corruption in Taiwan.

Findings

The literature review and eight interviews confirm that individual cases of police corruption have replaced systemic police corruption in Taiwan. The author concludes that police corruption should be addressed in the context of both environment and institutional design. Even though the public perceptions of police integrity in Taiwan have been trending positively over the years, the individual cases of police corruption which occur within certain precincts indicate the continued importance of initiating institutional reforms. The public perceptions of Taiwan’s police force will be further improved if police corruption can be minimized and properly controlled.

Practical implications

This paper can serve as a benchmark to evaluate future development of Taiwan police corruption.

Originality/value

This paper provides an analysis of the causes of police corruption in Taiwan and the measures taken to curb it.
Epidemiological shift of hepatitis A in EAGLE countries – a projection
Authors: Ghildayal Nidhi
Published: January 2020

Purpose

Many world regions are developing quickly and experiencing increasing levels of sanitation, causing an epidemiological shift of hepatitis A in these areas. The shift occurs when children avoid being infected with the disease until a later age due to cleaner water sources, food, and hygiene practices in their environment; but if they are infected at later age, the disease is much more severe and lost productivity costs are higher. The purpose of this paper is to examine what could occur if an epidemiological shift of the disease continues in these regions, and what type of future burden hepatitis A may have in a hypothetical rapidly developing country.

Design/methodology/approach

Initially, annual hepatitis A mortality was regressed on the Human Development Index (HDI) for each country classified as an emerging and growth-leading economy (EAGLE) to provide an overview of how economic development and hepatitis A mortality related. Data from the various EAGLE countries were also fit to a model of hepatitis A mortality rates in relation to HDI, which were both weighted by each country’s 1995–2010 population of available data, in order to create a model for a hypothetical emerging market country. A second regression model was fit for the weighted average annual hepatitis A mortality rate of all EAGLE countries from the years 1995 to 2010. Additionally, hepatitis A mortality rate was regressed on year.

Findings

Regression results show a constant decline of mortality as HDI increased. For each increase of one in HDI value in this hypothetical country, mortality rate declined by 2.3016 deaths per 100,000 people. The hypothetical country showed the HDI value increasing by 0.0073 each year. Also, results displayed a decrease in hepatitis A mortality rate of 0.0168 per 100,000 people per year. Finally, the mortality rate for hepatitis A in this hypothetical country is projected to be down to 0.11299 deaths per 100,000 people by 2030 and its economic status will fall just below the HDI criteria for a developed country by 2025.

Originality/value

The hypothetical country as a prototype model was created from the results of regressed data from EAGLE countries. It is aimed to display an example of the health and economic changes occurring in these rapidly developing regions in order to help understand potential hepatitis A trends, while underscoring the importance of informed and regular policy updates in the coming years. The author believes this regression provides insight into the patterns of hepatitis A mortality and HDI as these EAGLE countries undergo rapid development.
From PBL to innovation: a decennial case-study from an HPV student team
Authors: Baldissera Paolo , Delprete Cristiana
Published: January 2020

Purpose

The implementation of project-based learning (PBL) activities in the curricula of engineering students has become a consolidated method to improve their skills. The purpose of this paper is to share the experience acquired by the authors from a decennial case-study on a student team PBL activity focused on design and development of human-powered vehicles (HPVs). A review of the project evolution, boundary constraints and management choices could provide inspiration and suggestions to faculty staff that would like to set-up similar experiences for engineering students in their universities.

Design/methodology/approach

A student team was funded by the authors in 2008 to gather engineering students interested in design and construction of HPVs. In the past decade, the team has grown from 10 up to 60 students enrolled per year and stimulated to develop a range of HPV designs for sports and mobility. The project management evolved as a consequence to com ply with the growing ambitions of the group and complexity of the goals.

Findings

A thorough analysis of factors contributing to the success of the project led to identification of the key factors to increase student participation: persistence of the faculty staff is essential, attending competitions and challenges increases students’ recruitment and formal recognition of the activity through credits and the implementation of intermediate assessment steps increase the active participation rate. Bigger teams reduce the negative impact of recruits eventually abandoning the project in an early stage. Ambitious goals keep students motivated for longer periods and enable a virtuous circle by transferring enthusiasm and knowledge to new members.

Research limitations/implications

The activity is analyzed starting from a subjective experience perspective and some of the findings/conclusions may be not applicable in a different context. However, such review can suggest strategies on the long-term period to create similar conditions elsewhere.

Social implications

In the last part of the paper, it is pointed out how PBL projects can provide a fertile ground for innovation and lead to patents and development of new products aiming at the market.

Originality/value

This study contributes to provide an insight view of how a student team PBL activity can grow over a decade if guided by faculty staff.
Trade credit and the speed of leverage adjustment
Authors: Abuhommous Ala’a Adden
Published: January 2020

Purpose

The purpose of this paper is to examine the impact of trade credit on the speed of adjustment (SOA) of short-term leverage. Bankruptcy cost is higher for over-levered firms, generating a good incentive to use trade credit as a lower cost substitute; hence, firms adjust capital more quickly.

Design/methodology/approach

Firm-level data are used from five countries, in two different economic orientations, during the period 2000–2017: bank-oriented economies include France, Germany and Japan, and market-oriented economies include the UK and the USA. First, using the two-step GMM the study estimates the target short-term leverage ratio. Then, it examines the impact of trade credit on the SOA of the actual leverage towards the target leverage ratio.

Findings

It finds a positive impact of a low amount of trade credit (high capacity) on the SOA for over-levered firms. This is in line with the substitution effect, where the bankruptcy cost is higher for over-levered firms, which leads them to substitute bank loans with trade credit.

Research limitations/implications

The study uses data from publicly traded firms; data from non-listed and small firms may be considered as a good opportunity for future research.

Practical implications

The policy implication that can be derived from the empirical results is that firms’ management should recognise the relationship between trade credit and deviation from target short-term leverage. During periods of high short-term leverage firms should use trade credit as a source of finance when adjusting the short-term leverage towards the target ratio.

Originality/value

This study is the first to examine the influence of trade credit on the SOA.