bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous hydrogen sulfide improves vascular remodeling through PPARδ/SOCS3 signaling
Authors: Tian Danyang , Wu Yuming , Teng Xu , Jin sheng , Chen Yuhong
Published: April 2020

Mounting evidences demonstrated the deficiency of hydrogen sulfide (H2S) implicated the progression of cardiovascular diseases. This study aimed to investigate the beneficial role of endogenous H2S on vascular remodeling in CSE inhibitor, DL‐propargylglycine (PPG), treated mice. The deficiency of endogenous H2S exhibited aggravated active and passive contraction, coupled with thicken aortic walls, vascular remodeling with collagen deposition, increased phosphorylation of STAT3 and decreased PPARδ, SOCS3, which were reversed by sodium hydrosulfide chronic treatment for 4 weeks. Aggravated active and passive contraction, upregulated p‐STAT3, downregulated SOCS3 in PPG mice aortas could be corrected by PPARδ agonist GW501516. On the contrary, PPARδ antagonist GSK0660 exhibited opposite effects on vascular contraction, expressions of p‐STAT3, SOCS3 in aortas. PPG inhibited expression of PPARδ and SOCS3, stimulated the phosphorylation of STAT3, inflammatory molecules production in vascular smooth muscle cells (VSMCs). PPARδ agonist normalized the phenotype transformation from contractile to synthetic in both PPG mice aortas and PPG treated VSMCs. NaHS offered similar functions with PPARδ agonist. In a word, endogenous H2S benefits against vascular remodeling through preserving PPARδ/SOCS3 inflammatory signaling pathway. Deficiency of endogenous H2S should be considered as a risk factor for VSMCs dysfunction.

Support or Funding Information

This study was supported by the National Natural Science Foundation of China (Grant 31671185, 31871154, 91849120), the Natural Science Foundation of Hebei Province of China (H2017206269), the Hebei Province for Innovation Talents Support Plan (Grant LJRC017), and the Research Foundation for Higher Education of Hebei Province (GCC2014032, ZD2019027).

The loss of endogenous H2S aggravated LPS‐induced myocardial dysfunction.

Figure 1
p65‐mediated Mettl3/Mettl14 transactivation and m6A‐dependent TGF‐β1 translation aggravates fibrosis progression in nonalcoholic steatohepatitis
Authors: Feng Yue , Dong Haibo , Sun Bo , Hu Yun , Guo Shihui , Yang Yang , Jia Yimin , Zhao Ruqian
Published: April 2020

N6‐methyladenosine (m6A) RNA modification has been reported to play an important role in hepatic carcinoma (HCC). Non‐alcoholic steatohepatitis (NASH) predisposes the progressive development of liver fibrosis, cirrhosis and HCC, yet whether and how m6A is involved in the critical transition of NASH to fibrosis remains elusive. Here we demonstrate an up‐regulation of Mettl3/Mettl14 and global m6A hypermethylation in the liver of high‐fat diet‐induced NASH and fibrosis rat model, with increased serum lipopolysaccharide (LPS). LPS‐induced profibrotic TGF‐β1 translation in Kupffer cells (KC), which is prevented by Mettl3/Mettl14 knockdown, coincides with higher m6A level on 5’UTR of TGF‐β1 mRNA. NF‐κB p65 transactivates Mettl3/Mettl14, which leads to
m
6
A‐dependent translation of TGF‐β1 mRNA in a cap‐independent manner. Our findings identify m6A modification as a new player in p65‐mediated inflammatory signaling and TGF‐β1‐activated fibrosis progression in NASH.

Support or Funding Information

This work was supported by the National Key Research and Development Program of China (2016YFD0500502), the National Natural Science Foundation of China (31672512) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

m6A modification is essential in the process of NASH to liver fibrosis by connecting gene transcription with Mettl3/Mettl14. The regulatory role of the classic transcriptional factors NF‐κB p65, that keeps high m6A modification of the TGF‐β1 mRNA 5’UTR provides fundamental insight into the post‐transcriptional gene regulation network in KC activation, revealing potential novel ways to regulate the process of NASH to liver fibrosis.

Figure 1
Reproducibility of NIRS Oxidative Capacity Measurements in the Vastus Lateralis and Medial Hamstring Muscles
Authors: Gosalia Jigar , Hanna Rewais B. , Vairo Giampietro L. , Irving Brian A. , McCully Kevin M. , Proctor David N.
Published: April 2020

Oxidative capacity within selected muscles can be measured non‐invasively using Near Infrared Spectroscopy (NIRS) by employing a series of transient arterial occlusion cuffs after a metabolic stimulus. Traditionally, this protocol involves voluntary contraction of a single limb followed by up to 22 transient ischemic occlusions per measurement. Our lab has adapted an established protocol
1 to develop a novel protocol that allows for an increased number of measurements using fewer (i.e. 6) ischemic occlusions combined with surface electrical stimulation (E‐stim) in both limbs simultaneously. However, reproducibility has not yet been established with this protocol.

PURPOSE

To determine the within‐day and between‐day reproducibility of this protocol in both the vastus lateralis and medial hamstring muscles.

METHODS

The protocol involved 2 NIRS probes placed over the vastus lateralis (VL) muscles or the medial hamstring (MH) muscles in healthy adults to sense changes in muscle oxygenation. E‐stim pads were placed adjacent to the NIRS probe and were used to increase metabolic rate (>3 fold) using a biphasic setting at 20 Hz, with an intensity (mV) that is within the participant’s tolerance. The mitochondrial oxidative capacity protocol involved 4 consecutive sets of 30 seconds of E‐stim followed by 6 x 5 sec cuff inflation/5 sec cuff deflation cycles using upper thigh rapid inflation cuffs. Analysis consisted of calculating oxygenation recovery rate constants (k) for each muscle (i.e., 4 repeated measurements per muscle, per limb) using a customized software program. Coefficient of variation (CV) and intraclass correlation coefficients [ICC(2,k)] were used to assess reproducibility.

RESULTS

Variability of within‐day repeated tests (CV) averaged 3.8% (0.9%–6.7%) in the VL (n=12) with an average rate constant (min−1) of 1.96 +/− 0.07 and 4.9% (1.0%–14.1%) in the MH (n=10) with an average rate constant (min−1) of 2.05 +/− 0.11. Variability of between‐day repeated tests averaged 11.7% (8.7% – 14.8%) in the VL (n=4) and 10.4% (7.5% – 12.0%) in the MH (n=4). [ICC(2,k)] was calculated as 0.98, 95% CI [0.95, 0.99] for the VL and 0.93, 95% CI [0.81, 0.98] for the MH muscles.

CONCLUSION

These results suggest the proposed protocol demonstrates good to excellent reproducibility in both muscles, with a higher rate associated with the VL. These outcomes provide investigators with an efficient alternative for measuring muscle oxidative capacity non‐invasively in the vastus lateralis and medial hamstring muscles.

Support or Funding Information

Center for Orthopedic Research and Translational Science, Penn State College of Medicine

Experimental setup of bilateral NIRS oxidative capacity protocol

Figure 1
Abductor Pollicis Longus distal muscle belly variation in a male human cadaver
Authors: Bowman Carley , Rosario Martin
Published: April 2020

Background

Typically, five muscles of the posterior forearm intersect the wrist joint and contribute tendons to the first two digits.

Purpose

Depict the anatomical variation in the muscles and tendons of the extrinsic musculature of the thumb in one human cadaver.

Methods

One specimen was dissected and reported in this work. During dissection, an extra muscle belly was found embedded within the tendon of abductor pollicis longus. This variation was discovered near the distolateral attachment site at the base of the first metacarpal joint.

Results

The additional muscle belly is located between abductor pollicis brevis and extensor carpi radialis muscles. Typically, the proximal muscle belly originates at the posterior proximal half of the ulna and middle one‐third of the radius inserting at the typical site of attachment, lateral aspect of the base of the first metatarsal, via the tendon. However, the tendon continues distally to a second muscle belly embedded within the distolateral one‐third of the abductor pollicis longus tendon where the attachment site can be found at the traditional lateral aspect of the base of the first metacarpal bone.

Conclusion

The extrinsic extensors of the thenar region in this cadaver had an additional distal muscle belly embedded within the distal (extra) portion of the tendon differing from the standard structures. Knowledge of this additional structure may help medical professionals understand possible functional differences among individuals with this morphological variation.

Picture of thumb with extra tendon anatomy variation.

Figure 1
PROTECTIVE EFFECT OF LOW LEVEL LASER THERAPY ON DORSAL SKIN FLAPS SURVIVAL: RELEVANCE TO CYTOKINES SECRETION.
Authors: Chang Alexandre Jin Bok Audi , Silva Luciana Miato Gonçalves , Silva Deiwet Ribeiro , Zamuner Stella Regina
Published: April 2020

The loss of skin flaps (SF) due to tissue necrosis can be catastrophic, even with mortality, especially when there is exposure of large vessels or noble structures. This outcome occurs between 2 to 20% of the procedures performed. There is no currently adjuvant treatment that improves the survival of cutaneous flaps, without side effects or significant risks. Recent studies have sought to prove the efficiency of photobiomodulation (PBM) by means of Low Level Laser Therapy (LLLT) and present promising results for increased SF survival.

OBJECTIVE

To evaluate the effect of LLLT in dorsal skin flaps of mice in terms of tissue necrosis extent as well as biochemical analysis of pro and anti‐inflammatory cytokines.

METHODS

Forty‐eighth Balb/C (20–25 g) male mice were randomly distributed into two groups with twenty‐four animals each; (1) control group that was not submitted to laser irradiation and (2) experimental group that was submitted to laser irradiation on the flap pedicle with a 660 nm wavelength, exposure radiant of 2.25 J/cm2 for a total time of 20 s/point. The treatment started immediately after performing the cranial base random skin flap (3× 1 cm dimension). The animals were euthanized after the evaluation of the percentage of necrosis area, blood and skin tissue was collected for analysis of cytokines and histology on 4th, 7th and 10th postoperative days. Results demonstrated that LLLT irradiation reduced the area of necrosis, significantly decreased IL‐1, IL‐6 and TNF‐α and increased IL‐10 cytokines compared to the non‐irradiated control group. In conclusion, LLLT may improve the healing of skin flaps by decreasing pro‐inflammatory cytokines and increasing the anti‐inflammatory IL‐10.

Serum Interleukines after low level laser therapy (gray) versus control group (black). Significant decrease in pro‐inflamatories interleukines 1, 6 and tumor necrosis factor alfa and significant increase in anti‐inflamatory interleukin 10 after 4, 7 and 10 days post‐op.

Figure 1
Cerebellar Transcranial Magnetic Stimulation Disrupts Vestibular Reflexes in Standing Balance
Authors: Donald Joshua R. , Peters Ryan M. , Kiss Zelma H. T. , Day Trevor A. , Strzalkowski Nicholas D.J.
Published: April 2020

Despite its seemingly effortless execution, standing balance is a complex task maintained by the integration of sensory feedback from visual, somatosensory (muscle, skin, joint receptors), and vestibular (inner ear) systems. The vestibular system provides feedback about head acceleration and can be manipulated experimentally by passing an electrical current percutaneously through the mastoid processes. The cerebellum plays an important role in standing balance by integrating sensory feedback to refine activity in postural muscles. A recent study has shown that experimentally depressing cerebellar activity with repetitive transcranial magnetic stimulation can influence postural sway and muscle reflex responses following electrical vestibular stimulation. The aim of this study was to investigate the impact of acute cerebellar stimulation on vestibular muscle reflex responses in different head positions during standing balance. We applied a novel combination of stochastic electrical vestibular stimulation (SVS, ±2.5 mA, 0–20 Hz) and single‐pulse cerebellum transcranial magnetic stimulation (TMS, 60% maximum stimulator output) on fifteen healthy adults (6 males, 9 females; 21–32 years old) in two head positions: head forward and head right. Muscle reflexes were recorded bilaterally with surface electromyography (EMG) from lower leg (soleus and medial gastrocnemius) and neck (sternocleidomastoid) muscles. Time‐based cumulant density and frequency‐based coherence analyses were used to evaluate the relationship between the SVS and evoked EMG responses one second before (Pre) and one second after (Post) cerebellar TMS. 50 TMS pulses were delivered per head position. Preliminary analysis performed on left medial gastrocnemius (LMG) head right data indicated a significant reduction in the short latency (SL, P = 0.0377) and medium latency (ML, P < 0.0001) reflexes following cerebellar TMS (Fig.
1). In addition, a significant drop in the coherence between the SVS and LMG Pre to Post was found using a difference of coherence test. These findings support the cerebellum to be an important center for the integration of vestibular feedback for the control of standing balance.

Support or Funding Information

Mount Royal University Faculty of Science and Technology

Figure 1
Sugar Responsive Ubiquitylation mediated Endosomal Trafficking of N‐acetylglucosamine Transporter (Ngt1) in Candida albicans.
Authors: Rao Kongara Hanumantha , Ghosh Swagata
Published: April 2020

N‐acetylglucosamine (GlcNAc) signals a wide array of functions in diverse organisms ranging from bacteria to humans but in Candida albicans the dynamics associated with GlcNAc import, a prerogatory step in GlcNAc signalling is unrevealed. In this study, we have shown the molecular mechanism involved in the dynamics of a novel GlcNAc transporter (Ngt1) at the cell surface. Ngt1 showed sugar responsive endosomal trafficking to modulate its cell surface levels by interacting with key players of ubiquitylation machinery, viz. CaRsp5 ubiquitin ligase, CaArt1 adaptor protein and Snf1 protein kinase by following trafficking route of endosomes‐TransGolgi and finally vacuole. We have employed time‐lapse microscopy, LC‐MS/MS analysis, Fat‐blot technique and Site Directed Mutagenesis (SDM) along Immuno‐precipitation and immunoblot analysis to understand the intricate molecular events involved in the Endosomal trafficking. Ngt1 showed interaction with novel sphingolipids, disialoganglioside (GD3) and sulfatides that confirms its localization within lipid rafts of the plasma membrane. This study also elucidates the role of UBI4 locus and Ras1 signalling component in Ngt1 ubiquitylation and its endocytosis. Being a first of its kind report, elaborating the molecular mechanism of endosomal trafficking in Candida albicans, this study can undoubtedly provide a platform for basic research in trafficking as well as applied research towards the development of therapeutics.

Support or Funding Information

Science and Engineering Research Board (SERB), Govt of India

GlcNAc transporter (Ngt1) undergoes ubiquitylation and internalization in response to GlcNAc.

A‐Western blotting analysis showing expression, ubiquitylation and degradation of Ngt1‐GFPγ. The upshifted bands indicate ubiquitylated (Ubi) form of Ngt1‐GFPγ, supported by western blot analysis with anti‐ubiquitin antibody in panel C. B‐Localization pattern of Ngt1‐GFPγ in response to GlcNAc at 60 and 120 min after induction and it is co‐localized with a vacuole specific maker‐CMAC.

Figure 1

Life Cycle of Ngt1.

Ngt1 is a membrane resident protein having 12 membrane‐spanning domains as predicted by TMHMM server v. 2.0. Ngt1 undergoes sugar‐responsive ubiquitylation followed by Endosomal trafficking to undergo degradation in the vacuole. The transporter shows association with novel components of the lipid rafts.

Figure 2
Identification of Predictors of Physical Frailty and Sarcopenia through a New Multi‐ Marker Approach
Authors: Marzetti Emanuele
Published: April 2020

Background and Objectives

Physical frailty & sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. Biomarker discovery for PF&S requires a comprehensive approach to cope with the multifaceted pathophysiology of the condition. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy.

Methods

Two‐hundred older community‐dwellers, 100 with PF&S and 100 non‐sarcopenic, non‐frail (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 circulating analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO‐CovSel) analysis.

Results

Several SO‐CovSel models were constructed. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet‐derived growth factor‐BB, heat shock protein 72, myeloperoxidase, and alpha‐aminobutyric acid defined the serum profile of nonPF&S participants.

Conclusion

SO‐CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.

Support or Funding Information

‐ Innovative Medicines Initiative – Joint Undertaking (IMI‐JU 115621)‐ Fondazione Roma (NCDs Call for Proposals 2013)‐ Nonprofit research foundation “Centro Studi Achille e Linda Lorenzon”

Candidate biomarkers for physical frailty & sarcopenia (PF&S) identified through sequential and orthogonalized covariance selection (SOCovSel) analysis and their putative roles in PF&S pathophysiology. Abbreviations: Hsp72, heat shock protein 72; MPO, myeloperoxidase; PDGF‐BB, platelet‐derived growth factor BB.

Figure 1
Phosphorylation of SR Proteins and the Effect of Hydrogen Peroxide Stress on the Splicing Cycle in S. pombe Fission Yeast
Authors: Davis Moriah Hope , Piening Cole , Marvin Micheal
Published: April 2020

The spliceosome, a large and dynamic RNA‐protein complex, is responsible for effective pre‐mRNA splicing. Correct spliceosome assembly, function, and regulation have often been shown to involve SR proteins, which are dynamically phosphorylated. Alterations in the splicing process can lead to a variety of human diseases and the fission yeast, Schizosaccharomyces pombe, is one model organism for this research. It was previously determined that the conserved SR protein kinase in fission yeast, Dsk1 (Srpk1 in humans), is required for efficient splicing of introns. Previous identification of Dsk1 substrates and alanine mutation to prevent phosphorylation showed a minor splicing defect in the two fission yeast SR proteins (Srp1 and Srp2) under optimal growth conditions. Our current research takes a chemical‐genetic approach to exploring phosphorylation’s physical effects on specifically Srp1 and Srp2 protein substrates, and whether environmental stress, simulated by hydrogen peroxide exposure, can cause a higher retention rate of introns in a regulated way. Through the use of RT‐qPCR we can determine whether there is a splicing defect under the stress condition, and how phosphorylation of SR proteins affects the level of pre‐mRNA splicing defect.

Support or Funding Information

Previous work in Christine Guthrie’s lab in collaboration with Kevan Shokat and postdoctoral fellow Jesse Lipp, as well as previous work by Alex Piening of Rockhurst class 2018 and Clayton Carroll of Rockhurst class 2019. Thanks to Jeff Pleiss for microarray design as well as Nick Hertz & Alma Burlingame for mass spectrometry analysis. In addition, NIH NRSA postdoctoral fellowship for funding. Current funding and support provided by Rockhurst University.

Rpl25a intron splicing in WT SR protein yeast strains and alanine mutated strains under optimal conditions.

Figure 1

S. pombe cell responses due to increasing concentrations of hydrogen peroxide (Veal, E. 2014).

Figure 2
FLAVi‐Web: A Web Annotator for Viral Genomes of Flaviviridae with a Revised Phylogeny of the Family
Authors: Guirales Sayal , Machado Denis Jacob , de Bernardi Schneider Adriano , Janies Daniel
Published: April 2020

The ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and zika, demand a greater understanding of how these viruses evolve, emerge and spread in order to respond. Central to this understanding is an updated phylogeny of the entire family. Accurate gene annotations are pivotal to allow researchers to question how the fundamental genetic elements for these viruses evolve and function knowing they are comparing homologous genomic regions. To tackle these problems, our team has published a pipeline called FLAVi ("Fast Loci Annotation of Viruses"), an annotation pipeline for Flaviviridae that uses a combination of ab initio and homology‐based strategies. The pipeline recovered 100% of the genes in reference genomes and annotated over 97% of the expected genes in the remaining noncurated sequences. It was also further demonstrated that the combined analysis of genomes of all genera of Flaviviridae (Flavivirus, Hepacivirus, Pegivirus, and Pestivirus), as made possible by this annotation strategy, improves the phylogenetic analyses of these viruses for all optimality criteria that were tested (parsimony, maximum likelihood, and posterior probability). Here, we propose a user‐friendly web‐based application version of FLAVi, FLAVi‐Web (available at flavi‐web.com). FLAVi‐Web was created using Flask (Grinberg, 2018), a Python‐based application for the creation of web interfaces. Flask uses HTML and JavaScript to create the aesthetic properties of the web interface. The web application takes as input a FASTA file with the pathogen genomic information and outputs a compressed file with the main annotation results in a GFF3 file format. This novel web implementation enhances our ability to maintain and improve the FLAVi pipeline over time, ultimately promoting its usage among the virology community.

Left ‐ Homepage of flavi‐web. com, Right ‐ Flowchart describing the application pipeline.

Figure 1
Wind drives temporal variation in pollinator visitation in a fragmented tropical forest
Authors: Crall James D. , Brokaw Julia , Gagliardi Susan F. , Mendenhall Chase D. , Pierce Naomi E. , Combes Stacey A.
Published: April 2020

Wind is a critical factor in the ecology of pollinating insects such as bees. However, the role of wind in determining patterns of bee abundance and floral visitation rates across space and time is not well understood. Orchid bees are an important and diverse group of neotropical pollinators that harvest pollen, nectar and resin from plants. In addition, male orchid bees collect volatile scents that they store in special chambers in their hind legs, and for which the wind-based dispersal of odours may play a particularly crucial role. Here, we take advantage of this specialized scent foraging behaviour to study the effects of wind on orchid bee visitation at scent sources in a fragmented tropical forest ecosystem. Consistent with previous work, forest cover increased orchid bee visitation. In addition, we find that temporal changes in wind speed and turbulence increase visitation to scent stations within sites. These results suggest that the increased dispersal of attractive scents provided by wind and turbulence outweighs any biomechanical or energetic costs that might deter bees from foraging in these conditions. Overall, our results highlight the significance of wind in the ecology of these important pollinators in neotropical forests.
Ecological implications of removing a concrete gas platform in the North Sea
Authors: Coolen Joop W.P. , Bittner Oliver , Driessen Floor M.F. , van Dongen Udo , Siahaya Midas S. , de Groot Wim , Mavraki Ninon , Bolam Stefan G. , van der Weide Babeth
Published: April 2020

Artificial structures such as offshore oil and gas platforms can significantly alter local species communities. It has been argued that this effect should be considered during decisions over their removal during decommissioning. In the North Sea, leaving such structures in place is prohibited but derogations are allowed for large concrete installations. To assess removal options for one such installation, the Halfweg GBS (gravity-based structure) a concrete platform foundation off the Dutch coast, we studied the resident fouling macrofauna community. The faunal structure, biomass and trophic composition of the Halfweg was then compared with those from the surrounding seabed sediments, other local artificial structures and a natural rocky reef.

In total, 65 macrofaunal species were observed on the concrete (52 species), steel legs (32) and surrounding rock dump (44) of Halfweg. Mean Simpson diversity per sample was highest on the rock dump (0.71) but concrete (0.54) and steel (0.60) of the GBS were lower than seabed (0.69). Ten of the species observed on the concrete were not reported on other substrates while 10 of the species were also observed in the surrounding seabed. The GBS structure was numerically dominated by Arthropoda which comprised 98% of the total abundance. Mean ash free dry weight (AFDW) was significantly higher (p<0.001) on the Halfweg substrates (204 g AFDW per m2) than in the surrounding seabed (65 g AFDW per m2). Over 94% of the biomass on Halfweg consisted of the plumose anemoneMetridium senile. While common on other reefs, this species was absent from the surrounding seabed. Macrofaunal feeding mechanisms of the concrete and rock dump communities on the GBS were similar to those of nearby sediments, although these differed from those on the Halfweg steel legs. Therefore, the presence of Halfweg alters the local community feeding modes. Multivariate analysis revealed that taxonomic structure of the GBS and other artificial structures significantly differed from that of the sedimentary habitats. Low numbers of non-indigenous species on Halfweg indicated that the structure does not act as a stepping stone for species invasions.

Our data show that the Halfweg structures significantly increase local biodiversity and biomass. Removal of the concrete and steel legs of the GBS (leaving the rock dump) will significantly reduce local macrofauna biodiversity. The long-term impact on macrofaunal biomass is low. Leaving the complete Halfweg structure in place will result in an enriched local macrofaunal biodiversity and feeding mode diversity.
Multi-task Deep Learning Based CT Imaging Analysis For COVID-19: Classification and Segmentation
Authors: Amyar A. , Modzelewski R. , Ruan S.
Published: April 2020

The fast spreading of the novel coronavirus COVID-19 has aroused worldwide interest and concern, and caused more than one million and a half confirmed cases to date. To combat this spread, medical imaging such as computed tomography (CT) images can be used for diagnostic. An automatic detection tools is necessary for helping screening COVID-19 pneumonia using chest CT imaging. In this work, we propose a multitask deep learning model to jointly identify COVID-19 patient and segment COVID-19 lesion from chest CT images. Our motivation is to leverage useful information contained in multiple related tasks to help improve both segmentation and classification performances. Our architecture is composed by an encoder and two decoders for reconstruction and segmentation, and a multi-layer perceptron for classification. The proposed model is evaluated and compared with other image segmentation and classification techniques using a dataset of 1044 patients including 449 patients with COVID-19, 100 normal ones, 98 with lung cancer and 397 of different kinds of pathology. The obtained results show very encouraging performance of our method with a dice coefficient higher than 0.78 for the segmentation and an area under the ROC curve higher than 93% for the classification.
Comprehensive Genome Based Analysis ofVibrio parahaemolyticusfor Identifying Novel Drug and Vaccine Molecules: Subtractive Proteomics and Vaccinomics Approach
Authors: Hasan Mahmudul , Azim Kazi Faizul , Imran Abdus Shukur , Chowdhury Ishtiak Malique , Akhter Urme Shah Rucksana , Parvez Md Sorwer Alam , Uddin Md Bashir , Uddin Ahmed Syed Sayeem
Published: April 2020

Multidrug-resistantVibrio parahaemolyticushas become a significant threat to human health as well as aquaculture, prioritizing the development of effective drug and vaccine candidates. Hence, the study was designed to identify novel therapeutics using a comprehensive genome-based analysis ofV. parahaemolyticus.FromV. parahaemolyticusproteome, a total of 4822 proteins were investigated in order to find out effective drug and vaccine targets. A range of diverse subtractive proteomics approaches – namely, identification of human non-homologous and pathogen-specific essential proteins, druggability and ‘anti-target’ analysis, prediction of subcellular localization, human microbiome non-homology screening, analysis of virulence factors, protein-protein interactions studies. Among 16 novel cytoplasmic proteins, ‘VIBPA Type II secretion system protein L’ and ‘VIBPA Putative fimbrial protein Z’ were allowed to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, ‘Sensor histidine protein kinase UhpB’ and ‘Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T and B cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking were adopted to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules that suggested the superiority of construct V1. Besides, the binding affinity of human TLR1/2 heterodimer and construct V1 was also biologically significant. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector ofE. colistrain K12. However, the predicted drug molecules and vaccine constructs could be further studied to combatV. parahaemolyticusassociated infections.
Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy
Authors: Zeng Xin , Li Lingfang , Lin Jing , Li Xinlei , Liu Bin , Kong Yang , Zeng Shunze , Du Jianhua , Xiao Huahong , Zhang Tao , Zhang Shelin , Liu Jianghai
Published: April 2020

The infection of the novel coronavirus SARS-CoV-2 have caused more than 150,000 deaths, but no vaccine or specific therapeutic antibody is currently available. SARS-CoV-2 relies on its spike protein, in particular the receptor binding domain (RBD), to bind human cell receptor angiotensin-converting enzyme 2 (ACE2) for viral entry, and thus targeting RBD holds the promise for preventing SARS-CoV-2 infection. In this work, a competitive biopanning strategy of a phage display antibody library was applied to screen blocking antibodies against RBD. High-affinity antibodies were enriched after the first round using a standard panning process in which RBD-His recombinant protein was immobilized as a bait. At the next two rounds, immobilized ACE2-Fc and free RBD-His proteins were mixed with the enriched phage antibodies. Antibodies binding to RBD at epitopes different from ACE2-binding site were captured by the immobilized ACE2-Fc, forming a “sandwich” complex. Only antibodies competed with ACE2 for recognizing RBD at the same or similar epitopes can bind to the free RBD-His in the supernatant and be subsequently separated by the Ni-NTA magnetic beads. Top 1 lead from the competitive biopanning of a synthetic antibody library, Lib AB1, was produced as the full-length IgG1 format. It was proved to competitively block the binding of RBD to ACE2 protein, and potently inhibit SARS-CoV-2 pseudovirus infection of ACE2-overexpressing Hela cells with IC50 values of 12nM. Nevertheless, top 1 lead from the standard biopanning of Lib AB1, can only bind to RBDin vitrobut not have the blocking or neutralization activity. Our strategy can efficiently isolate the blocking antibodies of RBD, and it would speed up the discovery of neutralizing antibodies against SARS-CoV-2.
A refined method to monitor arousal from hibernation in the European hamster
Authors: Markussen Fredrik A. S. , Melum Vebjørn J. , Bothorel Béatrice , Hazlerigg David G. , Simonneaux Valérie , Wood Shona H.
Published: April 2020

Background

Hibernation is a physiological and behavioural adaptation that permits survival during periods of reduced food availability and extreme environmental temperatures. This is achieved through cycles of metabolic depression and reduced body temperature (torpor) and rewarming (arousal). Rewarming from torpor is achieved through the activation of brown adipose tissue (BAT) associated with a rapid increase in ventilation frequency. Here, we studied the rate of rewarming in the European hamster (Cricetus cricetus) by measuring both BAT temperature, core body temperature and ventilation frequency.

Results

Temperature was monitored in parallel in the BAT (IPTT tags) and peritoneal cavity (iButtons) during hibernation torpor-arousal cycling. We found that increases in brown fat temperature preceded core body temperature rises by about 48 min, with a maximum re-warming rate of 20.9°C*h−1. Re-warming was accompanied by a significant increase in ventilation frequency. The rate of rewarming was slowed by the presence of a spontaneous thoracic mass in one of our animals. Core body temperature re-warming was reduced by 6.2°C*h−1and BAT rewarming by 12°C*h−1. Ventilation frequency was increased by 77% during re-warming in the affected animal compared to a healthy animal. Inspection of the position and size of the mass indicated it was obstructing the lungs and heart.

Conclusions

We have used a minimally invasive method to monitor BAT temperature during arousal from hibernation illustrating BAT re-warming significantly precedes core body temperature re-warming, informing future study design on arousal from hibernation. We also showed compromised re-warming from hibernation in an animal with a mass obstructing the lungs and heart, likely leading to inefficient ventilation and circulation.
A shared neural substrate for action verbs and observed actions in human posterior parietal cortex
Authors: Aflalo T. , Zhang C. , Rosario E.R. , Pouratian N. , Orban G.A. , Andersen R.A.
Published: April 2020

High-level sensory and motor cortical areas are activated when processing the meaning of language, but it is unknown whether, and how, words share a neural substrate with corresponding sensorimotor representations. We recorded from single neurons in human posterior parietal cortex (PPC) while participants viewed action verbs and corresponding action videos from multiple views. We find that PPC neurons exhibit a common neural substrate for action verbs and observed actions. Further, videos were encoded with mixtures of invariant and idiosyncratic responses across views. Action verbs elicited selective responses from a fraction of these invariant and idiosyncratic neurons, without preference, thus associating with a statistical sampling of the diverse sensory representations related to the corresponding action concept. Controls indicated the results are not the product of visual imagery nor arbitrary learned associations. Our results suggest that language may activate the consolidated visual experience of the reader.
Studies on CRMP2 SUMOylation-deficient transgenic mice identify sex-specific NaV1.7 regulation in the pathogenesis of chronic neuropathic pain
Authors: Moutal Aubin , Cai Song , Yu Jie , Stratton Harrison J. , Chefdeville Aude , Gomez Kimberly , Ran Dongzhi , Madura Cynthia L. , Boinon Lisa , Soto Maira , Zhou Yuan , Shan Zhiming , Chew Lindsey A. , Rodgers Kathleen E. , Khanna Rajesh
Published: April 2020

The sodium channel NaV1.7 is a master regulator of nociceptive neuronal firing. Mutations in this channel can result in painful conditions as well as produce insensitivity to pain. Despite being recognized as a “poster child” for nociceptive signaling and human pain, targeting NaV1.7 has not yet produced a clinical drug. Recent work has illuminated the NaV1.7 interactome, offering insights into the regulation of these channels and identifying potentially new druggable targets. Amongst the regulators of NaV1.7 is the cytosolic collapsin response mediator protein 2 (CRMP2). CRMP2, modified at Lysine 374 (K374) by addition of a small ubiquitin-like modifier (SUMO), bound NaV1.7 to regulate its membrane localization and function. Corollary to this, preventing CRMP2 SUMOylation was sufficient to reverse mechanical allodynia in rats with neuropathic pain. Notably, loss of CRMP2 SUMOylation did not compromise other innate functions of CRMP2. To further elucidate thein vivorole of CRMP2 SUMOylation in pain, we generated CRMP2 K374A knock-in (CRMP2K374A/K374A) mice in which Lys374 was replaced with Ala. CRMP2K374A/K374Amice had reduced NaV1.7 membrane localization and function in female, but not male, sensory neurons. Behavioral appraisal of CRMP2K374A/K374Amice demonstrated no changes in depressive or repetitive, compulsive-like behaviors, and a decrease in noxious thermal sensitivity. No changes were observed in CRMP2K374A/K374Amice to inflammatory, acute, or visceral pain. In contrast, in a neuropathic model, CRMP2K374A/K374Amice failed to develop persistent mechanical allodynia. Our study suggests that CRMP2 SUMOylation-dependent control of peripheral NaV1.7 is a hallmark of chronic, but not physiological, neuropathic pain.
PyRice: a Python package for queryingOryza Sativadatabases
Authors: Do Quan , Hai Ho Bich , Larmande Pierre
Published: April 2020

Currently, gene information available forOryza sativaspecies is located in various online heterogeneous data sources. Moreover, methods of access are also diverse, mostly web-based and sometimes query APIs, which might not always be straightforward for domain experts. The challenge is to collect information quickly from these applications and combine it logically, to facilitate scientific research. We developed a Python package named PyRice, a unified programming API to access all supported databases at the same time with consistent output. PyRice design is modular and implements a smart query system which fits the computing resources to optimize the query speed. As a result, PyRice is easy to use and produces intuitive results.

Availability and implementation

https://github.com/SouthGreenPlatform/PyRice

Documentation

https://pyrice.readthedocs.io

Contact

pierre.larmande@ird.fr

Licence information

MIT

Supplementary information

Supplementary data are available online.
Ecosystem Entanglement and the Propagation of Nutrient-Driven Instability
Authors: McCann Kevin S. , MacDougall A.S , Fussmann G.F. , Bieg C. , Cazelles K. , Cristescu M.E. , Fryxell J.M. , Gellner G. , Lapointe B. , Gonzalez A.
Published: April 2020

Almost 50 years ago, Michael Rosenzweig pointed out that nutrient addition can destabilize food webs, leading to loss of species and reduced ecosystem function through the paradox of enrichment. Around the same time, David Tilman demonstrated that increased nutrient loading would also be expected to cause competitive exclusion leading to deleterious changes in food web diversity. While both concepts have greatly illuminated general diversity-stability theory, we currently lack a coherent framework to predict how nutrients influence food web stability across a landscape. This is a vitally important gap in our understanding, given mounting evidence of serious ecological disruption arising from anthropogenic displacement of resources and organisms. Here, we combine contemporary theory on food webs and meta-ecosystems to show that nutrient additions are indeed expected to drive loss in stability and function in human-impacted regions. However, this loss in stability occurs not just from wild oscillations in population abundance, but more frequently from the complete loss of an equilibrium due to edible plant species being competitively excluded. In highly modified landscapes, spatial nutrient transport theory suggests that such instabilities can be amplified over vast distances from the sites of nutrient addition. Consistent with this theoretical synthesis, the empirical frequency of these distant propagating ecosystem imbalances appears to be growing. This synthesis of theory and empirical data suggests that human modification of the Earth’s ecological connectivity is “entangling” once distantly separated ecosystems, causing rapid, expansive, and costly nutrient-driven instabilities over vast areas of the planet. The corollary to this spatial nutrient theory, though -- akin to weak interaction theory from food web networks -- is that slow spatial nutrient pathways can be potent stabilizers by moderating flows across a landscape.
Deep learning model can predict water binding sites on the surface of proteins using limited-resolution data
Authors: Zaucha Jan , Softley Charlotte A. , Sattler Michael , Popowicz Grzegorz M.
Published: April 2020

The surfaces of proteins are generally hydrophilic but there have been reports of sites that exhibit an exceptionally high affinity for individual water molecules. Not only do such molecules often fulfil critical biological functions, but also, they may alter the binding of newly designed drugs. In crystal structures, sites consistently occupied in each unit cell yield electron density clouds that represent water molecule presence. These are recorded in virtually all high-resolution structures obtained through X-ray diffraction. In this work, we utilized the wealth of data from the RCSB Protein Data Bank to train a residual deep learning model named ‘hotWater’ to identify sites on the surface of proteins that are most likely to bind water, the so-called water hot spots. The model can be used to score existing water molecules from a PDB file to provide their ranking according to the predicted binding strength or to scan the surface of a protein to determine the most likely water hot-spotsde novo. This is computationally much more efficient than currently used molecular dynamics simulations. Based on testing the model on three example proteins, which have been resolved using both high-resolution X-ray crystallography (providing accurate positions of trapped waters) as well as low-resolution X-ray diffraction, NMR or CryoEM (where structure refinement does not yield water positions), we were able to show that the hotWater method is able to recover in the “water-free” structures many water binding sites known from the high-resolution structures. A blind test on a newly solved protein structure with waters removed from the PDB also showed good prediction of the crystal water positions. This was compared to two known algorithms that use electron density and was shown to have higher recall at resolutions >2.6 Å. We also show that the algorithm can be applied to novel proteins such as the RNA polymerase complex from SARS-CoV-2, which could be of use in drug discovery. The hotWater model is freely available at (https://pypi.org/project/hotWater/).
Cold adaptation drives population genomic divergence in the ecological specialist,Drosophila montana
Authors: Wiberg R. A. W. , Tyukmaeva V. , Hoikkala A. , Ritchie M. G. , Kankare M.
Published: April 2020

Detecting signatures of ecological adaptation in comparative genomics is challenging, but analysing population samples with characterised geographic distributions, such as clinal variation, can help identify genes showing covariation with important ecological variation. Here we analysed patterns of geographic variation in the cold-adapted speciesDrosophila montanaacross phenotypes, genotypes and environmental conditions and tested for signatures of cold adaptation in population genomic divergence. We first derived the climatic variables associated with the geographic distribution of 24 populations across two continents to trace the scale of environmental variation experienced by the species, and measured variation in the cold tolerance of the flies of six populations from different geographic contexts. We then performed pooled whole genome sequencing of these six populations, and used Bayesian methods to identify SNPs where genetic differentiation is associated with both climatic variables and the population phenotypic measurements, while controlling for effects of demography and population structure. The top candidate SNPs were enriched on the X and 4thchromosomes, and they also lay near genes implicated in other studies of cold tolerance and population divergence in this species and its close relatives. We conclude that ecological adaptation has contributed to the divergence ofD. montanapopulations throughout the genome and in particular on the X and 4thchromosomes, which also showed highest interpopulation FST. This study demonstrates that ecological selection can drive genomic divergence at different scales, from candidate genes to chromosome-wide effects.
Efficacy and safety of decompressive craniectomy with non-suture duraplasty in patients with traumatic brain injury
Authors: Jeong Tae Seok , Yee Gi Taek , Lim Tae Gyu , Kim Woo Kyung , Yoo Chan Jong
Published: April 2020

Background

Decompressive craniectomy is an important surgical treatment for patients with severe traumatic brain injury (TBI). Several reports have been published on the efficacy of non-watertight sutures in duraplasty performed in decompressive craniectomy. This study aims to evaluate the effectiveness of dura closure without sutures (non-suture duraplasty) in decompressive craniectomy for TBI.

Methods

One hundred and six patients were enrolled at a single trauma center between January 2017 and December 2018. We retrospectively collected the data and classified the patients into non-suture and suture duraplasty craniectomy groups. We compared the characteristics of patients and their intra/post- operative findings such as operative time, blood loss, imaging findings, complications, and Glasgow outcome scale.

Results

There were 37 patients in the non-suture group and 69 in the suture craniectomy group. There were no significant differences between the two groups with regard to general characteristics. The operative time was 205 min for the suture duraplasty group and 150 min for the non-suture duraplasty group, and that for the non-suture duraplasty group was significantly lesser (p=0.002). Blood loss was significantly lesser in the non-suture duraplasty group (1000 mL) than in the suture duraplasty group (1500 mL, p=0.028). There were no other significant differences.

Conclusion

Non-suture duraplasty involved shorter operative time and lesser blood loss when compared to suture duraplasty. Other complications and prognosis were similar in both groups. Therefore, it can be concluded that decompressive craniectomy with non-suture duraplasty is a safe and useful surgical technique in patients with TBI.