bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fully Implantable Wireless Bidirectional Neuromodulation System for Mice
Authors: Wright Jason , Wong Jason , Mathew Jose , Mughrabi Ibrahim , Jayaprakash Naveen , Zanos Theodoros P. , Abed Yousef Al , Zanos Stavros , Datta-Chaudhuri Timir
Published: June 2021

Novel research in the field of bioelectronic medicine requires systems that pair high-performance neurostimulation and bio-signal acquisition hardware with advanced software signal processing and control algorithms. Although mice are the most commonly used animal in medical research, the size, weight, and power requirements of such systems either preclude their use or impose significant constraints on experimental design. Here, we describe a fully-implantable neuromodulation system suitable for use in mice, measuring 2.2 cm3 and weighing 2.8 g. A bidirectional wireless interface allows simultaneous readout of multiple physiological signals and complete control over stimulation parameters, and a wirelessly rechargeable battery provides a lifetime of up to 5 days on a single charge. The device was successfully implanted (N=12) and a functional neural interface (capable of inducing acute bradycardia) is demonstrated with functional lifetimes exceeding to three weeks. The design utilizes only commercially-available components and 3D-printed packaging, with the goal of accelerating discovery and translation of future bioelectronic therapeutics.
Klf5 establishes bi-potential cell fate by dual regulation of ICM and TE specification genes
Authors: Kinisu Martin , Choi Yong Jin , Cattoglio Claudia , Liu Ke , de Bezieux Hector Roux , Valbuena Raeline , Pum Nicole , Dudoit Sandrine , Huang Haiyan , Xuan Zhenyu , Kim Sang Yong , He Lin
Published: June 2021

Early blastomeres of mouse preimplantation embryos exhibit bi-potential cell fate, capable of generating both embryonic and extra-embryonic lineages in blastocysts. Here, we identified three major 2 cell (2C) specific endogenous retroviruses (ERVs) as the molecular hallmark of the bi-potential plasticity. Using the LTRs of all three 2C-ERVs, we identified Klf5 as their major upstream regulator. Klf5 is essential for bi-potential cell fate: a single Klf5-overexpressing ESC generated terminally differentiated embryonic and extra-embryonic lineages in chimeric embryos, and Klf5 directly induces both ICM and TE specification genes. Intriguingly, Klf5 and Klf4 act redundantly during ICM specification, whereas Klf5 deficiency alone impairs TE specification. Klf5 is regulated by multiple 2C-specific transcription factors, particularly Dux, and the Dux/Klf5 axis is evolutionarily conserved. Altogether, the 2C-specific transcription program converges on Klf5 to establish bi-potential cell fate, enabling a cell state with dual activation of ICM and TE genes.
Dive Performance and Aquatic Thermoregulation of the World’s Smallest Mammalian Diver, the American Water Shrew (Sorex palustris)
Authors: Gusztak Roman W. , MacArthur Robert A. , Campbell Kevin L.
Published: June 2021

Allometry predicts that the 12–17 g American water shrew (Sorex palustris)—the world’s smallest mammalian diver—will have the highest diving metabolic rate coupled with the lowest total body oxygen storage capacity, skeletal muscle buffering capacity, and glycolytic potential of any endothermic diver. Consistent with expectations, and potentially owing to their low thermal inertia, water shrews had a significantly higher diving metabolic rate in 10°C (8.77 mL O2 g−1 hr−1) compared to 30°C water (6.57 mL O2 g−1 hr−1). Unlike larger-bodied divers, muscle myoglobin contributed minimally (7.7–12.4%) to total onboard O2 stores of juvenile and adult water shrews, respectively, but was offset by high blood O2 carrying capacities (26.4–26.9 vol. %). Diving was predominantly aerobic, as only 1.2–2.3% of dives in 10 and 30°C water, respectively, exceeded the calculated aerobic dive limits at these temperatures (10.8–14.4 sec). The mean voluntary dive time of water shrews during 20-min trials in 3–30°C water was 5.0±0.1 sec (N=25, n=1628), with a mean maximum dive time of 10.1±0.4 sec. However, the average dive duration (6.9±0.2 sec, n=257) of radio-telemetered shrews exclusively foraging in a simulated riparian environment (3°C water) for 12- to 28-hr suggest that mean (but not maximum) dive times of water shrews in the wild may be longer. Mean dive duration, duration of the longest dive, and total time in water all decreased significantly as water temperature declined, suggesting that shrews employed behavioral thermoregulation to defend against immersion hypothermia. Additionally, free-diving shrews in the 24-hr trials consistently elevated core body temperature by ∼1°C immediately prior to initiating aquatic foraging bouts, and ended these bouts when body temperature was still at or above normal resting levels (∼37.8°C). We suggest this observed pre-dive hyperthermia aids to heighten the impressive somatosensory physiology, and hence foraging efficiency, of this diminutive predator while submerged.
Pseudouridine-free Ribosome Exhibits Distinct Inter-subunit Movements
Authors: Zhao Yu , Rai Jay , Yu Hongguo , Li Hong
Published: June 2021

Pseudouridine, the most abundant form of RNA modification, is known to play important roles in ribosome function. Mutations in human DKC1, the pseudouridine synthase responsible for catalyzing the ribosome RNA modification, cause translation deficiencies and are associated with a complex cancer predisposition. The structural basis for how pseudouridine impacts ribosome function remains uncharacterized. Here we report electron cryomicroscopy structures of a fully modified and a pseudouridine-free ribosome from Saccharomyces cerevisiae. In the modified ribosome, the rearranged N1 atom of pseudouridine is observed to stabilize key functional motifs by establishing predominately water-mediated close contacts with the phosphate backbone. The pseudouridine-free ribosome, however, is devoid of such interactions and displays conformations reflective of abnormal inter-subunit movements. The erroneous motions of the pseudouridine-free ribosome may explain its observed deficiencies in translation.
The Food Additive Xanthan Gum Drives Adaptation of the Human Gut Microbiota
Authors: Ostrowski Matthew P. , La Rosa Sabina Leanti , Kunath Benoit J. , Robertson Andrew , Pereira Gabriel , Hagen Live H. , Varghese Neha J. , Qiu Ling , Yao Tianming , Flint Gabrielle , Li James , McDonald Sean , Buttner Duna , Pudlo Nicholas A. , Schnizlein Matthew K. , Young Vincent B. , Brumer Harry , Schmidt Thomas , Terrapon Nicolas , Lombard Vincent , Henrissat Bernard , Hamaker Bruce , Eloe-Fadrosh Emiley A , Tripathi Ashootosh , Pope Phillip B. , Martens Eric
Published: June 2021

The diets of industrialized countries reflect the increasing use of processed foods, often with the introduction of novel food additives. Xanthan gum is a complex polysaccharide with unique rheological properties that have established its use as a widespread stabilizer and thickening agent1. However, little is known about its direct interaction with the gut microbiota, which plays a central role in digestion of other, chemically-distinct dietary fiber polysaccharides. Here, we show that the ability to digest xanthan gum is surprisingly common in industrialized human gut microbiomes and appears to be contingent on the activity of a single bacterium that is a member of an uncultured bacterial genus in the familyRuminococcaceae. We used a combination of enrichment culture, multi-omics, and recombinant enzyme studies to identify and characterize a complete pathway in this uncultured bacterium for the degradation of xanthan gum. Our data reveal that this keystone degrader cleaves the xanthan gum backbone with a novel glycoside hydrolase family 5 (GH5) enzyme before processing the released oligosaccharides using additional enzymes. Surprisingly, some individuals harbor aBacteroidesspecies that is capable of consuming oligosaccharide products generated by the keystoneRuminococcaceaeor a purified form of the GH5 enzyme. ThisBacteroidessymbiont is equipped with its own distinct enzymatic pathway to cross-feed on xanthan gum breakdown products, which still harbor the native linkage complexity in xanthan gum, but it cannot directly degrade the high molecular weight polymer. Thus, the introduction of a common food additive into the human diet in the past 50 years has promoted the establishment of a food chain involving at least two members of different phyla of gut bacteria.
Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies
Authors: Fenix Aidan M. , Miyaoka Yuichiro , Bertero Alessandro , Blue Steven , Spindler Matthew J. , Tan Kenneth K. B. , Perez-Bermejo Juan , Chan Amanda H. , Mayer Steven J. , Nguyen Trieu , Russell Caitlin R. , Lizarraga Paweena , Truong Annie , So Po-Lin , Kulkarni Aishwarya , Chetal Kashish , Sathe Shashank , Sniadecki Nathan J. , Yeo Gene W. , Murry Charles E. , Conklin Bruce R. , Salomonis Nathan
Published: June 2021

RNA binding motif protein 20 (RBM20) is a key regulator of alternative splicing in the heart, and its mutation leads to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic human induced pluripotent stem cells (iPSCs) with heterozygous or homozygous DCM-associated missense mutations in RBM20 (R636S) as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart tissues made from these cell lines recapitulated contractile dysfunction of RBM20-associated DCM and revealed greater dysfunction with missense mutations than KO. Analysis of RBM20 RNA binding by eCLIP revealed a gain-of-function preference of mutant RBM20 for 3′ UTR sequences that are shared with amyotrophic lateral sclerosis (ALS) and processing-body associated RNA binding proteins (FUS, DDX6). Deep RNA sequencing revealed that the RBM20 R636S mutant has unique gene, splicing, polyadenylation and circular RNA defects that differ from RBM20 KO, impacting distinct cardiac signaling pathways. Splicing defects specific to KO or R636S mutations were supported by data from R636S gene-edited pig hearts and eCLIP. Super-resolution microscopy verified that mutant RBM20 maintains limited nuclear localization potential; rather, the mutant protein associates with cytoplasmic processing bodies (DDX6) under basal conditions, and with stress granules (G3BP1) following acute stress. Taken together, our results highlight a novel pathogenic mechanism in cardiac disease through splicing-dependent and -independent pathways that are likely to mediate differential contractile phenotypes and stress-associated heart pathology.
Nanoparticle fragmentation at solid state under single picosecond laser pulse stimulation
Authors: Kang Peiyuan , Wang Yang , Wilson Blake A. , Randrianalisoa Jaona , Qin Zhenpeng
Published: June 2021

Understanding the laser-nanomaterials interaction including nanomaterial fragmentation has important implications in nanoparticle manufacturing, energy, and biomedical sciences. So far, three mechanisms of laser-induced fragmentation have been recognized including non-thermal processes and thermomechanical force under femtosecond pulses, and the phase transitions under nanosecond pulses. Here we show that single picosecond (ps) laser pulse stimulation leads to anomalous fragmentation of gold nanoparticles that deviates from these three mechanisms. The ps laser fragmentation was weakly dependent on particle size, and it resulted in a bimodal size distribution. Importantly, ps laser stimulation fragmented particles below the melting point and below the threshold for non-thermal mechanism. This study reveals a previously unknown regime of nanoparticle fragmentation.
COMMIT: Consideration of metabolite leakage and community composition improves microbial community models
Authors: Wendering Philipp , Nikoloski Zoran
Published: June 2021

Composition and functions of microbial communities affect important traits in diverse hosts, from crops to humans. Yet, mechanistic understanding of how metabolism of individual microbes is affected by the community composition and metabolite leakage is lacking. Here, we first show that the consensus of automatically generated metabolic models improves the quality of the draft models, measured by the genomic evidence for considered enzymatic reactions. We then devise an approach for gap filling, termed COMMIT, that considers exchangeable metabolites based on their permeability and the composition of the community. By applying COMMIT with two soil communities from the Arabidopsis thaliana culture collection, we could significantly reduce the gap-filling solution in comparison to filling gaps in individual models. Inspection of the metabolic interactions in the soil communities allows us to identify microbes with community roles of helpers and beneficiaries. Therefore, COMMIT offers a versatile automated solution for large-scale modelling of microbial communities for diverse biotechnological applications.
Chromatin enrichment for Proteomics in Plants (ChEP-P) implicates the histone reader ALFIN-LIKE 6 in jasmonate signalling
Authors: Vélez-Bermúdez Isabel Cristina , Schmidt Wolfgang
Published: June 2021

Covalent modifications of core histones govern downstream DNA-templated processes such as transcription by altering chromatin structure and function. Previously, we reported that the plant homeodomain protein ALFIN-LIKE 6 (AL6), abona fidehistone reader that preferentially binds trimethylated lysin 4 on histone 3 (H3K4me3), is critical for recalibration of cellular phosphate (Pi) homeostasis and root hair elongation under Pi-deficient conditions. Here, we demonstrate that AL6 is also involved in the response of Arabidopsis seedlings to jasmonic acid (JA) during skotomorphogenesis, possibly by modulating chromatin dynamics that affect the transcriptional regulation of JA-responsive genes. Dark-grownal6seedlings showed a compromised reduction in hypocotyl elongation upon exogenously supplied JA, a response that was calibrated by the availability of Pi in the growth medium. A comparison of protein profiles between wild-type andal6mutant seedlings using a quantitative Chromatin Enrichment for Proteomics (ChEP) approach, that we modified for plant tissue and designated ChEP-P (ChEP in Plants), yielded a comprehensive suite of chromatin-associated proteins and candidates that may be causative for the mutant phenotype. Altered abundance of proteins involved in chromatin organization inal6seedlings suggests a role of AL6 in coordinating the deposition of histone variants upon perception of internal or environmental stimuli.

Highlight

Cataloguing chromatin-associated proteins revealed that the plant homeodomain protein ALFIN-LIKE 6 orchestrates phosphate and jasmonate signaling in etiolated Arabidopsis seedlings through modulation of the chromatin structure.
NLoed: A Python package for nonlinear optimal experimental design in systems biology
Authors: Braniff Nathan , Pearce Taylor , Lu Zixuan , Astwood Michael , Forrest William S. R. , Receno Cody , Ingalls Brian
Published: June 2021

Motivation

Modelling in systems and synthetic biology relies on accurate parameter estimates and predictions. Accurate model calibration relies, in turn, on data, and on how well-suited the available data is to a particular modelling task. Optimal experimental design (OED) techniques can be used to identify experiments and data collection procedures that will most efficiently contribute to a given modelling objective. However, implementation of OED is limited by currently available software tools that are not well-suited for the diversity of nonlinear models and non-normal data commonly encountered in biological research. Moreover, existing OED tools do not make use of the state-of-the-art numerical tools, resulting in inefficient computation.

Results

Here we present the NLoed software package. NLoed is an open-source Python library providing convenient access to OED methods, with particular emphasis on experimental design for systems biology research. NLoed supports a wide variety of nonlinear, multi-input/output, and dynamic models, and facilitates modelling and design of experiments over a wide variety of data types. To support OED investigations, the NLoed package implements maximum likelihood fitting and diagnostic tools, providing a comprehensive modelling workflow. NLoed offers an accessible, modular, and flexible OED tool-set suited to the wide variety of experimental scenarios encountered in systems biology research. We demonstrate NLOED’s capabilities by applying it to experimental design for characterization of a bacterial optogenetic system.

Availability

NLoed is available via pip from the PyPi repository;https://pypi.org/project/nloed/. Source code, documentation and examples can be found on Github athttps://github.com/ingallslab/NLoed.

Contact

bingalls@uwaterloo.ca

Supplementary information

Supplementary materials are available online.
Unique role and vulnerability of EP300 KIX domain in small-cell lung cancer
Authors: Kim Kee-Beom , Kabra Ashish , Kim Dong-Wook , Xue Yongming , Hou Pei-Chi , Zhou Yunpeng , Miranda Leilani , Shi Xiaobing , Bender Timothy P. , Bushweller John H. , Park Kwon-Sik
Published: June 2021

EP300 (E1A binding protein p300) is a versatile transcription co-activator important in cell proliferation and differentiation. The gene EP300 is frequently mutated in diverse cancer types, including small-cell lung cancer (SCLC). While it is widely believed that these mutations result in loss of EP300 function, the impact on SCLC pathogenesis remains largely unknown. Here we demonstrate that mutant EP300 variants lacking histone acetyltransferase (HAT) domain accelerate tumor development in autochthonous mouse models of SCLC. However, unexpectedly, complete knockout of Ep300 suppresses tumor development and inhibits proliferation of both human and mouse SCLC cells. Genetic dissection of EP300 domains identifies kinase-inducible domain (KID)-interacting (KIX) domain, specifically its interaction with transcription factors such as CREB1 and MYB, as the determinant of pro-tumorigenic activity. Blockade of the KIX-mediated protein interactions using a small molecule and a recombinant peptide mimicking the KIX-binding sequences of EP300-interacting partners inhibits the growth of SCLC cells. These findings identify domain-specific roles of EP300 in SCLC and unique vulnerability of the EP300 KIX domain to potential therapeutics.
Organic stabilization of extracellular elemental sulfur in aSulfurovum-rich biofilm: a new role for EPS?
Authors: Cron Brandi , Macalady Jennifer L. , Cosmidis Julie
Published: June 2021

This work shines light on the role of extracellular polymeric substances (EPS) in the formation and preservation of elemental sulfur biominerals produced by sulfur-oxidizing bacteria. We characterized elemental sulfur particles produced within aSulfurovum-rich biofilm in the Frasassi Cave System (Italy). The particles adopt spherical and bipyramidal morphologies, and display both stable (α-S8) and metastable (β-S8) crystal structures. Elemental sulfur is embedded within a dense matrix of EPS and the particles are surrounded by organic envelopes rich in amide and carboxylic groups. Organic encapsulation and the presence of metastable crystal structures are consistent with elemental sulfur organomineralization, i.e. the formation and stabilization of elemental sulfur in the presence of organics, a mechanism that has previously been observed in laboratory studies. This research provides new evidence for the important role of microbial EPS in mineral formation in the environment. We hypothesize that extracellular organics are used by sulfur-oxidizing bacteria for the stabilization of elemental sulfur minerals outside of the cell wall as a store of chemical energy. The stabilization of energy sources (in the form of a solid electron acceptor) in biofilms is a potential new role for microbial EPS that requires further investigation.
Ring Finger Protein 213 Assembles into a Sensor for ISGylated Proteins with Antimicrobial Activity
Authors: Thery Fabien , Martina Lia , Asselman Caroline , Repo Heidi , Zhang Yifeng , Sedeyn Koen , Moschonas George D. , Bredow Clara , Teo Qi Wen , Zhang Jingshu , Vessely Madeleine , Leandro Kevin , Eggermont Denzel , De Sutter Delphine , Boucher Katie , Hochepied Tino , Festjens Nele , Callewaert Nico , Saelens Xavier , Dermaut Bart , Knobeloch Klaus-Peter , Beling Antje , Sanyal Sumana , Radoshevich Lilliana , Eyckerman Sven , Impens Francis
Published: June 2021

ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we used a viral-like particle trapping technology to identify ISG15-binding proteins and discovered Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly-characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We found that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We showed that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1 (HSV-1), human respiratory syncytial virus (RSV) and coxsackievirus B3 (CVB3), and we observed a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide novel molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.
Computational Neuroimaging of Cognition-Emotion Interactions: Affective and Task-similar Interference Differentially Impact Working Memory
Authors: Ji Jie Lisa , Repovs Grega , Yang Genevieve J. , Savic Aleksandar , Murray John D. , Anticevic Alan
Published: June 2021

Cognition depends on resisting interference and responding to relevant stimuli. Distracting information, however, varies based on content, requiring distinct filtering mechanisms. For instance, affective information captures attention, disrupts performance and attenuates activation along frontal-parietal regions during cognitive engagement, while recruiting bottom-up regions. Conversely, distraction matching task features (i.e. task-similar) increases fronto-parietal activity. Neural mechanisms behind unique effects of different distraction on cognition remain unknown. Using fMRI in 45 adults, we tested whether affective versus task-similar interference show distinct signals during delayed working memory (WM). We found robust differences between distractor types along fronto-parietal versus affective-ventral neural systems. We studied a hypothesized mechanism of this effect via a biophysically-based computational WM model that implements a functional antagonism between affective/cognitive neural ‘modules’. This architecture reproduced experimental effects: task-similar distractors increased, whereas affective distractors attenuated cognitive module activity while increasing affective module signals. The model architecture suggested that task-based connectivity may be altered in affective-ventral vs. fronto-parietal networks depending on distractor type. Empirically, affective interference significantly increased connectivity within the affective-ventral network, but reduced connectivity between affective-ventral and fronto-parietal networks, which predicted WM performance. These findings detail an antagonistic architecture between cognitive and affective systems, capable of flexibly engaging distinct distractions during cognition.
Novel GVHD resistant humanized-PBMC mouse model for preclinical HIV research
Authors: Holguin Leo , Echavarria Liliana , Burnett John C.
Published: June 2021

Humanized mouse models are based on the engraftment of human cells in immunodeficient mouse strains, most notably the NSG strain. Most used models have a major limitation in common, the development of graft-versus-host disease (GVHD). GVHD not only introduces variabilities into the research data but also leads to animal welfare concerns. A new mouse strain, B6.129S-Rag2tm1Fwa CD47tm1Fpl Il2rgtm1Wjl/J which lacks Rag1, IL2rg, and CD47 (triple knockout or TKO), is resistant to GVHD development. We transplanted TKO mice with human peripheral blood mononuclear cells (PBMCs) to establish a new humanized PBMC (hu-PBMC) mouse model. A cohort of these mice was infected with HIV-1 and monitored for plasma HIV viremia and CD4+ T cell depletion. The onset and progression of GVHD were monitored by clinical signs. This study demonstrates that TKO mice transplanted with human PBMCs support engraftment of human immune cells in primary and secondary lymphoid tissues, rectum, and brain. Moreover, the TKO hu-PBMC model supports HIV-1 infection via intraperitoneal, rectal, or vaginal routes, as confirmed by robust plasma HIV viremia and CD4+ T cell depletion. Lastly, TKO mice showed a delayed onset of GVHD clinical signs (∼21 days) and exhibited significant decreases in plasma levels of TNFβ. Based on these results, the TKO hu-PBMC mouse model not only supports humanization and HIV-1 infection but is also resistant to GVHD development, making this model a valuable tool in HIV research.

Importance

Currently, there is no cure or vaccine for HIV infection, thus continued research is needed to end the HIV pandemic. While many animal models are used in HIV research, none is used more than the humanized mouse model. A major limitation with current humanized mouse models is the development of graft-versus-host disease (GVHD). Here, we show a novel humanized mouse model that is resistant to GVHD development and supports and models HIV infection comparable to well-established humanized mouse models.
An exploration of metabolite and gene responses in mouse skeletal muscles responding to acute sedentary hypoxia
Authors: Xue Feng , Huang Gang , Wang Xi , Deng Jie , Pang Lingxia , Gan Zhuohui
Published: June 2021

Skeletal muscles are involved in responses to acute hypoxia as the largest organ in the body. However, as a hypoxic-tolerant tissue, responses in skeletal muscles caused by acute sedentary hypoxia are much less studied. We measured metabolites in skeletal muscles from mice exposed to 8% O2 for 0 minute, 15 minutes and 2 hours and studied the potential relationship between metabolite levels and mRNA levels by reconstructing genome-based metabolic networks and meta-analyzing differentially expressed genes acquired in skeletal muscles after 2 hours of 8% O2 exposure. The metabolite measurement indicated a significant increase in glutamine metabolism but not lactate metabolism in mouse skeletal muscles after 2 hours of hypoxia, where the metabolic responses as a whole were moderate. The central-dogma based metabolic flux analysis suggested an involvement of glutamine metabolism, though, as a whole, metabolite changes and gene changes didn’t show a high correlation. Among metaoblites, glutamine metabolism indicated a significant response and a consistent change which could be interpreted by genome-based network analysis. In summary, though this study suggested a moderate metabolic response which has a weak correlation with gene expression change as a whole, glutamine metabolism indicated rapid responses in skeletal muscles responding to acute sedentary hypoxia.
Estrogen regulates early embryonic development of the olfactory sensory system via estrogen-responsive glia
Authors: Takesono Aya , Schirrmacher Paula , Scott Aaron , Green Jon M. , Lee Okhyun , Winter Matthew J. , Kudoh Tetsuhiro , Tyler Charles R.
Published: June 2021

Estrogen is well-known to regulate development of sexual dimorphisms of the brain, however its role in the brain during early embryonic development prior to sex-differentiation is unclear.

Using estrogen biosensor zebrafish models, we found that estrogen activity in the embryonic brain occurs specifically in a type of glia located within the OB, which we name estrogen-responsive olfactory bulb/EROB cells. With estrogen activity, EROB cells extend their ramified projections that overlay the OB outermost layer and tightly interact with olfactory sensory neurons (OSNs) at the olfactory glomeruli. Pharmacologically inhibiting estrogen activity and/or EROB cell ablation impedes olfactory glomerular development, including OSN pathfinding, topological organisation of olfactory glomeruli and inhibitory neurogenesis in the OB. Furthermore, activation of this estrogen/EROB-dependent mechanism decreases the intrinsic neuronal activity primarily in the OB, and this alteration of estrogen signalling disrupts olfaction-mediated behaviour. We propose that estrogen acts on glia to regulate development of functional OB circuits, thereby modulating the local intrinsic excitability in the OB and olfaction-mediated behaviour. Our data also suggest a possibility that the estrogen/EROB cascade may be an important site of action for environmental estrogens causative of neurodevelopmental impairments in animals and humans.
Visually Induced Changes in Cytokine Production in the Chick Choroid
Authors: Summers Jody A. , Cano Elizabeth Martinez
Published: June 2021

Postnatal ocular growth is regulated by a vision-dependent mechanism which acts to minimize refractive error through coordinated growth of the ocular tissues. Of great interest is the identification of the chemical signals that control visually-guided ocular growth. Here we provide evidence that the pro-inflammatory cytokine, Interleukin-6 (IL-6), may play a pivotal role in the control of ocular growth using a chicken model of myopia. Microarray, real time RT-qPCR, and ELISA analyses identified IL-6 upregulation in the choroids of chick eyes under two visual conditions that introduce myopic defocus and slow the rate of ocular elongation (recovery from induced myopia and compensation for positive lenses). Intraocular administration of atropine, an agent known to slow ocular elongation, also resulted in an increase in choroidal IL-6 gene expression. Nitric oxide appears to directly or indirectly upregulate choroidal IL-6 gene expression, as administration of the non-specific nitric oxide synthase inhibitor, L-NAME, inhibited choroidal IL-6 gene expression, and application of a nitric oxide donor stimulated IL-6 gene and protein expression in isolated chick choroids. Considering the pleiotropic nature of IL-6 and involvement in many biological processes, these results suggest that IL-6 may mediate many aspects of the choroidal response in the control of ocular growth.
Philympics 2021: Prophage Predictions Perplex Programs
Authors: Roach Michael J. , McNair Katelyn , Giles Sarah K. , Inglis Laura , Pargin Evan , Roux Simon , Decewicz Przemysław , Edwards Robert A.
Published: June 2021

Most bacterial genomes contain integrated bacteriophages—prophages—in various states of decay. Many are active and able to excise from the genome and replicate, while others are cryptic prophages, remnants of their former selves. Over the last two decades, many computational tools have been developed to identify the prophage components of bacterial genomes, and it is a particularly active area for the application of machine learning approaches. However, progress is hindered and comparisons thwarted because there are no manually curated bacterial genomes that can be used to test new prophage prediction algorithms.

Here, we present a library of gold-standard bacterial genome annotations that include manually curated prophage annotations, and a computational framework to compare the predictions from different algorithms. We use this suite to compare all extant stand-alone prophage prediction algorithms to identify their strengths and weaknesses.

We provide a FAIR dataset for prophage identification, and demonstrate the accuracy, precision, recall, and f1score from the analysis of seven different algorithms for the prediction of prophages. We discuss caveats and concerns in this analysis and how those concerns may be mitigated.
A diagnostic primer pair to distinguish between wMel and wAlbB Wolbachia infection - A simplified real-time PCR approach for use in field collected Aedes aegypti in dengue reduction trials
Authors: Lau Meng-Jia , Hoffmann Ary A. , Endersby-Harshman Nancy M.
Published: June 2021

Detection of the Wolbachia endosymbiont in Aedes aegypti mosquitoes through real-time PCR assays is widely used during and after Wolbachia releases in dengue reduction trials involving the wMel and wAlbB strains. However, primers applied in current successful Wolbachia releases cannot be used in a single assay to distinguish between these strains. Here, we developed a new diagnostic primer pair wMA which can detect wMel or wAlbB infection in the same assay. We also tested current Wolbachia primers and show that there is variation in their performance when they are used to assess the relative density of Wolbachia. The new wMA primers provide an accurate and efficient estimate of the presence and density of both Wolbachia infections.
Spinal neurons innervating multiple local and distant motor pools
Authors: Ronzano Remi , Lancelin Camille , Bhumbra Gardave S. , Brownstone Robert M. , Beato Marco
Published: June 2021

Motor neurons control muscle contractions, and their recruitment by premotor circuits is tuned to produce accurate motor behaviours. To understand how these circuits coordinate movement across and between joints, it is necessary to understand whether spinal neurons pre-synaptic to motor pools, project to more than one motor neuron population. Here, we used modified rabies virus tracing in mice to investigate premotor INs projecting to synergist flexor or extensor motor neurons, as well as those projecting to antagonist pairs of muscles controlling the ankle joint. We show that similar proportions of premotor neurons diverge to agonist and antagonist motor pools. Divergent premotor neurons were seen throughout the spinal cord, with decreasing numbers but increasing proportion with distance from the hindlimb enlargement. In the cervical cord, divergent long descending propriospinal neurons were found in contralateral lamina VIII, had large somata, were excitatory, projected to both lumbar and cervical motoneurons, and were at least in part of the V0 class. We conclude that distributed spinal premotor neurons coordinate activity across multiple motor pools and that there are spinal neurons mediating co-contraction of antagonist muscles.
The Copper Responsive Transcription Factor SPL7 Represses Key Abscisic Acid Biosynthetic Genes to Balance Growth and Drought Tolerance
Authors: Yang Yanzhi , Du Jianmei , Tao Yihan , Hao Chen , Kuang Zheng , Li Zhan , Li Lei
Published: June 2021

Plants adapt to adverse environments by turning on defense against abiotic stresses, which is mainly orchestrated by the phytohormone abscisic acid (ABA). But how ABA homeostasis is modulated to balance growth and stress responses is still largely unknown. Here we report that prior treatment of Arabidopsis seedling with high copper retardates growth but enhances draught tolerance at later stages by modulating ABA accumulation. Subsequent genetic, physiological, transcriptomic, and molecular investigations revealed that the copper responsive transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 7 (SPL7) is a strong regulator of ABA accumulation. We showed that SPL7 is destabilized by high copper and consistently suppresses genes encoding three key oxygenases in the ABA biosynthetic pathway of land plants via binding to the GTAC copper response motifs in their promoters. These results revealed a new mechanism whereby copper availability, inversely reflected by SPL7 abundance, modulates de novo ABA biosynthesis to balance growth and drought tolerance.

One-sentence summary

High copper availability represses SPL7, releasing its suppression on key ABA biosynthetic genes and leading to increased ABA accumulation that inhibits growth but enhances drought tolerance.
Rapid Biomarker Screening of Alzheimer’s Disease by Interpretable Machine Learning and Graphene-Assisted Raman Spectroscopy
Authors: Wang Ziyang , Ye Jiarong , Zhang Kunyan , Ding Li , Granzier-Nakajima Tomotaroh , Ranasinghe Jeewan , Xue Yuan , Sharma Shubhang , Biase Isabelle , Terrones Mauricio , Choi Se Hoon , Ran Chongzhao , Tanzi Rudolph E. , Huang Sharon X. , Zhang Can , Huang Shengxi
Published: June 2021

As the most common cause of dementia, the study of Alzheimer’s disease (AD) faces challenges in terms of understanding the cause, monitoring the pathogenesis, and developing early diagnosis and effective treatment. Rapid and accurate identification of AD biomarkers in the brain is critical to provide key insights into AD and facilitate the development of early diagnosis methods. In this work, we developed a platform that enables a rapid screening of AD biomarkers by employing graphene-assisted Raman spectroscopy and machine learning interpretation in AD transgenic animal brains. Specifically, we collected Raman spectra on slices of mouse brains with and without AD and used machine learning to classify AD and non-AD spectra. By contacting monolayer graphene with the brain slices, the accuracy was significantly increased from 77% to 98% in machine learning classification. Further, using linear supporting vector machine (SVM), we identified a spectral feature importance map that reveals the importance of each Raman wavenumber in classifying AD and non-AD spectra. Based on this spectral feature importance map, we identified AD biomarkers including Aβ and tau proteins, and other potential biomarkers, such as triolein, phosphatidylcholine, and actin, which have been confirmed by other biochemical studies. Our Raman-machine learning integrated method with interpretability is promising to greatly accelerate the study of AD and can be extended to other tissues, biofluids, and for various other diseases.
Sea Turtle Facial Recognition Using Map Graphs of Scales
Authors: Rao Karun K. , Grabow Lars C. , Muñoz-Pérez Juan Pablo , Alarcón-Ruales Daniela , Azevedo Ricardo B. R.
Published: June 2021

Individual identification of sea turtles is important to study their biology and aide in conservation efforts. Traditional methods for identifying sea turtles that rely on physical or GPS tags can be expensive, and difficult to implement. Alternatively, the scale structure on the side of a turtle’s head has been shown to be specific to the individual and stable over its lifetime, and therefore can be used as the individual’s “fingerprint”.

Here we propose a novel facial recognition method where an image of a sea turtle is converted into a graph (network) with nodes representing scales, and edges connecting two scales that share a border. The topology of the graph is used to differentiate species.

We additionally develop a robust metric to compare turtles based on a correspondence between nodes generated by a coherent point drift algorithm and computing a graph edit distance to identify individual turtles with over 94% accuracy.

By representing the special and topological features of sea turtle scales as a graph, we perform more accurate individual identification which is robust under different imaging conditions and may be adapted for a wider number of species.
Modelling the effects of bioclimatic characteristics and climate change on the potential distribution of a monospecific speciesColophospermum mopane(Benth.) Léonard in southern Africa
Authors: Ngarega Boniface K. , Masocha Valerie Farai , Schneider Harald
Published: June 2021

Global climate change is gradually changing species distribution and their patterns of diversity. Yet, factors that influence the local distribution and habitat preferences for southern African species remain largely unexplored. Here, we computed the suitable habitats in the southern African region forColophospermum mopane(Benth.) using the maximum entropy (Maxent) modeling approach. We utilized one Global Circulation Model (GCM) and three Representative concentration pathways (RCPs) to determine the current and future distribution ofC. mopane. The results showed that the distribution ofC. mopanewas mainly influenced by solar radiation, annual temperature range, and annual precipitation. According to the species response curves, this species preferred habitats with annual precipitation of 130-200 mm, an annual temperature range of 28° C, and elevations of about 500 m above sea level. The results highlight that the geographic range ofC. mopaneis likely to expand along the borders of Zambia and Zimbabwe in the future, particularly in the miombo plains. Conversely, suitable habitat areas reduce significantly in the eastern area of the southern African region, while the western areas expand. Overall, the appropriate habitat areas will likely decline in the 2050s under both RCPs and expand in the 2070s under the two scenarios. This knowledge is important for landscape planners and rangeland managers working to safeguard biodiversity from extinction.

Highlights

High reliability of models in habitat suitability modelling forC. mopane

Solar radiation is the most significant variable for the current distribution of mopane.

Climate change is and will reduce the habitat suitability of our target species.
Why does Shariah governance framework important for Islamic banks?
Authors: Alam Md. Kausar , Islam Fakir Tajul , Runy Mahfuza Kamal
Published: June 2021

Purpose

The purpose of this paper is to explore the question “Why is Shariah Governance Framework (SGF) important for Islamic banks?”

Design/methodology/approach

A semi-structured face-to-face personal interview is used to accomplish the research objectives. This study has collected data from the concerned bodies related to Shariah Governance (SG) from the central bank and Islamic banks of Bangladesh.

Findings

This study states SG as a process of confirming Shariah compliance in the overall functions of the Islamic banks, while Shariah denotes some rules, regulations, guidelines, objectives and directions to enhance accurate functions and activities, which are solely based on Shariah principles. SGF is important for Islamic banks to implement Shariah principles, confirm Shariah compliance and monitor the functions of the banks. Besides, it is needed for a well, efficient, effective, profitable business and higher performance and, finally, to eliminate the confusion among the management, executives, conventional bankers and banks.

Research limitations/implications

This study significantly contributes to the national and global regulatory bodies by providing evidence that why do Islamic banks and financial institutions require a sound SGF. It is recommended that there should be a sound and robust SGF to protect and fulfill the interest, expectations and demands of different stakeholders, which can easily draw their attention, intention and interest.

Originality/value

This is the first research that extends the literature of Islamic banking and SG by highlighting the importance of SGF. This study claims that to be a complete Islamic bank as well as protecting the unique identity from the general banks and corporate governance system, SG manual is required.
A weak form temporal quadrature element formulation for linear structural dynamics
Authors: Qin Junning , Zhong Hongzhi
Published: June 2021

Purpose

Various time integration methods and time finite element methods have been developed to obtain the responses of structural dynamic problems, but the accuracy and computational efficiency of them are sometimes not satisfactory. The purpose of this paper is to present a more accurate and efficient formulation on the basis of the weak form quadrature element method to solve linear structural dynamic problems.

Design/methodology/approach

A variational principle for linear structural dynamics, which is inspired by Noble's work, is proposed to develop the weak form temporal quadrature element formulation. With Lobatto quadrature rule and the differential quadrature analog, a system of linear equations is obtained to solve the responses at sampling time points simultaneously. Computation for multi-elements can be carried out by a time-marching technique, using the end point results of the last element as the initial conditions for the next.

Findings

The weak form temporal quadrature element formulation is conditionally stable. The relation between the normalized length of element and the suggested number of integration points in one element is given by a simple formula. Results show that the present formulation is much more accurate than other time integration methods and its dissipative property is also illustrated.

Originality/value

The weak form temporal quadrature element formulation provides a choice with high accuracy and efficiency for solution of linear structural dynamic problems.
Time-dependent reliability and optimal design of scraper chains based on fretting wear process
Authors: Li Shuai , Zhu Zhencai , Lu Hao , Shen Gang
Published: June 2021

Purpose

This paper aims to present a dynamic reliability model of scraper chains based on the fretting wear process and propose a reasonable structural optimization method.

Design/methodology/approach

First, the dynamic tension of the scraper chain is modeled by considering the polygon effect of the scraper conveyor. Then, the numerical wear model of the scraper chain is established based on the tangential and radial fretting wear modes. The scraper chain wear process is introduced based on the diameter wear rate. Furthermore, the time-dependent reliability of scraper chains based on the fretting wear process is addressed by the third-moment saddlepoint approximation (TMSA) method. Finally, the scraper chain is optimized based on the reliability optimization design theory.

Findings

There is a correlation between the wear and the dynamic tension of the scraper conveyor. The unit sliding distance of fretting wear is affected by the dynamic tension of the scraper conveyor. The reliability estimation of the scraper chain with incomplete probability information is achieved by using the TMSA for the method needs only the first three statistical moments of the state variable. From the perspective of the chain drive system, the reliability-based optimal design of the scraper chain can effectively extend its service life and reduce its linear density.

Originality/value

The innovation of the work is that the physical model of the scraper chain wear is established based on the dynamic analysis of the scraper conveyor. And based on the physical model of wear, the time-dependent reliability and optimal design of scraper chains are carried out.
Relationship between subjective well-being, perceived organisational culture and individual propension to innovation
Authors: Bianchi Christine Elena , Tontini Gerson , Gomes Giancarlo
Published: June 2021

Purpose

This paper analyses the relationship between subjective well-being (SWB) and perceived organisational culture (POC) with the individual propensity to innovation (IPI).

Design/methodology/approach

To empirically test the hypotheses, the sample and data were collected through a cross-sectional survey with 614 professionals who work in Technological Knowledge-Intensive Business Service (T-Kibs) in Brazil. For data analysis, the authors applied the partial least squares path modelling (PLS-PM) algorithm.

Findings

The results identify that employees' perception of the organisational culture has a direct and indirect impact on the IPI. The perception of employees about the dimensions of clan and adhocracy of organisational culture influences the SWB of employees, which has a significant relationship with the individual propensity to innovation. Also, the perception of a market culture has a direct impact on the individual propensity to innovate. The results showed that the adhocracy culture has a more significant influence on the SWB of the female gender.

Originality/value

This work contributes to the expansion of scientific studies in the area of innovation, in addition to managerial contributions due to the identification of the factors that influence the IPI.