bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability by gating plasticity in recurrent neural networks
Authors: Wilmes Katharina A. , Clopath Claudia
Published: September 2020

With Hebbian learning ‘who fires together wires together’, well-known problems arise. Hebbian plasticity can cause unstable network dynamics and overwrite stored memories. Unstable dynamics can partly be addressed with homeostatic plasticity mechanisms. Unfortunately, the time constants of homeostatic mechanisms required in network models are much shorter than those measured experimentally.

We propose that homeostatic time constants can be slow if plasticity is gated. We investigate how gating plasticity influences network stability and memories in plastic balanced spiking networks of neurons with dendrites. We compare how different factors such as excitability, learning rate, and inhibition lift the requirements for homeostatic time constants. We investigate how dendritic versus perisomatic gating allows for different amounts of weight changes in stable networks. We suggest that the compartmentalisation of pyramidal cells enables dendritic synaptic changes while maintaining stability. We show that spatially restricted plasticity improves stability. Finally, we compare how different gates protect memories.

Significance statement

How does the brain maintain stable neural activity in the presence of synaptic changes? This question has been studied extensively in the past, but we argue that one crucial aspect is missing in previous studies. While all theoretical work has assumed plasticity to beonall the time, plasticity is in fact heavily gated. In this light, we must reconsider the theories on stability and homeostasis of neural activity. In particular, theoretical studies show that neural networks undergoing plasticity require fast compensatory homeostatic mechanisms to be stable. However, experimentally measured homeostatic processes operate on much slower time scales. We studied how the gating of plasticity can improve network stability and thereby reduce the discrepancy in the homeostatic time constant between models and experiments.
Acute depletion of METTL3 identifies a role forN6-methyladenosine in alternative intron/exon inclusion in the nascent transcriptome
Authors: Wei Guifeng , Almeida Mafalda , Pintacuda Greta , Coker Heather , Bowness Joseph S , Ule Jernej , Brockdorff Neil
Published: September 2020

RNAN6-methyladenosine (m6A) modification plays important roles in multiple aspects of RNA regulation. m6A is installed co-transcriptionally by the METTL3/14 complex, but its direct roles in RNA processing remain unclear. Here we investigate the presence of m6A in nascent RNA of mouse embryonic stem cells (mESCs). We find that around 10% m6A peaks are in introns, often close to 5’-splice sites. RNA m6A peaks significantly overlap with RBM15 RNA binding sites and the histone modification H3K36me3. Interestingly, acute dTAG depletion of METTL3 reveals that inclusion of m6A-bearing alternative introns/exons in the nascent transcriptome is disrupted. For terminal or variable-length exons, m6A peaks are generally located upstream of a repressed 5’-splice site, and downstream of an enhanced 5’-splice site. Intriguingly, genes with the most immediate effects on splicing include several components of the m6A pathway, suggesting an autoregulatory function. Our findings demonstrate a direct crosstalk between m6A machinery and the regulation of RNA processing.
FRC-QE: A robust and comparable 3D microscopy image quality metric for cleared organoids
Authors: Preusser Friedrich , dos Santos Natália , Contzen Jörg , Stachelscheid Harald , Costa Érico Tosoni , Mergenthaler Philipp , Preibisch Stephan
Published: September 2020

Three-dimensional stem-cell-derived organoids are a powerful tool for studying cellular processes in tissue-like structures, enabling in vitro experiments in an organ-specific context. While organoid research has been closely linked to advances in fluorescence microscopy, capturing cellular structures within their global context in an organoid often remains challenging due to the organoid’s dense structure and opacity. The development of optical clearing methods has provided a solution for fixed organoids but optimizing clearing protocols for a given sample type and staining can be challenging. Importantly, quantitative measures for assessing image quality throughout cleared fluorescent samples are missing. Here, we propose Fourier ring correlation quality estimation (FRC-QE) as a new metric for automated 3D image quality estimation in cleared organoids. We show that FRC-QE robustly captures differences in clearing efficiency within an organoid, across replicates and clearing protocols, as well as for different microscopy modalities. FRC-QE is open-source, written in ImgLib2 and provided as an easy-to-use and macro-scriptable plugin for the popular Fiji software. We therefore envision FRC-QE to fill the gap of providing a reliable quality metric for testing, optimizing and comparing optical clearing methods.
Two Are Better Than One: Solving the Problem of Vertical Sound Source Localization via Binaural Integration of HRTFs
Authors: Oess Timo , Neumann Heiko , Ernst Marc O.
Published: September 2020

Early studies have shown that the localization of a sound source in the vertical plane can be accomplished with only a single ear, thus assumed the localization mechanism to be based on monaural cues. Such cues are induced by the pinna and consist of notches and peaks in the perceived spectrum which vary systematically with the elevation of sound sources. These processes pose several problems to the auditory system like identifying and extracting spectral cues on a neural level, as well as, distinguishing pinna induced peaks and notches from features already present in the source spectrum. Interestingly, at the stage of elevation estimate binaural information from both ears is already available and it seems plausible that the auditory system takes advantage of this information. Especially, since such a binaural integration can improve the localization performance dramatically as we demonstrate in the current study. For that, we first introduce a computational model architecture that takes advantage of binaural signal integration to localize sound sources in the median plane. Model performance is tested under different conditions which reveal that localization of monaural, as well as binaural inputs is best when the model is trained with binaural inputs. Furthermore, modeling results lead to the hypothesis that sound type specific prior information is taken into account to further improve localization quality. This deduced hypothesis about vertical sound source localization is confirmed in a behavioral experiment. Based on these results, we propose that elevation estimation of sound sources is facilitated by an early binaural signal integration and can incorporate sound type specific prior information for higher accuracy.
Gene exchange networks define species-like units in marine prokaryotes
Authors: Stepanauskas R. , Brown J.M. , Mai U. , Bezuidt O. , Pachiadaki M. , Brown J. , Biller S.J. , Berube P.M. , Record N.R. , Mirarab S.
Published: September 2020

Post-submission note. Since the original submission of this manuscript to bioRxiv, we discovered that some of our results may be impacted by the limitations of some of the comparative genomics tools used in this study. We are working on a revised version of the manuscript.

Although horizontal gene transfer is recognized as a major evolutionary process in Bacteria and Archaea, its general patterns remain elusive, due to difficulties tracking genes at relevant resolution and scale within complex microbiomes. To circumvent these challenges, we analyzed a randomized sample of >12,000 genomes of individual cells of Bacteria and Archaea in the tropical and subtropical ocean - a well-mixed, global environment. We found that marine microorganisms form gene exchange networks (GENs) within which transfers of both flexible and core genes are frequent, including the rRNA operon that is commonly used as a conservative taxonomic marker. The data revealed efficient gene exchange among genomes with <28% nucleotide difference, indicating that GENs are much broader lineages than the nominal microbial species, which are currently delineated at 4-6% nucleotide difference. The 42 largest GENs accounted for 90% of cells in the tropical ocean microbiome. Frequent gene exchange within GENs helps explain how marine microorganisms maintain millions of rare genes and adapt to a dynamic environment despite extreme genome streamlining of their individual cells. Our study suggests that sharing of pangenomes through horizontal gene transfer is a defining feature of fundamental evolutionary units in marine planktonic microorganisms and, potentially, other microbiomes.
RRM2Bis frequently amplified across multiple tumor types: non-oncogenic addiction and therapeutic opportunities
Authors: Iqbal Waleed , Demidova Elena V. , Serrao Samantha , ValizadehAslani Taha , Rosen Gail , Arora Sanjeevani
Published: September 2020

RRM2Bplays a crucial role in DNA replication, repair and oxidative stress. While germlineRRM2Bmutations have been implicated in mitochondrial disorders, its relevance to cancer has not been established. Here, using TCGA data, we investigatedRRM2Balterations in cancer. We found thatRRM2Bis highly amplified in multiple tumor types, particularly inMYC-amplified tumors, and is associated with increasedRRM2BmRNA expression. We also observed that the chromosomal region 8q22.3–8q24, is amplified in multiple tumors, and includesRRM2B,MYCalong with several other cancer-associated genes. An analysis of genes within this 8q-amplicon showed that cases that have bothRRM2B-amplified along withMYChave a distinct pattern of amplification compared to unaltered cases or cases that have amplifications inRRM2BorMYConly. These other 8q-proteins were shown to interact functionally within the RRM2B network of DNA repair, hypoxia and apoptosis regulating proteins. Notably,RRM2B-amplified tumors are characterized by mutation signatures of defective DNA repair and oxidative stress, and in some cancers also associated with poor clinical outcome. These findings suggest that some cancers may require RRM2B for cellular survival, providing novel therapeutic opportunities in these cancers.
Chronically implantable LED arrays for behavioral optogenetics in primates
Authors: Rajalingham Rishi , Sorenson Michael , Azadi Reza , Bohn Simon , DiCarlo James J , Afraz Arash
Published: September 2020

Challenges in behavioral optogenetics in large brains demand development of a chronically implantable platform for light delivery. We have developed Opto-Array, a chronically implantable array of LEDs for high-throughput optogenetic perturbation in non-human primates. We tested the Opto-Array in the primary visual cortex of a macaque monkey, and demonstrated that optogenetic cortical silencing by the Opto-Array results in reliable retinotopic visual deficits on a luminance discrimination task.
Sphingosine Kinase 2 associates with the nsP3 of chikungunya virus and is required for replication
Authors: Oyewole Opeoluwa O. , Reid St Patrick
Published: September 2020

Sphingosine kinase 2 (SK2) is a lipid kinase that catalyzes the production of sphingosine-1-phosphate (S1P) from sphingosine. Previously, we have shown that SK2 is recruited to the viral replication complex (VRC) early during chikungunya virus (CHIKV) infection. In the present study, we demonstrate that SK2 is required for viral replication and protein production. Treatment with a SK2 inhibitor significantly impaired the function of a CHIKV replicon. Similarly, compound treatment or genetic targeting resulted in impaired viral protein production. Mechanistically, we demonstrate that CHIKV nsP3 binds to SK2. Association of nsP3 with SK2 was mediated, in part, through the FGDF motifs within the hypervariable domain (HVD) of nsP3. In a competition assay, SK2 competed with G3BP for binding to nsP3. Collectively, these results extend our previous findings and identify SK2 as a CHIKV host factor recruited by nsP3.
Augmin prevents merotelic attachments by promoting proper arrangement of bridging and kinetochore fibers
Authors: Štimac Valentina , Koprivec Isabella , Manenica Martina , Simunić Juraj , Tolić Iva M.
Published: September 2020

The human mitotic spindle is made of microtubules nucleated at centrosomes, at kinetochores, and from pre-existing microtubules by the augmin complex. However, it is unknown how the augmin-mediated nucleation affects distinct microtubule classes and thereby mitotic fidelity. Here we use superresolution microscopy to analyze the previously indistinguishable microtubule arrangements within the crowded metaphase plate area and demonstrate that augmin is vital for the formation of uniformly arranged parallel units consisting of sister kinetochore fibers connected by a bridging fiber. This ordered geometry helps both prevent and resolve merotelic attachments. Whereas augmin-nucleated bridging fibers prevent merotelic attachments by creating a nearly parallel and highly bundled microtubule arrangement unfavorable for creating additional attachments, augmin-nucleated k-fibers produce robust force required to resolve errors during anaphase. STED microscopy revealed that bridging fibers were impaired twice as much as k-fibers following augmin depletion. The complete absence of bridging fibers from a significant portion of kinetochore pairs, especially in the inner part of the spindle, resulted in the specific reduction of the interkinetochore distance. Taken together, we propose a model where augmin promotes mitotic fidelity by generating assemblies consisting of bridging and kinetochore fibers that align sister kinetochores to face opposite poles, thereby preventing erroneous attachments.
Direct phosphorylation of HY5 by SPA1 kinase to regulate photomorphogenesis in Arabidopsis
Authors: Wang Wenli , Paik Inyup , Kim Junghyun , Hou Xilin , Sung Sibum , Huq Enamul
Published: September 2020

ELONGATED HYPOCOTYL5 (HY5) is a key transcription factor which promotes photomorphogenesis by regulating complex downstream growth programs. Previous studies suggest that the regulation of HY5 mainly depends on the CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) - SUPPRESSOR OF PHYTOCHROME A-105 (SPA) E3 ubiquitin ligase complex, which degrades positively acting transcription factors of light signaling to repress photomorphogenesis in the dark. SPA proteins function not only as a component of the E3 ubiquitin ligase complex but also as a kinase of PHYTOCHROME INTERACTING FACTOR1 (PIF1) through its N-terminal kinase domain. Here, we show that HY5 is a new substrate of SPA1 kinase. SPA1 can directly phosphorylate HY5in vitroandin vivo. We also demonstrate that unphosphorylated HY5 strongly interacts with both COP1 and SPA1 than phosphorylated HY5, is the preferred substrate for degradation, whereas phosphorylated HY5 is more stable in the dark. In addition, unphosphorylated HY5 actively binds to the target promoters, and is physiologically more active form. Consistently, the transgenic plants expressing unphosphorylated mutant of HY5 displays enhanced photomorphogenesis. Collectively, our study revealed that SPA1 fine-tunes the stability and the activity of HY5 to regulate photomorphogenesis.
Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome
Authors: Bonnardel François , Haslam Stuart M. , Dell Anne , Feizi Ten , Liu Yan , Tajadura-Ortega Virginia , Akune Yukie , Sykes Lynne , Bennett Phillip R. , MacIntyre David A. , Lisacek Frédérique , Imberty Anne
Published: September 2020

Bacteria use protein receptors called lectins to anchor to specific host surface sugars. The role of lectins in the vaginal microbiome, and their involvement in reproductive tract pathophysiology is poorly defined. Here we establish a classification system based on taxonomy and protein 3D structure to identify 109 lectin classes. Hidden Markov Model (HMM) profiles for each class were used to search bacterial genomes, resulting in the prediction of >100 000 bacterial lectins available at unilectin.eu/bacteria. Genome screening of 90 isolates from 21 vaginal bacterial species showed that potential pathogens produce a larger variety of lectins than commensals indicating increased glycan-binding potential. Both the number of predicted bacterial lectins, and their specificities for carbohydrates correlated with pathogenicity. This study provides new insights into potential mechanisms of commensal and pathogen colonisation of the reproductive tract that underpin health and disease states.
CECR2 Drives Breast Cancer Metastasis by Suppressing Macrophage Inflammatory Responses
Authors: Zhang Meiling , Liu Zongzhi Z. , Aoshima Keisuke , Zhang Yangyi , An Yongyan , Aoshima Asako , Chan Lok Hei , Lang Sabine M. , Sun Hongyi , Tang Zhenwei , Rutter Sara J. , Booth Carmen J. , Bossuyt Veerle , Chen Xiang , Morrow Jon S. , Pusztai Lajos , Rimm David. L. , Yin Mingzhu , Yan Qin
Published: September 2020

Epigenetic and transcriptional changes are critical for metastasis, the major cause of cancer-related deaths. Metastatic tumor cells escape immune surveillance more efficiently than tumor cells in the primary sites, but the mechanisms controlling their immune evasion are poorly understood. We found that distal metastases are more immune inert with increased M2 macrophages compared to their matched primary tumors. Acetyl-lysine reader CECR2 is an epigenetic regulator upregulated in metastases and positively associated with M2 macrophages. CECR2 specifically promotes breast cancer metastasis in multiple mouse models, with more profound effect in the immunocompetent setting. Mechanistically, NF-κB family member RELA recruits CECR2 to activate CSF1 and CXCL1, which are critical for macrophage-mediated immunosuppression at the metastatic sites. Furthermore, pharmacological inhibition of CECR2 bromodomain impedes NF-κB-mediated immune suppression by macrophages and inhibits breast cancer metastasis. These results reveal novel therapeutic strategies to treat metastatic breast cancer.

Statement of Significance

Comparison of matched primary breast tumors and distal metastases show that metastases are more immune inert with increased tumor promoting macrophages. Depletion or pharmacological inhibition of CECR2 inhibits breast cancer metastasis by suppressing macrophage inflammatory responses, nominating CECR2 as a promising therapeutic target for cancer metastasis.
A visual pathway for skylight polarization processing inDrosophila
Authors: Hardcastle Ben J. , Omoto Jaison J. , Kandimalla Pratyush , Nguyen Bao-Chau M. , Keleş Mehmet F. , Boyd Natalie K. , Hartenstein Volker , Frye Mark A.
Published: September 2020

Many insects use patterns of polarized light in the sky to orient and navigate. Here we functionally characterize neural circuitry in the fruit fly,Drosophila melanogaster, that conveys polarized light signals from the eye to the central complex, a brain region essential for the fly’s sense of direction. Neurons tuned to the angle of polarization of ultraviolet light are found throughout the anterior visual pathway, connecting the optic lobes with the central complex via the anterior optic tubercle and bulb, in a homologous organization to the ‘sky compass’ pathways described in other insects. We detail how a consistent, map-like organization of neural tunings in the peripheral visual system is transformed into a reduced representation suited to flexible processing in the central brain. This study identifies computational motifs of the transformation, enabling mechanistic comparisons of multisensory integration and central processing for navigation in the brains of insects.
Does national power trigger ocean conservation?
Authors: Baldi Germán , Schauman Santiago A. , Gandini Patricia
Published: September 2020

States are reacting to the global crises of biodiversity and the provision of ecosystem services mainly through the expansion of their networks of protected areas. This reaction would have been boosted by the commitments made between the parties of the Convention on Biological Diversity, and facilitated by the opportunities offered by isolated territories, where economic interests are minimal. However, few studies have discussed the importance of national power as conservation conditionings, particularly in the ocean. In this regard, here we evaluate whether the relative extent of marine protected areas (MPAs) is related to different elements of national power. Following a quantitative approach and incorporating into analyses 155 countries, our models suggest that an increasing power (in terms of country size –land and ocean– and military capacity) is related to greater marine protection. Although these patterns could be initially associated with the ample human and economic resources of most powerful countries and with the opportunities provided by their overseas territories, different arguments would support national power elements as conservation drivers. Specifically, the exertion of such power through conservation could be linked to geopolitical strategies such as the (re)validation of a country’s sovereignty over its Exclusive Economic Zone (EEZ), the greater regulation of the circulation and use of this space, the greater influence in the regional context, and the assurance in the provision of future ecosystem goods and services. In this way, changes in geopolitical conditions could affect MPAs, compromising the effective conservation of biodiversity and ecosystem processes, as well as the sustainable management of assets.
Quantification of discrete gut bacterial strains following fecal transplantation for recurrentClostridioides difficileinfection demonstrates long-term stable engraftment in non-relapsing recipients
Authors: Aggarwala Varun , Mogno Ilaria , Li Zhihua , Yang Chao , Britton Graham J. , Chen-Liaw Alice , Mitcham Josephine , Bongers Gerold , Gevers Dirk , Clemente Jose C. , Colombel Jean-Frederic , Grinspan Ari , Faith Jeremiah
Published: September 2020

Fecal Microbiota Transplantation (FMT), while successful for the treatment of recurrentClostridioides difficile(rCDI) infection, lacks a quantitative identification of the discrete bacterial strains that transmit and stably engraft in recipients, and their association with clinical outcomes. Using >1,000 unique bacterial strains isolated and sequenced from a combination of 22 FMT donors and recipients, we develop a statistical approachStrainerto detect and track sequenced bacterial strains from low depth metagenomic sequencing data. On application to 14 FMT interventions, we detect stable and high engraftment of ∼71% of gut microbiota strains in recipients at even 5-years post-transplant, a remarkably durable therapeutic from a single administration. We found differential transmission and engraftment efficacy across bacterial taxonomic groups over short and long-time scales. Although ∼80% of the original pre-FMT recipient strains were eliminated by the FMT, those strains that remain persist even 5 years later, along with newer strains acquired from the environment. The precise quantification of donor bacterial strains in recipients independently explained the clinical outcomes of early and late relapse. Our framework identifies the consistently engrafting discrete bacterial strains for use in Live Biotherapeutic Products (LBP) as a safer, scalable alternative to FMT and enables systematic evaluation of different FMT and LBP study designs.
Detection of incipient pancreatic cancer with novel tumor-specific antibodies in mouse models
Authors: Oni Tobiloba E. , Bautista Carmelita , Merrill Joseph R. , Goos Jeroen A.C.M. , Rivera Keith D. , Miyabayashi Koji , Biffi Giulia , Garcia Libia , Plenker Dennis , Patel Hardik , Elyada Ela , Samaritano Maria , Yu Kenneth H. , Pappin Darryl J. , Goggins Michael G. , Hruban Ralph H. , Lewis Jason S. , Lyons Scott K. , Yeh Johannes T. , Tuveson David A.
Published: September 2020

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, as 90% of patients do not survive beyond five years from diagnosis. This dismal prognosis is largely due to the advanced stage of the disease at diagnosis, which precludes potentially curative surgical resection. Although early detection strategies hold significant promise for improving patient outcomes, there is still no accurate diagnostic tool to detect incipient PDAC. Here, we sought to develop antibodies for the early detection of PDAC by positron-emission tomography (PET) imaging. Accordingly, we establish a pipeline to generate novel tumor-specific monoclonal antibodies (mAbs) against cell-surface proteins of PDAC patient-derived organoids (PDOs). We identify a panel of 16 tumor organoid-binding antibodies (TOBi-bodies) that display high reactivity to human PDAC tissues but not to matched adjacent normal pancreas. We then employ biochemical, flow cytometric, mass spectrometric, and CRISPR/Cas9-mediated knockout methods to determine the cognate antigens of these TOBi-bodies. We identify two mAbs that bind to tumor-specific variants of the surface protein CEACAM6 and show minimal binding to normal tissues. PET imaging in mouse models using these TOBi-bodies enables the detection of incipient human organoid-derived PDAC tumors that are rather undetectable by palpation or high-resolution ultrasound imaging techniques. We propose that further development of these mAbs as PET radiotracers could facilitate the early detection and accurate staging of PDAC.
DyNeuMo Mk-1: Design and Pilot Validation of an Investigational Motion-Adaptive Neurostimulator with Integrated Chronotherapy
Authors: Zamora Mayela , Toth Robert , Morgante Francesca , Ottaway Jon , Gillbe Tom , Martin Sean , Lamb Guy , Noone Tara , Benjaber Moaad , Nairac Zachary , Sehgal Devang , Constandinou Timothy G. , Herron Jeffrey , Aziz Tipu Z. , Gillbe Ivor , Green Alexander L. , Pereira Erlick A. C. , Denison Timothy
Published: September 2020

There is growing interest in using adaptive neuro-modulation to provide a more personalized therapy experience that might improve patient outcomes. Current implant technology, however, can be limited in its adaptive algorithm capability. To enable exploration of adaptive algorithms with chronic implants, we designed and validated the ‘Picostim DyNeuMo Mk-1’ (DyNeuMo Mk-1 for short), a fully-implantable, adaptive research stimulator that titrates stimulation based on circadian rhythms (e.g. sleep, wake) and the patient’s movement state (e.g. posture, activity, shock, free-fall). The design leverages off-the-shelf consumer technology that provides inertial sensing with low-power, high reliability, and relatively modest cost. The DyNeuMo Mk-1 system was designed, manufactured and verified using ISO 13485 design controls, including ISO 14971 risk management techniques to ensure patient safety, while enabling novel algorithms. The system was validated for an intended use case in movement disorders under an emergency-device authorization from the Medicines and Healthcare Products Regulatory Agency (MHRA). The algorithm configurability and expanded stimulation parameter space allows for a number of applications to be explored in both central and peripheral applications. Intended applications include adaptive stimulation for movement disorders, synchronizing stimulation with circadian patterns, and reacting to transient inertial events such as posture changes, general activity, and walking. With appropriate design controls in place, first-in-human research trials are now being prepared to explore the utility of automated motion-adaptive algorithms.
A thousand metagenome-assembled genomes ofAkkermansiareveal new phylogroups and geographical and functional variations in human gut
Authors: Lv Qing-Bo , Li Sheng-Hui , Zhang Yue , Wang Yan-Chun , Peng Yong-Zheng , Zhang Xiao-Xuan
Published: September 2020

The present study revealed the genomic architecture ofAkkermansiain human gut by analyzing 1,119 near-complete metagenome-assembled genomes, 84 public available genomes, and 1 newly sequencedA. glycaniphilastrain. We found that 1) the genomes ofAkkermansiaformed 4 species (including 2 candidate species) with distinct interspecies similarity and differed genomic characteristics, and 2) the population ofA. muciniphilawas structured by 3 previously identified phylogroups (Amuc I, II, and III) referring to 1,132 genomes and 1 new phylogroup (defined as Amuc IV) that contained 62 genomes. Amuc III was presented in Chinese population and Amuc IV was mainly distributed in western populations. A large number of gene of functions, pathways, and carbohydrate active enzymes that specifically associated to phylogroups. Our findings based on over a thousand genomes strengthened the previous knowledge and provided new insights into the population structure and ecology ofAkkermansiain human gut.
Anti-NS1 antibodies induced by immunization with dendritic cell targeted hybrid monoclonal antibodies do not induce platelet dysfunction
Authors: Matos Vicentin Elaine Cristina , Silva Amorim Kelly Nazaré da , Yamamoto Marcio Massao , Santos Souza Higo Fernando dos , Rosa Daniela Santoro , Silva Gonçalves Antonio José da , de Barcelos Alves Ada Maria , Boscardin Silvia Beatriz
Published: September 2020

Dengue fever causes a disease whose symptoms range from asymptomatic to more severe, that may even lead to death. During infection, the non-structural (NS) 1 protein is produced in infected cells and subsequently shed to the circulation. Anti-NS1 antibodies have been implicated in disease pathogenesis as well as in protection against lethal infection. Here we analysed the role of anti-NS1 antibodies elicited when the NS1 protein was specifically targeted to two distinct dendritic cell (DC) subsets by chimeric monoclonal antibodies (mAbs) that bind to the DC surface receptors DEC205 and DCIR2. BALB/c mice received two doses of αDEC-NS1 or αDCIR2-NS1 mAbs in the presence of an adjuvant. We observed that anti-NS1 antibodies induced by immunization with chimeric αDEC-NS1 or αDCIR2-NS1 mAbs did not cause significant pathology or were able to protect BALB/c mice from an intracranial DENV2 NGC strain challenge.
Cellular mechanisms of chick limb bud morphogenesis
Authors: Lesnicar-Pucko Gaja , Belmonte Julio M , Musy Marco , Glazier James A. , Sharpe James
Published: September 2020

Although some of the molecular pathways involved in limb bud morphogenesis have been identified, the cellular basis of the process is not yet understood. Proposed cell behaviours include active cell migration and oriented cell division, but ultimately, these questions can only be resolved by watching individual mesenchymal cells within a completely normal developmental context. We developed a minimally-invasivein ovotwo-photon technique, to capture high quality time-lapse sequences up to 100 microns deep in the unperturbed growing chick limb bud. Using this technique, we characterized cell shapes and other oriented behaviours throughout the limb bud, and found that cell intercalation drives tissue movements, rather than oriented cell divisions or migration. We then developed a 3D cell-based computer simulation of morphogenesis, in which cellular extensions physically pull cells towards each other, with directional bias controlled by molecular gradients from the ectoderm (Wnts) and the Apical Ectodermal Ridge (FGFs). We defined the initial and target shapes of the chick limb bud in 3D by OPT scanning, and explored which orientations of mesenchymal intercalation correctly explain limb morphogenesis. The model made a couple of predictions: Firstly, that elongation can only be explained when cells intercalate along the direction towards the nearest ectoderm. This produces a general convergence of tissue towards the central proximo-distal (PD) axis of the limb, and a resultant extension of the tissue along the PD axis. Secondly, the correctin silicomorphology can only be achieved if the contractile forces of mesenchymal cells in the very distal region (under the Apical Ectodermal Ridge) have shorter life times than in the rest of the limb bud, effectively making the tissue more fluid by augmenting the rate of cell rearrangement. We argue that this less-organised region of mesenchyme is necessary to prevent PD-oriented intercalation events in the distal tip that would otherwise inhibit outgrowth.
Mutations infbiD (Rv2983)as a novel determinant of resistance to pretomanid and delamanid inMycobacterium tuberculosis
Authors: Rifat Dalin , Li Si-Yang , Ioerger Thomas , Shah Keshav , Lanoix Jean-Philippe , Lee Jin , Bashiri Ghader , Sacchettini James , Nuermberger Eric
Published: September 2020

The nitroimidazole pro-drugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Priorin vitrostudies suggest a relatively low barrier to nitroimidazole resistance inMycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistantM. tuberculosismutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5CFU. Whole genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, 91% of which occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance:fbiC(56%),fbiA(15%),ddn(12%),fgd(4%) andfbiB(4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations inRv2983, a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, althoughRv2983andfbiBmutants exhibited high-level pretomanid resistance, but relatively small changes in delamanid susceptibility. Complementing anRv2983mutant with wild-typeRv2983restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420biosynthesis. Finally,Rv2983mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.
Effects of order on memory of event times
Authors: Naim Michelangelo , Katkov Mikhail , Tsodyks Misha
Published: September 2020

Memorizing time of an event may employ two processes (i) encoding of the absolute time of events within an episode, (ii) encoding of its relative order. Here we study interaction between these two processes. We performed experiments in which one or several items were presented, after which participants were asked to report the time of occurrence of items. When a single item was presented, the distribution of reported times was quite wide. When two or three items were presented, the relative order among them strongly affected the reported time of each of them. Bayesian theory that takes into account the memory for the events order is compatible with the experimental data, in particular in terms of the effect of order on absolute time reports. Our results suggest that people do not deduce order from memorized time, instead people’s memory for absolute time of events relies critically on memorized order of the events.
Cell population migration cycle and response to environmental pH inBacillus subtilis
Authors: Tasaki Sohei , Nakayama Madoka , Takagi Izumi , Wakita Jun-ichi , Shoji Wataru
Published: September 2020

Microbial populations are ubiquitous and some form a robust, multicellular structure called biofilm that protects the cells from environmental damage. The dispersion cycle is critical for controlling the population of important target microbes (both pathogenic and beneficial). Here, we show that the hysteresis ofBacillus subtiliscell-type regulation with respect to auto-inducing signal strength triggers the migration cycle of the cell population. We investigate migration cycle and its dependence on environmental conditions by quantitative analysis of cyclically expanding, concentric circular colonies. Next, we construct an input/output model that controls cell types in response to environmental conditions and signal density. On the basis of this model, we propose a migration cycle model for cell populations. The proposed model will widely predict biofilm-related phenomena and provide the basis for the description of highly self-regulating multicellular systems.
Trajectory Mapping of the EarlyDrosophilaGermline Reveals Controls of Zygotic Activation and Sex Differentiation
Authors: Chen Hsing-Chun , Li Yi-Ru , Lai Hsiao Wen , Huang Hsiao Han , Fugmann Sebastian D. , Yang Shu Yuan
Published: September 2020

Germ cells inD. melanogasterare specified maternally shortly after fertilization and are transcriptionally quiescent until their zygotic genome is activated to sustain further development. To understand the molecular basis of this process, we analyzed the progressing transcriptomes of early male and female germ cells at the single-cell level between germline specification and coalescence with somatic gonadal cells. Our data comprehensively covered zygotic activation in the germline genome, and analyses on genes that exhibit germline-restricted expression revealed that polymerase pausing and differential RNA stability are important mechanisms that establish gene expression differences between the germline and soma. In addition, we observed an immediate bifurcation between the male and female germ cells as zygotic transcription begins. The main difference between the two sexes is an elevation in X chromosome expression in females relative to males signifying incomplete dosage compensation with a few select genes exhibiting even higher expression increases. These indicate that the male program is the default mode in the germline that is driven to female development with a second X chromosome.
The Sez6 family inhibits complement at the level of the C3 convertase
Authors: Qiu Wen Q. , Luo Shaopeiwen , Ma Stefanie A. , Saminathan Priyanka , Li Herman , Gunnersen Jenny , Gelbard Harris A. , Hammond Jennetta W.
Published: September 2020

The Sez6 family consists of Sez6, Sez6L, and Sez6L2. Its members are expressed throughout the brain and have been shown to influence synapse numbers and dendritic morphology. They are also linked to various neurological and psychiatric disorders. All Sez6 family members contain 2-3 CUB domains and 5 complement control protein (CCP) domains, suggesting that they may be involved in complement regulation. We show that all Sez6 family members inhibit C3 deposition by the classical and alterative pathways with varying degrees of efficacy. For the classical pathway, Sez6 is a strong inhibitor, Sez6L2 is a moderate inhibitor, and Sez6L is a weak inhibitor. Using Sez6L2 as the representative family member, we show that it specifically deactivates C3 convertases by accelerating the decay or dissociation of the C3 convertase components. Sez6L2 also deactivates C3 convertases of the alternative pathway by serving as a cofactor for Factor I to facilitate the cleavage of C3b. However, Sez6L2 has no cofactor activity toward C4b. In summary, the Sez6 family are novel complement regulators that inhibit C3 convertases.
Crystal structure of melaminium cyanoacetate monohydrate
Authors: Sigdel Regmi Bhawani , Apblett Allen , Powell Douglas
Published: September 2020

The asymmetric unit of the title compound, 2,4,6-triamino-1,3,5-triazin-1-ium cyanoacetate monohydrate, C3H7N6
+·NCCH2COO−·H2O, consists of a melaminium cation, a cyanoacetate anion and a water molecule, which are connected to each other via N—H...O and O—H...O hydrogen bonds, generating an eight-membered ring. In the crystal, the melaminium cations are connected by two pairs of N—H...N hydrogen bonds, forming tapes along [110]. These tapes develop a three-dimensional network through N—H...O, O—H...O, N—H...N and C—H...O hydrogen bonds between the cations, anions and water molecules.
Computerisation of a Police Department in ASWI
Authors: Verma Sanjay
Published: September 2020

The computerisation of a government department is a very challenging process as it involves multiple stakeholders and power centers. Stakeholder identification as well as designing a system specific to the needs of a particular department can be a complex process. The computerisation of a police department in ASWI was initiated in the mid 90s but had not been a success. The case illustrates the challenges of the computerisation process in a bureaucratic environment. With multiple touch points and interdependent processes, designing and successfully implementing a technology solution for such an environment could be a major challenge. The case provides an opportunity to understand the reasons for IT project failures. The managerial strategies that can make an IT project successful and the situations in which these strategies can also be discussed.
Hindustan Gum, Jodhpur: Managing Agribusiness Supply Chain Risks
Authors: Rana R. , Nachiappan G. , Raghuram G. , Hariprasad Jaju Darshit
Published: September 2020

Hindustan Gum is an agro-processor in Jodhpur, Rajasthan. It is primarily in the business of processing guar gum. The market volatility in demand and prices have shot up due to the need of guar gum in the new and growing shale gas fracking, primarily in the US. Hindustan Gum has been trying to respond to this by considering options like expansion in processing, and contract farming for guar seed sourcing.
Pradhan Chemicals: Connecting with the Community
Authors: Sharma Meenakshi
Published: September 2020

The case deals with a situation where the protagonist, Abhik Roy, who heads a manufacturing unit of Pradhan Chemicals has made a commitment to senior management on behalf of his unit. He now faces the challenge of getting the entire unit to go along with the initiative he has announced. He sees numerous potential advantages to be derived from the proposed initiative. However, he has to depend on voluntary participation from a very large number of employees at all levels, for the initiative to succeed. He needs to decide how to persuade the entire unit to come forward in order to make the initiative a success.
Exclusive books: applying a behavioural economics perspective
Authors: Naidoo Thiroshnee , Lew Charlene
Published: September 2020

Learning outcomes

The learning outcomes are as follows: understanding of the principles of choice overload and the impact of consumer choice overload on company sustainability and growth prospects; understanding of how several heuristics inform consumer decision-making; applying nudge theory to interpret and clarify the impact and consequences of nudges on consumer decision-making; and considering the challenge of a newly appointed CEO to influence consumer choice.

Case overview/synopsis

The case study and teaching note offers insights into the use of behavioural economics principles in consumer choice. The case study methodology was used to design, analyse and interpret the real-life application of behavioural economics in the retail sector. The case demonstrates how choice overload, dual process theory, decision heuristics and nudge theory play a role in consumer decision-making. The case offers insights into the application of behavioural economics to support the sustainability of a company in an emerging market context. Managers can use the findings to consider how to use behavioural economics principles to drive consumer choice. The application of behavioural economics to an industry facing challenges of sustainability offers new insights into how to design spaces and cues for consumer choice.

Complexity academic level

The case study is suitable for course in business administration, specifically at postgraduate level.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing
Students’ continuing personal development (S-CPD) - a scheme to promote student engagement in extra-curricular activities
Authors: Ooi Pei Cheng
Published: September 2020

Purpose

This paper presents an overview of a lifelong learning scheme. It outlines the design of the scheme that was initially targeted for electrical and electronic engineering students and later students across the faculty of engineering in the University of Nottingham Malaysia (UNM). The scheme named “Students’ Continuing Personal Development (S-CPD)” is developed to improve student participation in extra-curricular activities and at the same time, to create awareness among students of the importance of lifelong learning and to facilitate the development of such skills.

Design/methodology/approach

The scheme involves creating and developing more than 30 categories of activities together with a well-structured information technology infrastructure. Various strategies, such as offering awards, are applied to promote student engagement. In 2015 the pilot scheme was rolled out in the Department of Electrical and Electronic Engineering University of Nottingham Malaysia Campus and adopted by all departments in the faculty of engineering in the subsequent year.

Findings

S-CPD scheme is aligned to the importance institutions of engineers in the world places on continuing professional development and also to the importance industry and employer places on transferable skills. The scheme provides students with a structured way to plan, participate and record their participation in extra-curricular activities that is relevant to their future careers as engineers in a holistic way. S-CPD scheme not only provides a good platform for students to hone particular “soft” skills and they are also aware of the importance and engaging in lifelong learning to make the most out of their university and also life experience.

Research limitations/implications

This research could lead to many other studies including the factors that affect students' engagement in extra-curricular activities, short-term and long-term impacts of S-CPD scheme, and also involve psychology research such as psychological factors influencing students' engagement in the scheme.

Practical implications

This scheme could be repeated in worldwide university programmes.

Originality/value

The S-CPD scheme can be viewed as having a two-pronged growth strategy. The first is to engage students in extra-curricular activities that enhance and improve their learning and personal experiences. The second prong of the growth strategy is to inculcate the growth mindset for lifelong learning, hence adapting well when their profession involves fulfilling CPD requirements.
Thermoelastohydrodynamic characteristics of supercritical CO2 spiral groove face seals
Authors: Zhu Delei , Bai Shaoxian
Published: September 2020

Purpose

The purpose of this study is to determine the sealing performance of face seals by numerical analysis of thermoelastohydrodynamic characteristics of supercritical CO2 (S-CO2) spiral groove face seals in the supercritical regime.

Design/methodology/approach

The spiral groove face seal was used as the research object. The distribution of lubricating film pressure and temperature was analysed by solving the gas state, Reynolds and energy equations using the finite difference method. Furthermore, the influence law of sealing performance was obtained.

Findings

Close to the critical temperature of S-CO2, face distortions produced by increasing pressure lead to divergent clearance and resulted in reduced opening force. In the state of S-CO2, the face distortions generated by increasing seal temperature lead to convergent clearance, which enhances the opening force. In addition, near the critical temperature of S-CO2, the opening force may be reduced by 10%, and the leakage rate of the seal sharply increases by a factor of four.

Originality/value

The thermoelastohydrodynamic characteristics of supercritical CO2 face seals are illustrated considering the actual gas effect including compressibility, heat capacity and viscosity. Face distortions and sealing performance were calculated under different seal pressures and seal temperatures in the supercritical regime, as well as with N2 for comparison.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-05-2020-0169/