Automated home-cage behavioral phenotyping of mice

We describe a trainable computer vision system enabling the automated analysis of complex mouse behaviors. We provide software and a very large manually annotated video database used for training and testing the system. Our system outperforms leading commercial software and performs on par with human scoring, as measured from the ground-truth manual annotations of thousands of clips of freely behaving animals. We show that the home-cage behavior profiles provided by the system is sufficient to accurately predict the strain identity of individual animals in the case of two standard inbred and two non-standard mouse strains. Our software should complement existing sensor-based automated approaches and help develop an adaptable, comprehensive, high-throughput, fine-grained, automated analysis of rodent behavior

SCHEMA Recombination of a Fungal Cellulase Uncovers a Single Mutation That Contributes Markedly to Stability

A quantitative linear model accurately (R^2 = 0.88) describes the thermostabilities of 54 characterized members of a family of fungal cellobiohydrolase class II (CBH II) cellulase chimeras made by SCHEMA recombination of three fungal enzymes, demonstrating that the contributions of SCHEMA sequence blocks to stability are predominantly additive. Thirty-one of 31 predicted thermostable CBH II chimeras have thermal inactivation temperatures higher than the most thermostable parent CBH II, from Humicola insolens, and the model predicts that hundreds more CBH II chimeras share this superior thermostability. Eight of eight thermostable chimeras assayed hydrolyze the solid cellulosic substrate Avicel at temperatures at least 5 °C above the most stable parent, and seven of these showed superior activity in 16-h Avicel hydrolysis assays. The sequence-stability model identified a single block of sequence that adds 8.5 °C to chimera thermostability. Mutating individual residues in this block identified the C313S substitution as responsible for the entire thermostabilizing effect. Introducing this mutation into the two recombination parent CBH IIs not featuring it (Hypocrea jecorina and H. insolens) decreased inactivation, increased maximum Avicel hydrolysis temperature, and improved long time hydrolysis performance. This mutation also stabilized and improved Avicel hydrolysis by Phanerochaete chrysosporium CBH II, which is only 55–56% identical to recombination parent CBH IIs. Furthermore, the C313S mutation increased total H. jecorina CBH II activity secreted by the Saccharomyces cerevisiae expression host more than 10-fold. Our results show that SCHEMA structure-guided recombination enables quantitative prediction of cellulase chimera thermostability and efficient identification of stabilizing mutations

Neural correlates of quantity processing of numeral classifiers.

ObjectiveClassifiers play an important role in describing the quantity information of objects. Few studies have been conducted to investigate the brain organization for quantity processing of classifiers. In the current study, we investigated whether activation of numeral classifiers was specific to the bilateral inferior parietal areas, which are believed to process numerical magnitude.MethodUsing functional MRI, we explored the neural correlates of numeral classifiers, as compared with those of numbers, dot arrays, and nonquantity words (i.e., tool nouns).ResultsOur results showed that numeral classifiers and tool nouns elicited greater activation in the left inferior frontal lobule and left middle temporal gyrus than did numbers and dot arrays, but numbers and dot arrays had greater activation in the middle frontal gyrus, precuneus, and the superior and inferior parietal lobule in the right hemisphere. No differences were found between numeral classifiers and tool nouns.ConclusionThe results suggest that quantity processing of numeral classifiers is independent of that of numbers and dot arrays, supporting the notation-dependent hypothesis of quantity processing

Impact of Brain Injury on Processing of Emotional Prosodies in Neonates

Being able to appropriately process different emotional prosodies is an important cognitive ability normally present at birth. In this study, we used event-related potential (ERP) to assess whether brain injury impacts the ability to process different emotional prosodies (happy, fear, and neutral) in neonates; whether the ERP measure has potential value for the evaluation of neurodevelopmental outcome in later childhood. A total of 42 full-term neonates were recruited from the neonatology department of Peking University First Hospital from June 2014 to January 2015. They were assigned to the brain injury group (n = 20) or control group (n = 22) according to their clinical manifestations, physical examinations, cranial images and routine EEG outcomes. Using an oddball paradigm, ERP data were recorded while subjects listened to happy (20%, deviation stimulus), fearful (20%, deviation stimulus) and neutral (80%, standard stimulus) prosodies to evaluate the potential prognostic value of ERP indexes for neurodevelopment at 30 months of age. Results showed that while the mismatch responses (MMRs) at the frontal lobe were larger for fearful than happy prosody in control neonates, this difference was not observed in neonates with brain injuries. This finding suggests that perinatal brain injury may influence the cognitive ability to process different emotional prosodies in neonatal brain; this deficit could be reflected by decreased MMR amplitudes in response to fearful prosody. Moreover, the decreased MMRs at the frontal lobe was associated with impaired neurodevelopment at 30 months old

Response of Electric Field in Terrestrial Magnetosphere to Interplanetary Shock

Electric field impulses generated by interplanetary shocks can cause a series of dynamic processes in the Earth's magnetosphere and were previously explained by either fast-mode wave propagation or flow related to compression of the magnetopause. Based on a Space Weather Modeling Framework simulation, we suggest a new scenario in which the evolution of the impulse is due to both the propagation of the fast-mode wave and the compression of the magnetopause, which can explain the simulation and observations in previous related studies. The onset of the electric field impulse is determined by the propagation of the fast-mode wave in the magnetosphere while the peak of the impulse is determined by the propagation of the compression of the magnetopause. The new understanding of the impulse is important for the generation of subsequent ultralow frequency waves through the coupling of the fast-mode to Alfv&eacute;n waves and field line resonances and related radiation-belt electron acceleration. &nbsp;</p

Low-cost far-field wireless electrical load monitoring system applied in an off-grid rural area of Tanzania

This research article published by Elsevier Ltd., 2020Despite the rapid development of Internet of Things (IoT) technology, there is still a lack of practical wireless energy monitoring methods that can be implemented directly in rural areas with undeveloped infrastructure. To address this gap, this paper presents a novel far-field wireless electrical load monitoring system. By taking advantage of radio frequency (RF) technology, the system realizes one-point-to-multipoint and multichannel communication, thereby extending the effective communication distance of the system and improving its sustainability to the influence of the external environment. The design proposed in this study includes standby equipment to effectively ensure the normal operation of the system in the case of hardware malfunction. The proposed method can be implemented in most geographical regions, neither confined to specific geographic locations nor limited by the level of development of the local infrastructure. Moreover, the hardware of the proposed system is based on Arduino boards, resulting in a low-cost manufacturing process. This system has been applied in a rural area of Tanzania, with 46 households. This paper reports a 238 % increase in power consumption by the residents between the time of initial system deployment, when they had little access to electricity, and the time when accessibility became easy

Viral neutralization by antibody-imposed physical disruption

中和抗体是机体抵御病毒入侵的一类免疫球蛋白，也是疫苗发挥作用的主要效应分子。目前已知的中和抗体作用机制，主要包括阻断病毒-细胞相互作用和介导免疫调理作用。最近我校夏宁邵教授团队研究结果揭示了一种由抗体诱导病毒原位崩解的中和新机制。该研究首次揭示了抗体的直接物理碰撞中和机制，并提出诱导这类中和抗体的方法，有助于病毒保护性抗体和疫苗设计，适用于多种病原体，而不仅限于戊型肝炎病毒。分子疫苗学和分子诊断学国家重点实验室夏宁邵教授、李少伟教授和顾颖副教授为该论文的共同通讯作者，郑清炳博士、硕士生蒋婕、博士生何茂洲和郑子峥副教授为共同第一作者。In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.This research was supported by grants from the Natural Science Foundation of Fujian Province (Grant 2017J07005), the National Science and Technology Major Project of Infectious Diseases (Grant 2018ZX10101001-002), and the National Natural Science Foundation of China (Grants 81871247, 81991490, and 81571996).国家自然科学基金重大项目、海峡联合项目和面上项目、福建省自然科学杰出青年基金、国家传染病科技重大专项等资助了该项研究

Neutralization sites of human papillomavirus-6 relate to virus attachment and entry phase in viral infection.

Human papillomavirus type 6 (HPV6) is the major etiologic agent of genital warts and recurrent respiratory papillomatosis. Although the commercial HPV vaccines cover HPV6, the neutralization sites and mode for HPV6 are poorly understood. Here, we identify the HPV6 neutralization sites and discriminate the inhibition of virus attachment and entry by three potent neutralizing antibodies (nAbs), 5D3, 17D5, and 15F7. Mutagenesis assays showed that these nAbs predominantly target surface loops BC, DE, and FG of HPV6 L1. Cryo-EM structures of the HPV6 pseudovirus (PsV) and its immune complexes revealed three distinct binding modalities - full-occupation-bound to capsid, top-center-bound-, and top-rim-bound to pentamers - and illustrated a structural atlas for three classes of antibody-bound footprints that are located at center-distal ring, center, and center-proximal ring of pentamer surface for 5D3, 17D5, and 15F7, respectively. Two modes of neutralization were identified: mAb 5D3 and 17D5 block HPV PsV from attaching to the extracellular matrix (ECM) and the cell surface, whereas 15F7 allows PsV attachment but prohibits PsV from entering the cell. These findings highlight three neutralization sites of HPV6 L1 and outline two antibody-mediated neutralization mechanisms against HPV6, which will be relevant for HPV virology and antiviral inhibitor design. HighlightsMajor neutralization sites of HPV6 were mapped on the pseudovirus cryo-EM structuremAb 15F7 binds HPV6 capsid with a novel top-rim binding modality and confers a post-attachment neutralizationmAb 17D5 binds capsid in top-centre manner but unexpectedly prevents virus from attachment to cell surface

Viral neutralization by antibody-imposed physical disruption.

In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design