bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppression and Mitigation Strategies for Control of COVID-19 in New Zealand
Authors: James Alex , Hendy Shaun C. , Plank Michael J. , Steyn Nicholas
Published: March 2020

A standard SEIR-type compartment model, parameterised for New Zealand, was used to simulate the spread of Covid19 in New Zealand and to test the effectiveness of various control strategies. Control aims can be broadly categorised as either suppression or mitigation. Suppression aims to keep cases to an absolute minimum for as long as possible. Mitigation aims to allow a controlled outbreak to occur, with the aim of preventing significant overloads on healthcare systems and gradually allowing the population to develop herd immunity.

Both types of strategy are fraught with uncertainty. Suppression strategies can succeed in delaying an outbreak, but only for as long as such control measures can be sustained. Once controls are eased or restricted, an epidemic is likely to follow as no herd immunity has been acquired. The success or failure of mitigation strategies can depend sensitively on the timing and efficacy of control measures, and require the ability to bring rapidly growing outbreaks under immediate control when needed. This is as yet untested even for a combination of national interventions including case isolation, household quarantine, population-wide social distancing and closure of schools and universities.

Although there are disadvantages to both types of approach, suppression has the advantage of buying time until a vaccine and/or treatment become available and allowing NZ to learn from rapidly unfolding events in other countries. A combination of successful suppression, strong border measures, and widespread contact tracing and testing resulting in containment could allow periods when control measures can be relaxed, but only if cases are reduced to a handful.

Executive Summary

Suppression strategies aim to keep the number of cases to an absolute minimum for as long as possible. This requires early and effective control interventions.

Suppression can only delay an epidemic, not prevent it, but may buy enough time for a vaccine or treatment to become available.

Mitigation strategies aim to control an epidemic so that herd immunity is acquired by the population without overwhelming healthcare systems.

Mitigation strategies are likely to be very high risk: they are unproven internationally, potentially sensitive to uncertainty, and it may take years for herd immunity to be acquired.

Strategy can be switched from suppression to mitigation. For example, once successful mitigation strategies have been tested in other countries. It is likely to be difficult or impossible to switch from a mitigation to a suppression strategy.

A combination of successful suppression, strong border measures, and widespread contact tracing and testing resulting in containment could allow periods when control measures can be relaxed, but only if we can reduce cases to a handful.
Effectiveness of Isolation Policies in Schools: Evidence from a Mathematical Model of Influenza and COVID-19
Authors: Burns Adam A. C. , Gutfraind Alexander
Published: March 2020

Background

Non-pharmaceutical interventions such as social distancing, school closures and travel restrictions are often implemented to control outbreaks of infectious diseases. For influenza in schools, the Center of Disease Control (CDC) recommends that febrile students remain isolated at home until they have been fever-free for at least one day and a related policy is recommended for SARS-CoV2 (COVID-19). Other authors proposed using a school week of four or fewer days of in-person instruction for all students to reduce transmission. However, there is limited evidence supporting the effectiveness of these interventions.

Methods

We introduced a mathematical model of school outbreaks that considers both intervention methods. Our model accounts for the school structure and schedule, as well as the time-progression of fever symptoms and viral shedding. The model was validated on outbreaks of seasonal and pandemic influenza and COVID-19 in schools. It was then used to estimate the outbreak curves and the proportion of the population infected (attack rate) under the proposed interventions.

Results

For influenza, the CDC-recommended one day of post-fever isolation can reduce the attack rate by a median (interquartile range) of 29 (13 - 59)%. With two days of post-fever isolation the attack rate could be reduced by 70 (55 - 85)%. Alternatively, shortening the school week to four and three days reduces the attack rate by 73 (64 - 88)% and 93 (91 - 97)%, respectively. For COVID-19, application of post-fever isolation policy was found to be less effective and reduced the attack rate by 10 (5 - 17)% for a two-day isolation policy and by 14 (5 - 26)% for 14 days. A four-day school week would reduce the median attack rate in a COVID-19 outbreak by 57 (52 - 64)%, while a three-day school week would reduce it by 81 (79 - 83)%. In both infections, shortening the school week significantly reduced the duration of outbreaks.

Conclusions

Shortening the school week could be an important tool for controlling influenza and COVID-19 in schools and similar settings. Additionally, the CDC-recommended post-fever isolation policy for influenza could be enhanced by requiring two days of isolation instead of one.
A meta-analysis on the role of children in SARS-CoV-2 in household transmission clusters
Authors: Zhu Yanshan , Bloxham Conor J. , Hulme Katina D. , Sinclair Jane E. , Marcus Tong Zhen Wei , Steele Lauren E. , Noye Ellesandra C. , Lu Jiahai , Xia Yao , Chew Keng Yih , Pickering Janessa , Gilks Charles , Bowen Asha C. , Short Kirsty R
Published: March 2020

The role of children in the spread of SARS-CoV-2 remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n=213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a paediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate (SAR) in paediatric household contacts was assessed. The secondary attack rate in paediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.

40-word summary

In household transmission clusters of SARS-CoV-2 children are unlikely to be the index case. Children are also less likely than adults to be infected with SARS-CoV-2 from a family member.
Diagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2
Authors: Ying Liu , Yue-ping Liu , Bo Diao , Feifei Ren , Yue Wang , Jinya Ding , Qianchuan Huang
Published: March 2020

[Abstract]

Objective

Coronavirus disease 2019 (COVID-19) has become pandemic in the world. The need for IgG-IgM combined antibody test is booming, but data on diagnostic indexes evaluation was inadequate. The aim of this study was to evaluate diagnostic indexes of a rapid IgG-IgM combined antibody test for SARS-CoV-2.

Methods

A total of 179 patients were enrolled. Serum were collected for IgG-IgM combined antibody test and corresponding nasal and pharyngeal swab specimens were collected for SARS-CoV-2 RT-PCR. According to SARS-CoV-2 RT-PCR results, patients under study were categorized as PCR positive group in 90 patients and PCR negative group in 89 patients.

Results

1. Of the 90 PCR positive samples, 77 were tested positive by SARS-CoV-2 IgG-IgM test kit, yielding a sensitivity of 85.6%. Meanwhile, of the 89 PCR negative sample, 8 samples were detected positive, resulting in a specificity of 91%. Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively. Kappa efficiency between IgG/IgM test kit and RT-PCR were 0.75. 2. Accuracy in mild/common and severe/critical subgroup were 73.9% and 97.7%, respectively. Accuracy in clinical confirmed, suspected cases and other disease subgroups were 70%, 60%, and 100%, respectively. 3. Patients were further divided into ‘0 - 7’, ‘8 - 15’ and ‘>= 16’ groups according to the time from illness onset to sample collection. Sensitivity, specificity and accuracy in these three groups were 18.8%, 77.8% and 40%; 100%, 50% and 87.5%; 100%, 64.3%, and 93.9, respectively.

Conclusion

The sensitivity and specificity of this ease-of-use IgG/IgM combined test kit were adequate, plus short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contributed to its competence for mass testing. At the current stage, it cannot take the place of SARA-CoV-2 nucleic acid RT-PCR, but can be served as a complementary option for RT-PCR. The combination of RT-PCR and IgG-IgM combined test kit could provide further insight into SARS-CoV-2 infection diagnosis.
Visual featural topography in the human ventral visual pathway
Authors: Fan Shijia , Wang Xiaosha , Wang Xiaoying , Wei Tao , Bi Yanchao
Published: March 2020

Visual object recognition in humans and nonhuman primates is achieved by the ventral visual pathway (ventral occipital-temporal cortex, VOTC), which shows a well-documented object domain structure. An on-going question has been what type of information is processed in higher-order VOTC that underlies such observations, with recent evidence suggesting effects of certain visual features. Combining computational vision models, fMRI experiment using a parametric-modulation approach, and natural image statistics of common objects, we depicted the neural distribution of a comprehensive set of visual features in VOTC, identifying voxel sensitivities to specific feature sets across geometry/shape, Fourier power, and color. The visual feature combination pattern in VOTC is significantly explained by their relationships to different types of response-action computation (Fight-or-Flight, Navigation, and Manipulation), as derived from behavioral ratings and natural image statistics. These results offer the first comprehensive visual featural map in VOTC and a plausible theoretical explanation as a mapping onto different types of downstream response-action systems.
Efficient detection of pre-proinsulin by double antibody sandwich ELISA
Authors: Zhu Zhu , Ma Guoliang , Wang Li , Wang Han , Tang Hengfang , Wei Zhou , Wang Peng
Published: March 2020

Abstract Objective

To generate monoclonal antibodies against pre-proinsulin (PPI), and establish sandwich ELISA method to provide a basis for PPI detection in recombinant human insulin production.

Methods

The Balb /c mice were immunized with PPI, and the hybridomas secreting anti-PPI monoclonal antibodies were obtained by conventional cell fusion technique and ELISA screening.The antibody was purified using a Protein G gel column and identified for purity by SDS-PAGE. Pairing effect was found by the sandwich ELISA, and the specificity of the paired antibody was determined. A paired antibody with better specificity was selected to establish sandwich ELISA, and construct a quantitative curve, the accuracy and sensitivity of the method were evaluated.

Results

Six anti-PPI monoclonal antibodies were obtained, named P1, P2, P3, P4, P5 and P6, of which P5 had the highest titer. The sandwich ELISA method was established with P5 for plating and P2 for detection antibodie. The linear range of the quantitative curve of PPI by sandwich ELISA was 0. 645-82.5 pg/mL, the recovery was 89%–95%, and the limit of detection was 3.06 pg/mL.

Conclusion

Six monoclonal antibodies against PPI were generated and the sandwich ELISA method was established to detect PPI in process control and product release control for recombinant human insulin production.
Dynamic arm movements attenuate perceptual distortion of visual vertical induced during prolonged whole-body tilt
Authors: Tani Keisuke , Yamamoto Shinji , Kodaka Yasushi , Kushiro Keisuke
Published: March 2020

Additional gravitational cues generated by active body movements may play a role in the perception of gravitational space, but no experimental evidence has been shown on this. To investigate this possibility, we evaluated how arm movements made against gravity influenced the perceptual distortion of visual and postural vertical induced by prolonged whole-body tilt. In Experiment 1, participants were asked to perform static or dynamic arm movements during prolonged whole-body tilt and we assessed their effects on subjective visual vertical (SVV) at the tilt position (during-tiltsession) and after tilting back to the upright position (post-tiltsession). In Experiment 2, we evaluated how static or dynamic arm movements during prolonged tilt subsequently affected the subjective postural vertical (SPV). In Experiment 1, we observed that prolonged tilt induced the SVV shifts toward the side of body tilts in both sessions. The prolonged tilt-induced SVV shifts effectively decreased when performing dynamic arm movements in theduring-tiltsession, but not in thepost-tiltsession. In Experiment 2, the SPV shifted toward the side of prolonged body tilt, which was not significantly influenced by the performance of static or dynamic arm movements. Results of theduring-tiltsession suggest that the central nervous system utilizes additional cues generated by dynamic body movements for the perception of the visual vertical.
Effect of dioxins in milk on 3D-cultured primary buffalo granulosa cells, a pilot study for a prospective RT-LAMP colour reaction for dioxin toxicity
Authors: Singh Chhama , Pandey Mamta , Goud Emmagouni Sharath Kumar , Veerappa Vedamurthy G. , Singh Dheer , Onteru Suneel Kumar
Published: March 2020

Dioxins are highly toxic environmental persistent organic pollutants. In several countries, their presence was also reported in cow and human milk samples in the range of 0.023-26.46 and 0.88-19.0 pg/gm of fat, respectively. The detection of dioxns in food samples has been relied on several expensive technologies, which do not represent their toxic effects on consumers. However, mammalian cell based bioassays have such potential to detect the toxins, while representing their toxic effects. Therefore, we tried a three-dimensionally (3D) cultured buffalo granulosa cell based RT-LAMP colour reaction for detecting the presence of added model dioxin, 2,3,7,8-tetrachlorodibenzodioxin (TCDD), in commercial milk. The 3D spheroids on the fifth day of culture were treated with different concentrations of TCDD (i.e. 0.02– 20 pg/ml) directly as well as indirectly through milk fat. After 24hrs of treatment, gene expression studies were performed on certain granulosa cell-specific (CYP19A1, ER-beta, FSHRandLHR) and selective TCDD-responsive (CYP1A1, CYP1B1andAHR) genes to identify the potential dioxin responsive gene for further RT-LAMP reaction. As theAHRexpression in 3D cultured buffalo granulosa cells appears to be a potential gene marker for sensing the added TCDD in the milk, a colour based RT-LAMP reaction was successfully attempted for its expression. However, future studies are needed to develop a dose-responsive colour reaction by considering the treatment time less than 24 hrs.
Prion protein lowering is a disease-modifying therapy across prion disease stages, strains, and endpoints
Authors: Minikel Eric Vallabh , Zhao Hien T , Le Jason , O’Moore Jill , Pitstick Rose , Graffam Samantha , Carlson George A , Kavanaugh Michael P , Kriz Jasna , Kim Jae Beom , Ma Jiyan , Wille Holger , Aiken Judd , McKenzie Deborah , Doh-ura Katsumi , Beck Matthew , O’Keefe Rhonda , Stathopoulos Jacquelyn , Caron Tyler , Schreiber Stuart L , Carroll Jeffrey B , Kordasiewicz Holly B , Cabin Deborah E , Vallabh Sonia M
Published: March 2020

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that less than 25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease.
Acute toxicity of Leaf extracts ofEnydra fluctuansLour in Zebrafish (Danio rerioHamilton)
Authors: Xavier Jobi , Kripasana Kshetrimayum
Published: March 2020

The present study was focused on the concentration dependent changes in oral acute toxicity of leaf extracts ofE. fluctuansin zebrafish. The study was also aimed at the details of histopathological changes in gill, liver, brain and intestine of zebrafish exposed to the leaf extracts of the plantE. fluctuans.Enydra fluctuansLour is an edible semi-aquatic herbaceous plant used widely for the alleviation of the different diseases. Since there were no toxicity studies conducted on this plant the present study was an attempt to look into the elements of toxicity of the plants. Two types of experiments are conducted in the present study. First, the acute oral toxicity study was conducted as per the OECD guidelines 203. Second, histopathological changes were observed in the fishes exposed to the lethal concentrations of plant extract. The oral acute toxicity studies conducted on Zebrafish have revealed that the leave extracts ofE. fluctuanswere toxic to the tested fish at the concentration of 200 mg/kg body weight. The histopathological studies conducted on intestine of treated fishes showed that treatment has induced rupturing of villi structure and fusion of villi membrane and detachment of villi structure from basal membrane of intestine. The histology of the liver also showed severe vacuolization in the cells while it is not affected in control. The studies on gills showed the detachment of basal epithelial membrane in gills compared to control which might have led to death of the fish. The histopathological observations of brain tissues treated with test samples also revealed the marked impingement in brain parenchyma while the control is normal without impingement of brain.
Detection of four imperiled western North American freshwater mussel species from environmental DNA with multiplex qPCR assays
Authors: Rodgers Torrey W. , Dysthe Joseph C. , Tait Cynthia , Franklin Thomas W. , Schwartz Michael K. , Mock Karen E.
Published: March 2020

We developed multiplexed, species-specific, quantitative PCR assays for the detection of four freshwater mussel species native to western North America,Gonidea angulata, Margaritifera falcata,Anodonta nuttallianaandAnodonta oregonensis, from environmental DNA (eDNA). These species have experienced dramatic declines over the last century and are currently threatened in many portions of their ranges. Therefore, improved tools for detecting and monitoring these species are needed. Species-specificity and sensitivity of assays were empirically tested in the lab, and multiplex assays were also validated with field collected eDNA samples. All assays were species-specific, sensitive, and effective for detection from eDNA samples collected from streams and rivers. These assays will aid in the detection, monitoring, management, and conservation of these vulnerable species.
Body temperature maintenance acclimates in a winter-tenacious songbird
Authors: Stager Maria , Senner Nathan R. , Tobalske Bret W. , Cheviron Zachary A.
Published: March 2020

Flexibility in heat generation and dissipation mechanisms provides endotherms the ability to match their thermoregulatory strategy with external demands. However, the degree to which these two mechanisms account for seasonal changes in body temperature regulation is unexplored. Here we present novel data on the regulation of avian body temperature to investigate how birds alter mechanisms of heat production and heat conservation to deal with variation in ambient conditions. We subjected Dark-eyed Juncos (Junco hyemalis) to chronic cold acclimations of varying duration and subsequently quantified their metabolic rates, thermal conductance, and ability to maintain normothermia. Cold-acclimated birds adjusted traits related to both heat generation (increased summit metabolic rate) and heat conservation (decreased conductance) to improve their body temperature regulation. Increases in summit metabolic rate occurred rapidly, but plateaued after one week of cold exposure. In contrast, changes to conductance occurred only after nine weeks of cold exposure. Thus, the ability to maintain body temperature continued to improve throughout the experiment, but the mechanisms underlying this improvement changed through time. Our results demonstrate the ability of birds to adjust thermoregulatory strategies in response to thermal cues and reveal that birds may combine multiple responses to meet the specific demands of their environments.
Insulin-like growth factor 1 induces oxidative damage, but does not affect survival in a songbird
Authors: Lendvai Ádám Z. , Tóth Zsófia , Pénzes Janka , Vogel-Kindgen Sarah , Gander Bruno A. , Vágási Csongor I.
Published: March 2020

Lifespan evolves as a compromise between antagonistic selection forces. Insulin-like growth factor 1 (IGF-1) is a pleiotropic hormone that regulates several life-history traits. High levels of IGF-1 have been linked to increased mortality, partly by causing oxidative stress. However, these effects have no experimental evidence in wild animals. We implanted microspheres loaded with exogenous IGF-1 into bearded reedlings, a common short-lived Eurasian songbird. The treatment elevated plasma IGF-1 levels for at least 24 h. Oxidative damage to lipids significantly increased the day after the manipulation in treated birds, but returned to baseline levels four days post-treatment. The treatment had no effect on survival over 16 months; however, birds with higher pre-treatment (baseline) IGF-1 levels had better survival prospects. These results suggest that, although high IGF-1 levels may induce oxidative damage, natural variation in this hormone’s level may reflect the outcome of individual optimization.
Tracing theIn VivoFate of Nanoparticles with a “Non-Self” Biological Identity
Authors: Mohammad-Beigi Hossein , Scavenius Carsten , Jensen Pia Bomholt , Kjaer-Sorensen Kasper , Oxvig Claus , Boesen Thomas , Enghild Jan J. , Sutherland Duncan S. , Hayashi Yuya
Published: March 2020

Nanoparticles can acquire a biomolecular corona with a species-specific biological identity. However, “non-self” incompatibility of recipient biological systems is often not considered, for example, when rodents are used as a model organism for preclinical studies of biomolecule-inspired nanomedicines. Using zebrafish embryos as an emerging model for nano-bioimaging, here we unraveled thein vivofate of intravenously injected 70 nm SiO2nanoparticles with a protein corona pre-formed from fetal bovine serum (FBS), representing a non-self biological identity. Strikingly rapid sequestration and endolysosomal acidification of nanoparticles with the pre-formed FBS corona were observed in scavenger endothelial cells within minutes after injection. This led to loss of blood vessel integrity and inflammatory activation of macrophages over the course of several hours. As unmodified nanoparticles or the equivalent dose of FBS proteins alone failed to induce the observed pathophysiology, this signifies how the corona enriched with a differential repertoire of proteins can determine the fate of the nanoparticlesin vivo. Our findings thus reveal the adverse outcome triggered by incompatible protein coronas and indicate a potential pitfall in the use of mismatched species combinations during nanomedicine development.
Custom-molded headcases have limited efficacy in reducing head motion during naturalistic fMRI experiments
Authors: Jolly E , Sadhukha S , Chang L.J.
Published: March 2020

Effectively minimizing head motion continues to be a challenge for the collection of functional magnetic resonance imaging (fMRI) data. The use of individual-specific custom molded headcases is a promising solution to this issue, but there has been limited work to date. In the present work, we examine the efficacy of headcases in a larger group of participants engaged in naturalistic scanning paradigms including: long movie-watching scans (∼20-45min) and a recall task that involved talking aloud inside the MRI. Unlike previous work, we find that headcases do not reliably reduce motion during movie viewing compared to alternative methods such as foam pillows or foam pillows plus medical tape. Surprisingly, we also find that motion isworsewhen participants talk aloud while wearing headcases. These differences appear to be driven by large, brief rotations of the head as well as translations in the z-plane as participants speak. Smaller, constant head movements appear equivalent with or without headcases. The largest reductions in head motion are observable when participants were situated with both foam pillows and medical tape. Altogether, this work suggests that in a healthy adult population, custom-molded headcases may provide limited efficacy in reducing head motion beyond existing tools available to researchers. We hope this work can help improve the quality of custom headcases, motivate the investigation of additional solutions, and provide additional information about head motion in naturalistic contexts.
Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression
Authors: Wu Wennie , Howard Derek , Sibille Etienne , French Leon
Published: March 2020

Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and affects individuals of all ages. It causes significant psychosocial impairments and is a major cause of disability. A recent consortium study identified 102 genetic variants and 269 genes associated with depression. To provide targets for future depression research, we prioritized these recently identified genes using expression data. We examined differential expression of these genes in three studies that profiled gene expression of MDD cases and controls across multiple brain regions. In addition, we integrated anatomical expression information to determine which brain regions and transcriptomic cell-types highly express the candidate genes. We highlight 11 of the 269 genes with the most consistent differential expression:MANEA, UBE2M, CKB, ITPR3, SPRY2, SAMD5, TMEM106B, ZC3H7B, LST1, ASXL3andHSPA1A. The majority of these top genes were found to have sex-specific differential expression. We place greater emphasis onMANEAas it is the top gene in a more conservative analysis of the 269. Specifically, differential expression ofMANEAwas strongest in cerebral cortex regions and had opposing sex-specific effects. Anatomically, our results suggest the importance of the dorsal lateral geniculate nucleus, cholinergic, monoaminergic, and enteric neurons. These findings provide a guide for targeted experiments to advance our understanding of the genetic underpinnings of depression.
Arf1-Ablation-Induced Neuronal Damage Promotes Neurodegeneration Through an NLRP3 Inflammasome–Meningeal γδ T cell–IFNγ-Reactive Astrocyte Pathway
Authors: Wang Guohao , Yin Weiqin , Shin Hyunhee , Hou Steven X.
Published: March 2020

Neurodegenerative diseases are often initiated from neuronal injury or disease and propagated through neuroinflammation and immune response. However, the mechanisms by which injured neurons induce neuroinflammation and immune response that feedback to damage neurons are largely unknown. Here, we demonstrate that Arf1 ablation in adult mouse neurons resulted in activation of a reactive microglia–A1 astrocyte–C3 pathway in the hindbrain and midbrain but not in the forebrain, which caused demyelination, axon degeneration, synapse loss, and neurodegeneration. We further find that the Arf1-ablated neurons released peroxided lipids and ATP that activated an NLRP3 inflammasome in microglia to release IL-1β, which together with elevated chemokines recruited and activated γδT cells in meninges. The activated γδ T cells then secreted IFNγ that entered into parenchyma to activate the microglia–A1 astrocyte–C3 neurotoxic pathway for destroying neurons and oligodendrocytes. Finally, we show that the Arf1-reduction-induced neuroinflammation–IFNγ–gliosis pathway exists in human neurodegenerative diseases, particularly in amyotrophic lateral sclerosis and multiple sclerosis. This study illustrates perhaps the first complete mechanism of neurodegeneration in a mouse model. Our findings introduce a new paradigm in neurodegenerative research and provide new opportunities to treat neurodegenerative disorders.
A Controlled Slip: Training Propulsion via Acceleration of the Trailing Limb
Authors: Farrens Andria J. , Lilley Maria , Sergi Fabrizio
Published: March 2020

Walking function, which is critical to performing many activities of daily living, is commonly assessed by walking speed. Walking speed is dependent on propulsion, which is governed by ankle moment and the posture of the trailing limb during push-off. Here, we present a new gait training paradigm that utilizes a dual belt treadmill to train both components of propulsion by accelerating the belt of the trailing limb during push off. Accelerations require subjects to produce greater propulsive force to counteract inertial effects, and increase trailing limb angle through increased belt velocity.

We hypothesized that exposure to our training p rogram would produce after effects in propulsion mechanics and, consequently, walking speed. We tested our protocol on healthy subjects at two acceleration magnitudes–Perceptible (PE), and Imperceptible, (IM)–and compared their results to a third control group (VC) that walked at a higher velocity during training.

Results show that the PE group significantly increased walking speed following training (mean ± s.e.m: 0.073 ± 0.013 m/s, p < 0.001). The change in walking speed in the IM and VC groups was not significant at the group level (IM: 0.032 ± 0.013 m/s; VC: -0.003 ± 0.013 m/s). Responder analysis showed that changes in push-off posture and in neuro-motor control of ankle plantar-flexor muscles contributed to the larger increases in gait speed measured in the PE group compared to the IM and VC groups. Analysis of the effects during and after training suggest that changes in neuromotor coordination are consistent with use-dependent learning.
SCITO-seq: single-cell combinatorial indexed cytometry sequencing
Authors: Hwang Byungjin , Lee David S. , Tamaki Whitney , Sun Yang , Ogorodnikov Anton , Hartoularos George , Winters Aidan , Song Yun S. , Chow Eric D. , Spitzer Matthew H. , Ye Chun Jimmie
Published: March 2020

The development of DNA-barcoded antibodies to tag cell-surface molecules has enabled the use of droplet-based single cell sequencing (dsc-seq) to profile the surface proteomes of cells. Compared to flow and mass cytometry, the major limitation of current dsc-seq-based workflows is the high cost associated with profiling each cell, thus precluding its use in applications where millions of cells are required. Here, we introduce SCITO-seq, a new workflow that combines combinatorial indexing and commercially available dsc-seq to enable cost-effective cell surface proteomic sequencing of greater than 105cells per microfluidic reaction. We demonstrate SCITO-seq’s feasibility and scalability by profiling mixed species cell lines and mixed human T and B lymphocytes. To further demonstrate its applicability, we show comparable cellular composition estimates in peripheral blood mononuclear cells obtained with SCITO-seq and mass cytometry. SCITO-seq can be extended to include simultaneous profiling of additional modalities such as transcripts and accessible chromatin or tracking of experimental perturbations such as genome edits or extracellular stimuli.
Simulating the Influence of Conjugative Plasmids Kinetic Values on the Multilevel Dynamics of Antimicrobial Resistance in a Membrane Computing Model
Authors: Campos Marcelino , Millán Álvaro San , Sempere José M. , Lanza Val F. , Coque Teresa M. , Llorens Carlos , Baquero Fernando
Published: March 2020

Plasmids harboring antibiotic resistance genes differ in their kinetic values as plasmid conjugation rate, segregation rate by incompatibility with related plasmids, rate of stochastic loss during replication, cost reducing the host-cell fitness, and frequency of compensatory mutations to reduce plasmid cost, depending on the cell mutation frequency. How variation in these values influence the success of a plasmid and their resistance genes in complex ecosystems, as the microbiota? Genes are located in plasmids, plasmids in cells, cells in populations. These populations are embedded in ensembles of species in different human hosts, are able to exchange between them bacterial ensembles during cross-infection and are located in the hospital or the community setting, under various levels of antibiotic exposure. Simulations using new membrane computing methods help predict the influence of plasmid kinetic values on such multilevel complex system. In our simulation, conjugation frequency needed to be at least 10−3to clearly influence the dominance of a strain with a resistant plasmid. Host strains able to stably maintain two copies of similar plasmids harboring different resistances, coexistence of these resistances can occur in the population. Plasmid loss rates of 10−4or 10−5or plasmid fitness costs ≥0.06 favor the plasmids located in the most abundant species. The beneficial effect of compensatory mutations for plasmid fitness cost is proportional to this cost, only at high mutation frequencies (10−3-10−5). Membrane computing helps set a multilevel landscape to study the effect of changes in plasmid kinetic values on the success of resistant organisms in complex ecosystems.
A considerable proportion of individuals with asymptomatic SARS-CoV-2 infection in Tibetan population
Authors: Song Huan , Xiao Jun , Qiu Jiajun , Yin Jin , Yang Huazhen , Shi Rui , Zhang Wei
Published: March 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) quickly became a major epidemic threat in the whole China. We analysed SARS-Cov-2 infected cases from Tibetan Autonomous Prefecture, and noted divergent characteristics of these Tibetans infected cases compared to Han Chinese, characterizing by a considerable proportion of asymptomatic carriers (21.7%), and few symptomatic patients with initial symptom of fever (7.7%). Here, we did a descriptive study on clinical characteristics of 18 asymptomatic individuals with SARS-CoV-2 infection. The median age of these asymptomatic carriers was 31 years and one third of them were students, aged under 20 years. Notably, some of asymptomatic carriers had recognizable changes in radiological and laboratory indexes. Our finding indicates a potentially big number of SARS-CoV-2 asymptomatic carriers in prevalent area, highlighting a necessity of screening individuals with close contact of infected patients, for a better control on the spread of SARS-CoV-2 infection.
Evaluations of serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak
Authors: Lin Dachuan , Liu Lei , Zhang Mingxia , Hu Yunlong , Yang Qianting , Guo Jiubiao , Dai Youchao , Xu Yuzhong , Cai Yi , Chen Xinchun , Huang Kaisong , Zhang Zheng
Published: March 2020

The ongoing SARS-CoV-2 outbreak has killed over twenty-one thousand and sickened over four hundred thousand people worldwide, posing a great challenge to global public health. A sensitive and accurate diagnosis method will substantially help to control disease expansion. Here, we developed a chemiluminescence-immunoassay method based on the recombinant nucleocapsid antigen and the magnetic beads for diagnosis of SARS-CoV-2 infections and surveillance of antibody changing pattern.

Serums from 29 healthy individuals, 51 tuberculosis patients, and 79 SARS-CoV-2 confirmed patients were employed to evaluate the performance of this approach. Compared to the IgM testing, the IgG testing was more reliable in which it identified 65 SARS-CoV-2 infections from the 79 confirmed patients and only two false-positive cases from the 80 control group with a sensitivity and specificity reaching 82.28% and 97.5%, respectively. However, only a slight difference (not statistically significant) in the detected cases of SARS-CoV-2 infections was observed between the IgM and IgG testing manner in patients at a different time of onset of disease. A performance comparison between an ELISA kit using the same nucleocapsid antigen and our chemiluminescence method was undertaken. The same false-positive cases were seen in both methods from the paired control group, while ELISA kit can only detect half of the SARS-CoV-2 infections from paired SARS-CoV-2 confirmed patients group than that of the chemiluminescence method, indicating a higher performance for the chemiluminescence-immunoassay approach. Together, our studies provide a useful and valuable serological testing tool for the diagnosis of SARS-CoV-2 infections in the community.
Pyrethroid resistance in Anopheles gambiae not associated with insecticide-treated mosquito net effectiveness across sub-Saharan Africa
Authors: Larsen David A. , Church Rachael L.
Published: March 2020

Background

Pyrethroid resistance is a major concern for malaria vector control programs that predominantly rely on insecticide-treated mosquito nets (ITN). Contradictory results of the impact of resistance have been observed in field studies.

Methods

We combined continent-wide estimates of pyrethroid resistance in Anopheles gambiae from 2006-2017 with continent-wide survey data to assess the effect of increasing pyrethroid resistance on the effectiveness of ITNs to prevent malaria infections in sub-Saharan Africa. We utilized both a pooled-data approach and meta-regression of survey regions to assess how pyrethroid resistance affects the association between ITN ownership and malaria outcomes in children aged 6-59 months.

Findings

ITN ownership reduced the risk of malaria outcomes in both pooled and meta-regression approaches. In the pooled analysis, there was no observed interaction between ITN ownership and estimated level of pyrethroid resistance (Likelihood ratio [LR] test = 1.127 for the outcome of rapid diagnostic test confirmed malaria infection, p = 0.2885; LR test = 0.161 for the outcome of microscopy confirmed malaria infection, p = 0.161; LR test = 0.646 for the outcome of moderate or severe anemia, p = 0.4215). In the meta-regression approach the level of pyrethroid resistance did not explain any of the variance in subnational estimates of ITN effectiveness for any of the outcomes.

Interpretation

ITNs decreased risk of malaria outcomes independent of the levels of pyrethroid resistance in the malaria vector populations.

Funding

DAL did not receive funding and RC received a SOURCE grant from Syracuse University for this project.
Estrogen and sex-dependent loss of the vocal learning system in female zebra finches
Authors: Choe Ha Na , Tewari Jeevan , Zhu Kevin W. , Davenport Matthew , Matsunami Hiroaki , Jarvis Erich D.
Published: March 2020

Sex hormones alter the organization of the brain during early development and coordinate various behaviors throughout life. In zebra finches, song learning is limited to males, and the associated song learning brain pathway only matures in males and atrophies in females. This atrophy can be reversed by giving females exogenous estrogen during early post-hatch development, but whether normal male song system development requires estrogen is uncertain. For the first time in songbirds, we administered exemestane, a potent third generation estrogen synthesis inhibitor, from the day of hatching until adulthood. We examined the behavior, brain, and transcriptome of individual song nuclei of these pharmacologically manipulated animals. We found that males with long-term exemestane treatment had diminished male-specific plumage, impaired song learning, but retained normal song nuclei sizes and most, but not all, of their specialized transcriptome. Consistent with prior findings, females with long-term estrogen treatment retained a functional song system, and we further observed their song nuclei had specialized gene expression profiles similar, but not identical to males. We also observed that different song nuclei responded to estrogen manipulation differently, with Area X in the striatum being the most altered by estrogen modulation. These findings support the hypothesis that song learning is an ancestral trait in both sexes, which was subsequently suppressed in females of some species, and that estrogen has come to play a critical role in modulating this suppression as well as refinement of song learning.
Fright and Fight: Role of predation and competition on mate search tactics of wild male zebrafish
Authors: Ghoshal Aditya , Bhat Anuradha
Published: March 2020

Mate search tactics and association preferences among organisms in natural habitats can be dynamic and are determined by inherent trait preferences as well as the cost-benefit trade-offs associated with each mating decision. Two of the prime factors regulating mating decisions are the presence of competing conspecifics and predatory threats, both of which have important fitness consequences for the individual. We studied the influence of these two factors separately in mate search tactics and association preferences among zebrafish males. Male zebrafish were presented with a choice of two patches, consisting of different number of females, of which one patch was also associated with a predatory threat. We found that males made a preferential choice for the patch with more number of females only when the numerical difference between choices are starkly different, irrespective of the predatory threat associated with the patch. This points towards the role of numerical cognition in assessing cost-benefit tradeoffs in male zebrafish. We also studied the association preference of males in a multi-choice setup, consisting of four separate mixed-sex groups of zebrafish varying in densities. Our results showed that while test males preferred to visit the male-biased patches more often, they spent more time near female-biased patches or patches with equal sex ratio patches indicating the role of complex interplay of social cues in determining the associative behavior of males to a patch. This study, thus, sheds further light on the interactive roles of social cues and cognitive abilities in mate association patterns in this species.
Age dependent trans-cellular propagation of human tau aggregates inDrosophiladisease models
Authors: Aqsa  , Sarkar Surajit
Published: March 2020

Tauopathies is a class of neurodegenerative disorders which involves the transformation of physiological tau into pathogenic tau. One of the prime causes reported to drive this conversion is tau hyperphosphorylation and the subsequent propagation of pathogenic protein aggregates across the nervous system. Although past attempts have been made to deduce the details of tau propagation, yet not much is known about its mechanism. A better understanding of this aspect of disease pathology can prove to be beneficial for the development of diagnostic and therapeutic approaches. In our work, we utilize the plethora of advantages procured byDrosophilato introduce a novelin-vivotauopathy propagation model. For the first time, we demonstrate that the human tau (h-tau) possesses an intrinsic property to spread trans-cellularly in the fly nervous system irrespective of the tau allele or the neuronal tissue type. Aggregate migration restricted by targeted down-regulation of a specific kinase, elucidates the role of hyper-phosphorylation in its movement. On the contrary to the previous models, the present system enables a rapid, convenient and robustin-vivostudy of tau migration pathology. Henceforth, the developed model would not only be immensely helpful in uncovering the mechanistic in-depths of tau propagation pathology but also aid in modifier and/or drug screening for amelioration of tauopathies.
Non-retroviral endogenous viral element limits cognate virus replication inAedes aegyptiovaries
Authors: Suzuki Yasutsugu , Baidaliuk Artem , Miesen Pascal , Frangeul Lionel , Crist Anna B. , Merkling Sarah H. , Fontaine Albin , Lequime Sebastian , Moltini-Conclois Isabelle , Blanc Hervé , van Rij Ronald P. , Lambrechts Louis , Saleh Maria-Carla
Published: March 2020

Endogenous viral elements (EVEs) are viral sequences integrated in host genomes. A large number of non-retroviral EVEs was recently detected inAedesmosquito genomes, leading to the hypothesis that mosquito EVEs may control exogenous infections by closely related viruses. Here, we experimentally investigated the role of an EVE naturally found inAedes aegyptipopulations and derived from the widespread insect-specific virus, cell-fusing agent virus (CFAV). Using CRISPR/Cas9 genome editing, we created anAe. aegyptiline lacking the CFAV EVE. Absence of the EVE resulted in increased CFAV replication in ovaries, possibly modulating vertical transmission of the virus. Viral replication was controlled by targeting of viral RNA by EVE-derived piRNAs. Our results provide evidence that antiviral piRNAs are produced in the presence of a naturally occurring EVE and its cognate virus, demonstrating a functional link between non-retroviral EVEs and antiviral immunity in a natural insect-virus interaction.