bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioural barriers to COVID-19 testing in Australia
Authors: Bonner Carissa , Batcup Carys , Ayre Julie , Pickles Kristen , Dodd Rachael , Copp Tessa , Cornell Samuel , Cvejic Erin , Dakin Thomas , Isautier Jennifer , Nickel Brooke , McCaffery Kirsten
Published: September 2020

Background

The current suppression strategy for COVID-19 in Australia is dependent on people getting tested and self-isolating while they have COVID-19 symptoms. However, there is very little research on the behaviours and behavioural barriers involved in getting tested, both in Australia and worldwide, despite there being some evidence that these barriers do exist.

Methods

The Sydney Health Literacy Lab (SHeLL) has been conducting a national longitudinal survey in Australia since April 2020. A list of testing barriers was included in Wave 3 in June 2020 (n=1369), along with intentions to test and self-isolate if symptomatic. Open responses were also collected. The test barriers identified were categorised using the COM-B framework.

Results

Only 49% of people strongly agreed they would get tested if they had COVID-19 symptoms, but most people agreed to some extent that they would get tested (96%). The most common barriers selected from the list provided were that testing is painful (11%), not knowing how to get tested (7%), and worry about getting infected at the testing centre (5%). Many participants (10%) indicated other reasons, and open responses included many additional barriers to testing than those provided in the initial list. These covered all components of the COM-B model.

Conclusion

We identified a wide range of barriers using both quantitative and qualitative methods, which need to be addressed in order to increase COVID-19 testing behaviour.
Mechanisms and heterogeneity of mineral use by natural colonies of the cyanobacteriumTrichodesmium
Authors: Held Noelle A. , Sutherland Kevin M. , Webb Eric A. , McIlvin Matthew R. , Cohen Natalie R. , Devaux Alexander J. , Hutchins David A. , Waterbury John B. , Hansel Colleen M. , Saito Mak A.
Published: September 2020

The keystone marine nitrogen fixerTrichodesmiumthrives in high dust environments, and while experimental observations suggest thatTrichodesmiumcolonies can access the essential nutrient iron from dust particles, it is not known the extent to which this occurs in the field. Here we demonstrate thatTrichodesmiumcolonies actively process mineral particles in nature with direct molecular impacts. Microscopy and synchrotron-based imaging demonstrated heterogeneous associations with particles consistent with iron oxide and iron silicate minerals. Metaproteomic analysis of individual colonies revealed enrichment of biogeochemically-relevant proteins including photosynthesis proteins and metalloproteins containing iron, nickel, copper and zinc when particles were present. The iron-storage protein ferritin was particularly enriched implying accumulation of particle-derived iron, and multiple iron acquisition pathways including Fe(II), Fe(III), and Fe-siderophore transporters were engaged, including evidence of superoxide-driven particle dissolution. While the particles clearly provided iron, there was also evidence that the concentrated metals had toxic effects. The molecular mechanisms allowingTrichodesmiumto interact with particulate minerals are fundamental to its success and global impact on nitrogen biogeochemistry, and may contribute to the leaching of particulate trace metals with implications for global iron and carbon cycling.
Tissue Dynamics Spectroscopic Imaging: Functional Imaging of Heterogeneous Cancer Tissue
Authors: Li Zhe , Hu Bihe , Li Guang , Fox Sharon E. , Jalal Shadia , Turek John , Brown J. Quincy , Nolte David D.
Published: September 2020

Significance

Tumor heterogeneity poses a challenge for the chemotherapeutic treatment of cancer. Tissue dynamics spectroscopy (TDS) captures dynamic contrast and can capture the response of living tissue to applied therapeutics, but the current analysis averages over the complicated spatial response of living biopsy samples.

Aim

To develop tissue dynamics spectroscopic imaging (TDSI) to map the heterogeneous spatial response of tumor tissue to anticancer drugs.

Approach

TDSI is applied to tumor spheroids grown from cell lines and toex vivoliving esophageal biopsy samples. Doppler fluctuation spectroscopy is performed on a voxel basis to extract spatial maps of biodynamic biomarkers. Functional images and bivariate spatial maps are produced using a bivariate color merge to represent the spatial distribution of pairs of signed drug-response biodynamic biomarkers.

Results

We have mapped the spatial variability of drug responses within biopsies and have tracked sample-to-sample variability. Sample heterogeneity observed in the biodynamic maps is associated with histological heterogeneity observed using inverted Selective-Plane Illumination Microscopy (iSPIM).

Conclusion

We have demonstrated the utility of TDSI as a functional imaging method to measure tumor heterogeneity and its potential for use in drug-response profiling.
Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis
Authors: Vergoossen Dana L.E. , Plomp Jaap J. , Gstöttner Christoph , Fillié-Grijpma Yvonne E. , Augustinus Roy , Verpalen Robyn , Wuhrer Manfred , Parren Paul W.H.I. , Dominguez-Vega Elena , van der Maarel Silvère M. , Verschuuren Jan J. , Huijbers Maartje G.
Published: September 2020

Human IgG4 usually displays anti-inflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 antibodies naturally engage in a stochastic process termed Fab-arm exchange in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis (MG). In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a novel pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.

Graphical abstract
The Phage-shock-protein (PSP) Envelope Stress Response: Discovery of Novel Partners and Evolutionary History
Authors: Ravi Janani , Anantharaman Vivek , Chen Samuel Zorn , Brenner Evan Pierce , Datta Pratik , Aravind L , Gennaro Maria Laura
Published: September 2020

Bacterial phage shock protein (PSP) systems stabilize the bacterial cell membrane and protect against envelope stress. These systems have been associated with virulence, but despite their critical roles, PSP components are not well-characterized outside proteobacteria. Using comparative genomics and protein sequence-structure-function analyses, we systematically identified and analyzed PSP homologs, phyletic patterns, domain architectures, and gene neighborhoods. This approach underscored the evolutionary significance of the system, revealing that the core PspA gene (Snf7 in ESCRT outside bacteria) was present in the Last Universal Common Ancestor (LUCA), and that this ancestral functionality has since diversified into multiple novel, distinct PSP systems across life. Several novel partners of the PSP system were identified: (i) the Toastrack domain, likely facilitating assembly of sub-membrane stress-sensing and signaling complexes, (ii) the newly-defined HAAS-PadR-like transcriptional regulator pair system, and (iii) multiple independent associations with ATPase, CesT/Tir-like chaperone, and Band-7 domains in proteins thought to mediate sub-membrane dynamics. Our work also uncovered links between the PSP components and other domains, such as novel variants of SHOCT-like domains, suggesting roles in assembling membrane-associated complexes of proteins with disparate biochemical functions. Results are available athttps://jravilab.org/psp.

Importance

Phage shock proteins (PSP) are virulence-associated, cell membrane stress-protective systems. They have mostly been characterized in proteobacteria and firmicutes. We now show that PSP systems were present in the Last Universal Common Ancestor, and that homologs have evolved and diversified into newly identified functional contexts. Recognizing the conservation and evolution of PSP systems across bacterial phyla contributes to our understanding of stress response mechanisms in prokaryotes. Moreover, the newly discovered PSP modularity will likely prompt new studies of lineage-specific cell-envelope structures, lifestyles, and adaptation mechanisms. Finally, our results validate use of domain architecture and genetic context for discovery in comparative genomics.
Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade
Authors: Palmer Douglas C. , Webber Beau R. , Patel Yogin , Johnson Matthew J. , Kariya Christine M. , Lahr Walker S. , Parkhurst Maria R. , Gartner Jared J , Prickett Todd D , Lowery Frank J. , Kishton Rigel J. , Gurusamy Devikala , Franco Zulmarie , Vodnala Suman K. , Diers Miechaleen D. , Wolf Natalie K. , Slipek Nicholas J. , McKenna David H. , Sumstad Darin , Viney Lydia , Henley Tom , Bürckstümmer Tilmann , Baker Oliver , Hu Ying , Yan Chunhua , Meerzaman Daoud , Padhan Kartik , Lo Winnie , Malekzadeh Parisa , Jia Li , Deniger Drew C. , Patel Shashank J. , Robbins Paul F. , McIvor R. Scott , Choudhry Modassir , Rosenberg Steven A. , Moriarity Branden S. , Restifo Nicholas P.
Published: September 2020

While neoantigen-specific tumor infiltrating lymphocytes (TIL) can be derived from in antigen-expressing tumors, their adoptive transfer fails to consistently elicit durable tumor regression. There has been much focus on the role of activation/exhaustion markers such as PD1, CD39 and TOX in TIL senescence. We found these markers were inversely expressed to Cytokine-Induced SH2 protein (CISH), a negative regulator of TCR signaling and tumor immunity in mice. To evaluate the physiological role of CISH in human TIL we developed a high-efficiency CRIPSR-based method to knock out CISH in fully mature TIL. CISH KO resulted in increased T cell receptor (TCR) avidity, tumor cytolysis and neoantigen recognition. CISH expression in the tumor resections correlated with TIL inactivity against p53 hotspot mutations and CISH KO in TIL unmasked reactivity against these universal neoantigens. While CISH KO resulted in T cell hyperactivation and expansion it did not alter maturation, perhaps by preferential PLCγ-1 and not AKT inhibition. Lastly,CISHKO in T cells increased PD1 expression and the adoptive transfer ofCishKO T cells synergistically combines with PD1 antibody blockade resulting in durable tumor regression and survival in a preclinical animal model. These data offer new insights into the regulation of neoantigen recognition, expression of activation/exhaustion markers, and functional/maturation signals in tumor-specific T cells.
S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates
Authors: Liang Joshua G. , Su Danmei , Song Tian-Zhang , Zeng Yilan , Huang Weijin , Wu Jinhua , Xu Rong , Luo Peiwen , Yang Xiaofang , Zhang Xiaodong , Luo Shuangru , Liang Ying , Li Xinglin , Huang Jiaju , Wang Qiang , Huang Xueqin , Xu Qingsong , Luo Mei , Huang Anliang , Luo Dongxia , Zhao Chenyan , Yang Fan , Han Jian-Bao , Zheng Yong-Tang , Liang Peng
Published: September 2020

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.
Vitexin inhibited the invasion, metastasis, and progression of human melanoma cells by targeting STAT3 signaling pathway
Authors: Zhang WenHao , Zhou LiPing , Liu Guo
Published: September 2020

In human melanoma cells, resistance to conventional chemotherapy and radiotherapy and rapid metastasis give melanoma a remarkable feature of the most aggressive and lethal. The low response rate of melanoma to existing treatment modalities is a substantial threat to patients and researchers. It is crucial to identify new therapeutic agents for the fatal malignancy melanoma. Vitexin is a flavonoid compound in many traditional Chinese medicines that exhibits antioxidant, anti-inflammatory and anti-tumour activities in many cancer cells. In our study, we elucidated the inhibitory effects of vitexin on invasion and metastasis in human melanoma A375 and C8161 cellsin vitro. After vitexin treatment for 24 h or 48 h, the invasive ability and migration of melanoma cells were decreased in a dose- and time-dependent manners. In western blot analysis, we verified that vitexin inhibited the expression levels of MMP-2, MMP-9, vimentin, Slug and Twist which are known as the regulators of protein degradation and promote various cell behaviours such as migration and invasion. To further investigate the target signal that may be influenced by vitexin, immunofluorescence assay was performed to observe STAT3 localization and western blot results showed that vitexin decreased the expression of the phosphorylation of kinases that inducing STAT3 activation. Accordingly, we provide inspiring insight into the basic inhibition mechanism of vitexin, which will soon be an issue due to its scientific potential for further development as a novel anti-tumour agent for the clinical therapy of human melanoma.
Adverse drug reactions associated with the use of biological agents
Authors: Machado-Alba Jorge Enrique , Jiménez-Morales Anyi Liliana , Moran-Yela Yulieth Carolina , Parrado-Fajardo Ilsa Yadira , Valladales-Restrepo Luis Fernando
Published: September 2020

Introduction

Biotech drugs open new possibilities to treat diseases for which drug therapy is limited, but they may be associated with serious adverse drug reactions (ADRs).

Objective

To identify the ADRs associated with the use of biotech drugs in Colombia.

Methods

This was a retrospective study of ADR reports from 2014 to 2019, contained in the database of the pharmacovigilance program of Audifarma SA. The ADRs, groups of associated drugs, and affected organs were classified.

Results

A total of 5,415 reports of ADRs associated with biotech drugs were identified in 78 Colombian cities. A total of 76.1% of the cases corresponded to women. The majority were classified as type A (55.0%) and B (28.9%), and 16.7% were serious cases. The respiratory tract was the most commonly affected organ system (16.8%), followed by the skin and adnexa (15.6%). Antineoplastic and immunomodulatory drugs accounted for 70.6% of the reports, and the drugs related to the greatest number of ADRs were adalimumab (12.2%) and etanercept (11.6%).

Conclusions

There has been an incremental increase in the reporting of ADRs associated with the use of biotech drugs in the pharmacovigilance program, related to the strengthening and appropriation of the patient safety culture and improvement in the quality of the generated information. It is important to empower physicians and entire health teams to ensure the traceability of ADRs and to perform interdisciplinary interventions derived from pharmacovigilance at the individual and population levels.
The School Attachment Monitor - a novel computational tool for assessment of attachment in middle childhood
Authors: Rooksby Maki , Di Folco Simona , Tayarani Mohammad , Vo Dong-Bach , Huan Rui , Vinciarelli Alessandro , Brewster Stephen A. , Minnis Helen
Published: September 2020

Background

Attachment research has been limited by the lack of quick and easy measures. We report development and validation of the School Attachment Monitor (SAM), a novel measure for largescale assessment of attachment in children aged 5-9, in the general population. SAM offers automatic presentation, on computer, of story-stems based on the Manchester Child Attachment Story Task (MCAST), without the need for trained administrators. SAM is delivered by novel software which interacts with child participants, starting with warm-up activities to familiarise them with the task. Children’s story completion is video recorded and augmented by ‘smart dolls’ that the child can hold and manipulate, with movement sensors for data collection. The design of SAM was informed by children of users’ age range to establish their task understanding and incorporate their innovative ideas for improving SAM software.

Methods

130 5-9 year old children were recruited from mainstream primary schools. In Phase 1, sixty-one children completed both SAM and MCAST. Inter-rater reliability and rating concordance was compared between SAM and MCAST. In Phase 2, a further 44 children completed SAM complete and, including those children completing SAM in Phase 1 (total n=105), a machine learning algorithm was developed using a “majority vote” procedure where, for each child, 500 non-overlapping video frames contribute to the decision.

Results

Using manual rating, SAM-MCAST concordance was excellent (89% secure versus insecure; 97% organised versus disorganised; 86% four-way). Comparison of human ratings of SAM versus the machine learning algorithm showed over 80% concordance.

Conclusions

We have developed a new tool for measuring attachment at the population level, which has good reliability compared to a gold-standard attachment measure and has the potential for automatic rating – opening the door to measurement of attachment in large populations.
The Maintenance of Muscle Mass Is Independent of Testosterone in Adult Male Mice
Authors: Davidyan Arik , Baar Keith , Bodine Sue C.
Published: September 2020

Testosterone is considered a potent anabolic agent in skeletal muscle with a well-established role in adolescent growth and development in males. However, alterations in the role of testosterone in the regulation of skeletal muscle mass and function throughout the lifespan has yet to be established. While some studies suggest that testosterone is important for the maintenance of skeletal muscle mass, an understanding of the role this hormone plays in young, adult, and old males with normal and low serum testosterone levels is lacking. We investigated the role testosterone plays in the maintenance of muscle mass by examining the effect of orchiectomy-induced testosterone depletion in C57Bl6 male mice at ages ranging from early postnatal through old age; the age groups we used included 1.5-, 5-, 12-, and 24-month old mice. Following 28 days of testosterone depletion, we assessed mass and fiber cross-sectional-area (CSA) of the tibialis anterior, gastrocnemius, and quadriceps muscles. In addition, we measured global rates of protein synthesis and degradation using the SuNSET method, western blots, and enzyme activity assays. 28 days of testosterone depletion resulted in smaller muscle mass in the two youngest cohorts but had no effect in the two older ones. Mean CSA decreased only in the youngest cohort and only in the tibialis anterior muscle. Testosterone depletion resulted in a general increase in proteasome activity at all ages. We did not detect changes in protein synthesis at the terminal time point. This data suggest that within physiological serum concentrations, testosterone is not important for the maintenance of muscle mass in mature male mice; however, in young mice testosterone is crucial for normal growth.
Was facial width-to-height ratio subject to sexual selection pressures? A life course approach
Authors: Hodges-Simeon Carolyn R. , Albert Graham , Richardson George B. , McHale Timothy S. , Weinberg Seth M. , Gurven Michael , Gaulin Steven J.C.
Published: September 2020

Sexual selection researchers have traditionally focused on adult sex differences; however, the schedule and pattern of sex-specific ontogeny can provide insights unobtainable from an exclusive focus on adults. Recently, it has been debated whether facial width-to-height ratio (fWHR; bi-zygomatic breadth divided by midface height) is a human secondary sexual characteristic (SSC). Here, we review current evidence, then address this debate using ontogenetic evidence, which has been under-explored in fWHR research. Facial measurements collected from males and females aged 3 to 40 (Study 1; US,n=2449), and 7 to 21 (Study 2; Bolivia,n=179) were used to calculate three fWHR variants (which we call fWHRnasion, fWHRstomion, and fWHRbrow) and two other common facial masculinity ratios (facial width-to-lower-face-height ratio, fWHRlower,and cheekbone prominence). We test whether the observed pattern of facial development exhibits patterns indicative of SSCs, i.e. differential adolescent growth in either male or female facial morphology leading to an adult sex difference. Results showed that only fWHRlowerexhibited both adult sex differences as well as the classic pattern of ontogeny for SSCs—greater lower-face growth in male adolescents relative to females. fWHRbrowwas significantly wider among both pre- and post-pubertal males in the 2D sample; post-hoc analyses revealed that the effect was driven by large sex differences in brow height, with females having higher placed brows than males across ages. In both samples, all fWHR measures were inversely associated with age; that is, human facial growth is characterized by greater relative growth in the mid-face and lower face relative to facial width. This trend continues even into middle adulthood. BMI was also a positive predictor of most of the ratios across ages, with greater BMI associated with wider faces. Researchers collecting data on fWHR should target fWHRlowerand fWHRbrowand should control for both age and BMI.
Primate neuronal connections are sparse as compared to mouse
Authors: Wildenberg G.A. , Rosen M.R. , Lundell J. , Paukner D. , Freedman D.J. , Kasthuri N.
Published: September 2020

The mouse and macaque primary visual cortices are foundational models of cortical functioning, particularly at the level of single neurons. Therefore, detailing differences in how individual neurons connect across these species would inform models of cortical functioning and of how brains evolve. However, existing comparisons are limited, measuring synapse density without regard to where synapses are made or on what types of neurons. We use large volume electron microscopy to address this gap, reconstructing a total of 7735 synapses across 160 total neurons (146 excitatory, 14 inhibitory) from adult Rhesus macaque and mouse Layer 2/3 of primary visual cortex (V1). We find that primate connections are broadly sparse: primate excitatory and inhibitory neurons received 3-5 times fewer spine and somatic synapses with lower ratios of excitatory to inhibitory synapses than mouse equivalents. However, despite reductions in absolute synapse number, patterns of axonal innervation were preserved: inhibitory axons sparsely innervated neighboring excitatory neurons in macaque and mouse at similar rates and proportions. On the output side, most excitatory axons in mice myelinated close to the soma (81%) while most primate axons (68%) did not. Interestingly, primate axons, but not mouse axons, that myelinated had 3.3 fold more axon initial segment synapses than axons that did not myelinate, suggesting differential inhibitory control of long distance output in primate brains. Finally, we discover that when artificial recurrent neural networks (RNNs) are constrained by the metabolic cost of creating and maintaining synapses, increasing the number of nodes (e.g. neurons) as networks optimize for a cognitive task, reduces the number of connections per node, similar to primate neurons as compared to mice.

One Sentence Summary

Using large volume serial electron microscopy, we show that primate cortical neural networks are sparser than mouse and using recursive neural nets, we show that energetic costs of synaptic maintenance could underlie this difference.
Widespread methylation quantitative trait loci and their role in schizophrenia risk
Authors: Perzel Mandell Kira A. , Eagles Nicholas J. , Wilton Richard , Price Amanda J. , Semick Stephen A. , Collado-Torres Leonardo , Tao Ran , Han Shizhong , Szalay Alexander S. , Hyde Thomas M. , Kleinman Joel E. , Weinberger Daniel R. , Jaffe Andrew E.
Published: September 2020

DNA methylation (DNAm) regulates gene expression and may represent gene-environment interactions. Using whole genome bisulfite sequencing, we surveyed DNAm in a large sample (n=344) of human brain tissues. We identify widespread genetic influence on local methylation levels throughout the genome, with 76% of SNPs and 38% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting putative functional regions that explain much of the heritability associated with risk loci. Furthermore, some CpH sites associated with genetic variation. We have established a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.

One-sentence summary

Most genetic variants associated with DNA methylation levels, and implicated schizophrenia GWAS variants in the human brain.
Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice
Authors: Wells Alexandra I. , Grimes Kalena A. , Kim Kenneth , Branche Emilie , Bakkenist Christopher J. , DePas William H. , Shresta Sujan , Coyne Carolyn B.
Published: September 2020

Neonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR−/−, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR−/−mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR−/−mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establishin vivomodels that recapitulate echovirus disease.
A single-mode associates global patterns of brain network structure and behavior across the human lifespan
Authors: McPherson Brent , Pestilli Franco
Published: September 2020

Multiple human behaviors improve early in life, peaking in young adulthood, and declining thereafter. Several properties of brain structure and function progress similarly across the lifespan. Cognitive and neuroscience research has approached aging primarily using associations between a few behaviors, brain functions, and structures. Because of this, the multivariate, global factors relating brain and behavior across the lifespan are not well understood. We investigated the global patterns of associations between 334 behavioral and clinical measures and 376 brain structural connections in 594 individuals across the lifespan. A single-axis associated changes in multiple behavioral domains and brain structural connections (r=0.5808). Individual variability within the single association axis well predicted the age of the subject (r=0.6275). Representational similarity analysis evidenced global patterns of interactions across multiple brain network systems and behavioral domains. Results show that global processes of human aging can be well captured by a multivariate data fusion approach. [147]

Data availability

The source data are provided by the Cambridge Aging Neuroscience Projecthttps://camcan-archive.mrc-cbu.cam.ac.uk/. Brain data derived as part of this project and used as features for all the analyses are available on brainlife.io/pubs:

Code availability

Code is available on github athttps://github.com/bcmcpher/cca_agingand as web services reproducing the analyes at
Temporal evolution of single-cell transcriptomes ofDrosophilaolfactory projection neurons
Authors: Xie Qijing , Brbic Maria , Horns Felix , Kolluru Sai Saroja , Jones Bob , Li Jiefu , Reddy Anay , Xie Anthony , Kohani Sayeh , Li Zhuoran , McLaughlin Colleen , Li Tongchao , Xu Chuanyun , Vacek David , Luginbuhl David J. , Leskovec Jure , Quake Stephen R. , Luo Liqun , Li Hongjie
Published: September 2020

Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological features. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes ofDrosophilaolfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage—neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.
Song type variations of Louisiana Waterthrush (Parkesia motacilla) and their geographic distributions
Authors: Silcock W. Ross , Schwartz Shari L. , Carlini John U. , Dinsmore Stephen J.
Published: September 2020

Louisiana Waterthrush(Parkesia motacilla)is a familiar singer in the Western Hemisphere familyParulidae, yet apparent geographic variations in its song and potentially related causal mechanisms have not received detailed examination in previously published studies. Here, we analyzed song pattern variations of 651 Louisiana Waterthrush singers in audio spectrogram recordings obtained from our field work and publicly accessible bioacoustics archives. Visual and auditory assessment of the introductory note sequence of each song identified three distinct song types (A, B, and C) and 88.3% of the songs were assigned to one of these types. Linear Discriminant Analysis and Random Forest methods were used to verify the assignments and showed strong agreement (>90%) for Type A with slightly less agreement on Types B and C. User error rates (proportion of the Linear Discriminant Analysis classifications that were incorrect) were <10% for Types A and B, but 26% for Type C, while producer error rates (proportion of the song type for which the Linear Discriminant Analysis was incorrect) were >25% for Types A and C, but <5% for Type B. Our findings confirmed in a subset of 87 individuals that most between-individual variation was in the number of notes and note sequence duration while most within-individual variation resulted from the percent of downstrokes. The location of each singer was plotted on a map of the breeding range and results indicated the song types have large-scale discrete geographic distributions that co-occur in some regions but not range-wide. Evaluation of the distributions provided tentative support for a hypothesis that two of the song types may independently exhibit congruence with the geographic extent of Pleistocene glacial boundaries and the third song type may be distinguished by a lack of congruence, but further investigation is needed to elucidate whether the song variations represent subpopulations with three separate evolutionary histories.
Overview of the expression of key regeneration genes in embryo development and matured tissues in Axolotl (Ambystoma mexicanum)
Authors: Shah Harshil , Caballero Juan
Published: September 2020

The axolotl is a Mexican endangered species with the capability to perform tissue regeneration in amputated extremities. Being an important research model, the complete genome of the Axolotl was sequenced in 2018 for the first time, revealing an enormous genome: the largest of any animal ever sequenced, and about 10 times larger than the human genome, a new landmark achievement in biology research.

In this report, we collected 70 known genes that play an important role in tissue regeneration and searched for their expression during embryo development, regeneration, and in 6 adult tissues: the heart, liver, gills, front leg, rear leg, and tail. We observe those 70 genes expression levels in the 3 conditions and approximately 3 genes seem to be expressed exclusively in regeneration.

This report displays a few insights on how this marvelous species can modulate its regenerative capabilities. There is still much more to explore with the Axolotl. Further research into their regenerative capabilities could provide researchers with the perspicacity to possibly accomplish human limb regeneration.
Performance of a point of care test for detecting IgM and IgG antibodies against SARS-CoV-2 and seroprevalence in blood donors and health care workers in Panama
Authors: Villarreal Alcibiades , Rangel Giselle , Zhang Xu , Wong Digna , Britton Gabrielle , Fernandez Patricia L. , Pérez Ambar , Oviedo Diana , Restrepo Carlos , Carreirra María B. , Sambrano Dilcia , Eskildsen Gilberto , De La Guardia Carolina , Zaldivar Yamitzel , Franco Danilo , López-Vergès Sandra , Zhang Dexi , Fan Fanjing , Wang Baojun , Sáez-Llorens Xavier , DeAntonio Rodrigo , Torres-Atencio Ivonne , Ortega-Barria Eduardo , Kosagisharaf Rao , Lleonart Ricardo , Chong Li , Goodridge Amador ,   COVID-19 serology collaborator group
Published: September 2020

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in eight months. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay’s ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30thand July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, participants with other confirmed infectious diseases, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test sensitivity and specificity as well as the kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed akappaof 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement (87% (95% CI 67.0-96.3%)) was observed at ≥15 days post-symptom onset. We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.
Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
Authors: Ishihama Nobuaki , Choi Seung-won , Noutoshi Yoshiteru , Saska Ivana , Asai Shuta , Takizawa Kaori , He Sheng Yang , Osada Hiroyuki , Shirasu Ken
Published: September 2020

Salicylic acid (SA) and its structural analogs are nonsteroidal anti-inflammatory drugs (NSAIDs) that target mammalian cyclooxygenases. In plants, SA acts as a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identified a number of NSAIDs that enhance bacterial effector-induced cell death. Among them, the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent immune responses in plants. TNX treatment reduces NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. Surprisingly, however, cysteine modification associated with NPR1 oligomerizationviaintermolecular disulfide bonds is not affected by either SA or TNX. Therefore, oxicam-type NSAIDs highlight importance of SA effects on the cytosolic redox status, but not on cysteine modification or oligomerization of NPR1.
Chromosome-level genome ofPoropuntius huangchuchieniprovides a diploid progenitor-like reference genome for the allotetraploidCyprinus carpio
Authors: Chen Lin , Li Bijun , Chen Baohua , Li Chengyu , Zhou Zhixiong , Zhou Tao , Yang Weidi , Xu Peng
Published: September 2020

The diploidPoropuntius huangchuchieniin the cyprinid family, which is distributed in the Mekong and Red River basins, is one of the most closely related diploid progenitor-like species of allotetraploid common carp. Therefore, theP. huangchuchienigenome is essential for polyploidy evolution studies in Cyprinidae. Here, we report a chromosome-level genome assembly ofP. huangchuchieniby integrating Oxford Nanopore and Hi-C technology. The assembled genome size was 1021.38 Mb, 895.66 Mb of which was anchored onto 25 chromosomes with a N50 of 32.93 Mb. The genome contained 486.28 Mb repetitive elements and 24,099 protein-coding genes. Approximately 95.9% of the complete BUSCOs were detected, suggesting a high completeness of the genome. Evolutionary analysis revealed thatP. huangchuchienidiverged fromCyprinus carpioat approximately 12 Mya. Genome comparison betweenP. huangchuchieniand the B subgenome ofC. carpioprovided insights into chromosomal rearrangements during the allotetraploid speciation. With the complete gene set, 17,474 orthologous genes were identified betweenP. huangchuchieniandC. carpio, providing a broad view of the gene component in the allotetraploid genome, which is critical for future genomic and genetic analyses. The high-quality genomic dataset created forP. huangchuchieniprovides a diploid progenitor-like reference for the evolution and adaptation of allotetraploid carps.
WSB1 Regulates c-Myc Expression Through β-catenin Signaling and Forms a Feedforward Circuit Promoting the Development of Cancer
Authors: Gao Xiaomeng , Gong Yanling , You Jieqiong , Yuan Meng , Zhu Haiying , Fang Liang , Zhu Hong , Ying Meidan , He Qiaojun , Yang Bo , Cao Ji
Published: September 2020

The dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can directly transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies based on its regulatory mechanism hold great potential for cancer therapy. In this study, we found that WSB1, a direct target gene of c-Myc, can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. Luciferase-based promoter activity assays and RNA sequencing results confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and subsequently transactivated c-Myc. Of interest, the promoting effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, co-expression of WSB1 and c-Myc strongly enhanced the initiation and progression of tumours bothin vitroandin vivo. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.
High-throughput measurements of intra-cellular and secreted cytokine from single spheroids using anchored microfluidic droplets
Authors: Saint-Sardos Adrien , Sart Sebastien , Lippera Kevin , Brient-Litzler Elodie , Michelin Sebastien , Amselem Gabriel , Baroud Charles N.
Published: September 2020

While many single-cell approaches have been developed to measure secretion from anchorage-independent cells, these protocols cannot be applied to adherent cells, especially when these cells requires to be cultured in 3D formats. Here we demonstrate a platform to measure the secretions from individual spheroids of human mesenchymal stem cells, cultured within microfluidic droplets. The platform allows us to quantify the secretion from hundreds of individual spheroids in each device, by using a secondary droplet to bring functionalized micro-beads into proximity with each spheroid. We focus on vascular endothelial growth factor (VEGF) and measure a distribution of secretion levels that presents broad heterogeneity within the population of spheroids. Moreover, the intra-cellular level of VEGF-A on each spheroid, measured through immuno-staining, correlates well with the extra-cellular measurement, indicating that the heterogeneities observed at the spheroids level result from variations at the scale of individual cells. Finally, we model the molecular accumulation within the droplets and find that physical confinement is crucial for measurements of protein secretions. The model predicts the time to achieve a measurement, which scales with droplet volume. Therefore these first measurements of secretions from individual spheroids provide several new biological insights.
Genomic region associated with pod color variation in pea (Pisum sativum)
Authors: Shirasawa Kenta , Sasaki Kazuhiro , Hirakawa Hideki , Isobe Sachiko
Published: September 2020

Pea (Pisum sativum) was chosen as the research material by Gregor Mendel to discover the laws of inheritance. Out of seven traits studied by Mendel, genes controlling three traits including pod shape, pod color, and flower position have not been identified to date. With the aim to identify the genomic region controlling pod color, we determined the genome sequence of a pea line with yellow pods. Genome sequence reads obtained using a nanopore sequencing technology were assembled into 117,981 contigs that spanned 3.3 Gb in length and showed an N50 value of 51.2 kb. Using single nucleotide polymorphisms (SNPs) detected in a pea mapping population, these contigs were genetically anchored to the publicly available pseudomolecule sequences of the pea genome. Subsequent genetic and association analyses identified a genomic region responsible for pea pod color. At this genomic location, genes encoding 3’ exoribonucleases were selected as potential candidates controlling pod color, based on DNA sequencing and transcriptome analysis of green and yellow pod lines. The results presented in this study are expected to accelerate pan-genome studies in pea and facilitate the identification of the gene controlling one of the traits studied by Mendel.
Crystal structures of monohydrate and methanol solvate compounds of {1-[(3,5-bis{[(4,6-dimethylpyridin-2-yl)amino]methyl}-2,4,6-triethylbenzyl)amino]cyclopentyl}methanol
Authors: Stapf Manuel , Seichter Wilhelm , Mazik Monika
Published: September 2020

In the title monohydrate compound, 1a, and the methanol solvate compound, 1b, the triethylbenzene derivative, C35H51N5O, has three functionalized side arms and three ethyl groups, the former being located on one side of the central benzene ring, while the latter are directed to the opposite side. Both the crystals are constructed of structurally similar dimers of 1:1 host–guest complexes held together by N—H...O and O—H...N hydrogen bonds, and in 1a additionally by O—H...O hydrogen bonds. The structure of 1b contains additional highly disordered solvent molecules. Thus, the SQUEEZE routine [Spek (2015). Acta Cryst. C71, 9–18] in PLATON was used to generate a modified data set, in which the contribution of the disordered molecules to the structure amplitudes is eliminated. These solvent molecules are not considered in the reported chemical formula.
A new design strategy for bandwidth and efficiency enhancement in KA band CMOS power amplifier
Authors: Mirzajani Darestani Mohammad Sadegh , Tavakoli Mohammad Bagher , Amiri Parviz
Published: September 2020

Purpose

The purpose of this paper is to propose a new design strategy to enhance the bandwidth and efficiency of the power amplifier.

Design/methodology/approach

To realize the introduced design strategy, a power amplifier was designed using TSMC CMOS 0.18um technology for operating in the Ka-band, i.e. the frequency range of 26.5-40 GHz. To design the power amplifier, first, a power divider (PD) with a very wide bandwidth, i.e. 1-40 GHz, was designed to cover the whole Ka-band. The designed Doherty power amplifier consisted of two different amplification paths called main and auxiliary. To amplify the signal in each of the two pathways, a cascade distributed power amplifier was used. The main reason for combining the distributed structure and cascade structure was to increase the gain and linearity of the power amplifier.

Findings

Measurements results for designed power dividers are in good agreement with simulations results. The simulation results for the introduced structure of the power amplifier indicated that the gain of the proposed power amplifier at the frequency of 26-35 GHz was more than 30 dB. The diagram of return loss at the input and output of the power amplifier in the whole Ka-band was less than −8dB. The maximum power-added efficiency (PAE) of the designed power amplifier was 80%. The output P1dB of the introduced structure was 36 dB and the output power of the power amplifier was 36 dBm. Finally, the IP3 value of the power amplifier was about 17 dB.

Originality/value

The strategy presented in this paper is based on the usage of Doherty and distributed structures and a new wideband power divider to benefit from their advantages simultaneously.