bluuebunny/crossref_metadata_2025 huggingface dataset:
Early life and Adulthood Depression: Birth seasonality on demographic characteristics of depressive symptoms
Authors: Zhou Hao , Peng-Li Danni , Chen Juan , Sun Dong , Wan Bin
Published: July 2020

Background

Environmental and biological factors in early-life in-utero can have critical health implications in adulthood. However, despite the extensive literature on the association between depressive symptoms and female gender, higher age, lower education, and lower socio-economic status, no studies have thus far investigated these depression-related demographic factors in connection with early-life environment. Here, the present study aimed to explore the effects of birth seasonality on demographic characteristics of depressive symptoms in adults.

Methods

We employed data from the project of Chinese Labour-forces Dynamic Survey (CLDS) 2016, containing the epidemiological data of depressive symptoms with a probability proportional to size cluster and random cluster sampling method in 29 provinces of China with final sample of 16,181 participants was analysed. Logistic regression analyses were performed to test the relations between having depressive symptoms and various demographic characteristics in the overall population and different layers driven by the season of birth (Spring: March, April, and May; Summer: June, July, and August; Autumn: September, October, and November; Winter: December, January, and February).

Results

In line with previous studies, female gender, higher age, lower education, lower satisfaction of family income, and northern geographical region were the depressive symptoms-related factors. Season of birth did not significantly contribute to having depressive symptoms. Gender and satisfaction of family income were significant for the linear trend in people born in spring, summer, autumn, and winter. Age was significant for linear trend in people born in spring and winter. Education was only significant in spring. The categorical variable of geographical region had different associations with depressive symptoms across seasons of birth.

Conclusions

Our findings indicate that although season of birth is not significantly associated with depressive symptoms, it influences the effects of the demographic factors on depressive symptoms (particularly in age). The present study sheds lights on the discussion of environmental and biological effects related to season of birth on adult mental health.
Analysis of the association between hand grip strength and functionality in community elderly
Authors: Wieczorek Mariana Edinger , de Souza Cislaine Machado , da Silva Klahr Patrícia , da Rosa Luis Henrique Telles
Published: July 2020

Objective

To analyze an association between handgrip strength (HGS) and functional performance tests by healthy, non-institutionalized elderly.

Method

This is a cross-sectional study. A sample consisted of 36 elderly people (66.69 ± 4.84 years), all of whom responded to a cognitive assessment instrument and another to assess the level of physical activity, in addition to sociodemographic data and health conditions. The HGS was measured using the hydraulic dynamometer JAMAR and performed the six-minute walk test (6MWT) and the Timed Up and Go test (TUG) to assess the cardiorespiratory capacity submitted during displacement and body mobility.

Results

It was possible to verify through the Pearson coefficient the weak and significant association between the MPH and the variables 6MWT (p≤0.05) and TUG (p = 0.027).

Conclusion

For samples of healthy elderly and applied experimental conditions, the FPM is related to performance tests. Thus, it is believed that the evaluation of the HGS may be an alternative to interference in this population.
First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation
Authors: Graham Rachel S. , Zachs Daniel P. , Cotero Victoria , D’Agostino Catherine , Ntiloudi Despoina , Kaiser Claire R.W. , Graf John , Wallace Kirk , Ramdeo Richard , Coleman Thomas R. , Ashe Jeffrey , Pellerito John , Tracey Kevin J. , Binstadt Bryce A. , Chavan Sangeeta S. , Zanos Stavros , Puleo Christopher , Peterson Erik , Lim Hubert H.
Published: July 2020

Hyperinflammation and uncontrolled cytokine release in infections and autoimmune diseases require therapy to reduce the innate immune response. Here, we present first in-human data showing reduction in pro-inflammatory cytokine release with ultrasound stimulation of the spleen in healthy subjects and in rheumatoid arthritis patients. Single cell RNA sequencing reveals a decrease in IL-1β and IL-8 transcript levels in circulating monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and IFNγ- and NFκB-regulated genes. Additional pre-clinical studies reveal that ultrasound can boost B cell activation and antibody production. Splenic ultrasound offers a new non-invasive therapy for treating hyperinflammation without compromising the adaptive immune response.
Loss of integration of brain networks after sleep deprivation relates to the worsening of cognitive functions
Authors: Matteo Pesoli , Rosaria Rucco , Marianna Liparoti , Anna Lardone , Giula D’Aurizio , Roberta Minino , Emahnuel Troisi Lopez , Antonella Paccone , Carmine Granata , Giuseppe Sorrentino , Laura Mandolesi , Pierpaolo Sorrentino
Published: July 2020

The topology of brain networks changes according to environmental demands and can be described within the framework of graph theory. We hypothesized that 24-hours long sleep deprivation (SD) causes functional rearrangements of the brain topology so as to impair optimal communication, and that such rearrangements relate to the performance in specific cognitive tasks, namely the ones specifically requiring attention. Thirty-two young men underwent resting-state MEG recording and assessments of attention and switching abilities before and after SD. We found loss of integration of brain network and a worsening of attention but not of switching abilities. These results show that brain network changes due to SD affect switching abilities, worsened attention and induce large-scale rearrangements in the functional networks.
Acute Demyelinating Encephalomyelitis (ADEM) in COVID-19 infection: A Case Series
Authors: McCuddy Micheala , Kelkar Praful , Zhao Yu , Wicklund David
Published: July 2020

Objective

To report three patients infected with COVID-19 with severe respiratory syndrome requiring intubation, who developed acute demyelinating encephalomyelitis (ADEM).

Method

Patient data were obtained from medical records from the North Memorial Health Hospital, Robbinsdale, MN, USA

Results

Three patients (two men and one woman, aged 38 - 63) presented with fatigue, cough and fever leading to development of acute respiratory distress syndrome secondary to COVID-19 infection requiring intubation and ventilatory support. Two patients were unresponsive, one with strong eye deviation to the left and the third patient had severe diffuse weakness. MRI in all patients showed findings consistent with ADEM. CSF showed elevated protein in all patients with normal cell count and no evidence of infection, including negative COVID-19 PCR. All three of the patients received Convalescent plasma therapy for COVID-19. All patients were treated with intravenous corticosteroids and improved, although two responded minimally. Two patients treated with IVIG showed no further improvement.

Conclusion

Neurological complications from COVID-19 are being rapidly recognized. Our three cases highlight the occurrence of ADEM as a postinfectious/immune mediated complication of COVID-19 infection, which may be responsive to corticosteroid treatment. Early recognition of this complication and treatment is important to avoid long term complications.
Abdominal single-step quantitative susceptibility mapping with spherical mean value filter and structure prior-based regularization
Authors: Abyzov Anton , Van Beers Bernard E. , Garteiser Philippe
Published: July 2020

Abdominal quantitative susceptibility mapping (QSM), especially in small animals, is challenging because of respiratory motion and blood flow that, in addition to noise, deteriorate the quality of the input data. Efficient artefact suppression in QSM reconstruction is crucial in these conditions. Single-step QSM algorithms combine background field removal and magnetic field-to-susceptibility inverse problem regularization in a single optimization equation. Here, we propose a single-step QSM algorithm that uses spherical mean value kernels of different radii for background field removal and structure prior (consistency with magnitude image) withL1norm for regularization. The optimization problem is solved using the split-Bregman method on the graphic processor unit. The method was compared with previously reported singlestep methods: a method using discrete Laplacian instead of spherical mean value kernels, a method using total variational penalty instead of structure prior, and a method usingL2norm for structure prior. With the proposed method relative to the previous ones, a numerical susceptibility phantom was reconstructed more precisely. In living mice, susceptibility maps with more homogeneous liver, higher contrast between liver and blood vessels, and well-preserved structural details were obtained. In patients, susceptibility maps with more homogeneous subcutaneous fat and higher contrast between subcutaneous fat and liver were obtained. These results show the potential of the proposed single-step method for abdominal QSM in small animals and humans.
A systematic review uncovers a wide-gap between COVID-19 in humans and animal models
Authors: Ehaideb Salleh N. , Abdullah Mashan L. , Abuyassin Bisher , Bouchama Abderrezak
Published: July 2020

Background

Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of humans COVID-19.

Methods

We searched the Medline, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1, to May 20, 2020. We used the search terms “COVID-19” OR “SARS-CoV-2” AND, “animal models”, “hamsters”, “nonhuman primates”, “macaques”, “rodent”, “mice”, “rats”, “ferrets”, “rabbits”, “cats”, and “dogs”. Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19.

Findings

13 peer-reviewed studies and 14 preprints met inclusion criteria. The animals used were nonhuman primates (n=13), mice (n=7), ferrets (n=4), hamsters (n=4), and cats (n=1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in Rhesus macaques, hamsters, and mice. Notably, none of the animals unveiled cytokine storm or coagulopathy.

Conclusions

Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.

Funding

There was no funding source for this study.
Seroprevalence of SARS-CoV-2 antibodies in an entirely PCR-sampled and quarantined community after a COVID-19 outbreak - the CoNAN study
Authors: Weis Sebastian , Scherag André , Baier Michael , Kiehntopf Michael , Kamradt Thomas , Kolanos Steffi , Ankert Juliane , Glöckner Stefan , Makarewicz Oliwia , Hagel Stefan , Bahrs Christina , Kimmig Aurelia , Proquitté Hans , Guerra Joel , Löffler Bettina , Pletz Mathias W. ,   CoNAN study group.
Published: July 2020

Background

Due to the substantial proportion of asymptomatic and mild courses many SARS-CoV-2 infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed at determining and characterizing the rate of SARS-CoV-2 infections and the resulting immunity in a defined population.

Methods

CoNAN is a population-based cohort study in the previously quarantined community Neustadt-am-Rennsteig, Germany six weeks after a SARS-CoV-2 outbreak with 49 cases identified by PCR screening of all 883 inhabitants. The primary objective of the study was to assess SARS-CoV-2 antibody seroconversion rate using six different IgG detecting immunoassays. Secondary objectives of the study were: i.) to determine the rate of seroconversion in children; ii.) to determine potential risk factors for symptomatic vs. asymptomatic Covid19 courses; iii.) to investigate the rate of virus persistence.

Findings

We enrolled 626 participants (71% of the community population). All actual SARS-CoV-2 PCR tests were negative; while a total of 8·4% (52 of 620 tested) had antibodies against SARS-CoV-2 in at least two independent tests. Twenty of the antibody positive participants had previously a positive SARS-CoV-2 PCR. On the contrary, of those 38 participants with SARS-CoV-2 infection, only 20 (52·6%) were antibody positive.

Interpretation

Several antibody tests conducted six weeks after an outbreak of SARS-CoV-2 did not detect all previously PCR-positive tested individuals. Cautious evaluation of antibody testing strategies to assess immunity against the infection is warranted.

Funding

CoNAN was funded by the Thuringian Ministry for Economic Affairs, Science and Digital Society (TMWWDG).
Ferroportin 3 is a dual-targeted mitochondrial/chloroplast iron exporter necessary for iron homeostasis in Arabidopsis
Authors: Kim Leah J. , Tsuyuki Kaitlyn M. , Hu Fengling , Park Emily Y. , Zhang Jingwen , Iraheta Jennifer Gallegos , Chia Ju-Chen , Huang Rong , Tucker Avery E. , Clyne Madeline , Castellano Claire , Kim Angie , Chung Daniel D. , DaVeiga Christopher T. , Parsons Elizabeth M. , Vatamaniuk Olena K. , Jeong Jeeyon
Published: July 2020

Mitochondria and chloroplasts are organelles with high iron demand that are particularly susceptible to iron-induced oxidative stress. Despite the necessity of strict iron regulation in these organelles, much remains unknown about mitochondrial and chloroplast iron transport in plants. Here, we propose that Arabidopsis Ferroportin 3 (FPN3) is an iron exporter dual-targeted to mitochondria and chloroplasts.FPN3is expressed in shoots regardless of iron conditions, but its transcripts accumulate under iron deficiency in roots.fpn3mutants cannot grow as well as wild type under iron-deficient conditions and shoot iron levels are reduced infpn3mutants compared to wild type. ICP-MS measurements show that iron levels in the mitochondria and chloroplasts are increased relative to wild type, consistent with the proposed role of FPN3 as a mitochondrial/plastid iron exporter. In iron deficientfpn3mutants, abnormal mitochondrial ultrastructure was observed, whereas chloroplast ultrastructure was not affected, implying that FPN3 plays a critical role in the mitochondria. Overall, our study suggests that FPN3 is essential for optimal iron homeostasis.

Significance statement

Iron homeostasis must be tightly controlled in the mitochondria and chloroplasts, but iron trafficking in these organelles is not fully understood. Our work suggests that FPN3 is an iron exporter required for maintaining proper iron levels in mitochondria and chloroplasts. Furthermore, FPN3 is necessary for the optimal growth and normal mitochondrial ultrastructure under iron deficiency. This study reveals the physiological role of FPN3 and advances our understanding of iron regulation in mitochondria and chloroplasts.
Retinoic acid fluctuation activates an uneven, direction-dependent network-wide robustness response in early embryogenesis
Authors: Parihar Madhur , Bendelac-Kapon Liat , Gur Michal , Abbou Tali , Belorkar Abha , Achanta Sirisha , Kinberg Keren , Vadigepalli Rajanikanth , Fainsod Abraham
Published: July 2020

Robustness is a feature of regulatory pathways to ensure signal consistency in light of environmental changes or genetic polymorphisms. The retinoic acid (RA) pathway, is a central developmental and tissue homeostasis regulatory signal, strongly dependent on nutritional sources of retinoids and affected by environmental chemicals. This pathway is characterized by multiple proteins or enzymes capable of performing each step and their integration into a self-regulating network. We studied RA network robustness by transient physiological RA signaling disturbances followed by kinetic transcriptomic analysis of the recovery during embryogenesis. The RA metabolic network was identified as the main regulated module to achieve signaling robustness using an unbiased pattern analysis. We describe the network-wide responses to RA signal manipulation and found the feedback autoregulation to be sensitive to the direction of the RA perturbation: RA knockdown exhibited an upper response limit, whereas RA addition had a minimal feedback-activation threshold. Surprisingly, our robustness response analysis suggests that the RA metabolic network regulation exhibits a multi-objective optimization, known as Pareto optimization, characterized by trade-offs between competing functionalities. We observe that efficient robustness to increasing RA is accompanied by worsening robustness to reduced RA levels and vice versa. This direction-dependent trade-off in the network-wide feedback response, results in an uneven robustness capacity of the RA network during early embryogenesis, likely a significant contributor to the manifestation of developmental defects.
Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria
Authors: Popa Alexandra , Genger Jakob-Wendelin , Nicholson Michael , Penz Thomas , Schmid Daniela , Aberle Stephan W. , Agerer Benedikt , Lercher Alexander , Endler Lukas , Colaço Henrique , Smyth Mark , Schuster Michael , Grau Miguel , Martinez Francisco , Pich Oriol , Borena Wegene , Pawelka Erich , Keszei Zsofia , Senekowitsch Martin , Laine Jan , Aberle Judith H. , Redlberger-Fritz Monika , Karolyi Mario , Zoufaly Alexander , Maritschnik Sabine , Borkovec Martin , Hufnagl Peter , Nairz Manfred , Weiss Günter , Wolfinger Michael T. , von Laer Dorothee , Superti-Furga Giulio , Lopez-Bigas Nuria , Puchhammer-Stöckl Elisabeth , Allerberger Franz , Michor Franziska , Bock Christoph , Bergthaler Andreas
Published: July 2020

Superspreading events shape the COVID-19 pandemic. Here we provide a national-scale analysis of SARS-CoV-2 outbreaks in Austria, a country that played a major role for virus transmission across Europe and beyond. Capitalizing on a national epidemiological surveillance system, we performed deep whole-genome sequencing of virus isolates from 576 samples to cover major Austrian SARS-CoV-2 clusters. Our data chart a map of early viral spreading in Europe, including the path from low-frequency mutations to fixation. Detailed epidemiological surveys enabled us to calculate the effective SARS-CoV-2 population bottlenecks during transmission and unveil time-resolved intra-patient viral quasispecies dynamics. This study demonstrates the power of integrating deep viral genome sequencing and epidemiological data to better understand how SARS-CoV-2 spreads through populations.

Graphical Abstract
Emergence of diauxie as an optimal growth strategy under resource allocation constraints in cellular metabolism
Authors: Salvy Pierre , Hatzimanikatis Vassily
Published: July 2020

The sequential rather than simultaneous consumption of carbohydrates in bacteria such asE. coli, a phenomenon termed diauxie, has been hypothesized to be an evolutionary strategy which allows the organism to maximize its instantaneous specific growth, thus giving the bacterium a competitive advantage. Currently, computational techniques used in industrial biotechnology fall short of explaining the intracellular dynamics underlying diauxic behavior, in particular at a proteome level.

Some hypotheses postulate that diauxie is due to limitations in the catalytic capacity of bacterial cells. We developed a robust iterative dynamic method based on expression- and thermodynamically enabled flux models (dETFL) to simulate the temporal evolution of carbohydrate consumption and cellular growth. The dETFL method couples gene expression and metabolic networks at the genome scale, and successfully predicts the preferential uptake of glucose over lactose inE. colicultures grown on a mixture of carbohydrates. The observed diauxic behavior in the simulated cellular states suggests that the observed diauxic behavior is supported by a switch in the content of the proteome in response to fluctuations in the availability of extracellular carbon sources. We are able to model both the proteome allocation and the proteomic switch latency induced by different types of cultures.

Our models suggest that the diauxic behavior of the cell is the result of the evolutionary objective of maximization of the specific growth of the cell. We propose that genetic regulatory networks, such as thelacoperon inE. coli, are the biological implementation of a robust control system to ensure optimal growth.
Application of Digital Colorimeter for Preliminary Characterization of Gold Nanoparticle Swarms Produced byTermitomyces heimiiUsing a novel Bioinspired Microfluidics Assay
Authors: Dabolkar Sujata , Kamat Nandkumar M.
Published: July 2020

In our laboratory work extending over several years we have successfully studied the biogeochemical role of termite mounds and their occupants the termites and the exosymbiont fungus-Termitomyces. Fungi appear to be promising for large scale production of nanoparticles (NPs) as these are simpler to grow both in laboratory and at industrial scale. This paper reports a novel microfluidic based assay system to detect Gold bioreduction capacity of different tissues in tissue based and cell free environment. Using sterile microtest wells, different tissues such as umbo, pileus, lamellae, stipe context, stipe epicutis, pseudorrhiza context, pseudorrhiza epicutis ofTermitomyces heimiimature fruitbodies were tested with 200μl chloroauric acid (one mM) and after an interval of 5, 10, 15, 30, 45, 60, 120 min and 12, 24 and 48 hours. The results in terms production of distinct nanoparticles were directly visualized microscopically and using mobile based digital colorimeter. Membrane filtered sterile water soluble extracts (SWSE) from the same tissues were similarly screened. The results manifested by mono and polydisperse GNPs and microparticles of mixed size groups demonstrated that cell free system can be potentially useful for bioinspired fabrication of GNPs. Further work in this direction is in progress using severaltermitomycespure cultures.
The Aging Brain and Executive Functions Revisited: Implications from Meta-Analytic and Functional-Connectivity Evidence
Authors: Heckner Marisa K. , Cieslik Edna C. , Eickhoff Simon B. , Camilleri Julia A. , Hoffstaedter Felix , Langner Robert
Published: July 2020

Healthy aging is associated with changes in cognitive performance including executive functions (EFs) and their associated brain activation patterns. However, it has remained unclear which EF-related brain regions are affected consistently, because the results of pertinent neuroimaging studies and earlier meta-analyses vary considerably. We, therefore, conducted new rigorous meta-analyses of published age differences in EF-related brain activity. Out of a larger set of regions associated with EFs, only left inferior frontal junction (IFJ) and left anterior cuneus/precuneus (aC/PrC) were found to show consistent age differences. To further characterize these two age-sensitive regions, we performed seed-based resting-state functional connectivity (RS-FC) analyses using fMRI data from a large adult sample with a wide age range. We also assessed associations of the two regions’ whole-brain RS-FC patterns with age and EF performance. Although functional profiling and RS-FC analyses point towards a domain-general role of left IFJ in EFs, the pattern of individual study contributions to the meta-analytic results suggests process-specific modulations by age. Our analyses further indicate that left aC/PrC is recruited differently by older (compared to younger) adults during EF tasks, potentially reflecting inefficiencies in switching the attentional focus. Overall, our findings question earlier meta-analytic results and suggest a larger heterogeneity of age-related differences in brain activity associated with EFs. Hence, they encourage future research that pays greater attention to replicability, investigates age-related differences in deactivation, and focuses on more narrowly defined EF subprocesses, combining multiple behavioral assessments with multi-modal imaging.

Highlights

- Healthy aging is linked to deterioration in executive functions (EFs)

- ALE meta-analyses examined consistent age differences in brain activity linked to EFs

- In a larger set of EF regions, only left IFJ and (pre)cuneus were sensitive to age

- Advanced age was linked to weaker functional coupling within EF-related networks

- Our findings question earlier meta-analytic findings
Red seaweed (Asparagopsis taxiformis)supplementation reduces enteric methane by over 80 percent in beef steers
Authors: Roque B.M. , Venegas M. , Kinley R. , deNys R. , Neoh T. L. , Duarte T.L. , Yang X. , Salwen J. K. , Kebreab E.
Published: July 2020

The red macroalgae (seaweed)Asparagopsis spp.has shown to reduce ruminant enteric methane (CH4) production up to 99%in vitro.The objective of this study was to determine the effect ofAsparagopsis taxiformison CH4production (g/day per animal), CH4yield (g CH4/kg dry matter intake (DMI)), average daily gain (ADG), feed conversion efficiency (FCE), and carcass and meat quality in growing beef steers. Twenty-one Angus-Hereford beef steers were randomly allocated to one of three treatment groups: 0% (Control), 0.25% (Low Dose; LD), and 0.5% (High Dose; HD)A. taxiformisinclusion based on organic matter intake. Steers were fed 3 diets: high, medium, and low forage total mixed ration (TMR) representing typical life-stage diets of growing beef steers. The LD and HD treatments over 147 days reduced enteric CH4yield 45 and 68%, respectively; however, there was an interaction between TMR type and the magnitude of CH4yield reduction. Supplementing the low forage TMR reduced CH4yield 69.8% (P<0.001) for LD and 80% (P<0.001) for HD treatment. Hydrogen (H2) yield (g H2/DMI) increased significantly (P<0.001) 336 and 590% compared to Control for the LD and HD treatments, respectively. No differences were found in carbon dioxide (CO2) yield (g CO2/DMI), ADG, carcass quality, strip loin proximate analysis and shear force, or consumer taste preferences. DMI tended (P= 0.08) to decrease 8% in steers in LD treatment but significantly (P= 0.002) reduced 14% in steers in HD treatment. Conversely, FCE tended to increase 7% in steers in LD treatment (P= 0.06) and increased 14% in steers in HD (P< 0.01) treatment compared to Control. The persistent reduction of CH4byA. taxiformissupplementation suggests that this is a viable feed additive to significantly decrease the carbon footprint of ruminant livestock and potentially increase production efficiency.
Computational approaches towards reducing contamination in single-cell RNA-seq data
Authors: Yousefi Siamak , Chen Hao , Ingels Jesse F. , McCarty Melinda S. , Centeno Arthur G. , Chintalapudi Sumana , Mulligan Megan K. , Williams Pete A. , John Simon J. , Jones Bryan W. , Jablonski Monica M. , Hollingsworth T J. , Geisert Eldon E. , Lu Lu , Williams Robert W.
Published: July 2020

Single cell RNA sequencing has enabled quantification of single cells and identification of different cell types and subtypes as well as cell functions in different tissues. Single cell RNA sequence analyses assume acquired RNAs correspond to cells, however, RNAs from contamination within the input data are also captured by these assays. The sequencing of background contamination as well as unwanted cells making their way to the final assay Potentially confound the correct biological interpretation of single cell transcriptomic data. Here we demonstrate two approaches to deal with background contamination as well as profiling of unwanted cells in the assays. We use three real-life datasets of whole-cell capture and nucleotide single-cell captures generated by Fluidigm and 10x technologies and show that these methods reduce the effect of contamination, strengthen clustering of cells and improves biological interpretation.
Positivity effect in aging: Evidence for the primacy of positive responses to emotional ambiguity
Authors: Petro Nathan M. , Basyouni Ruby , Neta Maital
Published: July 2020

Older compared to younger adults show greater amygdala activity to positive emotions, and are more likely to interpret emotionally ambiguous stimuli (e.g., surprised faces) as positive. While some evidence suggests this positivity effect results from a relatively slow, top-down mechanism, others suggest it emerges from early, bottom-up processing. The amygdala is a key node in rapid, bottom-up processing and patterns of amygdala activity over time (e.g., habituation) can shed light on the mechanisms underlying the positivity effect. Younger and older adults passively viewed neutral and surprised faces in an MRI. Only in older adults, we found that amygdala habituation was associated with the tendency to interpret surprised faces as positive or negative (valence bias), where a more positive bias was associated with greater habituation. Interestingly, although a positive bias in younger adults was associated with slower reaction times, consistent with an initial negativity hypothesis in younger adults, older adults showed faster ratings of positivity. Together, we propose that there may be a switch to a primacy of positivity in aging.
Multi-modal single cell analysis reveals brain immune landscape plasticity during aging and gut microbiota dysbiosis
Authors: Golomb Samantha M. , Guldner Ian H. , Zhao Anqi , Wang Qingfei , Palakurthi Bhavana , Lopez Jacqueline , Yang Kai , Zhang Siyuan
Published: July 2020

The brain contains a diverse array of immune cell types. The phenotypic and functional plasticity of brain immune cells collectively contribute to brain tissue homeostasis and disease progression. Immune cell plasticity is profoundly influenced by local tissue microenvironment cues and systemic factors. Yet, the transcriptional mechanism by which systemic stimuli, such as aging and gut microbiota dysbiosis, reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyzed compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. We first examined the discordance between canonical surface marker-defined immune cell types (Cell-ID) and their transcriptome signatures, which suggested transcriptional plasticity among immune cells despite sharing the same cell surface markers. Specifically, inflammatory and patrolling Ly6C+ monocytes were shifted predominantly to a pro-inflammatory transcriptional program in the aged brain, while brain ILCs shifted toward an ILC2 transcriptional profile. Finally, aging led to an increase of ILC-like cells expressing a T memory stemness (Tscm) signature in the brain. Antibiotics (ABX)-induced gut dysbiosis reduced the frequency of ILCs exhibiting Tscm-like properties in the aged mice, but not in the young mice. Enabled by high-resolution single-cell molecular phenotyping, our study revealed that systemic changes due to aging and gut dysbiosis prime the brain environment for an increased propensity for neuroinflammation, which provided insights into gut dysbiosis in age-related neurological diseases.

Manuscript Summary

Golombet al.performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) on immune cells from the brains of young and aged mice with and without antibiotics-induced gut dysbiosis. High resolution, single cell immunophenotyping enabled the dissection of extensive transcriptional plasticity of canonically identified monocytes and innate lymphoid cells (ILCs) in the aged brain. Through differential gene expression and trajectory inference analyses, the authors revealed tissue microenvironment-dependent cellular responses influenced by aging and gut dysbiosis that may potentiate neuroinflammatory diseases.

Graphical Abstract
Wing-pattern-specific effects of experience on mating behavior inHeliconius melpomenebutterflies
Authors: Rather Peyton A. , Herzog Abigail E. , Ernst David A. , Westerman Erica L.
Published: July 2020

Many animals have the ability to learn, and some taxa have shown learned mate preference. This learning may be important for speciation in some species. The butterflyHeliconius melpomeneis a model system for several areas of research, including hybridization, mate selection, and speciation, partially due to its widespread diversity of wing patterns. It remains unclear whether these butterflies can learn to prefer certain mates and if social experience shapes realized mating preferences. Here we test whether previous experience with a female influences male mate preference for two differentH. melpomenesubspecies,H. m. malletiandH. m. rosina. We conducted no-choice behavioral assays to determine if latency to court and whether males courted (vs no courtship) differed between naïve males and males with previous exposure to a young, sexually mature, virgin female. To test whether assortative courtship preference is learned inH. melpomene, males were either paired with a female who shared their phenotype or one who did not. NaïveH. m. mallettimales courted assortatively, while naïveH.m. rosinamales did not. ExperiencedH. m. malletimales reduced their courting relative to naïve males, suggesting that social experience with a sexually mature female that does not result in copulation may be perceived as a negative experience. In contrast, experiencedH. m. rosinamales exhibited similar courting rates to naïveH. m. rosinamales. Our results suggest that social experience can influence male mating behavior inH. melpomeneand that behavioral plasticity may differ across populations in this species.
Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish
Authors: Holmgren Melanie , Ravicz Michael E. , Hancock Kenneth E. , Strelkova Olga , Kallogjeri Dorina , Indzhykulian Artur A. , Warchol Mark E. , Sheets Lavinia
Published: July 2020

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.
IGT/LAZY family genes are differentially influenced by light signals and collectively required for light-induced changes to branch angle
Authors: Waite Jessica Marie , Dardick Christopher
Published: July 2020

Plants adjust their growth orientations in response to environmental signals such as light and gravity in order to optimize photosynthesis and access to nutrients. However, given the fixed nature of gravity, understanding how light and gravity signals are integrated is challenging. Branch orientation, or gravitropic set point angle, is a key aspect of plant architecture, set with respect to gravity and shown to be altered by changes in light conditions. The IGT gene family, also known as theLAZYfamily, contains important components for branch angle and gravity responses, including three gene clades:LAZY, DEEPER ROOTING (DRO), andTILLER ANGLE CONTROL (TAC). LAZYandDROgenes promote upward branch orientations downstream of amyloplast sedimentation, and upstream of auxin redistribution in response to gravity. In contrast,TAC1promotes downward branch angles in response to photosynthetic signals. Here, we investigated the influence of different light signaling pathways onLAZYandDROgene expression, and their role in light regulation of branch angle responses. We found differential effects of continuous light and dark, circadian clock, photoreceptor-mediated signaling, and photosynthetic signals onLAZYandDROgene expression. Phenotypic analysis revealed thatLAZYandDROgenes are collectively required for branch angle responses to light.

Highlight

LAZYandDROgene expression responds differentially to changes in light regime and signaling. Loss of multipleLAZYandDROgenes leads to loss of branch angle response to light.
Seasonal prevalence and characterization of Shiga toxin-producingEscherichia colion pork carcasses at three steps of the harvest process at two commercial processing plants in the US
Authors: Nastasijevic Ivan , Schmidt John W. , Boskovic Marija , Glisic Milica , Kalchayanand Norasak , Shackelford Steven D. , Wheeler Tommy L. , Koohmaraie Mohammad , Bosilevac Joseph M.
Published: July 2020

Shiga toxin (stx) -producingEscherichia coli(STEC) are foodborne pathogens that have a significant impact on public health, with those possessing the attachment factor intimin (eae) referred to as enterohemorrhagicE. coli(EHEC) associated with life threatening illnesses. Cattle and beef are considered typical sources of STEC, but their presence in pork products is a growing concern. Therefore, carcasses (n=1536) at two U.S. pork processors were sampled once per season at three stages of harvest (post-stunning skins; post-scald carcasses; chilled carcasses) then examined using PCR forstxandeae, aerobic plate count (APC) andEnterobacteriaceaecounts (EBC). Skins, post-scald, and chilled carcasses had prevalence ofstx(85.3, 17.5, and 5.4%, respectively), with 82.3, 7.8, and 1.7% respectively, havingstxandeaepresent. Allstxpositive samples were subjected to culture isolation that resulted in 368 STEC and 46 EHEC isolates. The most frequently identified STEC were serogroup O121, O8, and O91(63, 6.7, and 6.0% of total STEC, respectively). The most frequently isolated EHEC was serotype O157:H7 (63% of total EHEC). Results showed that scalding significantly reduced (P< 0.05) carcass APC and EBC by 3.00 and 2.50 log10CFU/100 cm2respectively. A seasonal effect was observed with STEC prevalence lower (P< 0.05) in winter. The data from this study shows significant (P< 0.05) reduction in the incidence of STEC (stx) from 85.3% to 5.4% and of EHEC (stx+eae) from 82.3% to 1.7% within slaughter-to-chilling continuum, respectively, and that potential EHEC can be confirmed present throughout using culture isolation.

IMPORTANCE

Seven serogroups of Shiga toxin-producingEscherichia coli(STEC) are responsible for most (>75%) cases of severe illnesses caused by STEC and are considered adulterants of beef. However, some STEC outbreaks have been attributed to pork products although the sameE. coliare not considered adulterants in pork because little is known of their prevalence along the pork chain. The significance of the work presented here is that it identifies disease causing STEC, enterohemorrhagicE. coli(EHEC), demonstrating that these same organisms are a food safety hazard in pork as well as beef. The results show that most STEC isolated from pork are not likely to cause severe disease in humans and that processes used in pork harvest, such as scalding, offer a significant control point to reduce contamination. The results will assist the pork processing industry and regulatory agencies to optimize interventions to improve the safety of pork products.
Joint CBC-ICT Interpretation for the pre-surgical screening of COVID 19 asymptomatic cases: A cross-sectional study
Authors: Imran Tanzeel , Naz Humera Altaf , Khan Hamza , Bangash Ali Haider , Khan Laraib Bakhtiar , Khan Haroon
Published: July 2020

Background

On 26th, February 2020, first cases of COVID 19 were confirmed in Pakistan. Since then, surgeries were halted in a bid to prevent transmission. However, since such a long halt is infeasible, a general protocol of screening the carriers, especially asymptomatic carries, is a dire need of time. The objective of our study is to propose an economically feasible protocol of COVID 19 screening. Simple but effective screening strategies can help to restore the workings of hospital surgical departments.

Methods

We analyzed the clinical data of patients turning up for elective surgeries at the Rawal General Hospital (RGH), Islamabad from the 24thof March to the 15thof May, 2020. Asymptomatic patients with negative COVID 19 contact and travel histories were screened with COVID 19 Immunochromatography (ICT) IgM / IgG Ab Test. Complete blood count (CBC) was done and interpreted in conjunction with the ICT results.

Results

39 patients with a mean age of 49 years were studied. The result of ICT for COVID-19 was positive in 9 cases (23%). The entire positive ICT patients population expressed significantly lower lymphocyte count (p<0.01); 8 patients had high monocyte count (p<0.05) whereas only 4 patients had a combined high neutrophil and monocyte count (P<0.05). All of these four patients with high neutrophil count were females. The combined interpretation of CBC and ICT IgM / IgG Ab Test had a high accuracy in diagnosing asymptomatic COVID-19 carriers that were later confirmed by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR).

Conclusion

We propose that joint CBC-ICT interpretation should be adopted on a large scale to help in the diagnoses of asymptomatic carriers as both tests are simple and inexpensive and thus suit the developing countries’ limited health budget. Future research projects should be adopted in order to assess the accuracy of the proposed protocol on a large scale.
Implementing Primary Care Mediated Population Genetic Screening within an Integrated Health System
Authors: David Sean P , Dunnenberger Henry M , Ali Raabiah , Matsil Adam , Lemke Amy A , Singh Lavisha , Zimmer Anjali , Hulick Peter J
Published: July 2020

Introduction

Genetic screenings can have a large impact on enabling personalized preventative care. However, this can be limited by the primary use of medical history-based screenings in determining care. The purpose of this study was to understand the impact of DNA10K, a population-based genetic screening program mediated by primary care physicians (PCPs) within an integrated health system to emphasize its contribution to preventative healthcare.

Methods

Construction of the patient experience as part of DNA10K shaped the context for PCP engagement within the program. A cross-sectional analysis of patient consents, orders, tests, and results of nearly 10,000 patients within the primary care specialties of family medicine, internal medicine or obstetrics/gynecology between April 1, 2019 and January 22, 2020 was conducted.

Results

Across all specialties, a median number of 7.5 cancer and cardiovascular disease variants per PCP was found. The average age of the study population was 49.6 years. Over 8% of these patients had at least one actionable genetic risk variant and almost 2% of patients had at least one CDC Tier 1 variant. The median number of patients per PCP with either hereditary breast and ovarian cancer, Lynch Syndrome, or Familial Hypercholesterolemia was 1 (Interquartile Range 0-2).

Discussion

The analysis of test results and the engagement of an integrated healthcare system in the implementation of a genetic screening program suggests that it can have a large impact on population health outcomes and minimal referral burden to PCPs if identified risks can lead to preventative care.
Genetic risk for Alzheimer’s disease influences neuropathology and cognition via multiple biological pathways
Authors: Hannon Eilis , Shireby Gemma L , Brookes Keeley , Attems Johannes , Sims Rebecca , Cairns Nigel J , Love Seth , Thomas Alan J , Morgan Kevin , Francis Paul T , Mill Jonathan
Published: July 2020

Alzheimer’s disease is a highly heritable, common neurodegenerative disease characterised neuropathologically by the accumulation of β-amyloid plaques and tau-containing neurofibrillary tangles. In addition to the well-established risk associated with the APOE locus, there has been considerable success in identifying additional genetic variants associated with Alzheimer’s disease. Major challenges in understanding how genetic risk influences the development of Alzheimer’s disease are clinical and neuropathological heterogeneity, and the high level of accompanying comorbidities. We report a multimodal analysis integrating longitudinal clinical and cognitive assessment with neuropathological data collected as part of the Brains for Dementia Research (BDR) study to understand how genetic risk factors for Alzheimer’s disease influence the development of neuropathology and clinical performance. 693 donors in the BDR cohort with genetic data, semi-quantitative neuropathology measurements, cognitive assessments and established diagnostic criteria were included in this study. We tested the association of APOE genotype and Alzheimer’s disease polygenic risk score - a quantitative measure of genetic burden - with survival, four common neuropathological features in Alzheimer’s disease brains (neurofibrillary tangles, β-amyloid plaques, Lewy bodies and TDP-43 proteinopathy), clinical status (clinical dementia rating) and cognitive performance (Mini-Mental State Exam, Montreal Cognitive Assessment). The APOE ε4 allele was significantly associated with younger age of death in the BDR cohort. Our analyses of neuropathology highlighted two independent pathways from APOE ε4, one where β-amyloid accumulation mediates the development of tauopathy, and a second characterized by direct effects on tauopathy independent of β-amyloidosis. Although we also detected association between APOE ε4 and dementia status and cognitive performance, these were all mediated by tauopathy, highlighting that they are a consequence of the neuropathological changes. Analyses of polygenic risk score identified associations with tauopathy and β-amyloidosis, which appeared to have both shared and unique contributions, suggesting that different genetic variants associated with Alzheimer’s disease affect different features of neuropathology to different degrees. Taken together, our results provide insight into how genetic risk for Alzheimer’s disease influences both the clinical and pathological features of dementia, increasing our understanding about the interplay between APOE genotype and other genetic risk factors.