bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing fisheries in a world with more sea turtles
Authors: Putman Nathan F. , Hawkins Jesse , Gallaway Benny J.
Published: July 2020

For decades, fisheries have been managed to limit the accidental capture of vulnerable species and many of these populations are now rebounding. While encouraging from a conservation perspective, as populations of protected species increase so will bycatch, triggering management actions that limit fishing. Here, we show that despite extensive regulations to limit sea turtle bycatch in a coastal gillnet fishery on the eastern United States, the catch per trip of Kemp's ridley has increased by more than 300% and green turtles by more than 650% (2001–2016). These bycatch rates closely track regional indices of turtle abundance, which are a function of increased reproductive output at distant nesting sites and the oceanic dispersal of juveniles to near shore habitats. The regulations imposed to help protect turtles have decreased fishing effort and harvest by more than 50%. Given uncertainty in the population status of sea turtles, however, simply removing protections is unwarranted. Stock-assessment models for sea turtles must be developed to determine what level of mortality can be sustained while balancing continued turtle population growth and fishing opportunity. Implementation of management targets should involve federal and state managers partnering with specific fisheries to develop bycatch reduction plans that are proportional to their impact on turtles.
Structural colours in diverse Mesozoic insects
Authors: Cai Chenyang , Tihelka Erik , Pan Yanhong , Yin Ziwei , Jiang Rixin , Xia Fangyuan , Huang Diying
Published: July 2020

Structural colours, nature's most pure and intense colours, originate when light is scattered via nanoscale modulations of the refractive index. Original colours in fossils illuminate the ecological interactions among extinct organisms and functional evolution of colours. Here, we report multiple examples of vivid metallic colours in diverse insects from mid-Cretaceous amber. Scanning and transmission electron microscopy revealed a smooth outer surface and five alternating electron-dense and electron-lucent layers in the epicuticle of a fossil wasp, suggesting that multilayer reflectors, the most common biophotonic nanostructure in animals and even plants, are responsible for the exceptional preservation of colour in amber fossils. Based on theoretical modelling of the reflectance spectra, a reflective peak of wavelength of 514 nm was calculated, corresponding to the bluish-green colour observed under white light. The green to blue structural colours in fossil wasps, beetles and a fly most likely functioned as camouflage, although other functions such as thermoregulation cannot be ruled out. This discovery not only provides critical evidence of evolution of structural colours in arthropods, but also sheds light on the preservation potential of nanostructures of ancient animals through geological time.
Active flow network generates molecular transport by packets: case of the endoplasmic reticulum
Authors: Dora M. , Holcman D.
Published: July 2020

Biological networks are characterized by their connectivity and topology but also by their ability to transport materials. In the case of random transportation, the efficacy is measured by the time it takes to travel between two nodes of the network. We study here the consequences of a unidirectional transport mechanism occurring in the endoplasmic reticulum (ER) network, a structure present in the cell cytoplasm. This unidirectional transport mechanism is an active-waiting transportation, where molecules have to wait a random time before being transported from one node to the next one. We develop here a general theory of transport in an active network and find an unusual network transportation, where molecules group together in redundant packets instead of being disperse. Finally, the mean time to travel between two nodes of the ER is of the order of 20 min, but is reduced to 30 s when we consider the fastest particles because it uses optimal paths. To conclude, the present theory shows that unidirectional transport is an efficient and robust mechanism for fast molecular redistribution inside the ER.
Community-level reorganizations following migratory pollinator dynamics along a latitudinal gradient
Authors: Magrach Ainhoa , Lara Carlos , Luna Ubaldo Márquez , Díaz-Infante Sergio , Parker Ingrid
Published: July 2020

Predicting how communities re-arrange in response to changes in species composition remains a key challenge in ecology. Migratory species, which enter and leave communities across latitudinal gradients, offer us a unique opportunity to evaluate community- and species-level responses to a shift in community composition. We focused on a migratory hummingbird and the communities that host it along a latitudinal and species diversity gradient. Our results show higher niche overlap in more diverse communities, allowing resident species to compensate for the loss of the migrant in providing pollination services. Contrastingly, in less diverse communities, the migrant behaves as a specialist, monopolizing abundant resources. In its absence, its role is not fully covered by resident species, resulting in a decrease in the fruit set of the migrant's preferred plant species. These results help us understand the potential impacts of biodiversity loss and have important implications for community persistence given expected changes in the migratory behaviours of some species.
Prior exposure to long-day photoperiods alters immune responses and increases susceptibility to parasitic infection in stickleback
Authors: Whiting James R. , Mahmud Muayad A. , Bradley Janette E. , MacColl Andrew D. C.
Published: July 2020

Seasonal disease and parasitic infection are common across organisms, including humans, and there is increasing evidence for intrinsic seasonal variation in immune systems. Changes are orchestrated through organisms' physiological clocks using cues such as day length. Ample research in diverse taxa has demonstrated multiple immune responses are modulated by photoperiod, but to date, there have been few experimental demonstrations that photoperiod cues alter susceptibility to infection. We investigated the interactions among photoperiod history, immunity and susceptibility in laboratory-bred three-spined stickleback (a long-day breeding fish) and its external, directly reproducing monogenean parasiteGyrodactylus gasterostei. We demonstrate that previous exposure to long-day photoperiods (PLD) increases susceptibility to infection relative to previous exposure to short days (PSD), and modifies the response to infection for the mucin genemuc2and Treg cytokinefoxp3ain skin tissues in an intermediate 12 L : 12 D photoperiod experimental trial. Expression of skinmuc2is reduced in PLD fish, and negatively associated with parasite abundance. We also observe inflammatory gene expression variation associated with natural inter-population variation in resistance, but find that photoperiod modulation of susceptibility is consistent across host populations. Thus, photoperiod modulation of the response to infection is important for host susceptibility, highlighting new mechanisms affecting seasonality of host–parasite interactions.
A global analysis of cultural tightness in non-industrial societies
Authors: Jackson Joshua Conrad , Gelfand Michele , Ember Carol R.
Published: July 2020

Human groups have long faced ecological threats such as resource stress and warfare, and must also overcome strains on coordination and cooperation that are imposed by growing social complexity. Tightness–looseness (TL) theory suggests that societies react to these challenges by becoming culturally tighter, with stronger norms and harsher punishment of deviant behaviour. TL theory further predicts that tightening is associated with downstream effects on social, political and religious institutions. Here, we comprehensively test TL theory in a sample of non-industrial societies. Since previous studies of TL theory have sampled contemporary countries and American states, our analysis allows us to examine whether the theory generalizes to societies in the ethnographic record and also to explore new correlates of tightness that vary more in non-industrial societies. We find that tightness covaries across domains of social norms, such as socialization, law and gender. We also show that tightness correlates with several theorized antecedents (ecological threat, complexity, residential homogeneity) and several theorized consequences (intergroup contact, political authoritarianism, moralizing religious beliefs). We integrate these findings into a holistic model of tightness in non-industrial societies and provide metrics that can be used by future studies on cultural tightness in the ethnographic record.
Dopamine mediates life-history responses to food abundance in
Daphnia
Authors: Issa Semona , Gamelon Marlène , Ciesielski Tomasz Maciej , Vike-Jonas Kristine , Asimakopoulos Alexandros G. , Jaspers Veerle L. B. , Einum Sigurd
Published: July 2020

Expression of adaptive reaction norms of life-history traits to spatio-temporal variation in food availability is crucial for individual fitness. Yet little is known about the neural signalling mechanisms underlying these reaction norms. Previous studies suggest a role for the dopamine system in regulating behavioural and morphological responses to food across a wide range of taxa. We tested whether this neural signalling system also regulates life-history reaction norms by exposing the zooplankton
Daphnia magna
to both dopamine and the dopamine reuptake inhibitor bupropion, an antidepressant that enters aquatic environments via various pathways. We recorded a range of life-history traits across two food levels. Both treatments induced changes to the life-history reaction norm slopes. These were due to the effects of the treatments being more pronounced at restricted food ration, where controls had lower somatic growth rates, higher age and larger size at maturation. This translated into a higher population growth rate (
r
) of dopamine and bupropion treatments when food was restricted. Our findings show that the dopamine system is an important regulatory mechanism underlying life-history trait responses to food abundance and that bupropion can strongly influence the life history of aquatic species such as
D. magna
. We discuss why
D. magna
do not evolve towards higher endogenous dopamine levels despite the apparent fitness benefits.
Total parietal peritonectomy leads to a low incidence of platinum resistance in patients undergoing interval cytoreductive surgery for advanced epithelial serous ovarian cancer- results of a prospective multi-centric study
Authors: Kammar Praveen , Sinukumar Snita , Parikh Loma , Shaikh Sakina , Jumale Nutan , Mallya Mrinal , Sheth Sandeep , Mehta Sanket , Bhatt Aditi
Published: July 2020

Background and Aim

Though interval cytoreductive surgery (CRS) following neoadjuvant chemotherapy (NACT) is considered non-inferior to primary CRS, the incidence of platinum resistance is high. A total parietal peritonectomy (TPP) can address occult microscopic disease more completely and could reduce the rates of early recurrence. The early results of a prospective study evaluating the role of TPP are presented in this manuscript.

Methods

This is a prospective, multi-centric interventional study. A TPP was performed in all patients undergoing interval CRS. A fixed surgical protocol was followed. Grade 3-4 morbidity was recorded. Factors affecting grade 3-4 morbidity, early recurrence and progression-free survival (PFS) were evaluated.

Results

From July 2018, 70 patients with serous carcinoma were included. The median surgical PCI was 15 [range 5-37]. A CC-0 resection was obtained in 55(78.5%) patients; CC-1 in 10(14.2%). Grade 3-4 complications were seen in 15(21.4%) patients of which the commonest complication was intraperitoneal fluid collection. Occult disease in the peritoneum was seen in 40%. Early recurrence (platinum resistance) was seen in 5(7.1%). The median PFS was 18 months [range 0-21months]. Patients with a lower PCI and with no grade 3-4 complications had a significantly longer PFS. A pathological PCI>15 was the only independent predictor of a shorter PFS (p=0.001).

Conclusions

TPP performed as a part of interval CRS resulted in a very low incidence of platinum resistance. The post-operative morbidity was acceptable. These findings should be confirmed in a larger series and a randomized trial performed to demonstrate demonstrate its benefit over conventional surgery.
Cluster analysis of epidemiological characteristic features of confirmed cases with the novel coronavirus (COVID-19) outside China: a descriptive study
Authors: Nguyen-Tran Minh-Duc , Abozaid Ali Ahmed-Fouad , Thang Tai Luu Lam , Nhat Minh Le Huu , Le Quang-Loc , Nguyen Hoang-Dung , Dao Khanh-Linh , Le Huu-Hoai , Huy Nguyen Tien
Published: July 2020

Background

Novel coronavirus COVID-19 has caused significant global outbreaks outside China. Many countries have closed their borders with China and performed obligate protective procedures, however, this disease was still rising worldwide. In this report, we aim to identify transmission patterns from China to other countries, along with describing the disease control situation of countries.

Methods

We retrospectively collected information about infected cases with COVID-19 from WHO situation reports, official notification websites of health ministries and reliable local newspapers from each country. Descriptive and cluster analysis was performed to describe the transmission characteristics while the logistic regression test was used to estimate the risk factors for the occurrence of an infected individual with an unknown source.

Results

A total of 446 infected cases were recorded from 24 countries outside China until 12 February 2020, with the number of reported infected cases were doubled every 3.08 ± 0.35 days (range from 2.6 to 3.9). Besides the spread from China, the transmission was originated from sub-endemic countries (Japan, Thailand, Singapore, Malaysia, France, German). Out of 6 countries got occurrence of an infected individual with unknown source and possible potential factors contributed to this occurrence was a time of epidemic circulating, number of patients and number of clusters when the occurrence still has not happened, and notably, the unreported situation of Chinese tourists’ information.

Conclusions

The situational reports of each country about COVID-19 should be more detailed mentioning the transmissions routes with keeping contact tracing of the unknown cases to increase the control of this disease.
The genome analysis ofTripterygium wilfordiireveals TwCYP712K1 andTwCYP712K2responsible for oxidation of friedelin in celastrol biosynthesis pathway
Authors: Pei Tianlin , Yan Mengxiao , Kong Yu , Liu Jie , Cui Mengying , Fang Yumin , Ge Binjie , Yang Jun , Zhao Qing
Published: July 2020

Tripterygium wilfordiiis a Traditional Chinese Medicine (TCM) from family Celastraceae and celastrol is one of the strongest active ingredients belonging to friedelane-type pentacyclic triterpenoid, which has a large clinical application value of anti-tumor, immunosuppression, and obesity treatment. The first committed biosynthesis step of celastrol is the cyclization of 2, 3-oxidosqualene to friedelin, catalyzed by the oxidosqualene cyclase, while the rest of this pathway is still unclear. In this study, we reported a reference genome assembly ofT. wilfordiiwith high-quality annotation by using a hybrid sequencing strategy (Nanopore, Bionano, Illumina HiSeq, and Pacbio), which obtained a 340.12 Mb total size and contig N50 reached 3.09 Mb. In addition, we successfully anchored 91.02% sequences into 23 pseudochromosomes using Hi-C technology and the super-scaffold N50 reached 13.03 Mb. Based on integration genome, transcriptom and metabolite analyses, as well asin vivoandin vitroenzyme assays, two CYP450 genes,TwCYP712K1andTwCYP712K2have been proven for C-29 position oxidation of friedelin to produce polpunonic acid, which clarifies the second biosynthesis step of celastrol. Syntenic analysis revealed thatTwCYP712K1 andTwCYP712K2derived from the common ancestor. These results have provided insight into illustrating pathways for both celastrol and other bioactive compounds found in this plant.
Decoding network-mediated retinal response to electrical stimulation: implications for fidelity of prosthetic vision
Authors: Ho Elton , Shmakov Alex , Palanker Daniel
Published: July 2020

Objective

Patients with the photovoltaic subretinal implant PRIMA demonstrated letter acuity by ~0.1 logMAR worse than the sampling limit for 100μm pixels (1.3 logMAR) and performed slower than healthy subjects, which exceeded the sampling limit at equivalently pixelated images by ~0.2 logMAR. To explore the underlying differences between the natural and prosthetic vision, we compare the fidelity of the retinal response to visual and subretinal electrical stimulation through single-cell modeling and ensemble decoding.

Approach

Responses of the retinal ganglion cells (RGC) to optical or electrical (1mm diameter arrays, 75μm pixels) white noise stimulation in healthy and degenerate rat retinas were recorded via MEA. Each RGC was fit with linear-non-linear (LN) and convolutional neural network (CNN) models. To characterize RGC noise level, we compared statistics of the spike-triggered average (STA) in RGCs responding to electrical or visual stimulation of healthy and degenerate retinas. At the population level, we constructed a linear decoder to determine the certainty with which the ensemble of RGCs can support theN-way discrimination tasks.

Main results

Although LN and CNN models can match the natural visual responses pretty well (correlation ~0.6), they fit significantly worse to spike timings elicited by electrical stimulation of the healthy retina (correlation ~0.15). In the degenerate retina, response to electrical stimulation is equally bad. The signal-to-noise ratio of electrical STAs in degenerate retinas matched that of the natural responses when 78±6.5% of the spikes were replaced with random timing. However, the noise in RGC responses contributed minimally to errors in the ensemble decoding. The determining factor in accuracy of decoding was the number of responding cells. To compensate for fewer responding cells under electrical stimulation than in natural vision, larger number of presentations of the same stimulus are required to deliver sufficient information for image decoding.

Significance

Slower than natural pattern identification by patients with the PRIMA implant may be explained by the lower number of electrically activated cells than in natural vision, which is compensated by a larger number of the stimulus presentations.
Exploring rare cellular activity in more than one million cells by a trans-scale-scope
Authors: Ichimura T. , Kakizuka T. , Horikawa K. , Seiriki K. , Kasai A. , Hashimoto H. , Fujita K. , Watanabe T. M. , Nagai T.
Published: July 2020

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate inDictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.
Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity
Authors: Hynes Tristan , Hrelja Kelly , Hathaway Brett , Hounjet Celine , Chernoff Chloe , Ebsary Sophie , Betts Graeme , Russell Brittney , Ma Lawrence , Kaur Sukhbir , Winstanley Catharine
Published: July 2020

Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision-making. Drug-associated cues have long been known to facilitate habitual drug-seeking, and the salient audiovisual cues embedded within modern gambling products may like-wise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward-paired cues, and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we first gained specific inhibitory control over VTA dopamine neurons by transducing a floxed inhibitory DREADD (AAV5-hSyn-DIO-hM4D(Gi)-mCherry) in rats expressing Cre recombinase in tyrosine hydroxylase neurons. We then trained rats in our cued rat gambling task (crGT), inhibiting dopamine neurons throughout task acquisition and performance, before allowing them to self-administer cocaine in the same diurnal period as crGT sessions. The trajectories of addiction differ in women and men, and the dopamine system may differ functionally across the sexes, therefore we used male and female rats here. We found that inhibition of VTA dopamine neurons decreased cue-induced risky choice and reduced motor impulsivity in males, but surprisingly, enhanced risky decision making in females. Inhibiting VTA dopamine neurons also prevented cocaine-induced deficits in decision making in both sexes, but nevertheless drove all animals to consume more cocaine. These findings show that chronic dampening of dopamine signalling can have both protective and deleterious effects on addiction-relevant behaviours, depending on biological sex and dependent variable of interest.
Optimizing Sequencing Resources in Genotyped Livestock Populations Using Linear Programming
Authors: Cheng Hao , Xu Keyu , Li Jinghui , Abraham Kuruvilla Joseph
Published: July 2020

Background

Low-cost genome-wide single-nucleotide polymorphisms (SNPs) are routinely used in animal breeding programs. Compared to SNP arrays, the use of whole-genome sequence data generated by the next-generation sequencing technologies (NGS) has great potential in livestock populations. However, a large number of animals are required to be sequenced to exploit the full potential of whole-genome sequence data. Thus, novel strategies are desired to allocate sequencing resources in genotyped livestock populations such that the entire population can be sequenced or imputed efficiently.

Methods

We present two applications of linear programming models called LPChoose for sequencing resources allocation. The first application is to identify the minimum number of animals for sequencing while meeting the criteria that each haplotype in the population is contained in at least one of the animals selected for sequencing. The second is to sequence a fixed number of animals whose haplotypes include as large a proportion as possible of the haplotypes present in the population given a limited sequencing budget.

Results

In both applications LPChoose has similar or better performance than some other methods. The linear programming models we proposed are based on rigorous and well defined optimization techniques and easy and straightforward to implement. LPChoose is available as an open-source package.
Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2
Authors: Wirden Marc , Feghoul Linda , Bertine Mélanie , Nere Marie-Laure , Le Hingrat Quentin , Abdi Basma , Boutolleau David , Ferre Valentine Marie , Jary Aude , Delaugerre Constance , Marcelin Anne-Genevieve , Descamps Diane , Legoff Jérôme , Visseaux Benoit , Chaix Marie-Laure
Published: July 2020

Background

RT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas® (Roche) and the RealStar® assay (Altona).

Methods

Assessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas® assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMérieux).

Results

Overall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct.

Conclusions

In this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar® assay, probably due to a low viral load close to the detection limit of both assays.
Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa
Authors: Reddy Krishna P. , Shebl Fatma M. , Foote Julia H. A. , Harling Guy , Scott Justine A. , Panella Christopher , Flanagan Clare , Hyle Emily P. , Neilan Anne M. , Mohareb Amir M. , Bekker Linda-Gail , Lessells Richard J. , Ciaranello Andrea L. , Wood Robin , Losina Elena , Freedberg Kenneth A. , Kazemian Pooyan , Siedner Mark J.
Published: July 2020

Background

Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19.

Methods

We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and diagnostic testing for symptomatic individuals (MS); and Quarantine Centres (QC), for contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (Re) of 1·5 and 1·2. We comparedHT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, andHT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER) <US$1,290/year-of-life saved (YLS) to be cost-effective.

Findings

With Re1·5,HTresulted in the most COVID-19 deaths and lowest costs over 360 days. Compared withHT, HT+CT+IC+MSreduced mortality by 76%, increased costs by 16%, and was cost-effective (ICER $350/YLS).HT+CT+IC+MS+QCprovided the greatest reduction in mortality, but increased costs by 95% compared withHT+CT+IC+MSand was not cost-effective (ICER $8,000/YLS). With Re1·2,HT+CT+IC+MSwas the least costly strategy, andHT+CT+IC+MS+QCwas not cost-effective (ICER $294,320/YLS).

Interpretation

In South Africa, a strategy of household contact tracing, isolation, and mass symptom screening would substantially reduce COVID-19 mortality and be cost-effective. Adding quarantine centres for COVID-19 contacts is not cost-effective.

Funding

Royal Society, Wellcome Trust, National Institutes of Health
Circulating Markers of Angiogenesis and Endotheliopathy in COVID-19
Authors: Meizlish Matthew L. , Pine Alexander B. , Goshua George , Chang C-Hong , Zhang Hanming , Bishai Jason , Bahel Parveen , Patel Amisha , Gbyli Rana , Kwan Jennifer , Price Christina , Dela Cruz Charles S. , Halene Stephanie , van Dijk David , Hwa John , Lee Alfred I. , Chun Hyung J.
Published: July 2020

Despite over 9.3 million infected and 479,000 deaths, the pathophysiological factors that determine the wide spectrum of clinical outcomes in COVID-19 remain inadequately defined. Importantly, patients with underlying cardiovascular disease have been found to have worse clinical outcomes,1 and autopsy findings of endotheliopathy as well as angiogenesis in COVID-19 have accumulated.2,3 Nonetheless, circulating vascular markers associated with disease severity and mortality have not been reliably established. To address this limitation and better understand COVID-19 pathogenesis, we report plasma profiling of factors related to the vascular system from a series of patients admitted to Yale-New Haven Hospital with confirmed diagnosis of COVID-19 via PCR, which demonstrate significant increase in markers of angiogenesis and endotheliopathy in patients hospitalized with COVID-19.
Male gender and kidney illness associated with an increased risk of severe laboratory-confirmed coronavirus disease
Authors: Murillo-Zamora Efrén , Trujillo Xóchitl , Huerta Miguel , Ríos-Silva Mónica , Mendoza-Cano Oliver
Published: July 2020

Objective

To identify factors predicting severe coronavirus disease 2019 (COVID-19) in adolescent and adult patients with laboratory-positive (quantitative reverse-transcription polymerase chain reaction) infection.

Methods

A retrospective cohort study took place, and data from 740 subjects, from all 32 states of Mexico, were analyzed. The association between the studied factors and severe (dyspnea requiring hospital admission) COVID-19 was evaluated through risk ratios (RRs) and 95% confidence intervals (CIs).

Results

Severe illness was documented in 28% of participants. In multiple analysis, male gender (RR = 1.13, 95% CI 1.06 - 1.20), advanced age ([reference: 15 - 29 years old] 30 - 44, RR = 1.02, 95% CI 0.94 - 1.11; 45 - 59, RR = 1.26, 95% CI 1.15 - 1.38; 60 years or older, RR = 1.44, 95% CI 1.29 - 1.60), chronic kidney disease (RR = 1.31, 95% CI 1.04 - 1.64) and thoracic pain (RR = 1.16, 95% CI 1.10 - 1.24) were associated with an increased risk of severe disease.

Conclusions

To the best of our knowledge, this is the first study evaluating predictors of COVID-19 severity in a large subset of the Latin-American population. It is also the first in documenting gender-related differences regarding the severity of the illness. These results may be useful for health care protocols for the early detection and management of COVID-19 patients that may benefit from opportune and specialized supportive medical treatment.
Resting-state fMRI Connectivity between Semantic and Phonologic Regions of Interest May Inform Language Targets in Aphasia
Authors: Ramage Amy E. , Aytur Semra , Ballard Kirrie J.
Published: July 2020

Purpose

Brain imaging has provided puzzle pieces in the understanding of language. In neurologically healthy populations, structure of certain brain regions is associated with particular language functions (e.g., semantics, phonology). In studies on focal brain damage, certain brain regions or connections are considered sufficient or necessary for a given language function. However, few of these account for the effects of lesioned tissue on the functional dynamics of the brain for language processing. Here, functional connectivity amongst semantic-phonologic regions of interest (ROIs) is assessed to fill a gap in our understanding about the neural substrates of impaired language and whether connectivity strength can predict language performance on a clinical tool in individuals with aphasia.

Method

Clinical assessment of language, using the Western Aphasia Battery-Revised (WAB-R), and resting-state fMRI data were obtained for 30 individuals with chronic aphasia secondary to left hemisphere stroke and 18 age-matched healthy controls. Functional connectivity (FC) between bilateral ROIs was contrasted by group and used to predict WAB-R scores.

Results

Network coherence was observed in healthy controls and participants with stroke. The left-right premotor cortex connection was stronger in healthy controls, as reported by New et al. (2015) in the same data set. FC of (1) bilateral connections between temporal regions, in the left hemisphere and bilaterally, predicted lexical semantic processing for Auditory Comprehension and (2) ipsilateral connections between temporal and frontal regions in both hemispheres predicted access to semantic-phonologic representations and processing for verbal production.

Conclusions

Network connectivity of brain regions associated with semantic-phonologic processing is predictive of language performance in post-stroke aphasia. The most predictive connections involved right hemisphere ROIs – particularly those for which structural adaptions are known to associate with recovered word retrieval performance. Predictions may be made, based on these findings, about which connections have potential as targets for neuroplastic functional changes with intervention in aphasia.
Implications of the COVID-19 San Francisco Bay Area Shelter-in-Place Announcement: A Cross-Sectional Social Media Survey
Authors: Elser Holly , Kiang Mathew V. , John Esther M. , Simard Julia F. , Bondy Melissa , Nelson Lorene M. , Chen Wei-ting , Linos Eleni
Published: July 2020

Background

The U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area.

Methods

We conducted an online, cross-sectional social media survey from March 14 – April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S.

Results

The percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement.

Conclusion

These results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed.
Computational Analysis of the Metal Selectivity of Matrix Metalloproteinase 8
Authors: Long Zheng
Published: July 2020

Matrix metalloproteinase (MMP) is a class of metalloenzyme that cleaves peptide bonds in extracellular matrices. Their functions are important in both health and disease of animals. Here using quantum mechanics simulations of the MMP8 protein, the coordination chemistry of different metal cofactors is examined. Comparisons found that Jhan-Teller effects in Cu(II) destabilize the wild-type MMP8 but a histidine to glutamine mutation at residue number 197 can potentially allow the MMP8 protein to utilize Cu(II) in reactions. Simulations also demonstrates the requirement of a conformational change in the ligand before enzymatic cleavage. The insights provided in here will assist future protein engineering efforts utilizing the MMP8 protein.
Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacyin vivo
Authors: Li Maohua , Zhao Rongqing , Chen Jianxin , Tian Wenzhi , Xia Chenxi , Liu Xudong , Li Yingzi , Yan Yuyuan , Li Song , Sun Hunter , Shen Tong , Ren Wenlin , Sun Le
Published: July 2020

Some cancer patients treated with Atezolizumab, PD-L1 antibody drug launched by Genentech, quickly developed anti-drug antibody (ADA), led to loss of efficacy. This was likely due to the heavy aggregation of Atezolizumab, caused by mutation of N297A for removing unwanted antibody-dependent cytotoxicity (ADCC) of IgG1 antibody drug. Here, we developed a new version of Atezolizumab (Maxatezo), which was demonstrated better anti-tumor efficacyin vivo. In Atezolizumab, we mutated 297A to 297N back to bring back the glycosylation, and inserted a short sequence GGGS between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Moreover, the insertion of GGGS, without altering the glycosylation profile of IgG1, increased the yields of anti-PD-L1 antibody considerately. Additionally, glycosylation improved the stability yet reduced the amounts of aggregations in the antibody solutions. In turn, the level of ADA in animals treated with Maxatezo was 70% lower than the ones treated with Atezolizumab. Most importantly, at the same 10mg/kg dose, the anti-tumor activity of Maxatezo had attained 98% compared to that of Atezolizumab at 68%.
Lung-to-ear sound transmission does not improve directional hearing in green treefrogs (Hyla cinerea)
Authors: Christensen-Dalsgaard Jakob , Lee Norman , Bee Mark A.
Published: July 2020

Amphibians are unique among extant vertebrates in having middle ear cavities that are internally coupled to each other and to the lungs. In frogs, the lung-to-ear sound transmission pathway can influence the tympanum’s inherent directionality, but what role such effects might play in directional hearing remain unclear. In this study of the American green treefrog (Hyla cinerea), we tested the hypothesis that the lung-to-ear sound transmission pathway functions to improve directional hearing, particularly in the context of interspecific sexual communication. Using laser vibrometry, we measured the tympanum’s vibration amplitude in females in response to a frequency modulated sweep presented from 12 sound incidence angles in azimuth. Tympanum directionality was determined across three states of lung inflation (inflated, deflated, reinflated) both for a single tympanum in the form of the vibration amplitude difference (VAD) and for binaural comparisons in the form of the interaural vibration amplitude difference (IVAD). The state of lung inflation had negligible effects (typically less than 0.5 dB) on both VADs and IVADs at frequencies emphasized in the advertisement calls produced by conspecific males (834 Hz and 2730 Hz). Directionality at the peak resonance frequency of the lungs (1558 Hz) was improved by ≅ 3 dB for a single tympanum when the lungs were inflated versus deflated, but IVADs were not impacted by the state of lung inflation. Based on these results, we reject the hypothesis that the lung-to-ear sound transmission pathway functions to improve directional hearing in frogs.

SUMMARY STATEMENT

Contrary to prevailing views on the mechanisms of hearing in frogs, the lung-to-ear pathway for sound transmission does not improve directional hearing in these vociferous vertebrates.
Anin-vitroBBB-on-a-chip open model of human blood-brain barrier enabling advanced optical imaging
Authors: Salman Mootaz , Marsh Graham , Küsters Ilja , Delincé Matthieu , Di Caprio Giuseppe , Upadhyayula Srigokul , de Nola Giovanni , Hunt Ronan , Ohashi Kazuka G. , Shimizu Fumitaka , Sano Yasuteru , Kanda Takashi , Obermeier Birgit , Kirchhausen Tom
Published: July 2020

We describe here the design and implementation of anin-vitroBBB-on-a-chip open model system capable of reconstituting the microenvironment of the blood brain barrier. This system allows controlled unidirectional flow of nutrients and biologicals on the lumen of the artificial microvessel. This BBB-on-a-chip is suitable for high resolution electron microscopy and it is amenable for quantitative 3D live fluorescence imaging using spinning confocal disk or lattice light sheet microscopy (LLSM) to follow, for example the transcytosis across the BBB-like barrier of fluorescently-tagged biological, viruses or nanoparticles.
Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain:In silicoanalysis
Authors: Chukwudozie Onyeka S. , Chukwuanukwu Rebecca C. , Onyekachi Iroanya O. , Daniel Eze M. , Vincent Duru C. , Onaopemipo Dele-Alimi T. , Kehinde Busuyi D. , Taiwo Bankole T. , Perpetua Obi C. , Elizabeth Okinedo U.
Published: July 2020

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we, therefore, designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of nucleocapsid protein that aid in viral replication. Promising antigenic B-cells and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and non-allergenic property. Two CD8+and Three CD4+T-cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and II alleles. With these selected epitopes, a non-allergenic chimeric peptide vaccine incapable of inducing a Type II hypersensitivity reaction was constructed. The molecular interaction between the toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally,in silicocloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.
Complete vertebrate mitogenomes reveal widespread gene duplications and repeats
Authors: Formenti Giulio , Rhie Arang , Balacco Jennifer , Haase Bettina , Mountcastle Jacquelyn , Fedrigo Olivier , Brown Samara , Capodiferro Marco , Al-Ajli Farooq O. , Ambrosini Roberto , Houde Peter , Koren Sergey , Oliver Karen , Smith Michelle , Skelton Jason , Betteridge Emma , Dolucan Jale , Corton Craig , Bista Iliana , Torrance James , Tracey Alan , Wood Jonathan , Uliano-Silva Marcela , Howe Kerstin , McCarthy Shane , Winkler Sylke , Kwak Woori , Korlach Jonas , Fungtammasan Arkarachai , Fordham Daniel , Costa Vania , Mayes Simon , Chiara Matteo , Horner David S. , Myers Eugene , Durbin Richard , Achilli Alessandro , Braun Edward L. , Phillippy Adam M. , Jarvis Erich D. ,   The Vertebrate Genomes Project Consortium
Published: July 2020

Modern sequencing technologies should make the assembly of the relatively small mitochondrial genomes an easy undertaking. However, few tools exist that address mitochondrial assembly directly. As part of the Vertebrate Genomes Project (VGP) we have developed mitoVGP, a fully automated pipeline for similarity-based identification of mitochondrial reads and de novo assembly of mitochondrial genomes that incorporates both long (>10 kbp, PacBio or Nanopore) and short (100-300 bp, Illumina) reads. Our pipeline led to successful complete mitogenome assemblies of 100 vertebrate species of the VGP. We have observed that tissue type and library size selection have considerable impact on mitogenome sequencing and assembly. Comparing our assemblies to purportedly complete reference mitogenomes based on short-read sequencing, we have identified errors, missing sequences, and incomplete genes in those references, particularly in repeat regions. Our assemblies have also identified novel gene region duplications, shedding new light on mitochondrial genome evolution and organization.
Potassium starvation induces autophagy in yeast
Authors: Rangarajan Nambirajan , Kapoor Ishani , Li Shuang , Drossopoulos Peter , White Kristen K. , Madden Victoria J. , Dohlman Henrik G.
Published: July 2020

Autophagy is a conserved process that recycles cellular contents to promote survival. Although nitrogen starvation is the canonical inducer of autophagy, recent studies have revealed several other nutrients important to this process. In this study, we used a quantitative, high-throughput assay to identify potassium starvation as a new and potent inducer of autophagy. We found that potassium-dependent autophagy requires the core pathway kinases Atg1, Atg5, Vps34, as well as other components of Phosphatidylinositol 3-kinase Complex I. Transmission electron microscopy revealed abundant autophagosome formation in response to both stimuli. RNA sequencing indicated distinct transcriptional responses – nitrogen affects transport of ions such as copper while potassium targets the organization of other cellular components. Thus, nitrogen and potassium share the ability to influence metabolic supply and demand but do so in different ways. Both inputs promote catabolism through bulk autophagy, but inhibit cellular anabolism through distinct mechanisms.
Complementation cloning identifies the essentials of mammalian Mastl kinase activation
Authors: Erguven Mehmet , Karaca Ezgi , Diril M. Kasim
Published: July 2020

Mastl is a mitotic kinase that is essential for error-free chromosome segregation. It is an atypical member of the AGC kinase family, possessing a unique non-conserved middle region (NCMR). The mechanism of its activation prior to mitosis has been extensively studied in Xenopus egg extracts. These studies found several residues (corresponding to T193 and T206 in the activation loop, and S861 in the C-terminal tail, i.e., C-tail of mouse Mastl) whose phosphorylations are crucial for enzymatic activation. To date, the significance of these phosphosites was not confirmed in live mammalian cells. Here, we utilize a complementation cloning approach to determine the essentials of mammalian Mastl kinase activity. We employed a tamoxifen-inducible conditional knockout system to delete the endogenous Mastl in mouse embryonic fibroblasts (MEF) and screened various mutants for their ability to complement its loss. MEFs, ectopically expressing different phosphorylation site mutants, were induced to undergo recombination-mediated knockout in their endogenous Mastl loci. S861A and S861D mutants were able to complement endogenous Mastl loss with proliferation rates comparable to WT. In parallel, we examined the available protein kinase structures having a phosphorylated C-tail. Among the published states, two distinct positionings of the C-tail phosphoresidue were observed. Energetic analysis of these states revealed that only one conformation highly contributes to the C-tail docking. Our in-depth sequence and structure analysis showed that Mastl pS861 does not belong to the conformational state, where the phosphoresidue contributes to the C-tail docking. The C-tail of Mastl is relatively short and it lacks the hydrophobic (HF) motif. In other AGC kinases, the C-tail phosphosite aids the anchoring of this motif over the N-lobe, leading to the final step of kinase activation. Together with the lack of HF motif in Mastl, our results suggest that phosphorylation of the C-tail turn motif phosphosite (S861) is auxiliary and is dispensable for mammalian Mastl kinase function. Furthermore, we demonstrated that complementation cloning is a powerful approach for screening the determinants of an essential protein’s functioning.