bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of analytical methods for rapid & reliable quantification of plant-based carbohydrates for the quintessential bioenergy educator
Authors: Chundawat Shishir P. S.
Published: May 2020

Biochemical conversion of plant-based insoluble carbohydrate polymers, such as starch from corn grains or cellulose-hemicellulose from corn stover, into soluble fermentable sugars (e.g., glucose and xylose) for bioenergy production has seen tremendous research activity and commercial-scale biorefineries deployment over the last three decades, particularly in regions around the world that have a dominant agricultural-based economy. Therefore, educators in schools and universities have developed various hands-on experimental activities to engage the general public and students either in outreach events or lab/classroom-based settings to instruct students on various inter-disciplinary concepts relevant to bioenergy and biochemicals production. One of the limitations of most available protocols is the lack of systematic and comprehensive comparison of educator-friendly analytical tools and protocols for quantitative analysis of water-soluble carbohydrates commonly encountered in a biorefinery backdrop during the biochemical conversion of lignocellulosic biomass to biofuels/biochemicals. Here, we systematically compare and validate findings from four leading analytical approaches for detection and quantification of lignocellulosic biomass derived soluble carbohydrates. We compare these assay methods based on the overall ease of use, detection accuracy/sensitivity, commercial availability, analytical cost per assay run, and suitability for use by instructors in biorefining specific hands-on activity protocols. Next, we provide a detailed instructional protocol that utilizes one of these validated soluble sugar assays as part of a ∼90 min hands-on bioenergy focused activity (called ‘Grass-to-Gas!’) conducted at Rutgers University with pre-university high school students. ‘Grass-to-Gas!’ activity involves students running biochemical assays that helps them understand the various facets of cellulosic biomass hydrolysis by commercial cellulase enzymes and monitoring the total glucose product released using our validated sugar assays to finally estimate the fractional conversion of cellulose-to-glucose. Lastly, we further demonstrate how such carbohydrate-based analytical methods can be used by instructors to help university students explore and understand various chemistry, biochemistry, and chemical engineering concepts relevant to other advanced operations involved in lignocellulose biorefining. These activity protocols would greatly aid educators teaching interdisciplinary science and engineering concepts to students in the backdrop of lignocellulose biorefining.
Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia
Authors: Rivera Osvaldo D. , Mallory Michael J. , Quesnel-Vallières Mathieu , Schultz David C. , Carroll Martin , Barash Yoseph , Cherry Sara , Lynch Kristen W.
Published: May 2020

Most genes associated with Acute Myeloid Leukemia (AML) are mutated in less than 10% of patients, suggesting alternative mechanisms for gene disruption contribute to this disease. Here we find a set of splicing events that disrupt the expression of a subset of AML-associated genes, including EZH2 and ZRSR2, independent of known somatic mutations. Most strikingly, in at least one cohort, aberrant splicing triples the number of patients with a reduction in functional EZH2 as compared to that predicted by somatic mutation of EZH2 alone. Together, these results demonstrate that classical mutation analysis underestimates the burden of functional gene disruption in AML and highlights the importance of assessing the contribution of alternative splicing to gene dysregulation in human disease.
Integrative Analysis of Metabolomic and Transcriptomic Profiles Uncovers Biological Mechanism of Feed Efficiency in Pigs
Authors: Banerjee Priyanka , Okstoft Carmelo Victor Adriano , Kadarmideen Haja N
Published: May 2020

Feed efficiency (FE) is an economically important trait. Thus, reliable predictors would help to reduce the production cost and provide sustainability to the pig industry. We carried out metabolome-transcriptome integration analysis on 40 purebred Duroc and Landrace male uncastrated pigs to identify potential gene-metabolite interactions and explore the molecular mechanism underlying FE. To this end, we applied untargeted metabolomics and RNA-seq approaches to the same animals. After data quality control, we used a linear model approach to integrate the data and find significant differently correlated gene-metabolite pairs separately for the breeds (Duroc and Landrace) and FE groups (low and high FE) followed by a pathway over-representation analysis. We identified 21 and 12 significant gene-metabolite pairs for each group. The valine-leucine-isoleucine biosynthesis/degradation and arginine-proline metabolism pathways were associated with unique metabolites. The unique genes obtained from significant metabolite-gene pairs were associated with sphingolipid catabolism, multicellular organismal process, cGMP, and purine metabolic processes. While some of the genes and metabolites identified were known for their association with FE, others are novel and provide new avenues for further research. Further validation of genes, metabolites, and gene-metabolite interactions in larger cohorts will help us to elucidate the regulatory mechanisms and pathways underlying FE.
Does the motor cortex want the full story? The influence of sentence context on corticospinal excitability in action language processing
Authors: Dupont W , Papaxanthis C , Lebon F , Madden-Lombardi C
Published: May 2020

The reading of action verbs has been shown to activate motor areas, whereby sentence context may serve to either globally strengthen this activation or to selectively sharpen it. To investigate this issue, we manipulated the presence of manual actions and sentence context, assessing the level of corticospinal excitability by means of transcranial magnetic stimulation. We hypothesized that context would serve to sharpen the neural representation of the described actions in the motor cortex, reflected in context-specific modulation of corticospinal excitability.

Participants silently read manual action verbs and non-manual verbs, preceded by a full sentence (rich context) or not (minimal context). Transcranial magnetic stimulation pulses were delivered at rest or shortly after verb presentation. The coil was positioned over the cortical representation of the right first dorsal interosseous (pointer finger).

We observed a general increase of corticospinal excitability while reading both manual action and non-manual verbs in minimal context, whereas the modulation was action-specific in rich context: corticospinal excitability increased while reading manual verbs, but did not differ from baseline for non-manual verbs. These findings suggest that sentence context sharpens motor representations, activating the motor cortex when relevant and eliminating any residual motor activation when no action is present.
Heroin self-administration and extinction increases prelimbic cortical astroglia-synapse proximity and alters dendritic spine morphometrics that are reversed by N-acetylcysteine
Authors: Siemsen BM , Denton AR , Hooker KN , Carpenter EA , Prescott ME , Brock AG , Leath MN , McFaddin JA , McGinty JF , Scofield MD
Published: May 2020

Clinical and preclinical studies indicate that adaptations in corticostriatal neurotransmission significantly contribute to heroin relapse vulnerability. In animal models, heroin self-administration and extinction produce cellular adaptations in both neurons and astrocytes within the nucleus accumbens (NA) core that are required for cue-induced heroin seeking. Specifically, decreased glutamate clearance and reduced association of perisynaptic astrocytic processes with NAcore synapses allow glutamate release from prelimbic (PrL) cortical terminals to engage synaptic and structural plasticity in NAcore medium spiny neurons. Normalizing astroglial glutamate homeostasis with drugs like the antioxidant N-acetylcysteine (NAC) prevents cue-induced heroin seeking. Surprisingly, little is known about heroin-induced alterations in astrocytes or pyramidal neurons projecting to the NAcore in the PrL cortex (PrL-NAcore). Here, we observed increased complexity of the glial fibrillary acidic protein (GFAP) cytoskeletal arbor and increased association of the astroglial plasma membrane with synaptic markers following heroin SA and extinction training in the PrL cortex. Repeated treatment with NAC during extinction reversed both the enhanced astroglial complexity and synaptic association. In PrL-NAcore neurons, heroin SA and extinction decreased apical tuft dendritic spine density and enlarged dendritic spine head diameter in male Sprague-Dawley rats. Repeated NAC treatment during extinction prevented decreases in spine density but not dendritic spine head expansion. Moreover, heroin SA and extinction increased co-registry of the GluA1 subunit of AMPA receptors in both the dendrite shaft and spine heads of PrL-NAcore neurons. Interestingly, accumulation of GluA1 immunoreactivity in spine heads was further potentiated by NAC treatment during extinction. Taken together, our data reveal circuit-level adaptations in cortical dendritic spine morphology potentially linked to heroin-induced alterations in astrocyte complexity and association at synapses. Additionally, these data demonstrate, for the first time, that NAC reverses PrL cortical heroin SA and extinction-induced adaptations in both astrocytes and corticostriatal neurons.
Ramping activity in midbrain dopamine neurons signifies the use of a cognitive map
Authors: Guru Akash , Seo Changwoo , Post Ryan J. , Kullakanda Durga S. , Schaffer Julia A. , Warden Melissa R.
Published: May 2020

Journeys to novel and familiar destinations employ different navigational strategies. The first drive to a new restaurant relies on map-based planning, but after repeated trips the drive is automatic and guided by local environmental cues1,2. Ventral striatal dopamine rises during navigation toward goals and reflects the spatial proximity and value of goals3, but the impact of experience, the neural mechanisms, and the functional significance of dopamine ramps are unknown4,5. Here, we used fiber photometry6–8to record the evolution of activity in midbrain dopamine neurons as mice learned a variety of reward-seeking tasks, starting recordings before training had commenced and continuing daily for weeks. When mice navigated through space toward a goal, robust ramping activity in dopamine neurons appeared immediately – after the first rewarded trial on the first training day in completely naïve animals. In this task spatial cues were available to guide behavior, and although ramps were strong at first, they gradually faded away as training progressed. If instead mice learned to run a fixed distance on a stationary wheel for reward, a task that required an internal model of progress toward the goal, strong dopamine ramps persisted indefinitely. In a passive task in which a visible cue and reward moved together toward the mouse, ramps appeared and then faded over several days, but in an otherwise identical task with a stationary cue and reward ramps never appeared. Our findings provide strong evidence that ramping activity in midbrain dopamine neurons reflects the use of a cognitive map9,10– an internal model of the distance already covered and the remaining distance until the goal is reached. We hypothesize that dopamine ramps may be used to reinforce locations on the way to newly-discovered rewards in order to build a graded ventral striatal value landscape for guiding routine spatial behavior.
Immunoglobulin T genes in Neopterygii
Authors: Mirete-Bachiller Serafin , Olivieri David N. , Gambón-Deza Francisco
Published: May 2020

In teleost fishes there are three immunoglobulin isotypes named immunoglobulin M (IgM), D (IgD) and T (IgT). IgT has been the last to be described and is considered a teleosts-fish specific isotype. From the recent availability of genome sequences of fishes, an in-depth analysis of Actinopterygii immunoglobulin heavy chain genes was undertaken. With the aid of a bioinformatics pipeline, a machine learning software, CHfinder, was developed that identifies the coding exons of the CH domains of fish immunoglobulins. Using this pipeline, a high number of such sequences were obtained from teleosts and holostean fishes. IgT was found in teleost and holostean fishes that had not been previously described. A phylogenetic analysis reveals that IgT CH1 exons are similar to the IgM CH1. This analysis also demonstrates that the other three domains (CH2, CH3 and CH4) were not generated by recent duplication processes of IgM in Actinopterygii, indicating it is an immunoglobulin with an earlier origin.
Genetic Risk Scores for Cardiometabolic Traits in Sub-Saharan African Populations
Authors: Ekoru Kenneth , Adeyemo Adebowale A. , Chen Guanjie , Doumatey Ayo P. , Zhou Jie , Bentley Amy R. , Shriner Daniel , Rotimi Charles N.
Published: May 2020

There is growing support for the use of genetic risk scores (GRS) in routine clinical settings. Due to the limited diversity of current genomic discovery samples, there are concerns that the predictive power of GRS will be limited in non-European ancestry populations. Here, we evaluated the predictive utility of GRS for 12 cardiometabolic traits in sub-Saharan Africans (AF;n=5200), African Americans (AA;n=9139), and European Americans (EA;n=9594). GRS were constructed as weighted sums of the number of risk alleles. Predictive utility was assessed using the additional phenotypic variance explained and increase in discriminatory ability over traditional risk factors (age, sex and BMI), with adjustment for ancestry-derived principal components. Across all traits, GRS showed upto a 5-fold and 20-fold greater predictive utility in EA relative to AA and AF, respectively. Predictive utility was most consistent for lipid traits, with percent increase in explained variation attributable to GRS ranging from 10.6% to 127.1% among EA, 26.6% to 65.8% among AA, and 2.4% to 37.5% among AF. These differences were recapitulated in the discriminatory power, whereby the predictive utility of GRS was 4-fold greater in EA relative to AA and up to 44-fold greater in EA relative to AF. Obesity and blood pressure traits showed a similar pattern of greater predictive utility among EA. This work demonstrates the poorer performance of GRS in AF and highlights the need to improve representation of multiethnic populations in genomic studies to ensure equitable clinical translation of GRS.

Key Messages

Genetic Risk Score (GRS) prediction is markedly poorer in sub-Saharan Africans compared with African Americans and European Americans

To ensure equitable clinical translation of GRS, there is need need to improve representation of multiethnic populations in genomic studies
Defective folate metabolism causes germline epigenetic instability and distinguishesHiraas a phenotype inheritance biomarker
Authors: Blake Georgina E.T. , Zhao Xiaohui , Yung Hong wa , Burton Graham J. , Ferguson-Smith Anne C. , Hamilton Russell S. , Watson Erica D.
Published: May 2020

The mechanism behind transgenerational epigenetic inheritance (TEI) is unclear, particularly through the maternal grandparental line. We previously showed that disruption of folate metabolism in mice by theMtrrgthypomorphic mutation results in TEI of congenital malformations. Either maternal grandparent can initiate this phenomenon, which persists for at least four wildtype generations. In this work, we use a genome-wide approach to reveal genetic stability in theMtrrgtmodel and epigenome-wide differential DNA methylation in the germline ofMtrr+/gtmaternal grandfathers. While epigenetic reprogramming occurs, wildtype grandprogeny and great grandprogeny exhibit transcriptional memory of germline methylation defects. One region encompasses theHiragene, which is misexpressed in embryos at least until the F3 generation in a manner that distinguishesHiratranscript expression as a biomarker of maternal phenotypic inheritance.
Rolling Signal-based Ripley’s K: A new algorithm to identify spatial patterns in histological specimens
Authors: Healy Connor P. , Adler Frederick R. , Deans Tara L.
Published: May 2020

The spatial distribution of cells within a tissue underlies organ function. However, these spatial distributions are often difficult to identify, making it challenging to evaluate how cells establish these patterns during development or how diseases may disrupt these patterns and impair function. To address this, we developed an image analysis tool based on a novel algorithm that identifies spatial patterns within tissues. This analytical tool was used to study the bone marrow, a specialized microenvironment in which spatial patterning of regulatory cells may influence the differentiation and survival of hematopoietic stem cells. Using this algorithm, we discovered clusters of regulatory cells within the bone marrow that suggest an organization of micro-niches, which may form the basis of the hematopoietic stem cell microenvironment. This work provides a new tool for the detection and analysis of tissue morphology that enables identification of spatial patterns within tissues that can lead to a deeper understanding of tissue function, provide clues for early onset of disease, and be used as a tool for studying the impact of pharmaceutics on tissue development and regeneration.

In Brief

This work introduces a new statistic to analyze the patterning of cells and physiological features in histological images. This statistic was used on a published set of immunofluorescent images of murine bone to identify novel spatial structures within the bone marrow that may provide new inisghts to the organization of the hematopoietic stem cell microenvironment.

Highlights

RSRK, a statistical tool for analyzing the spatial distribution of features in histological images, is introduced.

RSRK incorporates the quantification of signal distribution to identify unique spatial patterns.

Spatial patterns in hematopoietic stem cell microenvironments are identified.

Graphical Abstract
How cells determine the number of polarity sites
Authors: Chiou Jian-geng , Moran Kyle D. , Lew Daniel J.
Published: May 2020

The diversity of cell morphologies arises, in part, through regulation of cell polarity by Rho-family GTPases. A poorly understood but fundamental question concerns the regulatory mechanisms by which different cells can generate different numbers of polarity sites. Theoretical models of polarity circuits develop multiple initial polarity sites, but then those sites engage in competition, leaving a single winner. The timescale of competition slows dramatically as GTPase concentrations at polarity sites approach a “saturation point”, allowing multiple sites to coexist. Here, we show that these principles hold in more complex mechanistic models of theSaccharomyces cerevisiaepolarity machinery, and confirm model predictionsin vivo. Further, we elucidate a novel design principle whereby cells can switch from competition to equalization among polarity sites. These findings provide insight into how cells determine the number of polarity sites.
Reconstruction of Fur pan-regulon uncovers the complexity and diversity of transcriptional regulation inE. coli
Authors: Gao Ye , Bang Ina , Seif Yara , Nam Gayoung , Sastry Anand V. , Chen Ke , Monk Jonathan M. , Choudhary Kumari Sonal , Seo Sang Woo , Lee Eun-Yeol , Kim Donghyuk , Palsson Bernhard O.
Published: May 2020

Regulons for many transcription factors have been elucidated in model strains leading to an understanding of their role in producing physiological states. Comparative analysis of a regulon and its target genes between different strains of the same species is lacking. Ferric uptake regulator (Fur), involved in iron homeostasis, is one of the most conserved TFs, and is present in a wide range of bacteria. Using ChIP-exo experiments, we performed a comprehensive study of Fur binding sites in nineEscherichia colistrains with different lifestyles. 79 of the 431 target genes (18%) found belong to Fur core regulon, comprising genes involved in ion transport and metabolism, energy production and conversion, and amino acid metabolism and transport. 179 of the target genes (42%) comprise the accessory regulon, most of which were related to cell wall structure and biogenesis, and virulence factor pathways. The remaining target genes (173 or 40%) were in the unique regulon, with gene functions that were largely unknown. Furthermore, deletion of thefurgene led to distinct phenotypes in growth, motility, antibiotic resistance, and the change of siderophore production. These results provide a more complete understanding of how Fur regulates a set of target genes with surprising variation in closely related bacteria.
Systemic Effects of Missense Mutations on SARS-CoV-2 Spike Glycoprotein Stability and Receptor Binding Affinity
Authors: Teng Shaolei , Sobitan Adebiyi , Rhoades Raina , Liu Dongxiao , Tang Qiyi
Published: May 2020

The spike (S) glycoprotein of SARS-CoV-2 is responsible for the binding to the permissive cells. The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. In this study, we used computational saturation mutagenesis approaches, including structure-based energy calculations and sequence-based pathogenicity predictions, to quantify the systemic effects of missense mutations on SARS-CoV-2 S protein structure and function. A total of 18,354 mutations in S protein were analyzed and we discovered that most of these mutations could destabilize the entire S protein and its RBD. Specifically, residues G431 and S514 in SARS-CoV-2 RBD are important for S protein stability. We analyzed 384 experimentally verified S missense variations and revealed that the dominant pandemic form, D614G, can stabilize the entire S protein. Moreover, many mutations in N-linked glycosylation sites can increase the stability of the S protein. In addition, we investigated 3,705 mutations in SARS-CoV-2 RBD and 11,324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction. The findings comprehensively provide potential target sites in the development of drugs and vaccines against COVID-19.
Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles
Authors: Zhang Jiyuan , Guan Xin , Yan Jiusheng
Published: May 2020

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-mobilizing second messenger which uniquely mobilizes Ca2+from acidic endolysosomal organelles. However, the molecular identity of the NAADP receptor remains unknown. Given the necessity of the endolysosomal two-pore channel (TPC1 or TPC2) in NAADP signaling, we performed affinity purification and quantitative proteomic analysis of the interacting proteins of NAADP and TPCs. We identified an Sm-like protein Lsm12 complexed with NAADP, TPC1, and TPC2. Lsm12 directly binds to NAADP via its Lsm domain, whereas TPC-containing membranes and isolated TPCs lose their affinities to NAADP in the absence of Lsm12. Lsm12 is essential and directly involved in NAADP-evoked TPC2 activation and Ca2+mobilization. These findings reveal a putative RNA-binding protein to function as an NAADP receptor and a TPC regulatory protein and provides a molecular basis for understanding the mechanisms of NAADP signaling.
Hospital admissions in inflammatory rheumatic diseases during the COVID-19 pandemic: incidence and role of disease modifying agents
Authors: Fernandez-Gutierrez Benjamin , Leon Leticia , Madrid Alfredo , Rodriguez-Rodriguez Luis , Freites Dalifer , Font Judit , Mucientes Arkaitz , Colomer Jose Ignacio , Jover Juan Angel , Abasolo Lydia
Published: May 2020

Background: In this pandemia, it is essential for rheumatologist and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRD). We want to assess the role of targeted synthetic or biologic disease modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD.
Methods: An observational longitudinal study was conducted (1stMar to 15thApr 2020). All patients from the rheumatology outpatient clinic from a hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, NSAIDs and conventional synthetic DMARDs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19, was expressed per 1,000 patients-month. Cox multivariate regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR.
Results: 3,591 IRD patients were included (5,896 patients-month). Concerning csDMARDs, methotrexate was the most used followed by antimalarials. 802 patients were on ts/bDMARDs, mainly anti-TNF agents, and rituximab. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 [95%CI: 7-11.9]. In the multivariate analysis, older, male gender, presence of comorbidities and specific systemic autoimmune conditions (Sjoegren, polychondritis, Raynaud and mixed connective tissue disease) had more risk of hospital admissions regardless other factors. Exposition to ts/bDMARDs did not achieve statistical signification. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model.
Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate-severe infection related to COVID-19.
What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate, serial interval, and asymptomatic infection
Authors: Koh Wee Chian , Naing Lin , Rosledzana Muhammad Ali , Alikhan Mohammad Fathi , Chaw Liling , Griffith Matthew , Pastore Roberta , Wong Justin
Published: May 2020

Background
Current SARS-CoV-2 containment measures rely on the capacity to control person-to-person viral transmission. Effective prioritization of these measures can be determined by understanding SARS-CoV-2 transmission dynamics. We conducted a systematic review and meta-analyses of three parameters: (i) secondary attack rate (SAR) in various settings, (ii) clinical onset serial interval (SI), and (iii) the proportion of asymptomatic infection.

Methods and Findings
We searched PubMed, medRxiv, and bioRxiv databases between January 1, 2020, and May 15, 2020, for articles describing SARS-CoV-2 attack rate, SI, and asymptomatic infection. Studies were included if they presented original data for estimating point estimates and 95% confidence intervals of the three parameters. Random effects models were constructed to pool SAR, mean SI, and asymptomatic proportion. Risk ratios were used to examine differences in transmission risk by setting, type of contact, and symptom status of the index case. Publication and related bias were assessed by funnel plots and Egger's meta-regression test for small-study effects.

Our search strategy for SAR, SI, and asymptomatic infection identified 459, 572, and 1624 studies respectively. Of these, 20 studies met the inclusion criteria for SAR, 18 studies for SI, and 66 studies for asymptomatic infection. We estimated the pooled household SAR at 15.4% (95% CI: 12.2%, 18.7%) compared to 4.0% (95% CI: 2.8%, 5.2%) in non-household settings. We observed variation across settings; however, the small number of studies limited power to detect associations and sources of heterogeneity. SAR of symptomatic index cases is significantly higher than cases that were symptom-free at diagnosis (RR 2.55, 95% CI: 1.47, 4.45). Adults appear to be more susceptible to transmission than children (RR 1.40, 95% CI: 1.00, 1.96). The pooled mean SI is estimated at 4.87 days (95% CI: 3.98, 5.77). The pooled proportion of cases who had no symptoms at diagnosis is 25.9% (95% CI: 18.8%, 33.1%).

Conclusions
Based our pooled estimates, 10 infected symptomatic persons living with 100 contacts would result in 15 additional cases in <5 days. To be effective, quarantine of contacts should occur within 3 days of symptom onset. If testing and tracing relies on symptoms, one-quarter of cases would be missed. As such, while aggressive contact tracing strategies may be appropriate early in an outbreak, as it progresses, control measures should transition to account for SAR variability across settings. Targeted strategies focusing on high-density enclosed settings may be effective without overly restricting social movement.
The Challenge of Using Epidemiological Case Count Data: The Example of Confirmed COVID-19 Cases and the Weather
Authors: Cohen Francois , Schwarz Moritz , Li Sihan , Lu Yangsiyu , Jani Anant
Published: May 2020

The publicly available data on COVID-19 cases provides an opportunity to better understand this new disease. However, strong attention needs to be paid to the limitations of the data to avoid making inaccurate conclusions. This article, which focuses on the relationship between the weather and COVID-19, raises the concern that the same factors influencing the spread of the disease might also affect the number of tests performed and who gets tested. For example, weather conditions impact the prevalence of respiratory diseases with symptoms similar to COVID-19, and this will likely influence the number of tests performed. This general limitation could severely undermine any similar analysis using existing COVID-19 data or similar epidemiological data, which could, therefore, mislead decision-makers on questions of great policy relevance.
Congregate Shelter Characteristics and Prevalence of Asymptomatic SARS-CoV-2
Authors: Samuels Elizabeth A. , Karb Rebecca , Vanjani Rahul , Trimbur M. Catherine , Napoli Anthony
Published: May 2020

Background

Individuals experiencing homelessness residing in congregate shelters have increased risk for SARS-CoV-2 infection. Prevalence of asymptomatic SARS-CoV-2 in congregate shelters is high, but shelter characteristics associated with SARS-CoV-2 transmission are currently unknown.

Methods

We conducted a cross-sectional, multicenter cohort study across five congregate shelters in Rhode Island. We tested people 18 years of age and older staying in Rhode Island congregate shelters in April 2020 during the COVID-19 pandemic. A survey instrument was designed and implemented based on an a priori sample size. All consented participants reported basic demographics, recent travel, duration of time at the shelter, any symptomatology, and had their temperature and pulse oximetry measured. Each participant was tested for COVID-19 using nasopharyngeal swabbing. Shelter characteristics about location, occupancy, resident length of stay, and COVID-19 mitigation strategies were collected through structured phone questionnaire with shelter staff.

Results

A total of 302 individuals were screened and 299 participated across five homeless shelters. The median age was 47.9 (range 18-85) and 20% were female. Of the 299 participants, 35 (11.7%) were positive for SARS-CoV-2; rates varied among shelters, ranging from 0% to 35%. Among the participants in the study, 5% had a new cough, 4% shortness of breath, and 3% reported loss of taste or smell. Symptom prevalence did not vary significantly between positive and negative SARS-CoV-2 groups. Regular symptom screening was not associated with lower infection rates. Shelters with higher rates of positivity were in more densely populated areas, cared for a more transient populations, and instituted fewer social distancing practices for sleeping arrangements or mealtimes.

Conclusions and Relevance

Residents of congregate shelters are at increased risk for asymptomatic transmission of SARS-CoV-2. To reduce transmission and enable continuation of low-threshold shelter services, there is a need for universal testing, implementation of infection control and physical distancing measures within congregate shelters, and expansion of non-congregate supportive housing.
A bipartite element with allele-specific functions safeguards DNA methylation imprints at theDlk1-Dio3locus
Authors: Aronson BE , Scourzic L , Shah V , Swanzey E , Kloetgen A , Polyzos A , Sinha A , Azziz A , Caspi I , Li J , Pelham-Webb B , Wichterle H , Tsirigos A , Stadtfeld M , Apostolou E
Published: May 2020

Dysregulation of imprinted gene loci also referred to as loss of imprinting (LOI) can result in severe developmental defects and other diseases, but the molecular mechanisms that ensure imprint stability remain incompletely understood. Here, we dissect the functional components of the imprinting control region of the essentialDlk1-Dio3locus (called IG-DMR) and the mechanism by which they ensure imprinting maintenance. Using pluripotent stem cells carrying an allele-specific reporter system, we demonstrate that the IG-DMR consists of two antagonistic regulatory elements: a paternally methylated CpG-island that prevents the activity of Tet dioxygenases and a maternally unmethylated regulatory element, which serves as a non-canonical enhancer and maintains expression of the maternalGtl2lncRNA by precludingde novoDNA methyltransferase function. Targeted genetic or epigenetic editing of these elements leads to LOI with either bi-paternal or bi-maternal expression patterns and respective allelic changes in DNA methylation and 3D chromatin topology of the entireDlk1-Dio3locus. Although the targeted repression of either IG-DMR orGtl2promoter is sufficient to cause LOI, the stability of LOI phenotype depends on the IG-DMR status, suggesting a functional hierarchy. These findings establish the IG-DMR as a novel type of bipartite control element and provide mechanistic insights into the control ofDlk1-Dio3imprinting by allele-specific restriction of the DNA (de)methylation machinery.

HIGHLIGHTS

The IG-DMR is a bipartite element with distinct allele-specific functions

A non-canonical enhancer within the IG-DMR prevents DNA methyltransferase activity

Targeted epigenome editing allows induction of specific imprinting phenotypes

CRISPRi reveals a functional hierarchy between DMRs that dictates imprint stability
Translocation of an arctic seashore plant reveals signs of maladaptation to altered climatic conditions
Authors: Hällfors M.H. , Lehvävirta S. , Aandahl T.R. , Lehtimäki I.-M. , Nilsson L.O. , Ruotsalainen A.L. , Schulman L.E. , Hyvärinen M.-T.
Published: May 2020

Ongoing anthropogenic climate change alters the local climatic conditions to which species may be adapted. Information on species’ climatic requirements and their intraspecific variation is necessary for predicting the effects of climate change on biodiversity. We used a climatic gradient to test whether populations of two allopatric varieties of an arctic seashore herb (Primula nutansssp.finmarchica) show adaptation to their local climates and how a future warmer climate may affect them. Our experimental set-up combined i) a reciprocal translocation within the distribution range of the species with ii) an experiment testing performance of the sampled populations in warmer climatic conditions south of their range. We monitored survival, size, and flowering over four growing seasons as measures of performance and, thus, proxies of fitness. We found that both varieties performed better in experimental gardens towards the north. Interestingly, highest up in the north, the southern variety outperformed the northern one. Supported by weather data, this suggests that the climatic optima of both varieties has moved at least partly outside their current range. Further warming would make the current environments of both varieties even less suitable. We conclude thatPrimula nutansssp.finmarchicais already suffering from adaptation-lag due to climate change, and that further warming may be increase this maladaptation, especially for the northern variety. The study also highlights that it is not sufficient to run only reciprocal translocation experiments. Climate change is already shifting the optimum conditions for many species and adaptation needs also to be tested outside the current range of the focal taxon in order to include both historic conditions and future conditions.
Single-particle cryo-EM at atomic resolution
Authors: Nakane Takanori , Kotecha Abhay , Sente Andrija , McMullan Greg , Masiulis Simonas , Brown Patricia M.G.E. , Grigoras Ioana T. , Malinauskaite Lina , Malinauskas Tomas , Miehling Jonas , Yu Lingbo , Karia Dimple , Pechnikova Evgeniya V. , de Jong Erwin , Keizer Jeroen , Bischoff Maarten , McCormack Jamie , Tiemeijer Peter , Hardwick Steven W. , Chirgadze Dimitri Y. , Murshudov Garib , Aricescu A. Radu , Scheres Sjors H.W.
Published: May 2020

The three-dimensional positions of atoms in protein molecules define their structure and provide mechanistic insights into the roles they perform in complex biological processes. The more precisely atomic coordinates are determined, the more chemical information can be derived and the more knowledge about protein function may be inferred. With breakthroughs in electron detection and image processing technology, electron cryo-microscopy (cryo-EM) single-particle analysis has yielded protein structures with increasing levels of detail in recent years1,2. However, obtaining cryo-EM reconstructions with sufficient resolution to visualise individual atoms in proteins has thus far been elusive. Here, we show that using a new electron source, energy filter and camera, we obtained a 1.7 Å resolution cryo-EM reconstruction for a prototypical human membrane protein, the β3 GABAAreceptor homopentamer3. Such maps allow a detailed understanding of small molecule coordination, visualisation of solvent molecules and alternative conformations for multiple amino acids, as well as unambiguous building of ordered acidic side chains and glycans. Applied to mouse apo-ferritin, our strategy led to a 1.2 Å resolution reconstruction that, for the first time, offers a genuine atomic resolution view of a protein molecule using single particle cryo-EM. Moreover, the scattering potential from many hydrogen atoms can be visualised in difference maps, allowing a direct analysis of hydrogen bonding networks. Combination of the technological advances described here with further approaches to accelerate data acquisition and improve sample quality provide a route towards routine application of cryo-EM in high-throughput screening of small molecule modulators and structure-based drug discovery.
Seasonal environments drive convergent evolution of a faster pace-of-life in tropical butterflies
Authors: Halali Sridhar , van Bergen Erik , Breuker Casper J , Brakefield Paul M , Brattström Oskar
Published: May 2020

Global change can trigger shifts in habitat stability and shape the evolution of organismal life-history strategies, with unstable habitats typically favouring a faster pace-of-life. We test this hypothesis in species-rich Mycalesina butterflies that have undergone parallel radiations in Africa, Asia, and Madagascar. First, our ancestral state reconstruction of habitat preference, using ~85% of extant species, revealed that early forest-linked lineages began to invade seasonal savannahs during the Late Miocene-Pliocene. Second, rearing replicate pairs of forest and savannah species from the African and Malagasy radiation in a common garden experiment, and utilising published data from the Asian radiation, demonstrated that savannah species consistently develop faster, have smaller bodies, higher fecundity with an earlier investment in reproduction, and reduced longevity, compared to forest species across all three radiations. We argue that time-constraints for reproduction favoured the evolution of a faster pace-of-life in savannah species that facilitated their persistence in seasonal habitats.
Orderly assembly underpinning built-in asymmetry in the yeast centrosome duplication cycle requires cyclin-dependent kinase
Authors: Geymonat Marco , Peng Qiuran , Guo Zhiang , Yu Zulin , Unruh Jay R. , Jaspersen Sue L. , Segal Marisa
Published: May 2020

Asymmetric astral microtubule organization drives the polarized orientation of theS. cerevisiaemitotic spindle and primes the invariant inheritance of the old spindle pole body (SPB, the yeast centrosome) by the bud. This model has anticipated analogous centrosome asymmetries featuring in self-renewing stem cell divisions. We previously implicated Spc72, the cytoplasmic receptor for the gamma-tubulin nucleation complex, as the most upstream determinant linking SPB age, functional asymmetry and fate. Here we used structured illumination microscopy and biochemical analysis to explore the asymmetric landscape of nucleation sites inherently built into the spindle pathway and under the control of cyclin-dependent kinase (CDK). We show that CDK enforces Spc72 asymmetric docking by phosphorylating Nud1/centriolin. Furthermore, CDK-imposed order in the construction of the new SPB promotes the correct balance of nucleation sites between the nuclear and cytoplasmic faces of the SPB. Together these contributions by CDK inherently link correct SPB morphogenesis, age and fate.
No fruits without color: Cross-modal priming and EEG reveal different roles for different features across semantic categories
Authors: Argiris Georgette , Rumiati Raffaella I. , Crepaldi Davide
Published: May 2020

Category-specific impairments witnessed in patients with semantic deficits have broadly dissociated into natural and artificial kinds. However, how the category of food (more specifically, fruits and vegetables) fits into this distinction has been difficult to interpret, given a pattern of deficit that has inconsistently mapped onto either kind, despite its intuitive membership to the natural domain. The present study explores the effects of a manipulation of a visual sensory (i.e., color) or functional (i.e., orientation) feature on the consequential semantic processing of fruits and vegetables (and tools, by comparison), first at the behavioral and then at the neural level. The categorization of natural (i.e., fruits/vegetables) and artificial (i.e., utensils) entities was investigated via cross–modal priming. Reaction time analysis indicated a reduction in priming for color-modified natural entities and orientation-modified artificial entities. Standard event-related potentials (ERP) analysis was performed, in addition to linear classification. For natural entities, a N400 effect at central channel sites was observed for the color-modified condition compared relative to normal and orientation conditions, with this difference confirmed by classification analysis. Conversely, there was no significant difference between conditions for the artificial category in either analysis. These findings provide strong evidence that color is an integral property to the categorization of fruits/vegetables, thus substantiating the claim that feature-based processing guides as a function of semantic category.
A Study of Secondary School Students’ Participation in a Novel Course on Genomic Principles and Practices
Authors: Stefanile Adam
Published: May 2020

This paper presents the design, development, and validation of a study among secondary school students’ participation in a novel course on genomic principles and practices by analyzing and documenting evidence of their participation, and educational outcomes, in a novel course on genomic principles and practices. A mixed methods approach, using qualitative and quantitative methods, was used to address three research questions. 1) Based on affective evidence, how did secondary school students perceive and critically judge, content topics learned in a course on modern genomic principles and practices? 2) Based on cognitive evidence, how much of the content did secondary school students learn when they participated in a course on modern genomic principles and practices? 3) Using individual interview evidence, what are the major perceptions that the secondary school students expressed throughout the duration of the course? The participants were provided an opportunity to comment on the course through individual and collaborative interviews, in order to find out to what extent they perceived the course to be interesting and challenging. Future inquiry expanding from this research would help to establish the foundational pathway for designing a more inclusive genomics curriculum. In conclusion, the course offered real-life/real-world applications that encourage all students to conceptualize genomics, human health, diseases, medicine, ethics, beliefs, research, and careers.
Effect of mechanical properties of monofilament twines on the catch efficiency of biodegradable gillnets
Authors: Grimaldo Eduardo , Herrmann Bent , Jacques Nadine , Vollstad Jørgen , Su Biao
Published: May 2020

Gillnets made of the biodegradable resin polybutylene succinate co-adipate-co-terephthalate (PBSAT) were tested under commercial fishing conditions to compare their fishing performance with that of conventional nylon polyamide (PA) gillnets. Both types of gillnets were made of 0.55 mm Ø monofilaments. However, since the biodegradable nets are weaker than nylon PA nets when using the same monofilament diameter, we also used biodegradable nets made of 0.60 mm Ø monofilament that had a similar tensile strength to the 0.55 mm Ø nylon PA nets. The relative catch efficiency of the different gillnet types was evaluated over the 2018 autumn fishing season for saithe and cod in northern Norway. For cod, both biodegradable gillnets (0.55 and 0.60 mm) had a significantly lower catch efficiency compared to the traditional nylon PA net (0.55 mm) with estimated catch efficiencies of 62.38% (CI: 50.55–74.04) and 54.96% (CI: 35.42–73.52) compared with the nylon PA net, respectively. Similarly for saithe, both biodegradable gillnets (0.55 and 0.60 mm) had a lower estimated catch efficiency compared to the traditional nylon PA net (0.55 mm) with estimated catch efficiencies of 83.40% (71.34–94.86) and 83.87% (66.36–104.92), compared with the nylon PA net, respectively. Tensile strength does not explain the differences in catch efficiency between the two gillnet types, since increasing the twine diameter of the biodegradable gillnets (to match the strength of nylon PA gillnets) did not yield similar catch efficiencies. However, the elasticity and stiffness of the materials may be responsible for the differences in catch efficiency between the nylon PA and biodegradable gillnets.
Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2
Authors: Anderson Cole , Castillo Fritz , Koenig Michael , Managbanag Jim
Published: May 2020

The recent emergence of SARS-CoV-2 has lead to a global pandemic of unprecedented proportions. Current diagnosis of COVID-19 relies on the detection of SARS-CoV-2 RNA by RT-PCR in upper and lower respiratory specimens. While sensitive and specific, these RT-PCR assays require considerable supplies and reagents, which are often limited during global pandemics and surge testing. Here, we show that a nasopharyngeal swab pooling strategy can detect a single positive sample in pools of up to 10 samples without sacrificing RT-PCR sensitivity and specificity. We also report that this pooling strategy can be applied to rapid, moderate complexity assays, such as the BioFire COVID-19 test. Implementing a pooling strategy can significantly increase laboratory testing capacity while simultaneously reducing turnaround times for rapid identification and isolation of positive COVID-19 cases in high risk populations.