bluuebunny/crossref_metadata_2025 huggingface dataset:
Arch Asymmetry in Patients With Cleft Lip and Palate After Rehabilitation Treatment Using Stereophotogrammetry
Authors: Pucciarelli Maria Giulia Rezende , Toyoshima Guilherme Hideki , Cardoso Jefferson Freire , de Oliveira Thaís Marchini , Neppelenbroek Karin Hermana , Soares Simone
Published: January 2021

Arch asymmetry in cleft patients is a current problem that interdisciplinary treatment aims to solve. This research proposed to analyze the final rehabilitation, according to the arch symmetry of these patients. Thirty-five patients aged between 18 and 30 years, rehabilitated with a fixed partial denture or implants in the cleft area. The analysis was performed using digitalized dental casts with a laser model scanner (R700TM; 3Shape A/S, Holmens Kanal 7, 1060, Copenhagen/Denmark), analyzed with a Vectra Analysis Module software program (VECTRA H1; Canfield Scientific, 4 Wood Hollow Road, Parsippany, NJ 07054). Three linear measurements were evaluated, incisal-canine, canine-molar, and incisal-molar distance. The Student t test was applied to test the significance (P = 0.05) of an observed sample by correlation coefficient test (r-value). Female patients showed a significant correlation in arch symmetry. According to the rehabilitation treatment, patients who received implants showed a high correlation and significant symmetry at all maxillary distances. Finally, according to the cleft side in the maxillary dimensions, even though the majority of patients had clefts on the left side, only patients with a cleft on the right side showed symmetry in this area. Patients rehabilitated with implants in the cleft area showed a more symmetrical maxillary arch than those restored with fixed partial dentures.
Pseudomonas paracarnis sp. nov., isolated from refrigerated beef
Authors: Lick Sonja , Wibberg Daniel , Winkler Annika , Blom Jochen , Grimmler Christina , Goesmann Alexander , Kalinowski Jörn , Kröckel Lothar
Published: January 2021

During a project focusing on the diversity of meat microbiota associated with beef ripening, a

Pseudomonas

strain was isolated exhibiting high 16S rRNA gene sequence similarities (>99 %) to

Pseudomonas carnis

DSM 107652T,

P. lactis

DSM 29167T,

P. paralactis

DSM 29164T and

P. azotoformans

DSM 18862T. Phylogenetic analysis of the complete rpoB gene sequences of the isolate V5/DAB/2/5T indicated a separate branch with about 99.0 % nucleotide identities to the closest relatives

P. carnis

DSM 107652T,

P. lactis

DSM 29167T and

P. paralactis

DSM 29164T, while average nucleotide identities (ANIb) calculated from the draft genomes were 94.8, 94.2 and 90.2 %, respectively. Pairwise genome-to-genome distance calculations (GGDC) resulted in values of 67.7, 63.5 and 45.7 %, respectively, lying below the actual species demarcation line as well. A second isolate, UBT403, was detected some years later by using matrix-assisted laser desorption ionization-time of flight MS of the microbiota of minced beef. The fatty acid profile of V5/DAB/2/5T consisted of C16 : 0, summed feature C 16 : 1
ω7c/iso-C15 : 0 2-OH, C18 : 1
ω7c, C17 : 0 cyclo, C12 : 0, C12 : 0 3-OH, C10 : 0 3-OH and C12 : 0 2-OH. The major cellular lipids were aminopholipids, phospholipids, phosphatidylethanolamine and phosphatidylglycerol; the major quinone was Q9 with a minor proportion of Q8. Based on phenotypic and chemotaxonomic characterizations, the isolates can be considered as representing a novel species, for which the name Pseudomonas paracarnis sp. nov. is proposed. The type strain is V5/DAB/2/5T (=DSM 111363T=LMG 31846T); a second strain is UBT403 (=DSM 111362=LMG 31847).
Jinshanibacter, a new genus of Budviciaceae: identification of Jinshanibacter zhutongyuii sp. nov. and Jinshanibacter xujianqingii sp. nov. isolated from cloacal content of snow finch (Montifringilla taczanowskii)
Authors: Ge Yajun , Wang Bin , Yang Jing , Lai Xin-He , Zhang Gui , Lu Shan , Jin Dong , Huang Ying , Cheng Yanpeng , Zhang Xiaoyan , Xu Jianguo
Published: January 2021

Four novel strains isolated from the cloacal contents of snow finches (Montifringilla taczanowskii) were characterized as aerobic, Gram-stain-negative, slightly motile, and rod-shaped. Analysis of the 16S rRNA gene sequence revealed that strain CF-458T had the highest similarities of 96.9 and 96.4 % with

Limnobaculum parvum

HYN0051T and

Pragia fontium

DSM 5563T, while strain CF-1111T shared the highest similarities of 96.4 and 96.1 % with

Pantoea rodasii

LMG 26273T and

Pectobacterium punjabense

SS95T. Phylogenomic analysis showed the four isolates were separated into group Ⅰ (CF-458T and CF-917) and group Ⅱ (CF-1111T and CF-509), and clustered independently in the vicinity of the genera

Limnobaculum

and

Pragia

. Summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c, 23.9 and 17.2 %, respectively), C16 : 0 (21.8 and 22.1 %, respectively) and C14 : 0 (10.6 and 17.7 %, respectively) were the common major fatty acids, and summed feature 8 (C18 : 1
 ω7c and/or C18 : 1
 ω6c, 12.3 %) was also a major fatty acid for strain CF-458T while cyclo-C17 : 0 (13.1%) was for strain CF-1111T. Both had Q-8 as the sole quinone and contained phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol as the major polar lipids. The DNA G+C content of strains CF-458T and CF-1111T was 45.7 and 45.4 mol%, respectively. Based on taxonomic position in the phylogenomic tree and phenotypic properties, two novel species of a new genus within the family

Budviciaceae

are thus proposed, with the name Jinshanibacter gen. nov., zhutongyuii sp. nov. (type strain CF-458T=CGMCC 1.16483T=GDMCC 1.1586T=JCM 33489T) and Jinshanibacter xujianqingii sp. nov. (type strain CF-1111T=CGMCC 1.16786T=GDMCC 1.1587T=JCM 33490T), respectively.
Mutants libraries reveal negative design shielding proteins from mis-assembly and re-localization in cells
Authors: Seisdedos Hector Garcia , Levin Tal , Shapira Gal , Freud Saskia , Levy Emmanuel
Published: January 2021

Understanding the molecular consequences of mutations in proteins is essential to map genotypes to phenotypes and interpret the increasing wealth of genomic data. While mutations are known to disrupt protein structure and function, their potential to create new structures and localization phenotypes has not yet been mapped to a sequence space. To map this relationship, we employed two homo-oligomeric protein complexes where the internal symmetry exacerbates the impact of mutations. We mutagenized three surface residues of each complex and monitored the mutations’ effect on localization and assembly phenotypes in yeast cells. While surface mutations are classically viewed as benign, our analysis of several hundred mutants revealed they often trigger three main phenotypes in these proteins: nuclear localization, the formation of puncta, and fibers. Strikingly, more than 50% of random mutants induced one of these phenotypes in both complexes. Analyzing the mutant’s sequences showed that surface stickiness and net charge are two key physicochemical properties associated with these changes. In one complex, more than 60% of mutants self-assembled into fibers. Such a high frequency is explained by negative design: charged residues shield the complex from misassembly, and the sole removal of the charges induces its assembly. A subsequent analysis of several other complexes targeted with alanine mutations suggested that negative design against mis-assembly and mislocalization is common. These results highlight that minimal perturbations in protein surfaces’ physicochemical properties can frequently drive assembly and localization changes in a cellular context.
Population dynamics of the primary malaria vectorNyssorhynchus darlingiin a high transmission setting dominated by fish farming in western Amazonian Brazil
Authors: Rufalco-Moutinho Paulo , Kadri Samir Moura , Alonso Diego Perez , Moreno Marta , Carrasco-Escobar Gabriel , Prussing Catharine , Gamboa Dionicia , Vinetz Joseph M. , Mureb Sallum Maria Anice , Conn Jan E. , Martins Ribolla Paulo Eduardo
Published: January 2021

Vale do Rio Juruáin western Acre, Brazil, has reported highest malaria numbers since 2005, and is considered persistent transmission hotspot. Fish farming development was encouraged to improve standard of living, resulting in productive breeding sites for Amazonian malaria vector species, includingNyssorhynchus darlingithat, combined with the high human density and mobility, adds to the local malaria burden. This study reports entomological profile of immature and adultNy. darlingiat three sites in Mâncio Lima, Acre, during the rainy and dry season (February to September, 2017). From 63 fishponds, 10,859 larvae were collected, including 5,512 first-instar Anophelinae larvae and 4,927 second, third and fourth-instars, of which 8.5% (n = 420) wereNy. darlingi. This species was most abundant in not-abandoned fishponds and in the presence of emerging aquatic vegetation. Seasonal analysis of immatures in urban landscapes found no significant difference in the numbers ofNy. darlingi, corresponding to equivalent population density during the rainy to dry transition period. However, in the rural landscape, significantly higher numbers ofNy. darlingilarvae were collected in August (IRR = 5.80,p= 0.037) and September (IRR = 6.62,p= 0.023) (dry season), compared to February (rainy season), suggesting important role of fishponds for vector population maintenance during the seasonal transition in this landscape type. Adult sampling detected mainlyNy. darlingi(~93%), with similar outdoor feeding behavior, but different abundance according to landscape profile: urban site 1 showed higher peaks of human biting rate in May (46 bites/person/hour), than February (4) and September (15), while rural site 3 shows similar HBR during the same sampling period (22, 24 and 21, respectively). This study contributes to a better understanding of the larvae biology of the main malaria vector in theVale do Rio Juruáregion and, ultimately will support vector control efforts.
Conserved epigenetic programming and enhanced heme metabolism drive memory B cell reactivation
Authors: Price Madeline J. , Scharer Christopher D. , Kania Anna K. , Randall Troy D. , Boss Jeremy M.
Published: January 2021

Memory B cells (MBCs) have enhanced capabilities to differentiate to plasma cells and generate a rapid burst of antibodies upon secondary stimulation. To determine if MBCs harbor an epigenetic landscape that contributes to increased differentiation potential, we derived the chromatin accessibility and transcriptomes of influenza-specific IgM and IgG MBCs compared to naïve cells. MBCs possessed an accessible chromatin architecture surrounding plasma cell specific genes, as well as altered expression of transcription factors and genes encoding cell cycle, chemotaxis, and signal transduction processes. Intriguingly, this MBC signature was conserved between humans and mice. MBCs of both species possessed a heightened heme signature compared to naïve cells. Differentiation in the presence of hemin enhanced oxidative phosphorylation metabolism and MBC differentiation into antibody secreting plasma cells. Thus, these data define conserved MBC transcriptional and epigenetic signatures that include a central role for heme and multiple other pathways in augmenting MBC reactivation potential.

Key Points

Influenza-specific memory B cells have accessible chromatin structure.

Human and mouse memory B cells upregulate heme metabolic pathways.

Heme enhances PC differentiation and augments mitochondrial metabolism in ex vivo.
The elephant retina examined across a range of ages
Authors: Freed James , Joyce Saskia , Whalley Rachel , Purse Edward , Ingram Thomas L , Yon Lisa , Chakrabarti Lisa
Published: January 2021

The effect of aging in the human retina has been well documented, as have the signs of age-related retinal disease. Comparative studies in animals allow us to further investigate how the retina ages in different species. The African bush elephant (Loxodonta africana) has a retina comparable to other mammalian species, but with some reported distinctive differences in retinal ganglion cell (RGC) distribution and type. This is a first survey of the retina ofLoxodonta africanafrom individuals aged 2 months to 32 years old. Gross examination, H&E staining and cell counts were used to compare calves (0-5 years), juveniles (6-10 years), sub-adults (11-20 years) and adults (>20 years). Dorsal-ventral eye diameter was shown to be significantly greater with age, whilst no significant changes in photoreceptor number were found. Changes in retinal thickness differed from past findings in elephants and humans, with thickness decreasing, then increasing in adults. Various morphological differences were evident in the samples including the presence of nuclei in the outer plexiform layer (OPL), degeneration of the inner plexiform layer (IPL), interruptions in nuclei columns of the outer nuclear layer (ONL), and larger unidentified cells within the inner nuclear layer (INL). These are initial observations provide some baseline information for a species where this range of samples has not been described previously.
Indirect restoration of ecological interactions: reintroduction of a dung-beetle associated primate increases the recruitment of large seeds
Authors: Landim Anna R. , Fernandez Fernando A. S. , Pires Alexandra S.
Published: January 2021

The biased loss of large and medium frugivores alters seed dispersal and plant regeneration. Species reintroductions have been proposed as a strategy to reverse the consequences of species loss. However, the effects of reintroductions on ecological processes are seldom accessed, which hinders the comprehension of reintroductions’ potential to reestablish functioning ecosystems. In this study, we investigate the effect of howler monkey (Alouatta guariba) reintroduction on the plant regeneration of Tijuca National Park (TNP), a defaunated Atlantic Forest fragment. Howlers are folivore-frugivore primates, whose large clumped defecations attract dung beetles, which provide secondary dispersal by burying seeds present in the howlers’ feces. Thus, we expect that the fate of seeds dispersed by howlers will differ from those dispersed by other frugivores present in the Park. We followed the fate of seeds between 3 and 14mm in diameter in three steps of the seed dispersal loop, each one consisting of a different experiment. First, we estimated secondary seed dispersal and burial depth probabilities according to the frugivores’ defecation pattern; then, predation probability in different burial depths and defecation patterns; and, finally, recruitment probability in different burial depths. Considering the final result of the three experiments, the howlers’ reintroduction affected positively the regeneration of large seeds. The fate of 3mm seeds was little affected because they were seldom preyed upon at shallower depths anyway and could not recruit when deeply buried. On the other hand, seeds larger than 3mm reached the seedling stage more frequently when dispersed by howlers than when dispersed by other animals present in the Park. Thus, howler monkey reintroduction in defaunated areas, in addition to smaller frugivores, whose defecation patterns are less attractive for dung beetles, improves the regeneration of large seeds. We hope that this study will stimulate new howler reintroductions in defaunated areas.
Data-poor stock assessment of fish stocks co-exploited by commercial and recreational fisheries: applications to pike (Esox lucius) in the western Baltic Sea
Authors: van Gemert Rob , Koemle Dieter , Winkler Helmut , Arlinghaus Robert
Published: January 2021

Information on catch and effort of recreational angling in mixed-use fisheries (co-exploited by commercial and recreational fishers) is often scarce, preventing the application of data-rich stock assessments typically performed for industrialized commercial fisheries. Here, we show how data-poor stock assessment methods developed for marine fisheries, particularly a class of models labelled as “catch-only” models (COMs), offer a possible solution. As a case study, we use COMs to assess a northern pike stock around the German Baltic island of Rügen. We fit multiple COMs to a time-series of total pike removals, and use their outputs as explanatory variables in superensemble models. We conclude that the stock is fully exploited and currently declining. Our study highlights the potential for using COMs to determine status of previously-unassessed coastal and freshwater stocks facing recreational fishing pressure, and demonstrates how incorporating recreational removals is crucial for achieving reliable insights into the status of mixed-use stocks.
Anterior expansion and posterior addition to the notochord mechanically coordinate embryo axis elongation
Authors: McLaren Susannah B.P. , Steventon Benjamin J.
Published: January 2021

During development the embryo body progressively elongates from head-to-tail along the anterior-posterior (AP) axis. Multiple tissues contribute to this elongation through a combination of convergence and extension and/or volumetric growth. How force generated by the morphogenesis of one tissue impacts the morphogenesis of other axial tissues to achieve an elongated axis is not well understood. The notochord, a rod-shaped tissue possessed by all vertebrates, runs across the entire length of the somitic compartment and is flanked on either side by the developing somites in the segmented region of the axis and presomitic mesoderm in the posterior. Cells in the notochord undergo an expansion that is constrained by a stiff sheath of extracellular matrix, that increases the internal pressure in the notochord allowing it to straighten and elongate. Therefore, it is appropriately positioned to play a role in mechanically elongating the somitic compartment. Here, we use multi-photon mediated cell ablation to remove specific regions of the developing notochord and quantify the impact on axis elongation. We show that anterior notochord cell expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues and contributes to the elongation of segmented tissue during post-tailbud stages of development. Crucially, unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for force generation across the AP axis. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo AP axis.
The human olfactory bulb process odor valence representation and initiate motor avoidance behavior
Authors: Iravani Behzad , Schaefer Martin , Wilson Donald A. , Arshamian Artin , Lundström Johan N.
Published: January 2021

Determining the valence of an odor to provide information to guide rapid approach-avoidance behavior is thought to be one of the core tasks of the olfactory system, yet little is known of its initial neural mechanisms or subsequent behavioral manifestation in humans. In two experiments, we measured the functional processing of odor valence perception in the human olfactory bulb (OB)—the first processing stage of the olfactory system—using a non-invasive method as well as assessed subsequent motor avoidance response. We demonstrate that odor valence perception is associated with both gamma and beta activity in the human OB. Moreover, we show that negative, but not positive, odors initiate an early beta response in the OB, a response that is linked to a preparatory neural motor response in motor cortex. Finally, in a separate experiment we show that negative odors trigger a full-body motor avoidance response, manifested as a rapid leaning away from the odor, in the time period predicted by the OB results. Taken together, these results demonstrate that the human OB processes odor valence in a sequential manner in both the gamma and beta frequency bands and suggest that early processing of unpleasant odors in the OB might underlie rapid approach-avoidance decisions.
Characterising the spatio-temporal threats, conservation hotspots, and conservation gaps for the most extinction-prone bird family (Aves: Rallidae)
Authors: Lévêque Lucile , Buettel Jessie C. , Carver Scott , Brook Barry W.
Published: January 2021

With thousands of vertebrate species now threatened with extinction, there is an urgent need to understand and mitigate the causes of wildlife collapse. As distinct evolutionary clades can follow different routes to endangerment, there is value in taxon-specific analyses when assessing species’ vulnerability to threats and identifying gaps in conservation actions. Rails (Aves: Rallidae), being the most extinction-prone bird Family globally, and with one third of extant rail species now threatened or near-threatened, are an emphatic case in point. Yet even for this well-studied group, there is uncertainty in our understanding of what factors might be causing this vulnerability, whether the current threats are consistent with those that led to recent extinctions, and ultimately, what conservation actions might be necessary to mitigate further losses. Here, we undertook a global synthesis of the temporal and spatial threat patterns for Rallidae and determined conservation priorities and gaps. We found two key pathways in the threat pattern for rails. One follows the same trajectory as extinct rails, where island endemic and flightless rails are most threatened, mainly due to invasive predators. The second, created by the recent diversification of anthropogenic activities, involves continental rails (generally in the Neotropics), threatened most commonly by agriculture, natural-system modifications and residential and commercial development. Conservation efforts around most-at-risk species should be adapted according to the most relevant geographic scale (bioregions or countries), and principal locality type of the population (continental or island endemic). Indonesia, the U.S.A., the United Kingdom, New Zealand, and Cuba were the priority countries identified by our classification system incorporating species’ unique evolutionary features and level of endangerment, but also among the countries that lack conservation actions the most. Future efforts should predominantly target improvements in ecosystem protection and management, as well as ongoing research and monitoring. Forecasting the impacts of climate change on island endemic rails and disentangling the specific roles of extrinsic and intrinsic traits (like flightlessness), will be particularly valuable avenues of research for improving our forecasts of rail vulnerability.
Deconvolving clinically relevant cellular immune crosstalk from bulk gene expression using CODEFACS and LIRICS
Authors: Wang Kun , Patkar Sushant , Lee Joo Sang , Gertz E. Michael , Robinson Welles , Schischlik Fiorella , Crawford David R. , Schäffer Alejandro A. , Ruppin Eytan
Published: January 2021

The tumor microenvironment (TME) is a complex mixture of cell types whose interactions affect tumor growth and clinical outcome. To discover such interactions, we developed CODEFACS (COnfident DEconvolution For All Cell Subsets), a tool deconvolving cell-type-specific gene expression in each sample from bulk expression, and LIRICS (LIgand Receptor Interactions between Cell Subsets), a statistical framework prioritizing clinically relevant ligand-receptor interactions between cell types from the deconvolved data. We first demonstrate the superiority of CODEFACS versus the state-of-the-art deconvolution method, CIBERSORTx. Second, analyzing the TCGA, we uncover cell-type-specific interactions of mismatch-repair-deficient tumors that are associated with their higher anti-PD1 response rates, including specific T-cell co-stimulating interactions that enhance immunotherapy response independently of the tumors mutation burden levels. Finally, we identify a subset of ligand-receptor interactions in the melanoma TME that predict patient response to anti-PD1 therapy better than recently published transcriptomics-based methods.
Striatal fiber photometry reflects primarily non-somatic activity
Authors: Legaria Alex A. , Yang Ben , Ahanonu Biafra , Licholai Julia A. , Parker Jones G. , Kravitz Alexxai V.
Published: January 2021

Calcium recording via fiber photometry is commonly used as a proxy for recording population neuronal activityin vivo, yet the biological source of the photometry signal remains unclear. Here, using simultaneousin vivoextracellular electrophysiology and fiber photometry in the striatum, along with endoscopic 1-photon and 2-photon calcium imaging, we determined that the striatal fiber photometry signal reflects primarily non-somatic, and not somatic, changes in calcium.
Redeployment and training of healthcare professionals to Intensive Care during COVID-19: a systematic review
Authors: Vera San Juan Norha , Camilleri Matthew , Jeans John Paul , Monkhouse Alexandra , Chisnall Georgia , Vindrola-Padros Cecilia
Published: January 2021

Background

A rapid influx of patients to intensive care and infection control measures during the COVID-19 pandemic required the rapid development of innovative redeployment and training strategies.

Methods

We conducted a systematic search of 9 databases including key terms related to intensive care AND training AND redeployment AND healthcare workers. Analysis consisted of a narrative synthesis of quantitative study outputs, and a framework-based thematic analysis of qualitative study outputs and grey literature. These results were then combined applying an interpretative synthesis.

Results

Twenty papers were analysed. These took place primarily in the UK (N=8, 40%) and USA (N=5, 25%). Themes included in the results are Redeployment: Implementation strategies and learnings; Redeployed staff experience and strategies to address their needs; Redeployed staff learning needs; Training formats offered and training evaluations; and Future redeployment and training concerns. Some of the redeployment implementation and training strategies documented in this review are: Skills-based redeployment, buddy support systems, and agreeing on locally-specific principles, rather than strict procedures.

Conclusion

The COVID-19 pandemic presented unique challenges to deliver training promptly while following infection control recommendations and develop flexible redeployment strategies. This study synthesises original approaches to tackle these challenges which are relevant to inform the development of targeted and adaptative training and redeployment plans.
Potential contribution of climate conditions on COVID-19 pandemic transmission over West and North African countries
Authors: Diouf Ibrahima , Sy Souleymane , Senghor Habib , Fall Papa , Diouf Diarra , Diakhaté Moussa , Thiaw Wassila M. , Gaye Amadou T.
Published: January 2021

The COVID-19 disease, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a very contagious disease that has killed many people around the world. According to the World Health Organization (WHO) data, the spread of the disease appears to be slower in Africa. Although a number of studies have been published on the relationship between meteorological parameters and COVID-19 transmission, the effects of climate conditions on COVID-19 remain largely unexplored and without consensus following the main research finding over Africa (often based on a single country or city). Here, using available epidemiological data over 275 days (i.e., from March 1 to November 30, 2020) taken from the European Center for Disease Prevention and Control of the European Union database and daily data of surface air temperature and humidity from the National Center for Environmental Prediction (NCEP), this paper investigates the potential contributions of climate conditions on COVID-19 transmission over 16 countries selected from three bioclimatic regions of Africa (i.e., Sahel, Maghreb and Gulf of Guinea). On average, our main findings highlight statistically significant inverse correlations between COVID-19 cases and temperature over the Maghreb and the Gulf of Guinea regions, whereas positive correlations are found in the Sahel, especially over the central part including Niger and Mali. Correlations with specific humidity and water vapor parameters display significant and positive values over the Sahelian and the Gulf of Guinean countries and negative values over the Maghreb countries. In other word, results imply that the COVID-19 pandemic transmission is influenced differently across the three bioclimatic regions: i) cold and dry environmental conditions over the Maghreb; ii) warm and humid conditions over the Sahel iii) cold and humid conditions over the Gulf of Guinea. These findings could be useful for decision-makers who plan public health and control measures in affected African countries and would have substantial implications for directing respiratory disease surveillance activities.
Agent-Based Simulation of Covid-19 Vaccination Policies in CovidSIMVL
Authors: Chang Ernie , Moselle Kenneth A.
Published: January 2021

An agent-based infectious disease modeling tool (CovidSIMVL) is employed in this paper to explore outcomes associated with MRNA two-dose vaccination regimens set out in Emergency Use Authorization (EUA) documents submitted by Pfizer and Moderna to the US Department of Health & Human Services. As well, the paper explores outcomes associated with a third “Hybrid” policy that reflects ranges of expected levels of protection according to Pfizer and Moderna EUA’s, but entails a 35 day separation between first and second dose, which exceeds the 21 days set out in Pfizer documentation or the 28 days in Moderna documentation.

Four CovidSIMVL parameters are varied in the course of 75 simulated clinical trials. Two relate directly to the vaccines and their impacts (duration between doses; degree of expected protection conferred by different vaccines following first or second dose). Two relate to the simulation contexts to which the vaccines are applied (degree of infectivity; duration of infectivity). The simulated trials demonstrate expected effects for timing of second dose, and for degree of protection associated with first and second dose of Pfizer and Moderna vaccines, and the effects are consistent with an assumed value of 75% for degree of protection after first and second doses for the Hybrid vaccine. However, the simulated trials suggest a more complex interaction between expected level of protection following first dose, timing of second dose and degree of infectivity. These results suggest that policy options should not be considered independent of the transmission dynamics that are manifested in the contexts in which the policies could be applied.

CovidSIMVL embodies stochasticity in the mechanisms that govern viral transmission, and it treats the basic reproduction number (R0)as an emergent characteristic of transmission dynamics, not as a pre-set value that determines those dynamics. As such, results reported in this paper reflect outcomes that could happen, but do not necessarily reflect what is more or less likely to happen, given different configurations of parameters. The discussion section goes into some measure of detail regarding next steps that could be pursued to enhance the potential for agent-based models such as CovidSIMVL to inform exploration of possible vaccination policies, and to project outcomes that are possible or likely in local contexts, where stochasticity and heterogeneity of transmission must be featured in models that are intended to reflect local realism.
Assessing the efficacy of interventions to control indoor SARS-Cov-2 transmission: an agent-based modeling approach
Authors: Farthing Trevor S. , Lanzas Cristina
Published: January 2021

Intervention strategies for minimizing indoor SARS-CoV-2 transmission are often based on anecdotal evidence because there is little evidence-based research to support them. We developed a spatially-explicit agent-based model for simulating indoor respiratory pathogen transmission, and used it to compare effects of four interventions on reducing individual-level SARS-CoV-2 transmission risk by simulating a well-known case study. We found that imposing movement restrictions and efficacious mask usage appear to have the greatest effects on reducing infection risk, but multiple concurrent interventions are required to minimize the proportion of susceptible individuals infected. Social distancing had little effect on reducing transmission if individuals move during the gathering. Furthermore, our results suggest that there is potential for ventilation airflow to expose susceptible people to aerosolized pathogens even if they are relatively far from infectious individuals. Maximizing rates of aerosol removal is the key to successful transmission-risk reduction when using ventilation systems as intervention tools.

Article Summary Line

Imposing mask usage requirements, group size restrictions, duration limits, and social distancing policies can have additive, and in some cases multiplicative protective effects on SARS-CoV-2 infection risk during indoor events.
Air passenger travel and international surveillance data predict spatiotemporal variation in measles importations to the United States
Authors: Poterek Marya L. , Kraemer Moritz U.G. , Watts Alexander , Khan Kamran , Perkins T. Alex
Published: January 2021

Measles incidence in the United States has grown dramatically, as vaccination rates are declining and transmission internationally is on the rise. Measles virus is highly infectious and can cause severe symptoms and even death. Because imported cases are necessary drivers of outbreaks in non-endemic settings, predicting measles outbreaks in the US depends on predicting imported cases. To assess the predictability of imported measles cases, we performed a regression of imported measles cases in the US against an inflow variable that combines air travel data with international measles surveillance data. To understand the contribution of each data type to these predictions, we repeated the regression analysis with alternative versions of the inflow variable that replaced each data type with averaged values and with versions of the inflow variable that used modeled inputs. We assessed the performance of these regression models using correlation, coverage probability, and area under the curve statistics, including with resampling and cross-validation. Our regression model had good predictive ability with respect to the presence or absence of imported cases in a given state in a given year (AUC = 0.78) and the magnitude of imported cases (Pearson correlation = 0.84). By comparing alternative versions of the inflow variable averaging over different inputs, we found that both air travel data and international surveillance data contribute to the model’s ability to predict numbers of imported cases, and individually contribute to its ability to predict the presence or absence of imported cases. Predicted sources of imported measles cases varied considerably across years and US states, depending on which countries had high measles activity in a given year. Our results emphasize the importance of the relationship between global connectedness and the spread of measles.
Personalized Virus Load Curves of SARS-CoV-2 Infection
Authors: Hillen Thomas , Contreras Carlos , Newby Jay M.
Published: January 2021

We introduce an explicit function that describes virus-load curves on a patient-specific level. This function is based on simple and intuitive model parameters. It allows virus load analysis without solving a full virus load dynamic model. We validate our model on data from influenza A as well as SARS-CoV-2 infection data for Macaque monkeys and humans. Further, we compare the virus load function to an established target model of virus dynamics, which shows an excellent fit. Our virus-load function offers a new way to analyse patient virus load data, and it can be used as input to higher level models for the physiological effects of a virus infection, for models of tissue damage, and to estimate patient risks.
Do Pandemics Obey the Elliott Wave Principle of Financial Markets?
Authors: Dogra Prashant , Koay Eugene J. , Wang Zhihui , Vahidy Farhaan S. , Ferrari Mauro , Pasqualini Renata , Arap Wadih , Boom Marc L. , Sostman H. Dirk , Cristini Vittorio
Published: January 2021

The Elliott Wave principle is a time-honored, oft-used method for predicting variations in the financial markets. It is based on the notion that human emotions drive financial decisions. In the fight against COVID-19, human emotions are similarly decisive, for instance in that they determine one’s willingness to be vaccinated, and/or to follow preventive measures including the wearing of masks, the application of social distancing protocols, and frequent handwashing. On this basis, we postulated that the Elliott Wave Principle may similarly be used to predict the future evolution of the COVID-19 pandemic. We demonstrated that this method reproduces the data pattern especially well for USA (daily new cases). Potential scenarios were then extrapolated, from the best-case corresponding to a rapid, full vaccination of the population, to the utterly disastrous case of slow vaccination, and poor adherence to preventive protocols.
Profiling of open chromatin in developing pig (Sus scrofa) muscle to identify regulatory regions
Authors: Salavati Mazdak , Woolley Shernae A. , Araya Yennifer Cortés , Halstead Michelle M. , Stenhouse Claire , Johnsson Martin , Ashworth Cheryl J. , Archibald Alan L. , Donadeu Francesc X. , Hassan Musa A. , Clark Emily L.
Published: January 2021

There is very little information about how the genome is regulated in domestic pigs (Sus scrofa). This lack of knowledge hinders efforts to define and predict the effects of genetic variants in pig breeding programmes. In order to address this knowledge gap, we need to identify regulatory sequences in the pig genome starting with regions of open chromatin. We have optimised the ‘Improved Protocol for the Assay for Transposase-Accessible Chromatin (Omni-ATAC-Seq)’ to profile regions of open chromatin in flash frozen pig muscle tissue samples. This protocol has allowed us to identify putative regulatory regions in semitendinosus muscle from 24 male piglets. We collected samples from the smallest, average, and largest sized male piglets from each litter through five developmental time points. The ATAC-Seq data were mapped to Sscrofa11.1 using Bowtie2 and Genrich was used for post-alignment peak-calling. Of the 4,661 ATAC-Seq peaks identified that represent regions of open chromatin, >50% were within 1 kb of known transcription start sites. Differential read count analysis revealed 377 ATAC-Seq defined genomic regions where chromatin accessibility differed significantly across developmental time points. We found regions of open chromatin associated with down regulation of genes involved in muscle development that were present in small sized foetal piglets but absent in large foetal piglets at day 90 of gestation. The dataset that we have generated provides: i) a resource for studies of genome regulation in pigs, and ii) contributes valuable functional annotation information to filter genetic variants for use in genomic selection in pig breeding programmes.
HLA-G gene editing: a novel therapeutic alternative in cancer immunotherapy
Authors: Palma María Belén , Roux Diana Tronik-Le , Amín Guadalupe , Castañeda Sheila , Möbbs Alan M. , Scarafia María Agustina , La Greca Alejandro , Daouya Marina , Poras Isabelle , Inda Ana María , Moro Lucía N. , Carosella Edgardo D. , García Marcela N. , Miriuka Santiago G.
Published: January 2021

Cancer immunotherapies based mainly on the blockade of immune-checkpoint (IC) molecules by anti-IC antibodies offer new alternatives for treatment in oncological diseases. However, a considerable proportion of patients remain unresponsive to them. Hence, the development of novel clinical immunotherapeutic approaches and/or targets are crucial. In this context, targeting the immune-checkpoint HLA-G/ILT2/ILT4 has caused great interest since it is abnormally expressed in several malignancies generating a tolerogenic microenvironment. Here, we used CRISPR/Cas9 gene editing to block the HLA-G expression in two tumor cell lines expressing HLA-G, including a renal cell carcinoma (RCC7) and a choriocarcinoma (JEG-3). Different sgRNA/Cas9 plasmids targetingHLA-Gexon 1 and 2 were transfected in both cell lines. Downregulation of HLA-G was reached to different degrees, including complete silencing. Most importantly, HLA-G – cells triggered a higherin vitroresponse of immune cells with respect to HLA-G + wild type cells. Altogether, we demonstrated for the first time the HLA-G downregulation through gene editing. We propose this approach as a first step to develop novel clinical immunotherapeutic approaches in cancer.
A chromosomal inversion drives evolution of multiple adaptive traits in deer mice
Authors: Hager Emily R. , Harringmeyer Olivia S. , Wooldridge T. Brock , Theingi Shunn , Gable Jacob T. , McFadden Sade , Neugeboren Beverly , Turner Kyle M. , Hoekstra Hopi E.
Published: January 2021

A long-standing question in evolutionary biology is how differences in multiple traits can evolve quickly and be maintained together during local adaptation. Using forest and prairie ecotypes in deer mice, which differ in both tail length and coat color, we discovered a 41 Mb chromosomal inversion that is strongly linked to variation in both traits. The inversion maintains highly divergent loci in strong linkage disequilibrium and likely originated ~170 kya, long before the forest-prairie divergence ~10 kya. Consistent with a role in local adaptation, inversion frequency is associated with phenotype and habitat across both a local transect and the species range. Still, although eastern and western forest subspecies share similar phenotypes, the inversion is absent in eastern North America. This work highlights the significance of inversion polymorphisms for the establishment and maintenance of multiple locally adaptive traits in mammals, and demonstrates that, even within a species, parallel phenotypes may evolve through nonparallel genetic mechanisms.
Connectome: computation and visualization of cell-cell signaling topologies in single-cell systems data
Authors: Raredon Micha Sam Brickman , Yang Junchen , Garritano James , Wang Meng , Kushnir Dan , Schupp Jonas Christian , Adams Taylor S. , Greaney Allison M. , Leiby Katherine L. , Kaminski Naftali , Kluger Yuval , Levchenko Andre , Niklason Laura E.
Published: January 2021

Single-cell RNA-sequencing data can revolutionize our understanding of the patterns of cell-cell and ligand-receptor connectivity that influence the function of tissues and organs. However, the quantification and visualization of these patterns are major computational and epistemological challenges. Here, we presentConnectome, a software package for R which facilitates rapid calculation, and interactive exploration, of cell-cell signaling network topologies contained in single-cell RNA-sequencing data.Connectomecan be used with any reference set of known ligand-receptor mechanisms. It has built-in functionality to facilitate differential and comparative connectomics, in which complete mechanistic networks are quantitatively compared between systems.Connectomeincludes computational and graphical tools designed to analyze and explore cell-cell connectivity patterns across disparate single-cell datasets. We present approaches to quantify these topologies and discuss some of the biologic theory leading to their design.
Matriptase generates a tissue damage response via promoting Gq signalling, leading to RSK and DUOX activation
Authors: Jiajia MA , Scott Claire A. , Ying Na HO , Mahabaleshwar Harsha , Marsay Katherine S. , Zhang Changqing , Teow Christopher K. J. , Ser Sue NG , Zhang Weibin , Tergaonkar Vinay , Partridge Lynda J. , Roy Sudipto , Amaya Enrique , Carney Tom J.
Published: January 2021

Tissues respond to damage by increasing inflammation and epithelial cell motility. How damage detection and responses are orchestrated is unclear. Overexpression of the membrane bound protease, Matriptase, or mutation of its inhibitor, Hai1, results in inflamed epithelia, in which cells have increased motility and are prone to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafishhai1amutants show increased H2O2, NfκB signalling, and IP3R-mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit rescues both thehai1ainflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demonstrate thathai1ahas elevated pERK, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as pERK targets disrupting adherens junctions inhai1amutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression.
Legacy of draught cattle breeds of South India: Insights into population structure, genetic admixture and maternal origin
Authors: Manomohan Vandana , Saravanan Ramasamy , Pichler Rudolf , Murali Nagarajan , Sivakumar Karuppusamy , Sudhakar Krovvidi , Nachiappan Raja K , Periasamy Kathiravan
Published: January 2021

The present study is the first comprehensive report on diversity, population structure, genetic admixture and mitochondrial DNA variation in South Indian draught type zebu cattle. The diversity of South Indian cattle was moderately higher. A significantly strong negative correlation coefficient of −0.674 (P<0.05) was observed between the effective population size of different breeds and their estimated FIS. The phylogeny and genetic structure analysis revealed the distinctness of Kangayam, Vechur and Punganur cattle from the rest of the zebu breeds. The results showed the influence of Hallikar breed in the development of most Mysore type cattle breeds of South India with the exception of Kangayam. Bayesian clustering analysis was performed to assess the taurine admixture in South Indian zebu cattle using purebred Jersey and Holstein-Friesian as reference genotypes. Relatively high levels of taurine admixture (>6.25%) was observed in Punganur, Vechur, Umblachery and Pulikulam cattle breeds. Two major maternal haplogroups, I1 and I2, typical of zebu cattle were observed, with the former being predominant than the later. The pairwise differences among the I2 haplotypes of South Indian cattle were relatively higher than West Indian (Indus valley site) zebu cattle. The results indicated the need for additional sampling and comprehensive analysis of mtDNA control region variations to unravel the probable location of origin and domestication of I2 zebu lineage. The present study also revealed major concerns on South Indian zebu cattle (i) risk of endangerment due to small effective population size and high rate of inbreeding (ii) lack of sufficient purebred zebu bulls for breeding and (iii) increasing level of taurine admixture in zebu cattle. Availability of purebred semen for artificial insemination, incorporation of genomic/molecular information to identify purebred animals and increased awareness among farmers will help to maintain breed purity, conserve and improve these important draught cattle germplasms of South India.