bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradesulfitobacterium ferrireducens gen. nov., sp. nov., a Fe(III)-reducing bacterium from petroleum-contaminated soil and reclassification of Desulfitobacterium aromaticivorans as Paradesulfitobacterium aromaticivorans comb. nov.
Authors: Li Yanling , Yang Guiqin , Yao Sijie , Zhuang Li
Published: September 2021

A strictly anaerobic bacterium, strain PLL0T, was isolated from petroleum-contaminated soil sampled in Gansu Province, PR China. Cells were rods, non-motile and Gram-stain-positive. The strain grew at 25–37 °C (optimum, 30 °C) in the presence of 0–3 % (w/v) NaCl (optimum, 2 %). Strain PLL0T was able to reduce ferrihydrite, Fe(III) citrate and thiosulphate. The 16S rRNA gene analysis revealed that this strain clustered with the genus

Desulfitobacterium

, and showed highest similarity to

Desulfitobacterium aromaticivorans

UKTLT (95.4 %) followed by

Desulfitobacterium chlororespirans

Co23T (93.9 %). However, strains PLL0T and UKTLT showed no more than 94.0 % similarity to other species of the genus

Desulfitobacterium

, and formed an independent group in the phylogenetic tree. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain PLL0T and

Desulfitobacterium

species (except for

D. aromaticivorans

) were 67.4–68.5 % and 12.6–12.7 %, respectively, which are far below the threshold for delineation of a new species. Based on ANI, dDDH, average amino acid identity, phylogenetic analysis and physiologic differences from the previously described taxa, we suggest that strain PLL0T represents a novel species of a novel genus, for which the name Paradesulfitobacterium ferrireducens gen. nov. sp. nov. is proposed. The type strain is PLL0T (=MCCC 1K05549=KCTC 25248). We also propose the reclassification of

D. aromaticivorans

as Paradesulfitobacterium aromaticivorans comb. nov.
Readmissions in Patients with Cerebral Cavernous Malformations (CCMs): A National Readmission Database (NRD) Study
Authors: Padarti Akhil , Amritphale Amod , Eliyas Javed Khader , Rigamonti Daniele , Zhang Jun
Published: September 2021

BACKGROUND

Cerebral cavernous malformations (CCMs) are microvascular CNS lesions prone to hemorrhage leading to neurological sequela such as stroke and seizure. A subset of CCM patients have aggressive disease leading to multiple bleeding events, likely resulting multiple hospitalizations. Hospital admission rates are an important metric that has direct financial impact on hospitals and an indicator of overall disease burden. Furthermore, analysis of hospital readmissions can lead to early identification of high-risk patients and provides insight into the pathogenesis of CCM lesions. The purpose of this study is to identify high risk CCM patients with increased all cause readmission and comorbidities associated with increased readmissions.

METHODS

All US hospital admissions due to CCMs were searched using the 2017 National Readmission Database (NRD). Patients with readmissions within 30 days of discharge from index hospitalization were identified and analyzed, relative to the remaining population.

RESULTS

Among all patients hospitalized for CCM, 14.9% (13.7-16.2%) required all cause readmission within 30 days. Multivariate logistical regression analysis showed that substance abuse (p=0.003), diabetes (p=0.018), gastrointestinal bleed (p=0.002), renal failure (p=0.027), and coronary artery disease (p=0.010) were predictive of all cause readmissions, while age group 65-74 (p=0.042), private insurance (p<0.001), and treatment at a metropolitan teaching institution (p=0.039) were protective. Approximately half of all readmissions are caused by neurological (33.9%) and infectious (14.6%) etiologies. The 30-day lesion bleeding rate after index hospitalization is 0.8% (0.5-1.2%).

CONCLUSIONS

All identified comorbidities associated with increased risks of readmission contribute to vascular stress, suggesting its role in lesion pathogenesis. This is the first and only study to analyze readmission metrics for CCMs in order to identify high risk patient factors to date.
Cardiovascular Risk Factors and Outcomes in COVID-19: Hospital-Based Prospective Study in India
Authors: Sharma Arvind , Baig Vaseem Naheed , Sharma Sonali , Dalela Gaurav , Panwar Raja Babu , Katoch Vishwa Mohan , Gupta Rajeev
Published: September 2021

Background & Objectives

Presence of cardiovascular (CV) risk factors enhance adverse outcomes in COVID-19. To determine association of risk factors with clinical outcomes in India we performed a study.

Methods

Successive virologically confirmed patients of COVID-19 at a government hospital were recruited at admission and in-hospital outcome and other details obtained. The cohort was classified according to age, sex, hypertension, diabetes and tobacco use. To compare intergroup outcomes we performed univariate and multivariate logistic regression.

Results

From March-September 2020 we recruited 4645 (men 3386, women 1259) out of 5103 COVID-19 patients (91.0%). Mean age was 46±18y, hypertension was in 17.8%, diabetes in 16.6% and tobacco-use in 29.5%. Duration of hospital stay was 6.8±3.7 days, supplemental oxygen was in 18.4%, non-invasive ventilation in 7.1%, mechanical ventilation in 3.6% and 7.3% died. Unadjusted and age-sex adjusted odds ratio and 95% confidence intervals, respectively were, age ≥50y (4.16, 3.22-5.37 and 4.15,3.21-5.35), men (1.88,1.41-2.51 and 1.26,0.91-1.48); hypertension (2.22,1.74-2.83 and 1.32,1.02-1.70), diabetes (1.88,1.46-2.43 and 1.16,0.89-1.52) and tobacco (1.29,1.02-1.63 and 1.28,1.00-1.63). Need for invasive ventilation was greater in age >50y (3.06,2.18-4.28 and 3.06,2.18-4.29) and diabetes (1.64,1.14-2.35 and 1.12,0.77-1.62). Non-invasive ventilation was more in age ≥50y (2.27,1.80-2.86 and 2.26,1.79-2.85) and hypertension (1.82,1.41-2.35 and 1.29,0.99-1.69). Multivariate adjustment for presenting factors attenuated the significance.

Conclusion

Cardiovascular risk factors-age, male sex, hypertension, diabetes and tobacco-are associated with greater risk of death and adverse outcomes in COVID-19 patients in India.
Identification and quantification of chimeric sequencing reads in a highly multiplexed RAD-seq protocol
Authors: Martin Cerezo Maria Luisa , Raval Rohan , de Haro Reyes Bernardo , Kucka Marek , Chan Frank Yingguang , Bryk Jarosław
Published: September 2021

Highly multiplexed approaches have become a common practice in genomic studies. They have improved the cost-effectiveness of genotyping hundreds of individuals by using combinatorially-barcoded adapters. These strategies, however, can potentially misassign reads to incorrect samples. Here we used a modified quaddRAD protocol to analyse the occurrence of index hopping and PCR chimeras in a series of experiments with up to a 100 multiplexed samples per sequencing lane (total n = 639). We created two types of sequencing libraries: four libraries of Type A, where PCR reactions were run on individual samples before multiplexing, and three libraries of Type B, where PCRs were run on pooled samples. We used fixed pairs of inner barcodes to identify chimeric reads. Type B libraries show a higher percentage of misassigned reads (1.15%) compared to Type A libraries (0.65%). We also quantify the commonly undetectable chimeric sequences that occur whenever multiplexed groups of samples with different outer barcodes are sequenced together on a single flow cell. Our results suggest that these types of chimeric sequences represent up to 1.56% and 1.29% of reads in Type A and B libraries, respectively. We review the source of such errors, provide recommendations for developing highly-multiplexed RAD-seq protocols and analysing the resulting data to minimise the generation of chimeric sequences, allow their quantification, and provide finer control over the number of PCR cycles necessary to generate enough input DNA for library preparation.
Elevated alpha diversity in disturbed sites obscures regional decline and homogenization of amphibian diversity
Authors: Dehling D. Matthias , Dehling J. Maximilian
Published: September 2021

Loss of natural habitat is one of the major threats for biodiversity worldwide. Habitat conversion not only changes diversity and species composition locally (alpha diversity) but might also lead to large-scale homogenization of species communities and decrease in regional species richness (gamma diversity). We investigated the effect of farmland conversion on amphibian communities in Rwanda and compared local and regional (country-wide) taxonomic, functional and phylogenetic diversity between natural and farmland sites (agricultural marais). Alpha diversity was higher in the disturbed farmland than in natural sites. However, species turnover among farmland sites was much lower than among natural sites, resulting in highly homogenized amphibian communities and much lower country-wide taxonomic, functional and phylogenetic gamma diversity in farmland compared to natural sites. The few frog species found in farmland were mostly disturbance-tolerant species that are widespread in Eastern Africa and beyond. In contrast, most of the regionally endemic frog species that make this region a continent-scale hotspot of amphibian diversity were found only in the natural habitats. Ongoing farmland conversion might lead to a loss of regional endemism and a widespread homogenization of species communities across sub-Saharan Africa.
Optimised multiplex amplicon sequencing for mutation identification using the MinION nanopore sequencer
Authors: Whitford Whitney , Hawkins Victoria , Moodley Kriebashne , Grant Matthew J. , Lehnert Klaus , Snell Russell G. , Jacobsen Jessie C.
Published: September 2021

Objective

Rapid, cost-effective identification of genetic variants in small candiate genomic regions remains a challenge, particularly for less well equipped or lower throughput laboratories. Application of Oxford Nanopore Technologies’ MinION sequencer has the potential to fulfil this requirement. We have developed a multiplexing assay which pools PCR amplicons for MinION sequencing to enable sequencing of multiple templates from multiple individuals which could be applied to gene-targeted diagnostics.

Methods

A combined strategy of barcoding and sample pooling was developed for simultaneous multiplex MinION sequencing of 100 PCR amplicons, spanning 30 loci in DNA isolated from 82 neurodevelopmental cases and family members. The target regions were chosen for further interegation because a potentially disease-causative variants had been identified in affected individuals by Illumina exome sequencing. The pooled MinION sequences were deconvoluted by aligning to custom references using the guppy aligner software.

Results

Our multiplexing approach produced interpretable and expected sequence from 29 of the 30 targeted genetic loci. The sequence variant which was not correctly resolved in the MinION sequence was adjacent to a five nucleotide homopolymer. It is already known that homopolymers present a resolution problem with the MinION approach. Interstingly despite equimolar quantities of PCR amplicon pooled for sequencing, significant variation in the depth of coverage (139x – 21,499x; mean = 9,050, std err = 538.21) was observed. We observed independent relationships between depth of coverage and target length, and depth of coverage and GC content. These relationships demonstrate biases of the MinION sequencer for longer templates and those with lower GC content.

Conclusion

We demonstrate an efficient approach for variant discovery or confirmation from short DNA templates using the MinION sequencing device. With less than 140x depth of coverage required for accurate genotyping, the methodology described here allows for rapid highly multiplexed targeted sequencing of large numbers of samples in a minimally equipped laboratory.
Risk factors associated with development and persistence of long COVID
Authors: Miyazato Yusuke , Tsuzuki Shinya , Morioka Shinichiro , Terda Mari , Kutsuna Satoshi , Saito Sho , Shimanishi Yumiko , Takahashi Kozue , Sanada Mio , Akashi Masako , Kuge Chika , Osanai Yasuyo , Tanaka Keiko , Suzuki Michiyo , Hayakawa Kayoko , Ohmagari Norio
Published: September 2021

Background

Long COVID has been a social concern. Though patient characteristics associated with developing long COVID are partially known, those associated with persisting it have not been identified.

Methods

We conducted a cross-sectional questionnaire survey of patients after COVID-19 recovery who visited the National Center for Global Health and Medicine between February 2020 and March 2021. Demographic and clinical data, and the presence and duration of long COVID were obtained. We identified factors associated with development and persistence of long COVID using multivariate logistic and linear regression analysis, respectively.

Results

We analyzed 457 of 526 responses (response rate, 86.9%). The median age was 47 years, and 378 patients (84.4%) had mild disease in acute phase. The number of patients with any symptoms after 6 and 12 months after onset or diagnosis were 120 (26.3%) and 40 (8.8%), respectively. Women were at risk for development of fatigue (OR 2.03, 95% CI 1.31-3.14), dysosmia (OR 1.91, 95% CI 1.24-2.93), dysgeusia (OR 1.56, 95% CI 1.02-2.39), and hair loss (OR 3.00, 95% CI 1.77-5.09), and were at risk for persistence of any symptoms (coefficient 38.0, 95% CI 13.3-62.8). Younger age and low body mass index were risk factors for developing dysosmia (OR 0.96, 95% CI 0.94-0.98, and OR 0.94, 95% CI 0.89-0.99, respectively) and dysgeusia (OR 0.98, 95% CI 0.96-1.00, and OR 0.93, 95% CI 0.88-0.98, respectively).

Conclusion

We identified risk factors for the persistence as well as development of long COVID. Many patients suffer from long-term residual symptoms, even in mild cases.

Our cross-sectional questionnaire survey of patients recovering from COVID-19 revealed that women, young age, and low body mass index were risk factors for the development of multiple symptoms, and that even mild cases of COVID-19 suffered from long-term residual symptoms.
How Our Cells Become Our Selves: The Cellular Phylodynamic Biology of Growth and Development
Authors: Chodrow Philip , Su Jessica , Lee Daniel , Ahmed Tahmid , He Neil , Ruben De Man , Tiwari Ankur , Mannherz William , Citi Luca , DiCorpo Daniel , Michaelson James Selib
Published: September 2021

Our lives begin with 1 cell, then 2, then 4, then the trillion cell adult, comprised of cell lineages, tissues, organs. How does this occur? Examination in numbers of cells, N, Cellular Phylodynamics, revealed two previously unappreciated processes: UNI-GROWTH, the slowing of growth that occurs as we become larger, caused by fewer cells dividing, captured by the Universal Mitotic Fraction and Universal Growth Equations, with accuracy confirmed for 13 species, including nematodes, mollusks, and vertebrates; and ALLO-GROWTH, the creation of body parts from Founder Cells, captured by the Cellular Allometric Growth Equation, which describes mitotic expansion by Cell-Heritable change in the Cell Cycle Time. These equations can generate cell lineage approximations, bringing the power of coalescent theory to developmental biology.
Assessing the relationships between neurological and psychiatric diseases with astrocyte subtypes and psychotropic medications
Authors: Zhang Xiaolu , Wolfinger Alyssa , Shukla Rammohan , Lundh Anna , Wu Xiaojun , Abel Mackenzie , McCullumsmith Robert E. , O’Donovan Sinead M.
Published: September 2021

Astrocytes have many important functions in the brain, but their roles in CNS disorders and their responses to psychotropic medications are still being elucidated. In this study, we used gene enrichment analysis to assess the relationships between different astrocyte subtypes, neurological and psychiatric diseases, and psychotropic medications. We also carried out qPCR analyses and “look-up” studies to further assess the chronic effects of these drugs on astrocyte marker gene expression. Our bioinformatic analysis identified differential gene enrichment of different astrocyte subtypes in CNS disorders. The “common” astrocyte subtype was the most frequently enriched across disorders, but the highest level of enrichment was found in depression, supporting a role for astrocytes in this disorder. We also identified common enrichment of metabolic and signal transduction-related biological processes in astrocyte subtypes and CNS disorders. However, enrichment of different psychotropic medications, including antipsychotics, antidepressants, and mood stabilizers, was limited in astrocyte subtypes. These results were confirmed by “look-up” studies and qPCR analysis, which also reported little effect of common psychotropic medications on astrocyte marker gene expression, suggesting that astrocytes are not a primary target of these medications. Overall, this study provides a unique view of astrocyte subtypes and the effect of medications on astrocytes in disease, which will contribute to our understanding of their role in CNS disorders and offers insights into targeting astrocytes therapeutically.
Live Monitoring of Inflammation Reveals Tissue and Sex-specific Responses to Western Diet and Butyrate treatment
Authors: Bonomo Raiza , Talley Sarah , Hatahet Jomana , Gavini Chaitanya , Cook Tyler , Chun Ben , Kekenes-Huskey Pete , Aubert Gregory , Campbell Edward , Mansuy-Aubert Virginie
Published: September 2021

Obesity is a current epidemic, affecting millions of individuals worldwide. Chronic obesity is characterized by a low-grade systemic inflammation besides not being a classic inflammatory disease. Many studies have tried to identify inflammatory insults dysregulated by a Westernized diet – consisted of high fat, high sucrose, and high cholesterol –mainly focusing on production and secretion of inflammatory cytokines. The gut microbiome and derived metabolites, including the short-chain fatty acid butyrate, have received increased attention as underlying some of the obesogenic features. In the present work, we utilized a novel biosensor mouse model capable of monitoring in vivo inflammation. We observed tissue- and sex- specific caspase-1 activation patterns in obese mice and treated with butyrate. Our work utilizing a caspase-1 biosensor mouse model, flow cytometry and computational analyses and offers new mechanistic insights underlying the effect of butyrate in obesity and its complications.
Prolactin and the shared regulation of parental care and cooperative helping in white-browed sparrow weaver societies
Authors: Walker Lindsay A. , Tschirren Linda , York Jennifer E. , Sharp Peter J. , Meddle Simone L. , Young Andrew J.
Published: September 2021

In many cooperatively breeding species non-breeding individuals help to rear the offspring of breeders. The physiological mechanisms that regulate such cooperative helping behavior are poorly understood, but may have been co-opted, during the evolution of cooperative breeding, from pre-existing mechanisms that regulated parental care. Key among these may be a role for prolactin. Here we investigate whether natural variation in circulating prolactin levels predicts both parental and helper contributions to nestling provisioning in cooperatively breeding white-browed sparrow weavers,Plocepasser mahali. In sparrow weaver groups, a single dominant pair monopolize reproduction and non-breeding subordinates help with nestling feeding. We show that: (i) among parents, dominant females feed nestlings at higher rates, make longer provisioning visits, and have higher prolactin levels than dominant males; and (ii) among subordinates, engaged in cooperative helping behavior, those within their natal groups feed nestlings at higher rates and have higher prolactin levels than immigrants. Accordingly, continuous variation in prolactin levels positively predicts nestling-provisioning rates and mean provisioning visit durations when all bird classes are combined. These relationships are principally driven by differences among bird classes in both circulating prolactin levels and provisioning traits. The more limited within-class variation in prolactin and provisioning traits were not evidently correlated, highlighting a likely role for additional mechanisms in the fine-scale regulation of care. Our findings broadly support the hypothesis that parental care and cooperative helping behavior are regulated by a common underlying mechanism and highlight the need for experimentation to now establish the causality of any role for prolactin.
A multiplex serological assay for the characterization of IgG immune response to SARS-CoV-2
Authors: Brochot Etienne , Souplet Vianney , Follet Pauline , Ponthieu Pauline , Olivier Christophe , Even Gaël , Audebert Christophe , Malbec Rémi
Published: September 2021

Background

In the fight against SARS-COV-2, the development of serological assays based on different antigenic domains represent a versatile tool to get a comprehensive picture of the immune response or differentiate infection from vaccination beyond simple diagnosis.

Objectives

Here we use a combination of the Nucleoprotein (NP), the Spike 1 (S1) and Spike 2 (S2) subunits, and the receptor binding domain (RBD) and N-terminal domain (NTD) of the Spike antigens from the Syrius-CoViDiag® multiplex IgG assay, to follow the immune response to SARS-CoV-2 infection over a long time period and depending on disease severity.

Results

Using a panel of 209 sera collected from 61 patients up to eight months after infection, we observed that most patients develop an immune response against multiple viral epitope, but anti-S2 antibodies seemed to last longer. For all the tested IgGs, we have found higher titers for hospitalized patients than for non-hospitalized ones. Moreover the combination of the five different IgG titers increased the correlation to the neutralizing antibody titers than if considered individually.

Conclusion

Multiplex immunoassays have the potential to improve diagnostic performances, especially for ancient infection or mild form of the disease presenting weaker antibody titers. Also the combined detection of anti-NP and anti-Spike-derived domains can be useful to differentiate vaccination from viral infection and accurately assess the antibody potential to neutralize the virus.
Mechanism of the CBM35 domain in assisting catalysis by Ape1, a Campylobacter jejuni O-acetyl esterase
Authors: Lin Chang Sheng-Huei , Yen Ian Y. , Chan Anson C. K. , Murphy Michael E. P.
Published: September 2021

Peptidoglycan (PG) is O-acetylated by bacteria to resist killing by host lysozyme. During PG turnover, however, deacetylation is a prerequisite for glycan strand hydrolysis by lytic transglycosylases. Ape1, a de-O-acetylase from Campylobacter jejuni, is a bi-modular protein composed of an SGNH hydrolase domain and a CBM35 domain. The conserved Asp-His-Ser catalytic triad in the SGNH hydrolase domain confers enzymatic activity. The PG binding mode and function of the CBM35 domain in de-O-acetylation remained unclear. In this paper, we present a 1.8 Å resolution crystal structure of a complex between acetate and Ape1. An active site cleft is formed at the interface of the two domains and two large loops from the CBM35 domain form part of the active site. Site-directed mutagenesis of residues in these loops coupled with activity assays using p-nitrophenol acetate indicate the CBM35 loops are required for full catalytic efficiency. Molecular docking of a model O-acetylated hexasaccharide PG substrate to Ape1 using HADDOCK suggests the interaction is formed by the active cleft and the saccharide motif of PG. Together, we propose that the active cleft of Ape1 diverges from other SGNH hydrolase members by using the CBM35 loops to assist catalysis. The concave Ape1 active cleft may accommodate the long glycan strands for selecting PG substrates to regulate subsequent biological events.
Oligomerization of the FliF domains suggests a coordinated assembly of the bacterial flagellum MS ring
Authors: Mariano Giuseppina , Faba-Rodriguez Raquel , Bui Soi , Zhao Weilong , Ross James , Tsokov Svetomir , Bergeron Julien
Published: September 2021

The bacterial flagellum is a complex, self-assembling macromolecular machine that powers bacterial motility. It plays diverse roles in bacterial virulence, including aiding in colonization and dissemination during infection. The flagellum consists of a filamentous structure protruding from the cell, and the basal body, a large assembly that spans the cell envelope. The basal body is comprised of over 10 different proteins, forming several concentric ring structures, termed the M- S- L- P- and C-rings, respectively. In particular, the MS rings are formed by a single protein FliF, which consists of two trans-membrane helices anchoring it to the inner membrane and surrounding a large periplasmic domain. Assembly of the MS ring, through oligomerization of FliF, is one of the first steps of basal body assembly.

Previous computational analysis had shown that the periplasmic region of FliF consists of three structurally similar domains, termed Ring-Building Motif (RBM)1, RBM2 and RBM3. The structure of the MS-ring has been reported recently, and unexpectedly shown that these three domains adopt different symmetries, with RBM3 having a 34-mer stoichiometry, while RBM2 adopts two distinct positions in the complex, including a 23-mer ring. This observation raises some important question on the assembly of the MS ring, and the formation of this symmetry mis-match within a single protein. In this study, we analyze the oligomerization of the individual RBM domains in isolation, in the Salmonella typhimurium FliF orthologue. We demonstrate that the periplasmic domain of FliF assembles into the MS ring, in the absence of the trans-membrane helices. We also report that the RBM2 and RBM3 domains oligomerize into ring structures, but not RBM1. Intriguingly, we observe that a construct encompassing RBM1 and RBM2 is monomeric, suggesting that RBM1 interacts with RBM2, and inhibits its oligomerization. However, this inhibition is lifted by the addition of RBM3. Collectively, this data suggests a mechanism for the controlled assembly of the MS ring.
Early life sleep disruption potentiates lasting sex-specific changes in behavior in genetically vulnerable Shank3 heterozygous autism model mice
Authors: Lord Julia Sparks , Gay Sean Mitchell , Harper Kathryn M , Nikolova Viktoriya D , Smith Kirsten Monique , Moy Sheryl S , Diering Graham Hugh
Published: September 2021

Background: Patients with autism spectrum disorder (ASD) experience high rates of sleep disruption beginning early in life, however the developmental consequences of this disruption are not understood. We examined sleep behavior and the consequences of sleep disruption in developing mice bearing C-terminal truncation mutation in the high-confidence ASD risk gene SHANK3 (Shank3ΔC). We hypothesized that sleep disruption may be an early sign of developmental divergence, and that clinically-relevant Shank3WT/ΔC mice may be at increased risk of lasting deleterious outcomes following early-life sleep disruption. Methods: We recorded sleep behavior in developing Shank3ΔC/ΔC, Shank3WT/ΔC, and wild type siblings of both sexes using a non-invasive home cage monitoring system. Separately, litters of Shank3WT/ΔC and wildtype littermates were exposed to automated mechanical sleep disruption for 7 days prior to weaning (early-life sleep disruption: ELSD) or post-adolescence (PASD) or undisturbed control (CON) conditions. All groups underwent standard behavioral testing as adults. Results: Male and female Shank3ΔC/ΔC mice slept significantly less than wild type and Shank3WT/ΔC siblings shortly after weaning, with increasing sleep fragmentation in adolescence, indicating that sleep disruption has a developmental onset in this ASD model. ELSD treatment interacted with genetic vulnerability in Shank3WT/ΔC mice, resulting in lasting, sex-specific changes in behavior, whereas wildtype siblings were largely resilient to these effects. Male ELSD Shank3WT/ΔC subjects demonstrated significant changes in sociability, sensory processing, and locomotion, while female ELSD Shank3WT/ΔC subjects had a significant reduction in risk aversion. CON Shank3WT/ΔC mice, PASD mice, and all wildtype mice demonstrated typical behavioral responses in most tests. Limitations: This study tested the interaction between developmental sleep disruption and genetic vulnerability using a single ASD mouse model: Shank3ΔC (deletion of exon 21). The broader implications of this work should be supported by additional studies using ASD model mice with distinct genetic vulnerabilities. Conclusion: Our study shows that sleep disruption during sensitive periods of early life interact with underlying genetic vulnerability to drive lasting and sex-specific changes in behavior. As individuals progress through maturation they gain resilience to the lasting effects of sleep disruption. This work highlights developmental sleep disruption as an important vulnerability in ASD susceptibility.
A Discrete Formulation of Two Alternative Forced Choice Decision Dynamics Derived from a Double-Well Quantum Landscape
Authors: Rosendahl Morgan , Cohen Jonathan
Published: September 2021

Tools from quantum theory have been effectively leveraged in modeling otherwise poorly understood effects in decision-making such as apparent fallacies in probability judgments and context effects. This approach has described the dynamics of two alternative forced choice (2AFC) decisions in terms of the path of a single quantum particle evolving in a single potential well. Here, we present a variant on that approach, which we name the Multi-Particle and Multi-Well (MPMW) quantum cognitive framework, in which decisions among N alternatives are treated by the sum of positional measurements of many independent quantum particles representing stimulus information, acted on by an N-well landscape that defines the decision alternatives. In this article, we apply the MPMW model to the simplest and most common case of N-alternative decision making, 2AFC dynamics. This application calls for a multi-particle double-well implementation, which allows us to construct a simple, analytically tractable discrete drift diffusion model (DDM), in the form of a Markov chain, wherein the parameters of the attractor wells reflect bottom-up (automatic) and top-down (control-dependent) influences on the integration of external information. We first analyze this Markov chain in its simplest form, as a single integrator with a generative process arising from a static quantum landscape and fixed thresholds, and then consider the case of multi-integrator processing under the same conditions. Within this system, stochasticity arises directly from the double-well quantum attractor landscape as a function of the dimensions of its wells, rather than as an external parameter requiring independent fitting. The simplicity of the Markov chain component of this model allows for easy analytical computation of closed forms for response time distributions and response probabilities that match qualitative properties of the accuracies and reaction times of humans performing 2AFC tasks. The MPMW framework produces response time distributions following inverse gaussian curves familiar from previous DDM models and empirical data, including the common observation that mean response times are faster for incorrect than for correct responses. The work presented in this paper serves as a proof of concept, based on which the MPMW framework can be extended to address more complex decision-making processes, (e.g., N-alternative forced choice, dynamic control allocation, and nesting quantum landscapes to allow for modeling at both the task and stimulus levels of processing) that we discuss as future directions.
BionetBF: A Novel Bloom Filter for Faster Membership Identification of Large Biological Graph
Authors: Nayak Sabuzima , Patgiri Ripon
Published: September 2021

Big Graph is a graph having thousands of vertices and hundreds of thousands of edges. The study of graphs is crucial because the interlinkage among the vertices provides various insights and uncovers the hidden truth developed due to their relationship. The graph processing has non-linear time complexity. The overwhelming number of vertices and edges of Big Graph further enhances the processing complexity by many folds. One of the significant challenges is searching for an edge in Big Graph. This article proposes a novel Bloom Filter to determine the existence of a relationship in Big Graph, specifically biological networks. In this article, we propose a novel Bloom Filter called Biological network Bloom Filter (BionetBF) for fast membership identification of the biological network edges or paired biological data. BionetBF is capable of executing millions of operations within a second while occupying a tiny main memory footprint. We have conducted rigorous experiments to prove the performance of BionetBF with large datasets. The experiment is performed using 12 synthetic datasets and three biological network datasets. It takes less than 8 sec for insertion and query of 40 million biological edges. It demonstrates higher performance while maintaining a 0.001 false positive probability. BionetBF is compared with other filters: Cuckoo Filter and Libbloom, where small-sized BionetBF proves its supremacy by exhibiting higher performance compared with large-sized Cuckoo Filter and Libbloom. The source code is available at https://github.com/patgiri/BionetBF. The code is written in the C programming language. All data are available at the given link.

Highlights

Proposed a novel Bloom Filter, BionetBF, for faster boolean query on Big Graph.

BionetBF has a low memory footprint and the lowest false positive probability.

It has high performance with constant searching time complexity.

BionetBF has the potential to application in Big Graph, de-Bruijn Graph, and Drug Discovery.
Vertex-wise characterization of Non-Human Primate cortical development with prenatal insights
Authors: Ramirez Julian S.B. , Hermosillo Robert , Thomas Elina , Zhu Jennifer Y. , Sturgeon Darrick , Schifsky Emma , Galassi Anthony , Thompson Jacqueline R. , Bagley Jennifer L. , Milham Michael P. , Miranda-Dominguez Oscar , Papadakis Samantha , Bah Muhammed , Mitchell AJ , Xu Ting , Graham Alice M. , Feczko Eric , Sullivan Elinor L. , Fair Damien A.
Published: September 2021

Characterization of the interwoven complexities of early cortical thickness development has been an ongoing undertaking in neuroscience research. Longitudinal studies of Non-Human Primates (NHP) offer unique advantages to categorizing the diverse patterns of cortical growth trajectories. Here, we used latent growth models to characterize the trajectories of typical cortical thickness development in Japanese macaques at each cortical surface vertex (i.e. grayordinate). Cortical thickness from 4 to 36 months showed regional specific linear and non-linear trajectories and distinct maturation timing across the cortex. Intriguingly, we revealed a “accumulation/ablation phenomenon” of cortical maturation where the most profound development changes in cortical thickness occur in the accumulation or ablation zones surrounding the focal points (i.e., a center of a delineated regions where cortical thickness is thickest or thinnest) throughout the brain. We further examined maternal diet and inflammation in the context of these typical brain trajectories and known network architecture. A well-controlled NHP model of a maternal “Western-style” diet was used alongside measures of inflammatory cytokine interleukin-6 (IL-6) in the mothers during gestation. We observed that these accumulation and ablation zones of variable change might be most susceptible to environmental effects. The maternal factors, diet and inflammation during pregnancy were distinctively associated with different aspects of offspring cortical development reflected in regions related to distinctive functional networks. Our findings characterize the versatile intricacies of typical cortical thickness development and highlight how the maternal environment plays a role in offspring cortical development.
Developmental dynamics of sex reprogramming by high incubation temperatures in a dragon lizard
Authors: Whiteley Sarah L. , Holleley Clare E. , Georges Arthur
Published: September 2021

In some vertebrate species, gene-environment interactions can determine sex, driving bipotential gonads to differentiate into either ovaries or testes. In the central bearded dragon (Pogona vitticeps), the genetic influence of sex chromosomes (ZZ/ZW) can be overridden by high incubation temperatures, causing ZZ male to female sex reversal. Previous research showed ovotestes, a rare gonadal phenotype with traits of both sexes, develop during sex reversal, leading to the hypothesis that sex reversal relies on high temperature feminisation to outcompete the male genetic cue. To test this, we conducted temperature switching experiments at key developmental stages, and analysed the effect on gonadal phenotypes using histology and transcriptomics. We found sexual fate is more strongly influenced by the ZZ genotype than temperature. Any exposure to low temperatures (28°C) caused testes differentiation, whereas sex reversal required longer exposure to high temperatures. We revealed ovotestes exist along a spectrum of female-ness to male-ness at the transcriptional level. We found inter-individual variation in gene expression changes following temperature switches, suggesting both genetic sensitivity to, and the timing and duration of the temperature cue influences sex reversal. These findings bring new insights to the mechanisms underlying sex reversal, improving our understanding of thermosensitive sex systems in vertebrates.
Functional Communication between IP3R and STIM2 at sub-threshold stimuli is a critical checkpoint for initiation of SOCE
Authors: Ahmad Moaz , Ong Hwei Ling , Saadi Hassan , Son Ga Yeon , Shokatian Zahra , Terry Lara E. , Trebak Mohamed , Yule David I. , Ambudkar Indu
Published: September 2021

Stromal interaction molecules, STIM1 and STIM2, sense decreases in the endoplasmic reticulum (ER) [Ca2+] ([Ca2+]ER) and cluster in ER-plasma membrane (ER-PM) junctions where they recruit and activate Orai1. While STIM1 responds when [Ca2+]ER is relatively low, STIM2 displays constitutive clustering in the junctions and is suggested to regulate basal Ca2+ entry. The cellular cues that determine STIM2 clustering under basal conditions is not known. By using gene editing to fluorescently tag endogenous STIM2, we report that endogenous STIM2 is constitutively localized in mobile and immobile clusters. The latter associate with ER-PM junctions and recruit Orai1 under basal conditions. Agonist stimulation increases immobile STIM2 clusters which co- ordinate recruitment of Orai1 and STIM1 to the junctions. Extended synaptotagmin (E-Syt)2/3 are required for forming the ER-PM junctions, but are not sufficient for STIM2 clustering. Importantly, inositol 1,4,5-triphosphate receptor (IP3R) function and local [Ca2+]ER are the main drivers of immobile STIM2 clusters. Enhancing, or decreasing, IP3R function at ambient [IP3] causes corresponding increase, or attenuation, of immobile STIM2 clusters. We show that immobile STIM2 clusters denote decreases in local [Ca2+]ER mediated by IP3R that is sensed by the STIM2-N terminus. Finally, under basal conditions, ambient PIP2-PLC activity of the cell determines IP3R function, immobilization of STIM2, and basal Ca2+ entry while agonist stimulation augments these processes. Together, our findings reveal that immobilization of STIM2 clusters within ER-PM junctions, a first response to ER-Ca2+ store depletion, is facilitated by the juxtaposition of IP3R and marks a checkpoint for initiation of Ca2+ entry.

Significance

STIM proteins sense decreases in [Ca2+]ER and cluster in endoplasmic reticulum (ER)-plasma membrane (PM) junctions where they recruit and activate Orai1. While STIM1 clustering requires substantial [Ca2+]ER decrease, STIM2 displays pre-clustering under resting conditions and regulates basal Ca2+ entry. The mechanism(s) underlying constitutive clustering of STIM2 is not known. We show herein that endogenous STIM2 assembles as mobile and immobile clusters and that Orai1 is recruited to the latter. Anchoring of STIM2 clusters is triggered by decreases in local [Ca2+]ER that is mediated by ambient activity of IP3R and sensed by the STIM2 N-terminus. This functional link between IP3R and STIM2 governs constitutive STIM2 clustering and ensures coupling of [Ca2+]ER decrease at sub-threshold stimuli with activation of Ca2+ entry.
The mosquito microbiome includes habitat-specific but rare symbionts
Authors: Schrieke Hans , Maignien Loïs , Constancias Florentin , Trigodet Florian , Chakloute Sarah , Rakotoarivony Ignace , Marie Albane , L’Ambert Gregory , Makoundou Patrick , Pages Nonito , Eren A. Murat , Weill Mylène , Sicard Mathieu , Reveillaud Julie
Published: September 2021

Microbial communities are known to influence mosquito lifestyles by modifying essential metabolic and behavioral processes that affect reproduction, development, immunity, digestion, egg survival, and ability to transmit pathogens. Many studies have used 16S rRNA gene amplicons to characterize mosquito microbiota and investigate factors that influence host-microbiota dynamics. However, a relatively low taxonomic resolution due to clustering methods based on arbitrary threshold and the overall dominance of Wolbachia or Asaia populations obscured the investigation of rare members of mosquito microbiota in previous studies. Here, we used high resolution Shannon entropy-based oligotyping approaches to analyze the microbiota of Culex pipiens, Culex quinquefasciatus and Aedes individuals from continental and overseas regions in Southern France and Guadeloupe as well as from laboratories with or without antibiotics treatment. Our experimental design that resulted in a series of mosquito samples with a gradient of Wolbachia density and relative abundance along with high-resolution analyses of amplicon sequences enabled the recovery of a robust signal from typically less accessible bacterial taxa. Our data confirm species-specific mosquito-bacteria associations with geography as a primary factor that influences bacterial community structure. But interestingly, they also reveal co-occurring symbiotic bacterial variants within single individuals for both Elizabethkingia and Erwinia genera, distinct and specific Asaia and Chryseobacterium in continental and overseas territories and a putative rare Wolbachia variant. Overall, our study reveals the presence of previously-overlooked microdiversity and multiple closely related symbiotic strains within mosquito individuals with a remarkable habitat-specificity.
Towards a combined therapy for spinal muscular atrophy based on opposing effects of an antisense oligonucleotide on chromatin and splicing
Authors: Marasco Luciano E. , Dujardin Gwendal , Sousa-Luís Rui , Liu Ying Hsiu , Stigliano José , Nomakuchi Tomoki , Proudfoot Nick J. , Krainer Adrian R. , Kornblihtt Alberto R.
Published: September 2021

Spinal Muscular Atrophy (SMA) is a motor-neuron disease caused by loss-of-function mutations of the SMN1 gene. Humans have a paralog, SMN2, whose exon 7 is predominantly skipped, and so it cannot fully compensate for the lack of SMN1. Nusinersen (Spinraza) is a splicing-correcting antisense oligonucleotide drug (ASO) approved for clinical use. Nusinersen targets a splicing silencer located in SMN2 intron 7 pre-mRNA and, by blocking the binding of the splicing repressors hnRNPA1 and A2, it promotes higher E7 inclusion, increasing SMN protein levels. We show here that, by promoting transcriptional elongation, histone deacetylase (HDAC) inhibitors cooperate with a nusinersen-like ASO to upregulate E7 inclusion. Surprisingly, the ASO also elicits the deployment of the silencing histone mark H3K9me2 on the SMN2 gene, creating a roadblock to RNA polymerase II elongation that acts negatively on E7 inclusion. By removing the roadblock, HDAC inhibition counteracts the undesired chromatin effects of the ASO, resulting in higher E7 inclusion. Combined systemic administration of the nusinersen-like ASO and HDAC inhibitors in neonate SMA mice had strong synergistic effects on SMN expression, growth, survival, and neuromuscular function. Thus, we suggest that HDAC inhibitors have the potential to increase the clinical efficacy of nusinersen, and perhaps other splicing-modulatory ASO drugs, without large pleiotropic effects, as assessed by genome-wide analyses.
Dynamic pricing of perishable food as a sustainable business model
Authors: Scholz Michael , Kulko Roman-David
Published: September 2021

Purpose

The purpose of this paper is to (1) investigate the effect of freshness on consumers' willingness to pay, (2) derive static and dynamic pricing strategies and (3) compare the effect of these pricing strategies on a retailer's revenue and food waste. This investigation helps to reveal the potentials of dynamic pricing strategies for building more sustainable business models.

Design/methodology/approach

The authors conduct an online experiment to measure consumers' willingness to pay for fresh and three-days’ old strawberries. The impact of freshness on willingness to pay is analysed using univariate tests and regression analysis. Pricing strategies are compared using a Monte Carlo simulation.

Findings

The results of this study show that freshness largely determines consumers' willingness to pay and price sensitivity. This renders dynamic pricing a promising strategy from an economic point of view. The results of the simulation study show that food waste can be reduced by up to 53.6% with a dynamic pricing instead of a static pricing strategy in the case that there are as many consumers as strawberry packages in the inventory. Revenue can be increased by up to 10% compared to a static pricing strategy based on fresh strawberries.

Practical implications

This study suggests that food retailers can improve their revenue when switching from static to dynamic pricing. Furthermore, in most cases, food retailers can reduce food waste with a dynamic instead of a static-pricing strategy, which might help to improve their image through a more sustainable business model and attract additional consumers.

Originality/value

This study is the first to analyse the possibility of using food freshness to design a dynamic pricing strategy and to analyse the impact of such a pricing strategy on both, a retailer's revenue and a retailer's food waste.