bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a two-parabolic band model for thermoelectric transport modelling using Mg2Sn as an example
Authors: Naithani H , Müller E , de Boor J
Published: July 2022

Thermoelectrics is a field driven by material research aimed at increasing the thermal to electrical conversion efficiency of thermoelectric (TE) materials. Material optimisation is necessary to achieve a high figure of merit (zT) and in turn a high conversion efficiency. Experimental efforts are guided by the theoretical predictions of the optimum carrier concentration for which generally the single parabolic band (SPB) model is used which considers the contribution to electronic transport only from the majority carriers’ band. However, most TE materials reach peak performance (maximum zT) close to their maximum application temperature and when minority carrier effects become relevant. Therefore, single band modelling is insufficient to model the behaviour of TE materials in their most practically relevant temperature range. Inclusion of minority effects requires addition of the minority carrier band and necessitates the use of a two-band model—the simplest and, for most cases, sufficient improvement. In this study, we present a systematic methodology for developing a two-band model using one valence and one conduction band for any given TE material. The method utilises in part the SPB model and in part a simple cost function based analysis to extract material parameters like density of states masses, band gap, deformation potential constant etc., based on easily available experimental data. This simple and powerful method is exemplified using Mg2Sn, chosen due to its low band gap, the availability of experimental data in a wide range of dopant concentrations and its practical importance, being an end member of the highly popular Mg2(Si,Sn) solid solutions. Using the experimental data for p- and n-type Mg2Sn from literature, a two-band model was obtained. Optimum carrier concentration and maximum zT were predicted from both SPB and two-band models and at 650 K pronounced differences between the two models, which could prevent realisation of maximum zT, were observed, demonstrating the practical necessity to model the effect of minority carriers.
Evolutionary processes in an undescribed eucalypt: implications for the translocation of a critically endangered species
Authors: Rutherford Susan , Wilson Trevor C , Yap Jia-Yee Samantha , Lee Enhua , Errington Graeme , Rossetto Maurizio
Published: July 2022

Background and Aims

Knowledge of the evolutionary processes responsible for the distribution of threatened and highly localized species is important for their conservation. Population genomics can provide insights into evolutionary processes to inform management practices, including the translocation of threatened plant species. In this study, we focus on a critically endangered eucalypt, Eucalyptus sp. Cattai, which is restricted to a 40-km2 area of Sydney, Australia, and is threatened by increased urbanization. Eucalyptus sp. Cattai has yet to be formally described in part due to its suspected hybrid origin. Here, we examined evolutionary processes and species boundaries in E. sp. Cattai to determine whether translocation was warranted.

Methods

We used genome-wide scans to investigate the evolutionary relationships of E. sp. Cattai with related species, and to assess levels of genetic health and admixture. Morphological trait and genomic data were obtained from seedlings of E. sp. Cattai propagated in a common garden to assess their genetic provenance and hybrid status.

Key Results

All analyses revealed that E. sp. Cattai was strongly supported as a distinct species. Genetic diversity varied across populations, and clonality was unexpectedly high. Interspecific hybridization was detected, and was more prevalent in seedlings compared to in situ adult plants, indicating that post-zygotic barriers may restrict the establishment of hybrids.

Conclusions

Multiple evolutionary processes (e.g. hybridization and clonality) can operate within one rare and restricted species. Insights regarding evolutionary processes from our study were used to assist with the translocation of genetically ‘pure’ and healthy ex situ seedlings to nearby suitable habitat. Our findings demonstrate that it is vital to provide an understanding of evolutionary relationships and processes with an examination of population genomics in the design and implementation of an effective translocation strategy.
Role of the conserved pyridoxal 5ʹ-phosphate-binding protein YggS/PLPBP in vitamin B6 and amino acid homeostasis
Authors: Ito Tomokazu
Published: July 2022

The YggS/PLPBP protein (also called COG0325 or PLPHP) is a conserved pyridoxal 5ʹ-phosphate (PLP)-binding protein present in all 3 domains of life. Recent studies have demonstrated that disruption or mutation of this protein has multifaceted effects in various organisms, including vitamin B6-dependent epilepsy in humans. In Escherichia coli, disruption of this protein—encoded by yggS—perturbs Thr-Ile/Val metabolism, one-carbon metabolism, coenzyme A synthesis, and vitamin B6 homeostasis. This protein is critical for maintaining low levels of pyridoxine 5ʹ-phosphate (PNP) in various organisms. In the yggS-deficient E. coli strain, inhibition of PLP-dependent enzymes, such as the glycine cleavage system by PNP, is the root cause of metabolic perturbation. Our data suggest that the YggS/PLPBP protein may be involved in the balancing of B6 vitamers by mediating efficient turnover of protein-bound B6 vitamers. This paper reviews recent findings on the function of the YggS/PLPBP protein.
The conspicuousness contradiction: brighter males have lower mating chances in the damselfly Argia hasemani but not in Argia croceipennis
Authors: Massote Clara , Pessoa Daniel Marques Almeida , Peixoto Paulo Enrique Cardoso
Published: July 2022

In odonates, male coloration is often more conspicuous than female coloration. This difference is frequently attributed to the role of male colour in male–male competition to access females. However, there are sexually dimorphic odonate species, such as the damselflies Argia hasemani and Argia croceipennis, in which male–male interactions are much less intense. In these species, it might be that male coloration affects male success directly when interacting with females. Therefore, we hypothesized that males with more intense coloration present higher copulation success. To investigate this hypothesis, we registered which males copulated in the field during 4 days and estimated the coloration of all observed males in the female visual spectrum. Surprisingly, we found that dull males had higher chances of copulation in A. hasemani, whereas in A. croceipennis male coloration did not influence the chances of copulation. Our data also indicated that brighter males of A. hasemani were also more conspicuous to potential avian predators, whereas this was not the case in A. croceipennis. We suggest that females of A. hasemani might avoid brighter males owing to increased risk of predation during copulation.
Cerebral organoids containing an AUTS2 missense variant model microcephaly
Authors: Fair Summer R , Schwind Wesley , Julian Dominic L , Biel Alecia , Guo Gongbo , Rutherford Ryan , Ramadesikan Swetha , Westfall Jesse , Miller Katherine E , Kararoudi Meisam Naeimi , Hickey Scott E , Mosher Theresa Mihalic , McBride Kim L , Neinast Reid , Fitch James , Lee Dean A , White Peter , Wilson Richard K , Bedrosian Tracy A , Koboldt Daniel C , Hester Mark E
Published: July 2022

Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use a human cerebral organoid model to investigate the pathophysiology of a heterozygous de novo missense AUTS2 variant identified in a patient with multiple neurological impairments including primary microcephaly and profound intellectual disability.

Proband cerebral organoids exhibit reduced growth, deficits in neural progenitor cell (NPC) proliferation and disrupted NPC polarity within ventricular zone-like regions compared to control cerebral organoids. We used CRISPR-Cas9-mediated gene editing to correct this variant and demonstrate rescue of impaired organoid growth and NPC proliferative deficits. Single-cell RNA sequencing revealed a marked reduction of G1/S transition gene expression and alterations in WNT-β-catenin signalling within proband NPCs, uncovering a novel role for AUTS2 in NPCs during human cortical development.

Collectively, these results underscore the value of cerebral organoids to investigate molecular mechanisms underlying AUTS2 syndrome.
Faecal Myeloperoxidase as a Biomarker of Endoscopic Activity in Inflammatory Bowel Disease
Authors: Swaminathan Akhilesh , Borichevsky Grace M , Edwards Teagan S , Hirschfeld Esther , Mules Thomas C , Frampton Chris M A , Day Andrew S , Hampton Mark B , Kettle Anthony J , Gearry Richard B
Published: July 2022

Background and Aims

Inflammatory bowel disease [IBD], consisting of Crohn’s disease [CD] and ulcerative colitis [UC], is a relapsing-remitting illness. Treat-to-target IBD management strategies require monitoring of gastrointestinal inflammation. This study aimed to investigate faecal myeloperoxidase [fMPO], a neutrophil granule enzyme, as a biomarker of IBD activity.

Methods

Prospectively recruited participants with IBD, undergoing ileocolonoscopy for disease assessment, provided biological samples and completed symptom questionnaires prior to endoscopy. fMPO, C-reactive protein [CRP], and faecal calprotectin [fCal] were compared with validated endoscopic indices [simple endoscopic score for CD and UC endoscopic index of severity]. Receiver operating characteristic [ROC] curves assessed the performance of fMPO, CRP, and fCal in predicting endoscopic disease activity. Baseline biomarkers were used to predict a composite endpoint of complicated disease at 12 months [need for escalation of biologic/immunomodulator due to relapse, steroid use, IBD-related hospitalisation, and surgery].

Results

A total of 172 participants were recruited [91 female, 100 with CD]. fMPO was significantly correlated with endoscopic activity in both CD [r = 0.53, p < 0.01] and UC [r = 0.63, p < 0.01], and with fCal in all patients with IBD [r = 0.82, p < 0.01]. fMPO was effective in predicting moderate-to-severely active CD [AUROC 0.86, p < 0.01] and UC [AUROC 0.92, p < 0.01]. Individuals with a baseline fMPO > 26 µg/g were significantly more likely to reach the composite outcome at 12 months (hazard ratio [HR] 3.71, 95% confidence interval [CI] 2.07–6.64, p < 0.01).

Conclusions

Faecal myeloperoxidase is an accurate biomarker of endoscopic activity in IBD and predicted a more complicated IBD course during follow-up.
Let’s Stick Together: Peer Effects in Secondary School Choice and Variations by Student Socio-Economic Background
Authors: Zwier Dieuwke , Geven Sara , Bol Thijs , van de Werfhorst Herman G
Published: July 2022

Despite the vast body of research focusing on peer effects in education, the role of the immediate peer environment in school choice has been understudied to date. We study the extent to which students from the same primary school cluster in the same secondary school, and how this effect varies by a student’s socio-economic background. We use register data from the Netherlands, covering six cohorts of students (2013–2019), that enable us to account for selection into primary schools and other endogeneity issues when identifying peer effects. The results indicate that students are more likely to choose a secondary school when students from their primary school cohort also choose this school, even after accounting for school popularity trends. We find evidence that students from socially disadvantaged backgrounds are more likely to cluster in the same secondary school as their primary school peers, yet these differences are small.
Examination of vertical transmission of Bartonella quintana in body lice following multiple infectious blood meals
Authors: Kress Lauren , Potts Rashaun , Pietri Jose E
Published: July 2022

Bartonella quintana is a re-emerging louse-borne pathogen. Horizontal transmission from the body louse vector (Pediculus humanus humanus) to a human host occurs through contact with infectious louse feces containing a high concentration of the bacteria. However, questions have remained about whether vertical transmission from infected vectors to their progeny, which could significantly influence the dynamics of transmission to humans, occurs in body lice. To address this subject, we performed a series of controlled laboratory experiments that examined the presence of B. quintana on the surface of and within eggs produced by female body lice that were provisioned multiple infectious blood meals to recapitulate the natural pathogen acquisition process. Our results demonstrate that B. quintana DNA can be detected from the surface of eggs by qPCR due to vertical transfer of infectious feces to the egg sheath during or after oviposition. However, viable B. quintana could not be cultured from the hemolymph of adult female lice or from within eggs that were surface sterilized, indicating a lack of true transovarial transmission. Based on this evidence, vertical transfer of B. quintana from infected adult lice to their eggs probably has a limited impact on the dynamics of transmission to humans.
ADVANCE-C: A Qualitative Study of Experiences Caring for Nursing Home Residents with Advanced Dementia During the COVID-19 Pandemic
Authors: Hendricksen Meghan , Mitchell Susan L , Palan Lopez Ruth , Roach Ashley , Hendrix Rogers Anita , Akunor Harriet , McCarthy Ellen P
Published: July 2022

Objectives

Assessment of Disparities and Variation for Alzheimer’s disease Nursing home Care at End of life (ADVANCE) is a multisite qualitative study of regionally diverse Nursing homes (NHs; N = 14) providing varied intensity of advanced dementia care. ADVANCE-C explored the experiences of NH staff and proxies during the COVID-19 pandemic.

Methods

Data collection occurred in five of the ADVANCE facilities located in Georgia (N = 3) and New York (N = 2). Semistructured qualitative interviews with NH staff (N = 38) and proxies of advanced dementia residents (N = 7) were conducted. Framework analyses explored five staff domains: care processes, decision making, organizational resources, vaccinations, and personal experience, and five proxy domains: connecting with residents, NH response, communicating with NH, decision making, and personal impact of the pandemic.

Results

Staff mentioned difficulties implementing infection control policies specifically for advanced dementia residents. Staff reported trust between the facility and proxies as critical in making decisions during the pandemic. All staff participants spoke about “coming together” to address persistent staffing shortages. Proxies described their role as an “emotional rollercoaster,” emphasizing how hard it was being separate from their loved ones. The accommodations made for NH residents were not beneficial for those with advanced dementia. The majority of proxies felt NH staff were doing their best and expressed deep appreciation for their care.

Discussion

Caring for advanced dementia residents during the COVID-19 pandemic had unique challenges for both staff and proxies. Strategies for similar future crises should strive to balance best practices to contain the virus while maintaining family connections and person-centered care.
Time-varying uplift in Svalbard—an effect of glacial changes
Authors: Kierulf Halfdan Pascal , Kohler Jack , Boy Jean-Paul , Geyman Emily C , Mémin Anthony , Omang Ove C D , Steffen Holger , Steffen Rebekka
Published: July 2022

We analyse Global Navigation Satellite System (GNSS) data from Svalbard to understand how uplift rates are controlled by the elastic and viscoelastic response of the solid Earth to changes in glacier mass on annual, interannual, decadal, centennial and millennial timescales. To reveal local patterns of deformation, we filter the GNSS time-series with an enhanced common-mode filtering technique where the non-tidal loading signal is incorporated. This technique reduces the estimated uncertainties for 5-yr time-series from 0.8 to 0.3 mm yr–1. Analysis of the GNSS data with different software–GAMIT, GipsyX, and GINS–produce consistent results that all indicate large temporal variations in uplift. For example, at the Ny-Ålesund GNSS station, uplift varies between 6 and 12 mm yr–1 for different 5-yr periods, and also shows a significant increase in the last 15 yr. We show that this increase is due to climate change-related ice mass loss in Svalbard. We constrain recent glacier retreat on Svalbard using a series of digital elevation models, and then correct the GNSS-derived uplift records for the elastic signal from these ice mass changes. The residual uplift signal is relatively constant, confirming the hypothesis that current ice mass changes exert a strong influence on GNSS observations. The relatively constant record of residual uplift can be used to constrain other geophysical signals such as the viscoelastic response of the solid Earth to ice loading during the Little Ice Age and the Last Glacial Period. We review uplift results from previous viscoelastic modelling studies and show that the residual signal cannot yet be fully explained. Our new uplift results thus motivate the need for new viscoelastic modelling of the glacial isostatic adjustment process in Svalbard.
Interspecific Asymmetries in Behavioral Plasticity Drive Seasonal Patterns of Temporal Niche Partitioning in an Island Carnivore Community
Authors: Zhang Victor Y , Gagorik Calypso N , Brenner Lara J , Boser Christina L , Theimer Tad C , Buck C Loren
Published: July 2022

Animals vary considerably in the amount of behavioral plasticity they exhibit in daily activity timing and temporal niche switching. It is not well understood how environmental factors drive changes in temporal activity or how interspecific differences in the plasticity of activity timing ultimately manifest in free-living animals. Here, we investigated the temporal structure and organization of activity patterns of two insular mammalian carnivores living in sympatry, the island fox (Urocyon littoralis) and island spotted skunk (Spilogale gracilis amphiala). Using collar-mounted accelerometers, we assessed the plasticity of behavioral activity rhythms in foxes and skunks by investigating how environmental factors drive the distribution of locomotor activity across the day and year, and subsequently examined the dynamics of temporal niche overlap between the two species. We documented that foxes express phenotypic plasticity in daily activity timing across the year, ranging from nocturnal to diurnal to crepuscular rhythms depending on the individual and time of year. Most notably, foxes increased the proportion of daytime activity as seasonal temperatures decreased. Overall, activity patterns of foxes were consistent with the circadian thermoenergetics hypothesis, which posits that animals that switch their patterns of activity do so to coincide with the most energetically favorable time of day. In contrast to foxes, skunks exhibited little behavioral plasticity, appearing strictly nocturnal across the year. While the duration of skunk activity bouts increased with the duration of night, timing of activity onset and offset extended into daytime hours during summer when the duration of darkness was shortest. Analysis of temporal niche overlap between foxes and skunks suggested that niche overlap was highest during summer and lowest during winter and was dictated primarily by temporal niche switching in foxes, rather than skunks. Collectively, our results highlight how interspecific asymmetries in behavioral plasticity drive dynamic patterns of temporal niche overlap within an island carnivore community.
A framework for categorizing the interactions of offshore windfarms and fisheries
Authors: Stokesbury Kevin D E , Fay Gavin , Griffin Robert
Published: July 2022

The offshore windfarm industry has great potential for sustainable energy but requires space. The ability of fisheries to harvest within these windfarms varies. This has created a conflict between these two industries and discussions are hampered by differing approaches to the marine environment, a lack of understanding of what each industries requires, the significant money at stake, and the values the public place on marine conservation. To characterize, standardize, and quantify the scientific data addressing these concerns requires a framework. The framework should categorize data on spatial scales of 1 cm2 to 1 km2 (individual turbines/fishing vessels), 1–1000 km2 (companies), and >1000 km2 (regions), and by their ecological, economic, cultural, and institutional impacts. The framework should be repeated over temporal scales of the windfarm: pre-development (1–3 years), construction (1–2 years), post-construction (20–40 years), and decommission. Balancing the metrics used to describe the two industries will allow people to communicate clearly in an organized systematic way, hopefully resulting in a continuing supply of sustainable sea food and renewable energy to an increasingly hungry world.
The spread of Lessepsian fish does not track native temperature conditions
Authors: D'Amen Manuela , Smeraldo Sonia , Di Franco Antonio , Azzurro Ernesto
Published: July 2022

Global warming is enabling tropical invaders to expand into regions, where unsuitable climate conditions used to prevent the survival or reproduction. Here, using the occurrence data of 22 Lessepsian fish in the Mediterranean Sea, we aimed at (1) gaining a deeper understanding of temperature match dynamics over the spatio-temporal spread of each invasion event and (2) testing the hypothesis that successful invasions require a temperature match, as assumed in several bioinvasion risk assessments. For each species, we identified the areas of the Mediterranean lacking a temperature match with native ranges over the past six decades. We found that some species, particularly recent invaders, have spread far beyond temperature matching conditions. The populations at the expanding edge of the range are often found in sites that have experienced increases in temperature. Temperature match positively correlates with species spread rate and after 1990, higher temperatures in the Mediterranean provided analogous conditions for a growing number of non-indigenous species. Our results warn against the general use of temperature-based climate matching in bioinvasion risk and provide guidance for the application of species distribution models that incorporate temperature to marine bioinvasion research.
Reducing PV soiling and condensation using hydrophobic coating with brush and controllable curtains
Authors: Aldawoud Amer , Aldawoud Abdelsalam , Aryanfar Yashar , Assad Mamdouh El Haj , Sharma Shubham , Alayi Reza
Published: July 2022

Solar photovoltaic technology faces many challenges in climates that are characterized by arid nature with high dust frequencies and high relative humidity levels, which make dust build-up extremely problematic. Soiling and condensation affect the performance of PV systems and greatly degrades their power output. Covering the PV panels during non-operation will greatly improve the overall efficiency and reduce the PV soiling. In the present study, a motorized curtain is developed to cover the PV module surface during nights and dust storms. This system successfully reduced the impact of the condensation and the accumulation of soiling that could affect the performance of the PV panels and reduce their efficiencies. This study also experimentally investigates utilizing a superhydrophobic (Laboratory prepared nano-coating) and a superhydrophilic coating on the PV module surface to reduce the impact of soiling. These two proposals could heavily reduce the frequency of cleaning the PV panel; therefore, reducing water consumption; particularly for areas with limited water supply. This study uses experimental data as a method to demonstrate the impact of dust, humidity, and nano-coating on the performance of PV Panels. In addition, PVsyst was used to demonstrate and verify the soiling impact on the performance of PV modules.
Error estimates for the numerical approximation of optimal control problems with nonsmooth pointwise-integral control constraints
Authors: Casas Eduardo , Kunisch Karl , Mateos Mariano
Published: July 2022

The numerical approximation of an optimal control problem governed by a semilinear parabolic equation and constrained by a bound on the spatial $L^1$-norm of the control at every instant of time is studied. Spatial discretizations of the controls by piecewise constant and continuous piecewise linear functions are investigated. Under finite element approximations, the sparsity properties of the continuous solutions are preserved in a natural way using piecewise constant approximations of the control, but suitable numerical integration of the objective functional and of the constraint must be used to keep the sparsity pattern when using spatially continuous piecewise linear approximations. We also obtain error estimates and finally present some numerical examples.
The IDOze Study: The Link Between Sleep Disruption and Tryptophan-Kynurenine Pathway Activation in Women With Human Immunodeficiency Virus
Authors: Rogando Andrea C , Weber Kathleen M , Xing Jiaqian , Xue Xiaonan , Yohannes Tsion , Morack Ralph , Qi Qibin , Clish Clary , Bullock Kevin , Gustafson Deborah , Anastos Kathryn , Sharma Anjali , Burgess Helen J , French Audrey L
Published: July 2022

Background

Poor sleep is associated with human immunodeficiency virus (HIV), particularly among women with HIV (WWH), although mechanisms are unclear. We explored cross-sectional associations between sleep disruption and tryptophan-kynurenine (T/K) pathway activation, measured by the kynurenine-to-tryptophan ratio (K:T).

Methods

HIV-uninfected women (HIV–) and WWH aged 35–70 years and on stable antiretroviral therapy were included. Sleep metrics were measured using wrist actigraphy. Plasma T/K pathway metabolites were measured using liquid chromatography–tandem mass spectrometry. Multivariate linear regression models examined relationships between K:T and actigraphy-based sleep metrics by HIV status.

Results

WWH (n = 153) and HIV– women (n = 151) were demographically similar. Among WWH, median CD4 was 751 cells/µL; 92% had undetectable HIV RNA. Compared to HIV– women, WWH had higher K:T (P < .001) and kynurenine (P = .01) levels but similar tryptophan levels (P = .25). Higher K:T was associated with more wake bouts (P = .001), more time awake after sleep onset (P = .01), and lower sleep efficiency (P = .03) in WWH only.

Conclusions

HIV infection was associated with T/K pathway activation; this activation was associated with poorer sleep efficiency and more fragmented sleep. While longitudinal studies are needed to elucidate the directionality of these associations, these findings may help identify treatments to reduce sleep disruption in WWH by targeting residual inflammation and T/K pathway activation.
Design and validation of a FHIR-based EHR-driven phenotyping toolbox
Authors: Brandt Pascal S , Pacheco Jennifer A , Adekkanattu Prakash , Sholle Evan T , Abedian Sajjad , Stone Daniel J , Knaack David M , Xu Jie , Xu Zhenxing , Peng Yifan , Benda Natalie C , Wang Fei , Luo Yuan , Jiang Guoqian , Pathak Jyotishman , Rasmussen Luke V
Published: July 2022

Objectives

To develop and validate a standards-based phenotyping tool to author electronic health record (EHR)-based phenotype definitions and demonstrate execution of the definitions against heterogeneous clinical research data platforms.

Materials and Methods

We developed an open-source, standards-compliant phenotyping tool known as the PhEMA Workbench that enables a phenotype representation using the Fast Healthcare Interoperability Resources (FHIR) and Clinical Quality Language (CQL) standards. We then demonstrated how this tool can be used to conduct EHR-based phenotyping, including phenotype authoring, execution, and validation. We validated the performance of the tool by executing a thrombotic event phenotype definition at 3 sites, Mayo Clinic (MC), Northwestern Medicine (NM), and Weill Cornell Medicine (WCM), and used manual review to determine precision and recall.

Results

An initial version of the PhEMA Workbench has been released, which supports phenotype authoring, execution, and publishing to a shared phenotype definition repository. The resulting thrombotic event phenotype definition consisted of 11 CQL statements, and 24 value sets containing a total of 834 codes. Technical validation showed satisfactory performance (both NM and MC had 100% precision and recall and WCM had a precision of 95% and a recall of 84%).

Conclusions

We demonstrate that the PhEMA Workbench can facilitate EHR-driven phenotype definition, execution, and phenotype sharing in heterogeneous clinical research data environments. A phenotype definition that integrates with existing standards-compliant systems, and the use of a formal representation facilitates automation and can decrease potential for human error.
Field Comparison of Removed Substrate Sampling and Emergence Traps for EstimatingCulicoidesOrbivirus Vectors in Northern Florida
Authors: Black Theodore Vincent , Quaglia Agustin Ignacio , Wisely Samantha , Burkett-Cadena Nathan
Published: July 2022

The larval ecology of Culicoides (Diptera: Ceratopogonidae) influences their spatial distributions and the pathogens they transmit. These features are of special concern for deer farmers in Florida where epizootic hemorrhagic disease virus (EHDV) is a major source of mortality in captive herds. Rarity of larval morphological expertise leads many researchers to study larval ecology by quantifying emergence, either with field emergence traps or removing substrate from the field for observation under laboratory conditions. We investigated the comparability of these methods in Florida seepages where two recently implicated EHDV vectors, Culicoides stellifer Coquillett and Culicoides venustus Hoffman, are common. We compared the abundance and composition of emerging Culicoides collected from emergence traps with removed substrate samples (soil plugs) at three seepages. Soil plugs were sampled adjacent to the emergence trap and from underneath the trap footprint, and then monitored under laboratory conditions for 11–13 wk to compare the methods and to assess the role of incubation period for removed substrate samples. Emergence traps and removed substrate sampling largely agreed on community compositions and trends within different seepages. However, comparatively large numbers of C. stellifer emerged later than expected and well into the incubation period with emergence still occurring after 13 wk (90 d). Removed substrate samples were more similar to emergence traps at shorter incubation times. The importance of time for the capture of Culicoides in removed substrate sampling was more pronounced than we anticipated and is important from both a methodological and biological perspective.
Neuroprotection by Trans-Resveratrol in Rats With Intracerebral Hemorrhage: Insights into the Role of Adenosine A1 Receptors
Authors: Abd. Aziz Noor Azliza Wani , Iezhitsa Igor , Agarwal Renu , Bakar Nor Salmah , Abd. Latiff Azian , Ismail Nafeeza Mohd
Published: July 2022

Given the neuroprotective effects of trans-resveratrol (RV), this study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in RV-mediated neuroprotection in a rat intracerebral hemorrhage (ICH) model induced by intrastriatal injection of collagenase. Rats were divided into 5 groups: (1) control, (2) sham-operated, (3) ICH pretreated with vehicle, (4) ICH pretreated with RV, and (5) ICH pretreated with RV and the A1R antagonist DPCPX. At 48 hours after ICH, the rats were subjected to neurological testing. Brain tissues were assessed for neuronal density and morphological features using routine and immunohistochemical staining. Expression of tumor necrosis factor-α (TNF-α), caspase-3, and RIPK3 proteins was examined using ELISA. A1R, MAPK P38, Hsp90, TrkB, and BDNF genes were examined using RT-qPCR. RV protected against neurological deficits and neuronal depletion, restored the expression of TNF-α, CASP3, RIPK3, A1R, and Hsp90, and increased BDNF/TrkB. DPCPX abolished the effects of RV on neurological outcomes, neuronal density, CASP3, RIPK3, A1R, Hsp90, and BDNF. These data indicate that the neuroprotection by RV involves A1R and inhibits CASP3-dependent apoptosis and RIPK3-dependent necroptosis in the perihematoma region; this is likely to be mediated by crosstalk between A1R and the BDNF/TrkB pathway.
Inactivated Poliovirus Vaccine Closing the Type 2 Immunity Gap in Vietnam
Authors: Huyen Dang Thi Thanh , Anh Dang Duc , Trung Nguyen Thanh , Hong Duong Thi , Thanh Tran Trung , Truong Luong Ngoc , Jeyaseelan Visalakshi , Lopez Cavestany Rocio , Hendley William S , Mainou Bernardo A , Mach Ondrej
Published: July 2022

This was a cross-sectional community-based serological survey of polio antibodies assessing the immunogenicity of inactivated poliovirus vaccine (IPV) focusing on poliovirus serotype 2. IPV was administered to 5-month-old children. Type 2 antibody seroprevalence when measured 1 month after IPV administration was >95%. One IPV dose successfully closed the immunity gap.
Stool Toxin Concentration Does Not Distinguish Clostridioides difficile Infection from Colonization in Children Less Than 3 Years of Age
Authors: Sandora Thomas J , Williams David N , Daugherty Kaitlyn , Geer Christine , Cuddemi Christine , Kociolek Larry K , Chen Xinhua , Xu Hua , Savage Timothy J , Banz Alice , Garey Kevin W , Gonzales-Luna Anne J , Kelly Ciarán P , Pollock Nira R
Published: July 2022

In a prospective cohort study, stools from children <3 years with and without diarrhea who were Clostridioides difficile nucleic acid amplification test-positive underwent ultrasensitive and quantitative toxin measurement. Among 37 cases and 46 controls, toxin concentration distributions overlapped substantially. Toxin concentration alone does not distinguish C. difficile infection from colonization in young children.
Mycoplasma hominis Meningitis Diagnosed by Metagenomic Next-Generation Sequencing in a Preterm Newborn: a Case Report and Literature Review
Authors: Che Guanglu , Liu Fang , Chang Li , Lai Shuyu , Teng Jie , Yang Qiuxia
Published: July 2022

Mycoplasma hominis is mainly colonized in the genital tract and vertically transmitted to newborns; however, it rarely causes neonatal meningitis. We report a case of M. hominis meningitis in a premature infant. She was admitted to our hospital for treatment after 6 days of repeated fever. After admission, repeated cerebrospinal fluid (CSF) analysis showed that leukocytes and protein in CSF increased substantially and glucose decreased, but there was no growth in conventional CSF culture. The patient was diagnosed with M. hominis meningitis by metagenomic next-generation sequencing (mNGS). The antibiotic therapy used for the neonate was meropenem, vancomycin, and ampicillin against bacterial infection and azithromycin against mycoplasma infection. The child was subsequently considered cured and discharged from the hospital and followed up regularly in the neurology clinic. The mNGS may be a promising and effective diagnostic technique for identifying uncommon pathogens of meningitis in patients with meningitis symptoms and signs without microbial growth in routine CSF culture.
Atrophic autoimmune thyroiditis complicated with systemic lupus erythematosus
Authors: Wakatsuki Ryosuke , Shimizu Masaki , Shimbo Asami , Adachi Eriko , Kanamori Toru , Yamazaki Susumu , Udagawa Tomohiro , Takasawa Kei , Kashimada Kenichi , Morio Tomohiro , Mori Masaaki
Published: July 2022

Atrophic autoimmune thyroiditis (AAT) is a type of autoimmune thyroiditis that causes hypothyroidism without thyroid enlargement. AAT is distinguished from Hashimoto’s disease (HD) by the absence of thyroid enlargement. AAT is rare in children and clinically characterised by severe primary hypothyroidism. Autoimmune thyroiditis, especially HD, is commonly complicated with systemic lupus erythematosus (SLE). Here, we reported the patient with AAT as the initial presentation of SLE complicated with generalised myxoedema, whose presentation was a diagnostic challenge. This patient illustrates the importance of the early recognition of an atypical presentation of SLE patients with autoimmune thyroiditis. It is possible that similar cases have existed in the past but have been overlooked as HD. A large-scale study is necessary to clarify the reality of AAT in SLE.
P-bodies directly regulate MARF1-mediated mRNA decay in human cells
Authors: Brothers William R , Fakim Hana , Kajjo Sam , Fabian Marc R
Published: July 2022

Processing bodies (P-bodies) are ribonucleoprotein granules that contain mRNAs, RNA-binding proteins and effectors of mRNA turnover. While P-bodies have been reported to contain translationally repressed mRNAs, a causative role for P-bodies in regulating mRNA decay has yet to be established. Enhancer of decapping protein 4 (EDC4) is a core P-body component that interacts with multiple mRNA decay factors, including the mRNA decapping (DCP2) and decay (XRN1) enzymes. EDC4 also associates with the RNA endonuclease MARF1, an interaction that antagonizes the decay of MARF1-targeted mRNAs. How EDC4 interacts with MARF1 and how it represses MARF1 activity is unclear. In this study, we show that human MARF1 and XRN1 interact with EDC4 using analogous conserved short linear motifs in a mutually exclusive manner. While the EDC4–MARF1 interaction is required for EDC4 to inhibit MARF1 activity, our data indicate that the interaction with EDC4 alone is not sufficient. Importantly, we show that P-body architecture plays a critical role in antagonizing MARF1-mediated mRNA decay. Taken together, our study suggests that P-bodies can directly regulate mRNA turnover by sequestering an mRNA decay enzyme and preventing it from interfacing with and degrading targeted mRNAs.
Structural and functional characterization of DdrC, a novel DNA damage-induced nucleoid associated protein involved in DNA compaction
Authors: Banneville Anne-Sophie , Bouthier de la Tour Claire , De Bonis Salvatore , Hognon Cécilia , Colletier Jacques-Philippe , Teulon Jean-Marie , Le Roy Aline , Pellequer Jean-Luc , Monari Antonio , Dehez François , Confalonieri Fabrice , Servant Pascale , Timmins Joanna
Published: July 2022

Deinococcus radiodurans is a spherical bacterium well-known for its outstanding resistance to DNA-damaging agents. Exposure to such agents leads to drastic changes in the transcriptome of D. radiodurans. In particular, four Deinococcus-specific genes, known as DNA Damage Response genes, are strongly up-regulated and have been shown to contribute to the resistance phenotype of D. radiodurans. One of these, DdrC, is expressed shortly after exposure to γ-radiation and is rapidly recruited to the nucleoid. In vitro, DdrC has been shown to compact circular DNA, circularize linear DNA, anneal complementary DNA strands and protect DNA from nucleases. To shed light on the possible functions of DdrC in D. radiodurans, we determined the crystal structure of the domain-swapped DdrC dimer at a resolution of 2.5 Å and further characterized its DNA binding and compaction properties. Notably, we show that DdrC bears two asymmetric DNA binding sites located on either side of the dimer and can modulate the topology and level of compaction of circular DNA. These findings suggest that DdrC may be a DNA damage-induced nucleoid-associated protein that enhances nucleoid compaction to limit the dispersion of the fragmented genome and facilitate DNA repair after exposure to severe DNA damaging conditions.
Conjugation of chemical handles and functional moieties to DNA during solid phase synthesis with sulfonyl azides
Authors: Santorelli Angel , Gothelf Kurt V
Published: July 2022

Labelling of oligonucleotides with dyes, targeting ligands, and other moieties has become ever more essential in life-sciences. Conventionally, modifications are introduced to oligonucleotides during solid phase synthesis by special phosphoramidites functionalised with a chemical handle or the desired functional group. In this work, we present a facile and inexpensive method to introduce modifications to oligonucleotides without the need for special phosphoramidites. Sulfonyl azides are applied to react with one or more selected phosphite intermediates during solid phase synthesis. We have prepared 11 sulfonyl azides with different chemical handles such as amine, azide, alkyne, and thiol, and we have further introduced functionalities such as pyrene, other dyes, photo-switchable azobenzenes, and a steroid. The method is compatible with current phosphoramidite-based automated oligonucleotide synthesis and serves as a simple alternative to the unstable and expensive special phosphoramidites currently used for conjugation to oligonucleotides.
Small molecule-based detection of non-canonical RNA G-quadruplex structures that modulate protein translation
Authors: Katsuda Yousuke , Sato Shin-ichi , Inoue Maimi , Tsugawa Hisashi , Kamura Takuto , Kida Tomoki , Matsumoto Rio , Asamitsu Sefan , Shioda Norifumi , Shiroto Shuhei , Oosawatsu Yoshiki , Yatsuzuka Kenji , Kitamura Yusuke , Hagihara Masaki , Ihara Toshihiro , Uesugi Motonari
Published: July 2022

Tandem repeats of guanine-rich sequences in RNA often form thermodynamically stable four-stranded RNA structures. Such RNA G-quadruplexes have long been considered to be linked to essential biological processes, yet their physiological significance in cells remains unclear. Here, we report a approach that permits the detection of RNA G-quadruplex structures that modulate protein translation in mammalian cells. The approach combines antibody arrays and RGB-1, a small molecule that selectively stabilizes RNA G-quadruplex structures. Analysis of the protein and mRNA products of 84 cancer-related human genes identified Nectin-4 and CapG as G-quadruplex-controlled genes whose mRNAs harbor non-canonical G-quadruplex structures on their 5′UTR region. Further investigations revealed that the RNA G-quadruplex of CapG exhibits a structural polymorphism, suggesting a possible mechanism that ensures the translation repression in a KCl concentration range of 25–100 mM. The approach described in the present study sets the stage for further discoveries of RNA G-quadruplexes.
DBC1 is a key positive regulator of enhancer epigenomic writers KMT2D and p300
Authors: Kim Hwa Jin , Moon Sue Jin , Hong Sanghoon , Won Hong-Hee , Kim Jeong Hoon
Published: July 2022

Histone modification is a key epigenetic mechanism for regulation of chromatin dynamics and gene expression. Deleted in breast cancer 1 (DBC1) has been shown to act as a negative regulator of epigenetic modifiers and as a co-activator for nuclear receptors and other transcription factors. However, little is known about the role of DBC1 in the regulation of histone modifications and chromatin landscapes. Here, we analyzed genome-wide profiles of active enhancer and promoter marks in colorectal cancer cells and report DBC1 as a critical positive regulator of histone epigenetic writers KMT2D (H3K4 methyltransferase) and p300 (histone acetyltransferase). DBC1 is required for establishing the landscape of active enhancers, for genome-wide chromatin binding and enhancer recruitment of KMT2D and p300, and for gene activation involved in colorectal cancer progression. DBC1 interacts directly with KMT2D and p300, and enhances KMT2D-mediated histone H3K4 methylation (H3K4me1/2/3) and p300-mediated H3 acetylation. Importantly, DBC1 contributes to super-enhancer formation and function by facilitating the recruitment of KMT2D and p300 and by enhancing their functional interaction and cooperative cross-talk. Our results highlight the critical role of DBC1 as a key positive regulator of KMT2D and p300, and provide insights into regulatory mechanisms underlying the interplay between the enhancer epigenomic writers in enhancer activation.
Highly efficient CRISPR-mediated large DNA docking and multiplexed prime editing using a single baculovirus
Authors: Aulicino Francesco , Pelosse Martin , Toelzer Christine , Capin Julien , Ilegems Erwin , Meysami Parisa , Rollarson Ruth , Berggren Per-Olof , Dillingham Mark Simon , Schaffitzel Christiane , Saleem Moin A , Welsh Gavin I , Berger Imre
Published: July 2022

CRISPR-based precise gene-editing requires simultaneous delivery of multiple components into living cells, rapidly exceeding the cargo capacity of traditional viral vector systems. This challenge represents a major roadblock to genome engineering applications. Here we exploit the unmatched heterologous DNA cargo capacity of baculovirus to resolve this bottleneck in human cells. By encoding Cas9, sgRNA and Donor DNAs on a single, rapidly assembled baculoviral vector, we achieve with up to 30% efficacy whole-exon replacement in the intronic β-actin (ACTB) locus, including site-specific docking of very large DNA payloads. We use our approach to rescue wild-type podocin expression in steroid-resistant nephrotic syndrome (SRNS) patient derived podocytes. We demonstrate single baculovirus vectored delivery of single and multiplexed prime-editing toolkits, achieving up to 100% cleavage-free DNA search-and-replace interventions without detectable indels. Taken together, we provide a versatile delivery platform for single base to multi-gene level genome interventions, addressing the currently unmet need for a powerful delivery system accommodating current and future CRISPR technologies without the burden of limited cargo capacity.
NAT10-mediated N4-acetylcytidine modification is required for meiosis entry and progression in male germ cells
Authors: Chen Lu , Wang Wen-Jing , Liu Qiang , Wu Yu-Ke , Wu Yun-Wen , Jiang Yu , Liao Xiu-Quan , Huang Fei , Li Yang , Shen Li , Yu Chao , Zhang Song-Ying , Yan Li-Ying , Qiao Jie , Sha Qian-Qian , Fan Heng-Yu
Published: July 2022

Post-transcriptional RNA modifications critically regulate various biological processes. N4-acetylcytidine (ac4C) is an epi-transcriptome, which is highly conserved in all species. However, the in vivo physiological functions and regulatory mechanisms of ac4C remain poorly understood, particularly in mammals. In this study, we demonstrate that the only known ac4C writer, N-acetyltransferase 10 (NAT10), plays an essential role in male reproduction. We identified the occurrence of ac4C in the mRNAs of mouse tissues and showed that ac4C undergoes dynamic changes during spermatogenesis. Germ cell-specific ablation of Nat10 severely inhibits meiotic entry and leads to defects in homologous chromosome synapsis, meiotic recombination and repair of DNA double-strand breaks during meiosis. Transcriptomic profiling revealed dysregulation of functional genes in meiotic prophase I after Nat10 deletion. These findings highlight the crucial physiological functions of ac4C modifications in male spermatogenesis and expand our understanding of its role in the regulation of specific physiological processes in vivo.