bluuebunny/crossref_metadata_2025 huggingface dataset:
Are We Correctly Measuring Mandibular Stability After Surgery-First Approach? A Comparative Study Based on Novel 3-Dimensional Measurements
Authors: Mansour Nabil Mokhter , Abdelshaheed Mohamed Elsaid , El-Sabbagh Ahmed Hassan , El-Din Ahmed Mohamed Bahaa , Kim Young Chul , Choi Jong-Woo
Published: February 2023

Using traditional measures to assess mandibular stability after the surgery-first approach (SFA) may produce inaccurate results because unlike the conventional orthodontic-first approach (OFA), the main dental movements occur after surgery in SFA, which produce unavoidable mandibular movements, especially in cases with postsurgical premature dental contact. As these movements are part of the surgical-orthodontic plan, they should not be considered an actual relapse. In this study, to avoid postsurgical dental movement effects, the authors used the relationship between proximal and distal mandibular segments to evaluate stability after SFA. Four easily located points on computerized tomography/cone-beam computerized tomography reconstructed 3-dimensional images were used to calculate 4 measurements between proximal and distal mandibular segments across the osteotomy line in two matched groups of patients (SFA and OFA) at 3 different time points (before, immediately after, and 1 year after the surgery). A high level of skeletal stability was found in the SFA group, with changes 1 year after surgery not exceeding 0.5 mm. The SFA was as skeletally stable as OFA, and the mandibular counterclockwise rotation after surgery was related to the planned dental movements and not the instability of the surgery itself. To avoid the illusion of this preplanned relapse, stability should be measured as a relation between proximal and distal mandibular segments, across the osteotomy and fixation line, and not as a relation between maxillary and mandibular landmarks or between the mandible and facial planes as classically described.
Validation of a Guideline for Nurses Taking Care of Patients With Liver Cirrhosis in the Context of COVID-19 in the Emergency Department
Authors: Maia Jéssica Costa , Bertoncello Kátia Cilene Godinho , de Souza Sabrina da Silva , Locks Melissa Orlandi Honório , Martins Sabrina Regina , Lorenzini Elisiane
Published: February 2023

The objective of this study was to prepare and validate the content of a guideline for nursing care of adult patients with liver cirrhosis and COVID-19 treated in the emergency department. The study was conducted in two stages: first, the guideline was developed based on an integrative literature review and existing guidelines on the topic. The guideline was prepared with six domains and 64 care items. In the second stage, 15 specialists in urgency and emergency services performed content validation of the guideline. The data were analyzed using the Content Validity Index, with reliability assessed through Cronbach's α. The judges validated the guide regarding language clarity, objectivity, theoretical relevance, and practical pertinence. The value of the guideline's Content Validity Index was 0.96. Cronbach's α reliability reached a value of 0.93. The judges validated all domains and items of the guideline for theoretical relevance and practical pertinence, to be used by researchers and clinical practice professionals in the nursing area.
Buckling of lipidic ultrasound contrast agents under quasi-static load
Authors: Chabouh Georges , van Elburg Benjamin , Versluis Michel , Segers Tim , Quilliet Catherine , Coupier Gwennou
Published: February 2023

Collapse of lipidic ultrasound contrast agents under high-frequency compressive load has been historically interpreted by the vanishing of surface tension. By contrast, buckling of elastic shells is known to occur when costly compressible stress is released through bending. Through quasi-static compression experiments on lipidic shells, we analyse the buckling events in the framework of classical elastic buckling theory and deduce the mechanical characteristics of these shells. They are then compared with that obtained through acoustic characterization.

This article is part of the theme issue ‘Probing and dynamics of shock sensitive shells’.
Asymptotic derivation of a higher-order one-dimensional model for tape springs
Authors: Kumar Arun , Audoly Basile , Lestringant Claire
Published: February 2023

We derive a one-dimensional model for tape springs. The derivation starts from nonlinear thin-shell theory and uses a dimension reduction technique that combines a centreline-based parametrization of the tape-spring midsurface with the assumption that the strain varies slowly along the length of the tape spring. The one-dimensional model is effectively a higher-order rod model: at leading order, the strain energy depends on the extensional, bending and twisting strains and is consistent with classical results from the literature; the two following orders are novel and capture the dependence of the strain energy on the strain gradients. The cross-sectional displacements are solved as part of the dimension reduction process, making the one-dimensional model asymptotically exact. We expect that the model will accurately and efficiently capture the deformations and instabilities in tape springs, including those involving highly localized deformations.

This article is part of the theme issue ‘Probing and dynamics of shock sensitive shells’.
Probabilistic buckling of imperfect hemispherical shells containing a distribution of defects
Authors: Derveni Fani , Gueissaz William , Yan Dong , Reis Pedro M.
Published: February 2023

The buckling of spherical shells is plagued by a strong sensitivity to imperfections. Traditionally, imperfect shells tend to be characterized empirically by the knockdown factor, the ratio between the measured buckling strength and the corresponding classic prediction for a perfect shell. Recently, it has been demonstrated that the knockdown factor of a shell containing a single imperfection can be predicted when there is detailed
a priori
knowledge of the defect geometry. Still, addressing the analogous problem for a shell containing many defects remains an open question. Here, we use finite element simulations, which we validate against precision experiments, to investigate hemispherical shells containing a well-defined distribution of imperfections. Our goal is to characterize the resulting knockdown factor statistics. First, we study the buckling of shells containing only two defects, uncovering non-trivial regimes of interactions that echo existing findings for cylindrical shells. Then, we construct statistical ensembles of imperfect shells, whose defect amplitudes are sampled from a lognormal distribution. We find that a 3-parameter Weibull distribution is an excellent description for the measured statistics of knockdown factors, suggesting that shell buckling can be regarded as an extreme-value statistics phenomenon.

This article is part of the theme issue ‘Probing and dynamics of shock sensitive shells’.
High occupancy of European leaf-toed geckoEuleptes europaeain two island stands ofEucalyptus sp.: tree selection, co-occurrence and habitat effect
Authors: Deso Grégory , Priol Pauline , Reynier Thierry , Renet Julien
Published: February 2023

The effective conservation of a species requires a thorough knowledge of its ecology. Long considered to live exclusively in rocky habitats, the European leaf-toed gecko (Euleptes europaea)has in fact been observed in vegetated and wooded habitats at several locations throughout its range. The tendency of this species to use these habitats seems to be clearly supported by its prehensile tail characteristic of geckos with arboreal behaviour. To better assess tree occupation byE. europaeaand other co-occurring geckos, a site-occupancy survey was conducted in 2022 on the testing site of DGA (French MoD the Procurement Agency) of Levant Island (Hyères, France). Two stands ofEucalyptus sp. containing 68 trees were selected to monitor. One stand lies in an anthropised context, consisting of scattered woodland and clear ground (stand 1), and the other represents a ‘natural’ forest context with dense ground vegetation (stand 2). The results revealed high occupancy byE. europaeain both stands, with an average occupancy probability of 0.57 (CI 0.40–0.72). The Mediterranean house gecko (Hemidactylus turcicus) and Moorish gecko (Tarentola mauritanica) had an average occupancy probability of 0.28 (CI 0.16–0.44) and 0.07 (CI 0.03–0.16) respectively. In stand 2,E. europaeawas the only gecko species found, suggesting that it is better adapted to this type of forest habitat, which may represent a refuge for this species. In view of these results, the ecology of this species should be reconsidered and the research broadened by systematically including vegetated and forest habitats.
Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England
Authors: Perez-Guzman Pablo N , Knock Edward , Imai Natsuko , Rawson Thomas , Elmaci Yasin , Alcada Joana , Whittles Lilith K , Kanapram Divya Thekke , Sonabend Raphael , Gaythorpe Katy AM , Hinsley Wes , FitzJohn Richard G , Volz Erik , Verity Robert , Ferguson Neil M , Cori Anne , Baguelin Marc
Published: February 2023

As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.3 (95% credible interval (CrI) 7.7-8.8). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.9%, 95% CrI 2.7-3.2), followed by Delta (2.2%, 95% CrI 2.0-2.4), Wildtype (1.2%, 95% CrI 1.1-1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.
Relative effectiveness of BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines and homologous boosting in preventing COVID-19 in adults in the US
Authors: Nguyen Van Hung , Boileau Catherine , Bogdanov Alina , Sredl Meg , Bonafede Mac , Ducruet Thierry , Chavers Scott , Rosen Andrew , Martin David , Buck Philip , Esposito Diana , Van de Velde Nicolas , Mansi James A.
Published: February 2023

Background

Few head-to-head comparisons have been performed on the real-world effectiveness of COVID-19 booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 versus BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against medically-attended, outpatient, and hospitalized COVID-19.

Methods

A dataset linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients ≥18 years vaccinated with a primary series between February and October 2021 (Part 1) and a homologous mRNA booster between October 2021 and January 2022 (Part 2). Adjusted hazard ratios (HR) were derived from 1:1 matching adjusted across potential covariates. rVE was (1-HRadjusted) x 100. Additional analysis was performed across regions and age groups.

Results

Following adjustment, Part 1 rVE for mRNA-1273 versus BNT162b2 was 23% (95% CI: 22%–25%), 23% (22%–25%), and 19% (14%–24%) whilst the rVE for mRNA-1273 versus Ad26.COV2.S was 50% (48%–51%), 50% (48%–52%), and 57% (53%–61%) against any medically-attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 versus BNT162b2 was 14% (10%–18%), 13% (8%– 17%), and 19% (1%–34%) against any medically-attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically-attended COVID-19 was higher in adults ≥65 years (35%; 24%–47%) than those 18–64 years (13%; 9%–17%) after the booster.

Conclusions

In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following primary series during a Delta-dominant period, and than BNT162b2 as a booster during an Omicron-dominant period.

Key points

mRNA-1273 was associated with a lower risk than BNT162b2 or Ad26.COV2.S of any medically-attended, outpatient, or hospitalized COVID-19 after primary series and of any medically-attended, outpatient, or hospitalized COVID-19 vs BNT162b2 after a homologous mRNA booster
Androgen Signaling Restricts Glutaminolysis to Drive Sex-Specific Th17 Metabolism
Authors: Chowdhury Nowrin U , Cephus Jacqueline-Yvonne , Madden Matthew Z , Wolf Melissa M , Chi Channing , Sugiura Ayaka , Stier Matthew T , Voss Kelsey , Ye Xiang , Kuehnle Shelby N , Scales Kennedi , Gandhi Vivek D , Guzy Robert D. , Cahill Katherine N , Sperling Anne I , Peebles R. Stokes , Rathmell Jeffrey C , Newcomb Dawn C
Published: February 2023

Females have increased prevalence of many Th17-mediated diseases. While androgen signaling decreases Th17-mediated inflammation, the mechanisms are not fully understood. Th17 cells rely on glutaminolysis; however, it remains unclear whether androgen receptor (AR) signaling in males modifies glutamine metabolism to suppress Th17-mediated inflammation. We show that Th17 cells from male humans and mice had decreased glutaminolysis compared to females, and AR signaling attenuated Th17 cell mitochondrial respiration and glutaminolysis.

Using allergen-induced airway inflammation models, we determined females, but not males, had a critical reliance upon glutaminolysis for Th17-mediated airway inflammation, and AR signaling attenuated glutamine uptake by reducing expression of glutamine transporters. These findings were confirmed in circulating human Th17 cells with minimal reliance on glutamine uptake in male compared to female Th17 cells. We found that AR signaling attenuates glutaminolysis, demonstrating sex-specific metabolic regulation of Th17 cells with implications for design and implementation of Th17 or glutaminolysis targeted therapeutics.

Highlights

Human male CD4+ T cells have decreased expression of metabolic enzymes and decreased reliance on glutaminolysis compared to female CD4+ T cells.

Androgen signaling decreased mitochondrial metabolism in Th17 cells and decreased airway inflammation.

Androgen signaling decreased glutamine uptake and utilization in Th17 cells.
Co-inhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancerviareadthrough transcription
Authors: Cameron Donald P. , Grosser Jan , Ladigan Swetlana , Kuzin Vladislav , Iliopoulou Evanthia , Wiegard Anika , Benredjem Hajar , Liffers Sven T. , Lueong Smiths , Cheung Phyllis F. , Vangala Deepak , Pohl Michael , Viebahn Richard , Teschendorf Christian , Wolters Heiner , Usta Selami , Geng Keyi , Kutter Claudia , Arsenian-Henriksson Marie , Siveke Jens T. , Tannapfel Andrea , Schmiegel Wolff , Hahn Stephan A. , Baranello Laura
Published: February 2023

Pancreatic carcinoma is one of the most lethal cancers and the absence of efficient therapeutic strategies results in poor prognosis. Transcriptional dysregulation due to alterations in KRAS and MYC impacts initiation, development, and survival of this tumor type. Using patient-derived xenografts of pancreatic carcinoma driven by KRAS and MYC oncogenic transcription, we show that co-inhibition of Topoisomerase 1 (TOP1) and bromodomain containing protein 4 (BRD4) synergistically induce tumor regression through targeting promoter pause-release, a rate-limiting step in transcription elongation. By comparing the nascent transcriptome with the recruitment of elongation and termination factors along genes, we found that co-inhibition of TOP1 and BRD4, while globally impairing RNA production, disturbs recruitment of proteins involved in termination. Thus, RNA polymerases continue transcribing downstream of genes for hundreds of kilobases leading to readthrough transcription. This pervasive transcription also occurs during replication, perturbing replisome progression and leading to DNA damage. The synergistic effect of TOP1 and BRD4 inhibition is specific for cancer cells leaving normal cells unharmed, highlighting the sensitivity of the tumor to these transcriptional defects. This preclinical study provides a mechanistic understanding of the benefit of combining TOP1 and BRD4 inhibitors to treat pancreatic carcinomas addicted to oncogenic drivers of high transcription and replication.

One Sentence Summary

TOP1 and BRD4 inhibitors synergize to selectively kill pancreatic cancerin vivo viareadthrough transcription without emergence of drug resistance
Breast Density Analysis Using Digital Breast Tomosynthesis
Authors: Heine John , Fowler Erin E.E. , Weinfurtner R. Jared , Hume Emma , Tworoger Shelley S.
Published: February 2023

We evaluated an automated percentage of breast density (BD) technique (PDa) with digital breast tomosynthesis (DBT) data. The approach is based on the wavelet expansion followed by analyzing signal dependent noise. Several measures were investigated as risk factors: normalized volumetric; total dense volume; average of the DBT slices (slice-mean); a two-dimensional (2D) metric applied to the synthetic images; and the mean and standard deviations of the pixel values. Volumetric measures were derived theoretically, and PDawas modeled as a function of compressed breast thickness. An alternative method for constructing synthetic 2D mammograms was investigated using the volume results. A matched case-control study (n = 426 pairs) was analyzed. Conditional logistic regression modeling, controlling body mass index and ethnicity, was used to estimate odds ratios (ORs) for each measure with 95% confidence intervals provided parenthetically.

There were several significant findings: volumetric measure [OR = 1.43 (1.18, 1.72)], which produced an identical OR as the slice-mean measure as predicted; [OR =1.44 (1.18, 1.75)] when applied to the synthetic images; and mean of the pixel values (volume or 2D synthetic) [ORs ∼ 1.31 (1.09, 1.57)]. PDawas modeled as 2nddegree polynomial (concave-down): its maximum value occurred at 0.41×(compressed breast thickness), which was similar across case-control groups, and was significant from this position [OR = 1.47 (1.21, 1.78)]. A standardized 2D synthetic image was produced, where each pixel value represents the percentage of BD above its location.

The significant findings indicate the validity of the technique. Derivations supported by empirical analyses produced a new synthetic 2D standardized image technique. Ancillary to the objectives, the results provide evidence for understanding the percentage of BD measure applied to 2D mammograms. Notwithstanding the findings, the study design provides a template for investigating other measures such as texture.
Postnatal maturation ofin vivomembrane potential dynamics during hippocampal ripples
Authors: Noguchi Asako , Ikegaya Yuji
Published: February 2023

Sharp-wave ripples (SWRs) are transient high-frequency oscillations of local field potentials (LFPs) in the hippocampus and play a critical role in memory consolidation. During SWRs, CA1 pyramidal cells exhibit rapid spike sequences that often replay the sequential activity that occurred during behavior. This temporally organized firing activity gradually emerges during two weeks after the eye opening; however, it remains unclear how the organized spikes during SWRs mature at the intracellular membrane potential (Vm) level. Here, we recorded theVm of CA1 pyramidal cells simultaneously with hippocampal LFPs from immature mice after the developmental emergence of SWRs. On postnatal days 16–17,Vm dynamics around SWRs were premature, characterized by prolonged depolarizations without either pre- or post-SWR hyperpolarization. The biphasic hyperpolarizations, which are a typical feature of adult SWR-relevantVm, formed by approximately postnatal day 30. ThisVm maturation was associated with an increase in SWR-associated inhibitory inputs to pyramidal cells. Thus, the development of SWR-relevant inhibition restricts the temporal windows for spikes of pyramidal cells and allows CA1 pyramidal cells to organize their spike sequences during SWRs.

Significance statement

Sharp-wave ripples (SWRs) are prominent hippocampal oscillations and play a critical role in memory consolidation. During SWRs, hippocampal neurons synchronously emit spikes with organized temporal patterns. This temporal structure of spikes during SWRs develops during the third and fourth postnatal weeks, but the underlying mechanisms are not well-understood. Here, we recordedin vivomembrane potentials from hippocampal neurons in premature mice and suggest that the maturation of SWR-associated inhibition enables hippocampal neurons to produce precisely controlled spike times during SWRs.
Insight on physicochemical properties governing peptide MS1 response in HPLC-ESI-MS/MS proteomics: A deep learning approach
Authors: Abdul-Khalek Naim , Wimmer Reinhard , Overgaard Michael Toft , Gregersen Echers Simon
Published: February 2023

Accurate and absolute quantification of individual peptides in complex mixtures is a challenge not easily overcome. A potential solution is the use of quantitative mass spectrometry (MS) based methods, however, current state of the art requires foreground knowledge and isotopically labeled standards for each peptide to be accurately quantified. This increases analytical expenses, time consumption, and labor, limiting the number of peptides that can be quantified. A key step in developing less restrictive label-free quantitative peptidomics methods is understanding of the physicochemical properties of peptides that influence the MS response. In this work, a deep learning model was developed to identify the most relevant physicochemical properties based on repository MS data from equimolar peptide pools. Using an autoencoder with attention mechanism and correlating attention weights with corresponding physicochemical property indices from AAindex1, we were able to obtain insight on the properties governing the peptide-level MS1 response. These properties can be grouped in three main categories related to peptide hydrophobicity, charge, and structural propensities. Moreover, we present a model for predicting the MS1 intensity output based solely on peptide sequence input. Using a refined training dataset, the model predicted log-transformed peptide MS1 intensities with an average error of 11%.
Multiple hosts, multiple impacts: the role of vertebrate host diversity in shaping mosquito life history and pathogen transmission
Authors: Vantaux Amélie , Moiroux Nicolas , Dabiré Kounbobr Roch , Cohuet Anna , Lefèvre Thierry
Published: February 2023

The transmission of malaria parasites from mosquito to human is largely determined by the dietary specialization ofAnophelesmosquitoes to feed on humans. Few studies have explored the impact of blood meal sources on the fitness of both the parasite and the mosquito. Our study investigated the effects of 3-4 consecutive blood meals from one of four vertebrate species (human, cattle, sheep, or chicken) on several fitness traits, including mosquito feeding rate, blood meal size, susceptibility to wild isolates ofPlasmodium falciparum, survival, fecundity, F1 offspring development time, and size. Our findings revealed no significant effect on parasite development. Similarly, parasite exposure had no overall effects on mosquito fitness. However, blood meal type did have a strong impact on mosquito feeding rate, survival, lifetime fecundity, and offspring size. Specifically, mosquitoes that were fed successive chicken blood meals produced fewer eggs and fewer and smaller F1 adults compared to those fed human blood. Combining our results in a theoretical model, we show a decrease in the vectorial capacity of mosquitoes fed chicken or cow blood and an increase in the capacity of those fed sheep blood compared to those fed human blood. These findings emphasize the importance of considering the diversity of blood meal sources in understanding mosquito ecology and their role in the transmission intensity of malaria parasites.
Decoding the content of working memory in school-aged children
Authors: Turoman Nora , Fiave Prosper Agbesi , Zahnd Clélia , deBettencourt Megan T. , Vergauwe Evie
Published: February 2023

Developmental improvements in working memory (WM) maintenance predict many real-world outcomes, including educational attainment. It is thus critical to understand which WM mechanisms support these behavioral improvements, and how WM maintenance strategies might change through development. One challenge is that specific WM neural mechanisms cannot easily be measured behaviorally, especially in a child population. However, new multivariate decoding techniques have been designed, primarily in adult populations, that can sensitively decode the contents of WM. The goal of this study was to deploy multivariate decoding techniques known to decode memory representations in adults to decode the contents of WM in children. We created a simple computerized WM game for children, in which children maintained different categories of information (visual, spatial or verbal). We collected electroencephalography (EEG) data from 20 children (7-12-year-olds) while they played the game. Using Multivariate Pattern Analysis (MVPA) on children’s EEG signals, we reliably decoded the category of the maintained information during the sensory and maintenance period. Across exploratory reliability and validity analyses, we examined the robustness of these results when trained on less data, and how these patterns generalized within individuals throughout the testing session. Furthermore, these results matched theory-based predictions of WM across individuals and across ages. Our proof-of-concept study proposes a direct and age-appropriate potential alternative to exclusively behavioral WM maintenance measures in children. Our study demonstrates the utility of MVPA to measure and track the uninstructed representational content of children’s WM. Future research could use our technique to investigate children’s WM maintenance and strategies.
Towards a robust comparison of diversity between sampled TCR repertoires
Authors: de Greef Peter C. , de Boer Rob J.
Published: February 2023

T-cell receptor (TCR) repertoire sequencing data provides quantitative insight into the distribution of T-cell clones. The diversity of the TCR repertoire in humans tends do decrease with age, which may be a key determinant explaining immune senescence in older individuals. To address this, we first analyze how the diversity of a potential T-cell response against an unseen pathogen changes with age. Next, we discuss the complications with interpreting the outcomes of such an analysis. Specifically, the changes in T-cell subset sizes confound analyses of TCR diversity, and typical sample sizes do not easily allow for a robust quantification of this diversity. Thus, explaining immune senescence as a result of decreasing TCR diversity is far from straightforward and requires a detailed, robust, and quantitative analysis.
Housing conditions affect adult zebrafish (Danio rerio) behavior but not their physiological status
Authors: Jorge Sara , Félix Luís , Costas Benjamín , Valentim Ana M
Published: February 2023

Zebrafish is a valuable model for neuroscience research, but the housing conditions to which it is daily exposed may be impairing its welfare status. The use of environmental enrichment and the refinement of methodology for cortisol measurement could reduce stress, improving its welfare and its suitability as an animal model used in stress research. Thus, this study aimed to evaluate (I) the influence of different housing conditions on zebrafish physiology and behavior and (II) skin mucus potential for cortisol measurement in adult zebrafish. For this, AB zebrafish were raised under barren or enriched (PVC pipes and gravel image) environmental conditions. After 6 months, the behavior was assessed by different behavioral paradigms (shoaling, white-black box test, and novel tank). The physiological response was also evaluated through cortisol levels (whole-body homogenates and skin mucus) and brain oxidative stress markers. Results revealed that enriched-housed fish had an increased nearest neighbors’ distance and reduced activity. However, no effect on body length or stress biomarkers was observed; whole-body and skin mucus cortisol levels had the same profile between groups. In conclusion, this study highlights the skin mucus potential as a matrix for cortisol quantification and how environmental enrichment could influence the data in future studies.

Simple Summary

The delivery of proper housing conditions may translate into good fish welfare. As zebrafish housing is usually poorly enriched, the fish could be unable to express some natural behaviors, leading to distress and/ or stress mechanisms’ dysregulation. This work focused on the examination of zebrafish welfare raised under different housing conditions (barren or environmentally enriched) and the testing of a low-invasive technique (skin mucus collection) to measure the main stress hormone (cortisol). The data was processed to assess body length, behavior, and physiological status. Results revealed that enrichment induced minor alterations on zebrafish behavior. Thus, the influence of housing conditions should be considered in future research, depending on the purpose of the study. Also, skin mucus appears to be a promising matrix to replace whole-body to measure cortisol in zebrafish, since its collection is nonlethal and showed similar results to the traditional method.
Endosomal trafficking protein TBC-2 is required for the longevity of long-lived mitochondrial mutants
Authors: Traa Annika , Shields Hazel , AlOkda Abdelrahman , Rudich Zenith D. , Ko Bokang , Van Raamsdonk Jeremy M.
Published: February 2023

Mutations that result in a mild impairment of mitochondrial function can extend longevity. Previous studies have shown that the increase in lifespan is dependent on stress responsive transcription factors, including DAF-16/FOXO, which exhibits increased nuclear localization in long-lived mitochondrial mutants. We recently found that the localization of DAF-16 within the cell is dependent on the endosomal trafficking protein TBC-2. Based on the important role of DAF-16 in both longevity and resistance to stress, we examined the effect of disruptingtbc-2on lifespan and stress resistance in the long-lived mitochondrial mutantsnuo-6andisp-1inC. elegans. Loss oftbc-2markedly reduced the long lifespans of both mitochondrial mutants. Disruption oftbc-2also decreased resistance to specific exogenous stressors innuo-6andisp-1mutants. In contrast,tbc-2inhibition had no effect on oxidative stress resistance or lifespan inisp-1worms when DAF-16 is absent suggesting that the effect oftbc-2on mitochondrial mutant lifespan may be mediated by mislocalization of DAF-16. However, this result is complicated by the fact that deletion ofdaf-16markedly decreases both phenotypes inisp-1worms. Surprisingly, disruption oftbc-2did not prevent the upregulation of DAF-16 target genes in the long-lived mitochondrial mutants, suggesting the possibility that the effect oftbc-2on lifespan and stress resistance in the long-lived mitochondrial mutants is at least partially independent of its effects on DAF-16 localization. Overall, this work demonstrates the importance of endosomal trafficking for the extended longevity and enhanced stress resistance resulting from mild impairment of mitochondrial function.
Evolution of connectivity architecture in theDrosophilamushroom body
Authors: Ellis Kaitlyn Elizabeth , Bervoets Sven , Smihula Hayley , Ganguly Ishani , Vigato Eva , Auer Thomas O. , Benton Richard , Litwin-Kumar Ashok , Caron Sophie Jeanne Cécile
Published: February 2023

Brain evolution has primarily been studied at the macroscopic level by comparing the relative size of homologous brain centers between species. How neuronal circuits change at the cellular level over evolutionary time remains largely unanswered. Here, using a phylogenetically informed framework, we compare the olfactory circuits of three closely relatedDrosophilaspecies that differ radically in their chemical ecology: the generalistsDrosophila melanogasterandDrosophila simulansthat feed on fermenting fruit, andDrosophila sechelliathat specializes on ripe noni fruit. We examine a central part of the olfactory circuit that has not yet been investigated in these species — the connections between the projection neurons of the antennal lobe and the Kenyon cells of the mushroom body, an associative brain center — to identify species-specific connectivity patterns. We found that neurons encoding food odors — the DC3 neurons inD. melanogasterandD. simulansand the DL2d neurons inD. sechellia— connect more frequently with Kenyon cells, giving rise to species-specific biases in connectivity. These species-specific differences in connectivity reflect two distinct neuronal phenotypes: in the number of projection neurons or in the number of presynaptic boutons formed by individual projection neurons. Finally, behavioral analyses suggest that such increased connectivity enhances learning performance in an associative task. Our study shows how fine-grained aspects of connectivity architecture in an associative brain center can change during evolution to reflect the chemical ecology of a species.
PyBrOpS: a Python package for breeding program simulation and optimization for multi-objective breeding
Authors: Shrote Robert Z. , Thompson Addie M.
Published: February 2023

Plant breeding is a complex endeavor that is almost always multi-objective in nature. In recent years, stochastic breeding simulations have been used by breeders to assess the merits of alternative breeding strategies and assist in decision making. In addition to simulations, visualization of a Pareto frontier for multiple competing breeding objectives can assist breeders in decision making. This paper introduces Python Breeding Optimizer and Simulator (PyBrOpS), a Python package capable of performing multi-objective optimization of breeding objectives and stochastic simulations of breeding pipelines. PyBrOpS is unique among other simulation platforms in that it can perform multi-objective optimizations and incorporate these results into breeding simulations. PyBrOpS is built to be highly modular and has a script-based philosophy, making it highly extensible and customizable. In this paper, we describe some of the main features of PyBrOpS and demonstrate its ability to map Pareto frontiers for breeding possibilities and perform multi-objective selection in a simulated breeding pipeline.
Sensory innervation of masseter, temporal and lateral pterygoid muscles in common marmosets
Authors: Hovhannisyan Anahit H. , Lindquist Karen A. , Belugin Sergei , Mecklenburg Jennifer , Ibrahim Tarek , Tram Meilinn , Corey Tatiana M. , Salmon Adam B. , Perez Daniel , Ruparel Shivani , Akopian Armen N.
Published: February 2023

Myogenous temporomandibular disorders (TMDM) is associated with an increased responsiveness of nerves innervating the masseter (MM), temporal (TM), medial pterygoid (MPM) and lateral pterygoid muscles (LPM). This study aimed to examine sensory nerve types innervating MM, TM and LPM of adult non-human primate - common marmosets. Sensory nerves are localized in specific regions of these muscles. Pgp9.5, marker for all nerves, and NFH, a marker for A-fibers, showed that masticatory muscles were predominantly innervated with A-fibers. The proportion of C- to A-fibers was highest in LPM, and minimal (6-8%) in MM. All C-fibers (pgp9.5+/NFH-) observed in masticatory muscles were peptidergic (CGRP+) and lacked mrgprD, trpV1 and CHRNA3, a silent nociceptive marker. All fibers in masticatory muscles were labeled with GFAP+, a myelin sheath marker. There were substantially more peptidergic A-fibers (CGRP+/NFH+) in TM and LPM compared to MM. Almost all A-fibers in MM expressed trkC, with some of them having trkB and parvalbumin. In contrast, a lesser number of TM and LPM nerves expressed trkC, and lacked trkB. Tyrosine hydroxylase antibodies, which did not label TG, highlighted sympathetic fibers around blood vessels of the masticatory muscles. Overall, masticatory muscle types of marmosets have distinct and different innervation patterns.
Genomic Resources for Asian (Elephas maximus) and African Savannah Elephant (Loxodonta africana) Conservation and Health Research
Authors: Prado Natalia A. , Armstrong Ellie E. , Brown Janine L. , Goldenberg Shifra Z. , Leimgruber Peter , Pearson Virginia R. , Maldonado Jesús E. , Campana Michael G.
Published: February 2023

We provide novel genomic resources to help understand the genomic traits involved in elephant health and to aid conservation efforts. We sequence 11 elephant genomes (5 African savannah, 6 Asian) from North American zoos, including 9de novoassemblies. We estimate elephant germline mutation rates and reconstruct demographic histories. Finally, we provide an in-solution capture assay to genotype Asian elephants. This assay is suitable for analyzing degraded museum and non-invasive samples, such as feces and hair. The elephant genomic resources we present here should allow for more detailed and uniform studies in the future to aid elephant conservation efforts and disease research.
Streamline unsupervised machine learning to survey and graph indel-based haplotypes from pan-genomes
Authors: Zhang Bosen , Huang Haiyan , Tibbs-Cortes Laura E. , Vanous Adam , Zhang Zhiwu , Sanguinet Karen , Garland-Campbell Kimberly A. , Yu Jianming , Li Xianran
Published: February 2023

Identification and visualization of large insertion and deletion (indel) polymorphisms, which contribute significantly to natural phenotypic variation, are challenge from a pan-genome. Here, through streamlining two unsupervised machine learning algorithms, we developed a BRIDGEcereal webapp for surveying and graphing indel-based haplotypes for genes of interest from publicly accessible pangenomes. Over hundreds of assemblies from five major cereals were compiled. We demonstrated the potential of BRIDGEcereal in exploring natural variation with wheat candidate genes within QTLs and GWAS intervals. BRIDGEcereal is available fromhttps://bridgecereal.scinet.usda.gov.
Petagraph: A large-scale unifying knowledge graph framework for integrating biomolecular and biomedical data
Authors: Stear Benjamin J. , Ahooyi Taha Mohseni , Vasisht Shubha , Simmons Alan , Beigel Katherine , Callahan Tiffany J. , Silverstein Jonathan C. , Taylor Deanne M.
Published: February 2023

The use of biomedical knowledge graphs (BMKG) for knowledge representation and data integration has increased drastically in the past several years due to the size, diversity, and complexity of biomedical datasets and databases. Data extraction from a single dataset or database is usually not particularly challenging. However, if a scientific question must rely on integrative analysis across multiple databases or datasets, it can often take many hours to correctly and reproducibly extract and integrate data towards effective analysis. To overcome this issue, we created Petagraph, a large-scale BMKG that integrates biomolecular data into a schema incorporating the Unified Medical Language System (UMLS). Petagraph is instantiated on the Neo4j graph platform, and to date, has fifteen integrated biomolecular datasets. The majority of the data consists of entities or relationships related to genes, animal models, human phenotypes, drugs, and chemicals. Quantitative data sets containing values from gene expression analyses, chromatin organization, and genetic analyses have also been included. By incorporating models of biomolecular data types, the datasets can be traversed with hundreds of ontologies and controlled vocabularies native to the UMLS, effectively bringing the data to the ontologies. Petagraph allows users to analyze relationships between complex multi-omics data quickly and efficiently.
Curvature coding in early visual system revealed by scale variance during adaptation to flashing circles
Authors: Nisar Irfa , Elder James H.
Published: February 2023

How is curvature coded in the early human visual system? Humans are successful in recognizing objects and by extension, the shape representing the object, under varying scale conditions (Biederman & Cooper, 1992; Lindeberg, 2013). How do we neuro-physiologically code the invariance (or variance) in curvature and does the curvature coding change with scale? The circle-polygon illusion produces polygonal percepts during adaptation when a static dark outline circle is pulsed at 2 Hz alternating with a gradient luminance circle. We use the circle-polygon to study curvature processing with respect to size and scale. Both the radius and eccentricity of the stimulus were varied in a crossed design over 1-8 deg. Observers reported a circle or the polygon order and the strength of the percept. We test a lower level account that argues for curvature opponency between neurons against a higher level account that codes for whole shapes. This higher level account supports scale invariance, a property through which we recognize objects regardless of the object’s size on the retina. We show the following: (1) Scale invariance is not obeyed during adaptation. The mean order of the perceived polygon increased with stimulus size and decreased with eccentricity. This also demonstrates that curvature coding occurs in the early visual system. (2) Linear regression analysis reveals that the cortical size of the stimulus is a better predictor of perceived polygon order. We quantify the relationship parametrically between cortical size and polygon order. Using integration and regression, we identify the region of the cortex, V1, where the shape, a regular ordered polygon, is being computationally constructed.
Aberrant accumulation of age- and disease-associated factors following neural probe implantation in a mouse model of Alzheimer’s disease
Authors: Wellman Steven M. , Coyne Olivia A. , Douglas Madeline M. , Kozai Takashi D.Y.
Published: February 2023

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Electrical stimulation has had a profound impact on our current understanding of nervous system physiology and provided viable clinical options for addressing neurological dysfunction within the brain. Unfortunately, the brain’s immune suppression of indwelling microelectrodes currently presents a major roadblock in the long-term application of neural recording and stimulating devices. In some ways, brain trauma induced by penetrating microelectrodes produces similar neuropathology as debilitating brain diseases, such as Alzheimer’s disease (AD), while also suffering from end-stage neuron loss and tissue degeneration. To understand whether there may be any parallel mechanisms at play between brain injury from chronic microelectrode implantation and those of neurodegenerative disorder, we used two-photon microscopy to visualize the accumulation, if any, of age- and disease-associated factors around chronically implanted electrodes in both young and aged mouse models of AD. With this approach, we determined that electrode injury leads to aberrant accumulation of lipofuscin, an age-related pigment, in wild-type and AD mice alike. Furthermore, we reveal that chronic microelectrode implantation reduces the growth of pre-existing amyloid plaques while simultaneously elevating amyloid burden at the electrode-tissue interface. Lastly, we uncover novel spatial and temporal patterns of glial reactivity, axonal and myelin pathology, and neurodegeneration related to neurodegenerative disease around chronically implanted microelectrodes. This study offers multiple novel perspectives on the possible neurodegenerative mechanisms afflicting chronic brain implants, spurring new potential avenues of neuroscience investigation and design of more targeted therapies for improving neural device biocompatibility and treatment of degenerative brain disease.
The Small GTPase Rab7 Regulates Release of Mitochondria in Extracellular Vesicles in Response to Lysosomal Dysfunction
Authors: Liang Wenjing , Diao Rachel Y. , Quiles Justin M. , Najor Rita H. , Chi Liguo , Woodall Benjamin P. , Leon Leonardo J. , Duran Jason , Cauvi David M. , De Maio Antonio , Adler Eric D. , Gustafsson Åsa B.
Published: February 2023

Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.
Simple in-vitro single stranded linear and circular DNA preparation and validation via SELEX using phosphor-derived modifications
Authors: Hamidi Seyed Vahid , Perreault Jonathan
Published: February 2023

Interest in preparation of single stranded circular DNA library has been increasing recently, therefore developing a simple and efficient method for circular DNA generation will be very useful for all procedures and techniques that are dependent on single stranded circular DNA preparation. In this study a new simple method for in vitro preparation of circular single stranded DNA is proposed. We hypothesized that using a phosphorylated-phosphorothioated primer would not affect the efficiency of PCR reactions, but, more importantly, would suppress the activity of Lambda Exonuclease enzyme even if it is phosphorylated. The produced phosphorylated single stranded DNA is ready to be circularized via a ligation reaction using a bridging oligonucleotide. Several optimizations and enhancements have been conducted in the ligation reaction, notably by embedding an extra thymine nucleotide at the ligation site to compensate for the additional adenosine nucleotide added by Taq during the PCR reaction. In addition, the performance of the proposed method has been validated by selecting linear and circular aptamers against MERS-CoV spike protein during 15 successive cycles of SELEX. Because this new method is simple and user-friendly, it has a potential to be automated for high-throughput purposes and may further stir growing interests in preparation of single stranded circular DNA and its applications.