bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Evaluation of a Clinical Guideline for a Pediatric Telemedicine and Medication Delivery Service: A Prospective Cohort Study in Haiti
Authors: Klarman Molly B. , Chi Xiaofei , Cajusma Youseline , Flaherty Katelyn E. , Capois Anne Carine , Vladimir Dofiné Michel Daryl , Exantus Lerby , Friesen Jason , Beau de Rochars Valery M. , Becker Torben K. , Baril Chantale , Gurka Matthew J. , Nelson Eric J.
Published: February 2023

Objective

Despite the emergence of telemedicine as an important model for healthcare delivery, there is a lack of evidence-based telemedicine guidelines, especially for resource-limited settings. We sought to develop and evaluate a guideline for a pediatric telemedicine and medication delivery service (TMDS).

Methods

A prospective cohort study was conducted at a TMDS in Haiti; children ≤10 years were enrolled. Among non-severe cases, paired virtual and in-person exams were conducted at the call center and household; severe cases were referred to the hospital. The primary outcome was the performance of the virtual exam compared to the in-person exam (reference standard).

Findings

A total of 391 cases were enrolled. Among 320 cases with paired exams, no general World Health Organization (WHO) danger signs were identified at the household; problem-specific danger signs were identified in 6 cases (2%). Cohen’s kappa for the designation of mild cases was 0.78 (95%CI 0.69-0.87). Among components of the virtual exam, the sensitivity and specificity of a reported fever were 91% (87%-96%) and 69% (62%-74%), respectively; the sensitivity and specificity of ‘fast breathing’ were 47% (21%-72%) and 89% (85%-94%), respectively. Kappa for dehydration assessments indicated moderate congruence (0.69; 95%CI 0.41-0.98). At 10 days, 95% (273) of the 287 cases reached were better/recovered.

Conclusion

This study, and resulting guideline, represents a formative step towards an evidence-based pediatric telemedicine guideline built on WHO clinical principles. In-person exams for select cases were important to address limitations with virtual exams and identify cases for escalation.
The contribution of sub-optimal prescription of preoperative antiplatelets and statins to race and ethnicity-related disparities in major limb amputation
Authors: Kalbaugh Corey A. , Witrick Brian , Howard Kerry A. , Sivaraj Laksika Banu , McGinigle Katharine L. , Cykert Samuel , Robinson William P. , Lesko Catherine R.
Published: February 2023

Background

People undergoing revascularization for symptomatic peripheral artery disease (PAD) have a high incidence of major limb amputation in the year following their surgical procedure. The incidence of limb amputation is particularly high in patients from racial and ethnic minority groups. The purpose of our study was to investigate the role of sub-optimal prescription of preoperative antiplatelets and statins in producing disparities in risk of major amputation following revascularization for symptomatic PAD.

Methods

We used data from adult (≥18 years old) patients in the Vascular Quality Initiative (VQI) registry who underwent a revascularization procedure from 2011-2018. Patients were categorized as non-Hispanic Black, non-Hispanic White, and Hispanic. We estimated the crude probability of a patient being prescribed a preoperative antiplatelet and preoperative statin. We calculated one year risk incidence of amputation by prescription groups and by race/ethnicity. We estimated the amputation risk difference between race/ethnicity groups (the proportion of disparity) that could be eliminated under a hypothetical intervention where a pre-operative antiplatelet and statin was provided to all patients.

Results

Across 100,579 revascularizations recorded in the Vascular Quality Initiative, a vascular procedure-based registry in the United States and Canada, 1-year risk of amputation was 2.5% (95% CI: 2.4%,2.6%) in White patients, 5.3% (4.9%,5.6%) in Black patients and 5.3% (4.7%,5.9%) in Hispanic patients. Black (57.5%) and Hispanic patients (58.7%) were only slightly less likely than White patients (60.9%) to receive recommended antiplatelet and statin therapy prior to their procedures. However, the effect of antiplatelets and statins was greater in Black and Hispanic patients such that, had all patients received the appropriate guideline recommended medications, the estimated risk difference comparing Black to White patients would have reduced by 8.9% (−2.9%,21.9%) and the risk difference comparing Hispanic to White patients would have been reduced by 17.6% (−0.7%,38.6%).

Conclusions

Even though guideline-based care appeared evenly distributed by race/ethnicity, increasing access to such care may still decrease health care disparities in major limb amputation.
Prevalence of Elevated NT-proBNP and its Prognostic Value by Blood Pressure Treatment and Control- National Health and Nutrition Examination Survey, 1999-2004
Authors: Daya Natalie R. , McEvoy John W. , Christenson Robert , Tang Olive , Foti Kathryn , Juraschek Stephen P. , Selvin Elizabeth , Echouffo Tcheugui Justin B.
Published: February 2023

Background

The prognostic utility of NT-proBNP in the setting of hypertension has not been well-characterized in the general US adult population.

Methods

We measured NT-proBNP among adults aged 20 years who participated in the 1999-2004 National Health and Nutrition Examination Survey. In adults without a history of cardiovascular disease, we assessed the prevalence of elevated NT-pro-BNP by blood pressure (BP) treatment and control categories. We examined the extent to which NT-proBNP identifies participants at higher risk for mortality across BP treatment and control categories.

Results

The number of US adults without CVD with elevated NT-proBNP (≥125 pg/ml) was 6.2 million among those with untreated hypertension, 4.6 million among those with treated controlled hypertension, and 5.4 million among those with treated uncontrolled hypertension. After adjusting for age, sex, body mass index, and race/ethnicity, participants with treated controlled hypertension and elevated NT-proBNP had increased risk of all-cause mortality (HR 2.29, 95% CI 1.79, 2.95) and increased risk of cardiovascular mortality (HR 3.83, 95% CI: 2.34, 6.29), compared to those without hypertension and with low levels of NT-proBNP (<125 pg/ml). Among those on antihypertensive medication, those with SBP 130-139 mm Hg and elevated NT-proBNP had increased risk of all-cause mortality, compared to those with SBP<120 mm Hg and low levels of NT-proBNP.

Conclusions

Among a general population of adults free of cardiovascular disease, NT-proBNP can provide additional prognostic information within and across categories of BP. Measurement of NT-proBNP may have potential for clinical use to optimize hypertension treatment.
Characterization of the First Turtle Organoids: A Model for Investigating Unique Adaptations with Biomedical Potential
Authors: Zdyrski Christopher , Gabriel Vojtech , Gessler Thea B. , Ralston Abigail , Sifuentes-Romero Itzel , Kundu Debosmita , Honold Sydney , Wickham Hannah , Topping Nicholas E. , Sahoo Dipak Kumar , Bista Basanta , Tamplin Jeffrey , Ospina Oscar , Piñeyro Pablo , Meyerholz David K. , Allenspach Karin , Mochel Jonathan P. , Valenzuela Nicole
Published: February 2023

Painted turtles are remarkable for their well-developed freeze tolerance and associated resilience to hypoxia/anoxia, oxidative stress, and ability to supercool. They are, therefore, an ideal model for biomedical research on hypoxia-induced injuries (including strokes), tissue cooling during extensive surgeries, and organ cryopreservation. Yet, the seasonal reproduction and slow maturation of turtles hinder basic and applied biomedical research. To overcome these limitations, we developed the first adult stem cell-derived turtle hepatic organoids, which provide 3D self-assembled structures that mimic their original tissue and allow forin vitrotesting and experimentation without constantly harvesting donor tissue and screening offspring. Our pioneering work with turtles represents the first for this vertebrate Order and complements the only other organoid lines from non-avian reptiles, derived from snake venom glands. Here we report the isolation and characterization of hepatic organoids derived from painted, snapping, and spiny softshell turtles spanning ∼175 million years of evolution, with a subset being preserved in a biobank. Morphological and transcriptomics revealed organoid cells resembling cholangiocytes, which was then compared to the tissue of origin. Deriving turtle organoids from multiple species and life stages demonstrates that our techniques are broadly applicable to chelonians, permitting the development of functional genomic tools currently missing in most herpetological research. When combined with genetic editing, this platform will further support studies of genome-to-phenome mapping, gene function, genome architecture, and adaptive responses to climate change, among others. We discuss the unique abilities of turtles, including their overwintering potential, which has implications for ecological, evolutionary, and biomedical research.

SIGNIFICANCE

Here we developed the first turtle-derived organoid biobank from the liver of multiple chelonians with a subset characterized via histology, RNA sequencing transcriptomics, single-nuclei RNA sequencing, and transmission electron microscopy. Furthermore, we discuss the potential of the 3D organoid model to investigate unique physiological adaptations of turtles which could unravel the molecular mechanisms underlying their overwintering capacity, opening the door forin vitrobiomedical studies relevant to hepatic ischemia-reperfusion injury to organ cryopreservation, beyond fundamental ecology and evolution. This organoid biobank represents a novel resource for the scientific community to support research regarding the unique adaptations of this understudied Order of vertebrates.
Negative affect homogenizes and positive affect diversifies social memory consolidation across people
Authors: Iyer Siddhant , Collier Eleanor , Finn Emily S. , Meyer Meghan L.
Published: February 2023

We are often surprised when an interaction we remember positively is recalled by a peer negatively. What colors social memories with positive versus negative hues? We show that when resting after a social experience, individuals showing similar default network responding subsequently remember more negative information, while individuals showing idiosyncratic default network responding remember more positive information. Results were specific to rest after the social experience (as opposed to before or during the social experience, or rest after a nonsocial experience). The results provide novel neural evidence in support of the “broaden and build” theory of positive emotion, which posits that while negative affect confines, positive affect broadens idiosyncrasy in cognitive processing. For the first time, we identified post-encoding rest as a key moment and the default network as a key brain system in which negative affect homogenizes, whereas positive affect diversifies social memories.
High-throughput screening of functional neo-antigens and their specific TCRs via the Jurkat reporter system combined with droplet microfluidics
Authors: Li Yijian , Qi Jingyu , Liu Yang , Zheng Yuyu , Zhu Haibin , Zang Yupeng , Guan Xiangyu , Xie Sichong , Zhao Hongyan , Fu Yunyun , Xiang Haitao , Zhang Weicong , Chen Huanyi , Liu Huan , Zhao Yuntong , Feng Yu , Bu Fanyu , Liang Yanling , Li Yang , Xu Qumiao , He Ying , Sun Li , Liu Longqi , Gu Ying , Xu Xun , Hou Yong , Dong Xuan , Liu Ya
Published: February 2023

T-cell receptor (TCR)-engineered T cells can precisely recognize a broad repertoire of targets derived from both intracellular and surface proteins of tumor cells. TCR-T adoptive cell therapy has shown safety and promising efficacy in solid tumor immunotherapy. However, antigen-specific functional TCR screening is time-consuming and expensive, which limits its application clinically. Here, we developed a novel integrated antigen-TCR screening platform based on droplet microfluidics technology, enabling high-throughput peptide-major histocompatibility complex (pMHC) library-to-TCR library screening with high sensitivity and low background signal. We introduced DNA barcoding technology to label peptide antigen candidate-loaded antigen-presenting cells (APCs) and Jurkat reporter cells to check the specificity of pMHC-TCR candidates. Coupled with the next-generation sequencing pipeline, interpretation of the DNA barcodes and the gene expression level of the Jurkat T-cell activation pathway provided a clear peptide-MHC-TCR recognition relationship. Our proof-of-principle study demonstrates that the platform could achieve unbiased pMHC-TCR library-on-library screening, which is expected to be used in the cross-reactivity and off-target testing of candidate pMHC-TCR libraries in clinical applications.
Microwell-enhanced optical rapid antibiotic susceptibility testing of single bacteria
Authors: Rosłoń Ireneusz , Japaridze Aleksandre , Rodenhuis Stef , Hamoen Lieke , Ghatkesar Murali , Steeneken Peter , Dekker Cees , Alijani Farbod
Published: February 2023

Bacteria that are resistant to antibiotics present an increasing burden on healthcare. To address this emerging crisis, novel rapid Antibiotic Susceptibility Testing (AST) methods are eagerly needed. Here, we present an optical AST technique that can determine the bacterial viability within one hour down to a resolution of single bacteria. The method is based on measuring intensity fluctuations of a reflected laser focused on a bacterium in reflective microwells. Using numerical simulations, we show that both refraction and absorption of light by the bacterium contribute to the observed signal. By administering antibiotics that kill the bacteria, we show that the variance of the detected fluctuations vanishes within one hour, indicating the potential of this technique for rapid sensing of bacterial antibiotic susceptibility. We envisage the use of this method for massively parallelizable AST tests and fast detection of drug resistant pathogens.
Effects of different tradititonal and commercial aquafeed on proximate composition and growth performance of Grass carp (Ctenopharyngodon idella) reared in the semi-intensive composite culture system
Authors: Zulfiqar Talha , Sarwar Muhammad Sajjad , Ul Hassan Habib , Chaudhry Abdul Shakoor , Hafeez-ur-Rehman Muhammad
Published: February 2023

The objective of the research was to find the effects of numerous traditional and commercial aqua feed on proximate composition and growth performance of Grass carp (Ctenopharyngodon idella) reared in the semi intensive composite culture system. The aqua feeds of various companies (AMG, Supreme, Aqua, Star Floating, Hi-Pro and Punjab feed) used as commercial feed. Farm made feeds were Maize gluten and Rice polish. For confidentiality, these feeds were randomly assign code T1, T2, T3, T4, T5, T6, T7 and T8 which were only known to investigating staffs. There were two replicates for each treatment. In this research, significantly maximum growth was recorded in T3 as compared to other treatments. Lesser weight gain was observed in the T1 (270.30±60.5).The maximum body length (19.25±2.19) was found in T3. Similarly, the minimum body length (5.97±2.94) was seen in T2. FCR ratio (2.36±0.01) was recorded in T3. Simultaneously, FCR (1.86±0.002) was also recorded in T4 that is the perfect ratio for fish farmers. Higher SGR was found in T3 (1.62±0.05). Overall, T4 showed lesser SGR (1.05±0.001). T4 showed the higher Crude protein (28.66±0.24%). T3 showed more fat content level (5.46±0.33%) in the body. These outcomes also supported that enrichment in the dietary amount of protein and lipid level improve lipids content and crude protein in fish body weight. Thus, based on growth performance, survival and proximate composition, it is concluded that T3 & T4 may be recommended for commercial culture ofCtenopharyngodon idella.
A conserved gene regulatory network controls root epidermal cell patterning in superrosid species
Authors: Zhu Yan , Schiefelbein John
Published: February 2023

In superrosid species, root epidermal cells differentiate into root hair cells and non-hair cells. In some superrosids, the root hair cells and non-hair cells are distributed randomly (Type I pattern) and in others, they are arranged in a position-dependent manner (Type III pattern). The model plant Arabidopsis (Arabidopsis thaliana) adopts the Type III pattern, and the gene regulatory network (GRN) that controls this pattern has been defined. However, it is unclear whether the Type III pattern in other species is controlled by a similar GRN as in Arabidopsis, and it is not known how the different patterns evolved.

In this study, we analyzed superrosid speciesRhodiola rosea,Boehmeria nivea,andCucumis sativusfor their root epidermal cell patterns. Combining phylogenetics, transcriptomics, and cross-species complementation, we analyzed homologs of the Arabidopsis patterning genes from these species.

We identifiedR.roseaandB.niveaas Type III species andC.sativusas Type I species. We discovered substantial similarities in structure, expression, and function of Arabidopsis patterning gene homologs inR.roseaandB.nivea, and major changes inC.sativus.

We propose that in superrosids, diverse Type III species inherited the patterning GRN from a common ancestor, whereas Type I species arose by mutations in multiple lineages.
Cardinal v3 - a versatile open source software for mass spectrometry imaging analysis
Authors: Bemis Kylie Ariel , Föll Melanie Christine , Guo Dan , Lakkimsetty Sai Srikanth , Vitek Olga
Published: February 2023

Cardinal v3 is an open source software for reproducible analysis of mass spectrometry imaging experiments. A major update from its previous versions, Cardinal v3 supports most mass spectrometry imaging workflows. Its analytical capabilities include advanced data processing such as mass re-calibration, advanced statistical analyses such as single-ion segmentation and rough annotation-based classification, and memory-efficient analyses of large-scale multi-tissue experiments.
Proteome allocation is linked to transcriptional regulation through a modularized transcriptome
Authors: Patel Arjun , McGrosso Dominic , Hefner Ying , Campeau Anaamika , Sastry Anand V. , Maurya Svetlana , Rychel Kevin , Gonzalez David J , Palsson Bernhard O.
Published: February 2023

It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigated whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions could be modularized in the same way to reveal novel relationships between their compositions. We found that; 1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, 2) the modules in the proteome often represent combinations of modules from the transcriptome, 3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and 4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.
Targeting the MR1-MAIT Cell Axis Improves Vaccine Efficacy and Affords Protection against Viral Pathogens
Authors: Rashu Rasheduzzaman , Ninkov Marina , Wardell Christine M. , Benoit Jenna M. , Wang Nicole I. , D’Agostino Michael R. , Zhang Ali , Feng Emily , Saeedian Nasrin , Bell Gillian I. , Vahedi Fatemeh , Hess David A. , Troyer Ryan M. , Kang C. Yong , Ashkar Ali A. , Miller Matthew S. , Haeryfar S.M. Mansour
Published: February 2023

Mucosa-associated invariant T (MAIT) cells are MR1-restricted, innate-like T lymphocytes with tremendous antibacterial and immunomodulatory functions. MAIT cells also sense and respond to viral infections in an MR1-independent fashion. However, whether they can be directly targeted in immunization strategies against viral pathogens is unknown. We addressed this question in multiple wild-type and genetically altered but clinically relevant mouse strains using several vaccine platforms against influenza viruses, poxviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a riboflavin-based MR1 ligand of bacterial origin, can synergize with viral vaccines to expand MAIT cells in multiple tissues, reprogram them towards a pro-inflammatory MAIT1 phenotype, license them to bolster mainstream virus-specific CD8+T cell responses, and potentiate heterosubtypic antiviral protection. Repeated 5-OP-RU administration did not render MAIT cells anergic, thus allowing for its inclusion in prime-boost immunization protocols. Mechanistically, tissue MAIT cell accumulation was due to their robust proliferation, as opposed to altered migratory behavior, and required viral vaccine replication competency, Toll-like receptor 3 (TLR3) and cell-autonomous type I interferon receptor signaling. Furthermore, the observed phenomenon was manifest in young and old female and male mice, and could also be recapitulated in a human cell culture system in which peripheral blood mononuclear cells were exposed to replicating virions and 5-OP-RU. In conclusion, although viruses and virus-based vaccines are devoid of the riboflavin biosynthesis machinery that supplies MR1 ligands, targeting MR1 enhances the efficacy of vaccine-elicited antiviral immunity. We propose 5-OP-RU as a non-classic but potent and versatile vaccine adjuvant against respiratory viruses.
Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response
Authors: Sarkar Soumyadeep , Elliott Emily C. , Henry Hayden R. , Ludovico Ivo Díaz , Melchior John T. , Frazer-Abel Ashley , Webb-Robertson Bobbie-Jo , Davidson W. Sean , Holers V. Michael , Rewers Marian J. , Metz Thomas O. , Nakayasu Ernesto S.
Published: February 2023

Aims

Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development.

Methods

This systematic review was registered with Open Science Framework (DOI 10.17605/OSF.IO/N8TSA). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria.

Results

A total of 13 studies met our inclusion criteria, resulting in the identification of 251 unique proteins, with 27 (11%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found a subset of 3 proteins (C3, KNG1 & CFAH), 6 proteins (C3, C4A, APOA4, C4B, A2AP & BTD) and 7 proteins (C3, CLUS, APOA4, C6, A2AP, C1R & CFAI) have consistent regulation between multiple studies in samples from individuals at pre-seroconversion, post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development.

Conclusions

Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.
Metabolic sensor AMPK licenses CD103+dendritic cells to induce Treg responses
Authors: Patente Thiago A , Brombacher Eline C , Heieis Graham A , Pelgrom Leonard R , Zawistowska-Deniziak Anna , Otto Frank , Ozir-Fazalalikhan Arifa , van der Ham Alwin J , Guigas Bruno A , Barbuto José AM , Everts Bart
Published: February 2023

Dendritic cells (DCs) play a crucial role in promoting tolerance through priming of regulatory T cells (Treg). Several studies indicate DC tolerogenicity is dependent on catabolic metabolism. However, the role of AMP-activated Kinase (AMPK), a key energy and nutrient sensor driving catabolic metabolism, in this process is unclear. We found that human retinoic acid-induced tolerogenic CD103+DCs (RA-DCs) display increased AMPK signaling. Interestingly, RA-DCs, but not vitamin-D3- or dexamethasone-induced tolerogenic DCs, required AMPK for Treg induction. Mechanistically, AMPK underpinned RA-driven tolerogenicity by promoting RALDH activity in a FoxO3-dependent manner. Correspondingly, mice deficient for AMPK in DCs (CD11cΔAMPKα1) harbored reduced frequencies of intestinal CD103+CD11b+DCs with impaired RALDH activity. Importantly, upon infection with parasitic wormSchistosoma mansoni, that elicits strong Th2 and Treg responses, CD11cΔAMPKα1mice showed a defect in Treg accumulation and concomitantly, displayed an impaired ability to control Type 2 immunity-driven granulomatous inflammation against the parasite eggs. Together, our findings identify AMPK as a key regulator of tolerance by CD103+DCs.

Dendritic cells (DCs) are critical for inducing tolerance. However, how metabolic cues control their tolerogenicity is still poorly understood. Patente et al demonstrate that AMPK is crucial for Treg induction by retinoic acid-primed tolerogenic CD103+DCs.
Transgenerational exposure to deoxygenation and warming disrupts mate-detection inGammarus locusta
Authors: Pereira Beatriz P. , Neff Simon , Borges Francisco O. , Otjacques Eve , Barreto Guilherme , Ranucci Maddalena , Court Mélanie , Rosa Rui , Repolho Tiago , Paula José Ricardo
Published: February 2023

Ocean deoxygenation and warming have been shown to pose a growing threat to the health of marine organisms and ecosystems. Yet, the potential for acclimation and adaptation to these threats remains poorly understood. The aim of this study was to evaluate the effects of transgenerational exposure to reduced oxygen availability and elevated seawater temperature on the chemosensory-dependent mating mechanisms of male amphipodsGammarus locusta. After exposure, the number of individuals that reached adulthood (in F0 and F2) was gauged, and adult males from F0 and F1 were subjected to behavioral trials to assess their capacity of long-distance female cue detection through quantification of (i) response time; (ii) first direction of movement; (iii) activity rate and (iv) proportion of time spent in female scent cues. Ocean warming induced mortality (especially in F2), and reduced oxygen availability had adverse effects on each of the investigated behavioral traits, which were amplified when combined with elevated temperature. Still, when compared to F0, the F1 generation demonstrated more adaptability (i.e., higher activity rate and preference for female odors) to the combination of the two stressors, suggesting positive carry-over effects. Nevertheless, full recovery to control levels was not observed. Altogether, this study indicates that future scenarios of ocean deoxygenation and warming have the potential to disrupt chemosensory-dependent mate-detection in amphipods, but also suggests possible behavioral adaptations. We call for greater research efforts on long-term impacts of ocean change on the behavioral and physiological processes of benthic coastal communities.
The evolution of morphological castes under decoupled control
Authors: Flintham Lewis , Field Jeremy
Published: February 2023

Eusociality, where units that previously reproduced independently function as one entity, is of major interest in evolutionary biology. Obligate eusociality is characterised by morphologically differentiated castes and reduced conflict. We explore conditions under which morphological castes may arise in the Hymenoptera and factors constraining their evolution. Control over offspring morphology and behaviour seem likely to be decoupled. Provisioners (queens and workers) can influence offspring morphology directly through the nutrition they provide, while adult offspring control their own behaviour. Provisioners may, however, influence worker behaviour indirectly if offspring modify their behaviour in response to their morphology. If manipulation underlies helping, we should not see helping evolve before specialised worker morphology, yet empirical observations suggest that behavioural castes precede morphological castes. We use evolutionary invasion analyses to show how the evolution of a morphologically differentiated worker caste depends on the prior presence of a behavioural caste: specialist worker morphology will be mismatched with behaviour unless some offspring already choose to work. A mother’s certainty about her offspring’s behaviour is also critical – less certainty results in greater mismatch. We show how baseline worker productivity can affect the likelihood of a morphological trait being favoured by natural selection. We then show how under a decoupled control scenario, morphologically differentiated castes should be less and less likely to be lost as they become more specialised. We also suggest that for eusociality to be evolutionarily irreversible, workers must be unable to functionally replace reproductives and reproductives must be unable to reproduce without help from workers.
A cranial implant for stabilizing whole-cell patch-clamp recordings in behaving rodents
Authors: Dacre Joshua , Sanchez-Rivera Michelle , Schiemann Julia , Currie Stephen , Ammer Julian J. , Duguid Ian
Published: February 2023

Background

In vivopatch-clamp recording techniques provide access to the sub- and suprathreshold membrane potential dynamics of individual neurons during behavior. However, maintaining recording stability throughout behavior is a significant challenge, and while methods for head restraint are commonly used to enhance stability, behaviorally related brain movement relative to the skull can severely impact the success rate and duration of whole-cell patch-clamp recordings.

New method

We developed a low-cost, biocompatible, and 3D-printable cranial implant capable of locally stabilizing brain movement, while permitting equivalent access to the brain when compared to a conventional craniotomy.

Results

Experiments in head-restrained behaving mice demonstrate that the cranial implant can reliably reduce the amplitude and speed of brain displacements, significantly improving the success rate of recordings across repeated bouts of motor behavior.

Comparison with existing methods

Our solution offers an improvement on currently available strategies for brain stabilization. Due to its small size, the implant can be retrofitted to most in vivo electrophysiology recording setups, providing a low cost, easily implementable solution for increasing intracellular recording stability in vivo.

Conclusions

By facilitating stable whole-cell patch-clamp recordings in vivo, biocompatible 3D printed implants should accelerate the investigation of single neuron computations underlying behavior.
ABCH2 transporter in the first line of defense protects malaria vectors from pyrethroids
Authors: Kefi Mary , Balabanidou Vasileia , Sarafoglou Chara , Charamis Jason , Lycett Gareth , Ranson Hilary , Gouridis Giorgos , Vontas John
Published: February 2023

Contact insecticides are primarily used for the control ofAnophelesmalaria vectors. These chemicals penetrate mosquito legs and other appendages, the first barrier to reaching their neuronal targets. An ATP-Binding Cassette transporter from the H family (ABCH2) is highly expressed inAnopheles coluzziilegs, and further induced upon insecticide exposure. RNAi-mediated silencing of the ABCH2 caused a significant increase in deltamethrin mortality compared to control mosquitoes, coincident with a corresponding increase in14C-deltamethrin penetration. RT-qPCR analysis and immunolocalization revealed that ABCH2 is mainly localized in the legs and head appendages, and more specifically, the apical part of appendage epidermis, underneath the cuticle. To unravel the molecular mechanism underlying the role of ABCH2 in modulating pyrethroid toxicity, two hypotheses were investigated: An indirect role, based on the orthology with other insect ABCH transporters involved with lipid transport and deposition of CHC lipids inAnopheleslegs which may increase cuticle thickness, slowing down the penetration rate of deltamethrin; or the direct pumping of deltamethrin out of the organism. Evaluation of the leg cuticular hydrocarbon (CHC) content showed that this was not affected by ABCH2 silencing, indicating this transporter in is not associated with the transport of leg CHCs. Homology-based modeling suggested that the ABCH2 half-transporter adopts a physiological homodimeric state, in line with its ability to hydrolyze ATPin vitrowhen expressed on its own in insect cells. Docking analysis revealed a deltamethrin pocket on the homodimeric transporter. Furthermore, deltamethrin-induced ATP hydrolysis in ABCH2-expressing cell membranes, further supports that deltamethrin is indeed a ABCH2 substrate. Overall, our findings pinpoint ABCH2 as a key regulator of deltamethrin toxicity.
Two waves of evolution in the rodent pregnancy-specific glycoprotein (PSG) gene family lead to structurally diverse PSGs
Authors: Kammerer Robert , Zimmermann Wolfgang
Published: February 2023

The evolution of pregnancy-specific glycoproteins (PSGs) within the CEA gene family of primates correlates with the evolution of hemochorial placentation about 45 Myr ago. Thus, we hypothesized that hemochorial placentation with intimate contact between fetal cells and maternal immune cells favors the evolution and expansion of PSGs. With only a few exceptions, all rodents have hemochorial placentas thus the question arises whether PSGs evolved in most rodent genera.

Analyzing genomic data of 94 rodent species we could identify PSGs only in three families of the suborder Myomorpha (characteristic species in brackets) namely in the Muridae (mouse), Cricetidae (hamster) and Nesomyidae (giant pouched rat) families. No PSGs were detected in the suborders Anomaluromorpha (springhare), Castorimorpha (beaver), Hystricognatha (guinea pig) and Sciuromorpha (squirrel). Thus, PSGs evolved only recently in Myomorpha shortly upon their most recent common ancestor (MRCA) has coopted the retroviral genes syncytin-A and syncytin-B which enabled the evolution of the three-layered trophoblast. This may suggest that the evolution ofPsgsin rodents may have been favored by the challenge of the newly invented architecture of the maternal-fetal interface. In addition, a second hallmark of rodent PSG evolution seems to be the translocation of genes from the CEA gene family locus into a unique genomic region. Rodents without PSGs do not have any CEA-related genes in this locus. In contrast, rodent species in which PSGs evolved have lost ITAM-encoding CEACAM genes indicating that such a gene was translocated and thereby destroyed to form the new rodent PSG locus. This locus contains at least onePsgandCeacam9indicating that one of them was the founder gene of rodentPsgs. These genes are composed of various numbers of IgV-like domains (N domains) and one carboxy-terminal IgC-like domain of the A2-type. In a second wave of gene amplification in the PSG locus a gene encoding a protein composed of two N domain gave rise to four genes in mice (Ceacam11-14). In light of the divergent structure of PSGs in various mammalian species, we hypothesized that theCeacam11-14encode also functional PSGs and indeed we found that they are preferentially expressed by spongiotrophoblast cells, likePsggenes.
Comparing the transmission of carbapenemase-producing and extended-spectrum beta-lactamase-producingEscherichia colibetween broiler chickens
Authors: Dankittipong Natcha , Alderliesten Jesse B. , Van den Broek Jan , Dame-Korevaar M. Anita , Brouwer Michael S. M. , Velkers Francisca C. , Bossers Alex , de Vos Clazien J. , Wagenaar Jaap A. , Stegeman J. Arjan , Fischer Egil A. J.
Published: February 2023

The emergence of carbapenemase-producingEnterobacteriaceae(CPE) is a threat to public health, because of their resistance to clinically important carbapenem antibiotics. The emergence of CPE in meat-producing animals is particularly worrying because consumption of meat contaminated with resistant bacteria similar to CPE, such as extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, contributed to colonization in humans worldwide. Currently, no data on the transmission of CPE in livestock is available. We performed a transmission experiment to quantify the transmission of CPE between broilers to fill this knowledge gap and to compare the transmission rates of CPE and other antibiotic-resistantE. coli.

A total of 180 Ross 308 broiler chickens were distributed on the day of hatch (day 0) over 12 pens. On day 5, half of the chickens in each pen were orally inoculated with 5·102colony-forming units of CPE, ESBL, or chloramphenicol-resistantE. coli(catA1). Amoxicillin drinking water treatment was given twice daily in 6 of the 12 pens from days 2 to 6 to evaluate the effect of antibiotic treatment on the transmission rates. Cloacal swabs of all animals were taken to determine the number of infectious broilers. We used a Bayesian hierarchical model to quantify the transmission of theE. colistrains.E. colican survive in the environment and serve as a reservoir. Therefore, the susceptible-infectious transmission model was adapted to account for the transmission of resistant bacteria from the environment. In addition, the caecal microbiome was analyzed on day 5 and at the end of the experiment on day 14 to assess the relationship between the caecal microbiome and the transmission rates.

The transmission rates of CPE were 52 – 68 per cent lower compared to ESBL and catA1, but it is not clear if these differences were caused by differences between the resistance genes or between theE. colistrains. Differences between the groups in transmission rates and microbiome diversity did not correspond to each other, indicating that differences in transmission rates were probably not caused by major differences in the community structure in the caecal microbiome. Amoxicillin treatment from day 2 to 6 increased the transmission rate more than three-fold in all inoculums. It also increased alpha-diversity compared to untreated animals on day 5, but not on day 14, suggesting only a temporary effect.

Future research could incorporate more complex transmission models with different species of resistant bacteria into the Bayesian hierarchical model.
Alpha-synuclein oligomers activate NFAT proteins modulating synaptic homeostasis and apoptosis
Authors: Sant’Anna Ricardo , Robbs Bruno K , de Freitas Júlia Araújo , dos Santos Patrícia Pires , König Annekatrin , Outeiro Tiago Fleming , Foguel Debora
Published: February 2023

Soluble oligomeric forms of alpha-synuclein (aSyn-O) are believed to be one of the main toxic species in Parkinson’s disease (PD) leading to degeneration. aSyn-O can induce Ca2+influx, over activating downstream pathways leading to PD phenotype. Calcineurin (CN), a phosphatase regulated by Ca2+levels, activates NFAT transcription factors that are involved in the regulation of neuronal plasticity, growth and survival. Here, we investigate NFAT’s role in neuronal degeneration induced by aSyn-O. aSyn-O are toxic to neurons leading to cell death, loss of neuron ramification and reduction of synaptic proteins which are reversed by CN inhibition with ciclosporin-A or VIVIT, a NFAT specific inhibitor. aSyn-O induce NFAT nuclear translocation and transactivation. We found that aSyn-O modulates the gene involved in the maintenance of synapses, synapsin 1 (Syn 1). Syn1 mRNA and protein and synapticpunctaare drastically reduced in cells treated with aSyn-O which are reversed by NFAT inhibition. For the first time a direct role of NFAT in aSyn-O-induced toxicity andSyn1gene regulation was demonstrated, enlarging our understanding of the pathways underpinnings synucleinopathies.
Observation of coordinated cotranscriptional RNA folding events
Authors: Szyjka Courtney E. , Strobel Eric J.
Published: February 2023

RNA begins to fold as it is transcribed by an RNA polymerase. Consequently, RNA folding is constrained by the direction and rate of transcription. Understanding how RNA folds into secondary and tertiary structures therefore requires methods for determining the structure of cotranscriptional folding intermediates. Cotranscriptional RNA chemical probing methods accomplish this by systematically probing the structure of nascent RNA that is displayed from RNA polymerase. Here, we have developed a concise, high-resolution cotranscriptional RNA chemical probing procedure calledTranscriptionElongationComplex RNA structureprobing-Multilength (TECprobe-ML). We validated TECprobe-ML by replicating and extending previous analyses of ZTP and fluoride riboswitch folding, and mapped the folding pathway of a ppGpp-sensing riboswitch. In each system, TECprobe-ML identified coordinated cotranscriptional folding events that mediate transcription antitermination. Our findings establish TECprobe-ML as an accessible method for mapping cotranscriptional RNA folding pathways.
Pathways to cultural adaptation: the coevolution of cumulative culture and social networks
Authors: Smolla Marco , Akçay Erol
Published: February 2023

Humans have adapted to an immense array of ecologies by accumulating culturally transmitted knowledge and skills. Culture accumulates in at least two ways: via more distinct cultural traits, or via improvements of existing cultural trait. A trade-off is expected between these owing to the fact that social learning opportunities are finite and social learning often requires multiple exposures. Furthermore, what kind of culture accumulates depends on, and coevolves with, the social structure of societies. Here we show that the coevolution of social networks for learning and cumulative culture results in two distinct pathways to cultural adaptation: highly connected populations with high proficiency but low cultural trait diversity vs. sparsely connected populations with low proficiency but more cultural trait diversity. Importantly, we show there is a general conflict between group-level payoffs, which is maximised in highly connected groups that attain high proficiency, and individual level selection, which favours disconnection. This conflict emerges from the interaction of social learning with population structure and causes populations to cycle between the two cultural and network states. The same conflict creates a paradox where improving individual innovation rates lowers the payoffs of groups. Finally, we explore how populations navigate these two pathways in heterogeneous and changing environments, and show that high heterogeneity in payoffs and slow rate of environmental change favours high proficiency, while fast rate of environmental change favours more trait diversity. We also find that the proficiency pathway to cultural adaptation is favoured with increased population size, but only in slow changing environments. Our results uncover previously unrecognised trade-offs and tensions in the coevolutionary dynamics of cumulative culture and social structure, with broad implications for human social evolution.
Internalization-Responsive Nano-PLGA For Image-Guided Photodynamic Therapy Against HER2-Positive Breast Cancer
Authors: Sogomonyan Anna S. , Deyev Sergey M. , Shipunova Victoria O.
Published: February 2023

Oncotheranostic nanoagents are powerful artificial tools that significantly outperform traditional antitumor therapies. Among the wide variety of nanoagents, polymer nanoparticles have proven to be one of the most successful candidates for translation into clinical practice. Here we developed an oncotheranostic platform that is based on poly(lactic-co-glycolic acid) nanoparticles and possesses red/green light dual-activated diagnostic/therapeutic properties for targeted photodynamic therapy of HER2-positive aggressive breast cancer. PLGA nanoparticles were loaded with a red light-activated dye Nile Blue with pronounced solvatochromic properties for diagnostic applications and with a green light-activated photodynamic sensitizer Rose Bengal for photodynamic therapy. Targeted delivery was ensured by the non-covalent decoration of nanoparticles with anti-HER2 antibodies, which can be readily adapted for large-scale biotechnological production.In vitroandin vivostudies proved the effectiveness of red light-mediated HER2-specific imaging and green light-induced cytotoxicity of anti-HER2 PLGA. Interestingly, these particles fluoresced only after cellular internalization, which minimizes background signals inside the organism, thus facilitating real-time diagnostics. The particles allowed efficient and selective visualization of the HER2-positive primary tumor node and metastases spread and led to complete remission in BALB/c Nu/Nu mice with the HER2-positive xenografts after a single session of photodynamic therapy.
Zebra finches use brightness cues for gap selection in flight
Authors: Borsier Emma , Taylor Graham K.
Published: February 2023

Flying animals that are adapted to life in cluttered environments require effective and robust guidance mechanisms to avoid collisions. Birds and insects use optic flow cues to avoid obstacles when flying, but these are only generated by self-motion and are likely to be used in conjunction with other cues such as visual contrast between foreground and background objects. Orchid bees use a strategy based on relative brightness to find clear paths through dense environments. To investigate the possibility that birds use a similar strategy, we presented zebra finchesTaeniopygia guttatawith symmetric or asymmetric brightness distributions behind the aperture of a tunnel and recorded their flight through it. The background brightness conditions influenced both the birds’ decision to enter the tunnel and their flight direction upon exit. Zebra finches were more likely to initiate flight through the tunnel if they could see a bright background through its aperture and were more likely to fly to the bright side on exiting the tunnel. We found no evidence of a centring response during gap negotiation; instead, the zebra finches entered the tunnel by turning tightly around its near edge. These results hint at a possible pre-planning of the trajectories before the onset of flight.