bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of duplex real time PCR for quick detection of Cryptosporidia in goats
Authors: Sharma Atul Kumar , Gururaj K. , Sharma Rama , Goel Anjana , Paul Souvik , Sharma Dinesh Kumar
Published: February 2022

Cryptosporidium spp. is the most important foodborne and waterborne pathogens and the leading cause of mortality from foodborne and waterborne gastrointestinal disease. In neonates of domestic animals it is associated with consistent diarrhoea and dehydration. Cryptosporidium infection begins with the ingestion of sporulated oocytes disseminated by carrier animals that consistently contaminate the environment. Many diagnostic tests are available including microscopy, antigen trap ELISA, but none of the diagnostic tests available currently cannot differentiate between active and passive infection in the host. In the current study, to address this challenge an mRNA based duplex TaqMan® probe PCR (dRT-qPCR) was developed to target the Cryptosporidium oocyst wall protein (COWP) gene and 18ssu rRNA gene in a single tube that can detect metabolically active Cryptosporidial oocysts. The mRNA transcripts are the direct indicator of any actively replicating cell and it will help decipher the active stages of its lifecycle in host. This diagnostic assay was standardized by computing transcript copy number-based limit of detection. For COWP and 188ssu rRNA genes the limit of detection was 7.08×1004 and 5.95×1005 respectively. During active infections the oocyst wall protein will be active and so its COWP gene transcripts will act as marker for active infection. While transcripts for 18SSU rRNA are constitutively expressing in Cryptosporidial life cycle. This current diagnostic assay will be a quantitative marker that will help assess active stages of Cryptosporidium infection in neonates. The disease dynamics will help better understand to formulate the control strategies and contain infection among the healthy animals.

Importance

Cryptosporidiosis is an important neonatal disease affecting goats causing diarrhoea, dehydration and stunted growth. For diagnosing this condition, many diagnostic tests are available including microscopy, immunological tests, but none of the diagnostic tests available currently can differentiate between active and passive infection in the host. The mRNA transcripts are the direct indicator of any actively replicating cell and especially in intracellular parasites it will help decipher the infective stages of a lifecycle in the host, and hence the test was developed in a reverse transcriptional format in a duplex mode. The currently developed diagnostic assay for cryptosporidiosis was evaluated for sensitivity using Limit of detection (LOD). This diagnostic test will act as a quantitative marker to aid in detecting active stages of Cryptosporidium infection in neonatal goats and will eventually lead to better control strategies for managing cryptosporidial infections in the future.
Booster protection against Omicron infection in a highly vaccinated cohort
Authors: Tai Caroline G. , Maragakis Lisa L. , Connolly Sarah , DiFiori John , Sims Leroy , Adams Eleanor , Anderson Deverick J. , Merson Michael H. , Ho David D. , Grad Yonatan , Mack Christina DeFilippo
Published: February 2022

Background

Evaluation of COVID-19 vaccine booster effectiveness is essential as new variants of SARS-CoV-2 emerge. Data support the effectiveness of boosters in preventing severe disease and hospitalization; however, the real-world impact on reducing incident SARS-CoV-2 infections across specific variants is not yet clear.

Objectives

Assess the impact of COVID-19 boosters on protection against SARS-CoV-2 infection in a real-world setting from a highly vaccinated (99%) population curated from a linked database with test results, vaccination history, patient demographics, and genomic sequencing information from the National Basketball Association (NBA).

Methods

In this population, 1,613 fully vaccinated staff and players (median age 34.5 years, 88% male) who tested at least once between 1 December 2021 and 5 January 2022, were analyzed. Individuals were tested at the time of reporting any symptom, regardless of severity, after known exposure per self-report or contact tracing and/or during enhanced surveillance. Boosted individuals (n=1260) were compared to fully vaccinated and booster eligible individuals (n=162), defined as 2 months post-JNJ-78436735 or 5-months post-second dose of mRNA vaccine. Individuals not yet eligible for a booster and those who recovered from COVID-19 between 1 November and 30 November, 2021 (n=25) were examined in secondary analyses but excluded from the primary comparison. Individuals who were not fully vaccinated (n=27) or who received a booster within 14 days during or prior to the observation period (n=916) were excluded.

Results

In this closely monitored population, fully vaccinated booster-eligible individuals were 2.6 times more likely (RR = 2.6, 95% CI: 2.2 to 3.0, p<0.0001) to have a confirmed COVID-19 infection than boosted individuals. Secondary analysis including non-boosted individuals with recent vaccination or recent SARS-CoV-2 infection found that non-boosted individuals were at greater risk of infection compared with boosted individuals (RR = 2.1, 95% CI: 1.8 to 2.4, p<0.001). Results were similar when stratified by primary vaccination type with overlapping confidence intervals. No hospitalizations or deaths were observed in this cohort. Genetic sequencing confirmed 93% of infections to be Omicron (among n=330 sequenced).

Conclusions

These results highlight the protective benefit of boosters against incident SARS-CoV-19 infection, not only for severe symptoms and death. Assessment of booster effectiveness remains vital for COVID-19 vaccines as new variants of SARS-CoV-2 emerge, as there is still uncertainty around performance in real-world settings. These data are needed to convince the general public that boosters remain effective at preventing in the spread of COVID-19.
Influence of Lamina Vastoadductoria Dissection on the Outcomes of Femoral Artery Extensive Lesion Stenting: A Pilot Randomised Investigation
Authors: Karpenko Andrey A. , Rabtsun Artem A. , Popova Irina V. , Saaya Shoraan B. , Gostev Alexandr A. , Ignatenko Pavel V. , Starodubtsev Vladimir B. , Cheban Alexey V.
Published: February 2022

Objective

Aim of the study was to improve the immediate and long-term results of stenting of the superficial femoral artery in extended lesions with the changing of the biomechanics of SFA and of the first portion of the popliteal artery.

Methods

Pilot randomized prospective single-center study were included 70 patients. Patients were randomized into two groups in 1×1 format for 35 people using the envelope method. Self-expanding bare metal stents were used in all cases. At the first group standard revascularization procedures with SFA stenting were performed; in the second group, the superficial femoral artery stenting was supplemented with fasciotomy in the Hunter’s canal with the superficial femoral artery intersection. The total observation period was 2 years. During the observation period an assessment of the clinical symptoms of the lower extremities, measurement of the ankle-brachial index and ultrasound duplex scanning of the operated segment were performed.

Results

All procedures in both groups were successfully performed. Primary patency through 24 months was 28.5% (10 of 35) in group 1 and 60% (21 of 35) in group 2 (p=0,015).

Conclusions

Changing the biomechanical properties of the distal of the superficial femoral artery segment and of the first portion of the popliteal artery is safe and contributes to the primary patency improvement during the stenting of extended of the superficial femoral artery lesions compared to standard SFA stenting. Dissection of the lamina vastoadductoria with transection of the collateral branches of the knee joint network reduces frequent and severe damages of stents after the stenting of the superficial femoral artery extended lesion.

According to the frequency of complications in the early and mid-term postoperative period, limb salvage, mortality and the secondary patency rates, the new method is comparable with standard of the superficial femoral artery stenting.
NeuroEPO improves cognition in Parkinson’s disease. Preliminary report
Authors: Bringas Vega Maria L. , Shengnan Liu , Leon Yanetsy Rodriguez , Rodriguez Ania Mesa , Fernandez Enrique Casabona , Llano Marite Garcia , Gonzalez Daniel Amaro , Obaya Teresita Rodriguez , Ruiz Leslie Perez , Teste Iliana Sosa , Razzaq Fuleah A. , Jahanshahi Marjan , Ibañez Ivonne Pedroso , Valdes-Sosa Pedro
Published: February 2022

Background

Cognitive impairment is a feature of Parkinson’s Disease (PD) from the early stages, but currently, no treatment for cognitive deficits in PD is available. Erythropoietin (EPO) has been studied for its potential neuroprotective properties in neurologic disorders with a beneficial action on cognition.

Objective

To evaluate if NeuroEPO, a new formulation of EPO with low content of sialic acid, improves the cognitive function in PD patients.

Methods

A double-blind, randomized, placebo-controlled physician lead trial was conducted. The sample was composed of 26 PD patients (HY stages I-II), where 15 received intranasal NeuroEPO for 5 weeks, and another age and gender-matched 11 patients were randomly assigned to the Placebo. All the samples received 9 months of intensive NeuroEPO treatment during a post-trial. The cognitive functions were assessed using a comprehensive neuropsychological battery before, one week, and 6 months after the first intervention and one week after a 9months post-trial. The effects of NeuroEPO were evaluated using a multivariate linear mixed-effects model using a latent variable for cognition instead of the raw neuropsychological scores.

Results

A significant and direct effect of the Dose of NeuroEPO (p=0.00003) was found on cognitive performance with a strong positive influence of educational level (p=0.0032) and negative impact of age (p=0.0063).

Conclusions

These preliminary results showed a positive effect of NeuroEPO on cognition in PD patients with better benefit for younger and higher educated patients.
Pathway-based Rare Variant Burden Analysis Identifies a Role for the Complement System in an Extreme Phenotype of Sepsis with Coagulopathy
Authors: Bendapudi Pavan K. , Nazeen Sumaiya , Ryu Justine , Söylemez Onuralp , Rouaisnel Betty , Colling Meaghan , Pasko Bryce , Robbins Alissa , Bouzinier Michael , Tomczak Lindsay , Collier Lindsay , Ram Sanjay , Toth-Petroczy Agnes , Krier Joel , Fieg Elizabeth , Dzik Walter H. , Hudspeth James C. , Pozdnyakova Olga , Nardi Valentina , Maas Richard , Sunyaev Shamil , Losman Julie-Aurore
Published: February 2022

Extreme disease phenotypes have the potential to provide key pathophysiologic insights, but the study of these conditions is challenging due to their rarity and the limited statistical power of existing methods. Herein, we apply a novel pathway-based approach to investigate the role of rare genomic variants in infectious purpura fulminans (PF)1,2, an extreme phenotype of sepsis with hyperinflammation and coagulopathy for which the role of inherited risk factors is currently unknown. Using whole exome sequencing, we found a significantly increased burden of rare, putatively function-altering coding variants in the complement system in patients with PF compared to unselected patients with sepsis (p-value = 0.01). Functional characterization of a subset of PF-associated variants in integrin complement receptors 3 and 4 (CR3 and CR4) revealed that they exhibit a pro-inflammatory phenotype. Our results suggest that rare inherited defects in the complement system predispose individuals to the maladaptive hyperinflammatory response that characterizes severe sepsis.
Oral health and its association with self-rated health in Colombian community-dwelling older adults
Authors: Venegas-Sanabria Luis Carlos , Moreno-Echeverry María Manuela , Borda Miguel German , Chavarro-Carvajal Diego Andrés , Cano-Gutierrez Carlos Alberto
Published: February 2022

Objective

Determine the association between different parameters of oral health and the self-rated health (SRH) in Colombian community-dwelling older adults.

Methods

This is a secondary analysis of the SABE-Colombia study performed in 2015. The dependent variable was defined as the SRH status assessed by the question “Compared with other people your age: Do you consider your health status to be: better, equal or worse?” The oral health parameters were edentulism, the GOHAI score and the use of dental prosthesis. Three multivariable logistic regression was performed compared better vs. worse, better vs. equal and equal vs. worse health status, adjusted by socio-demographic variables, comorbidities, and geriatric syndromes.

Results

After the exclusion of missing data, 18180 persons were included in the final analysis. 10.6, 37.6 and 51.6% persons reported worse, equal and better SRH, respectively. The worse SRH group had a higher proportion of > 80 years old persons, dependence, cognitive impairment, and depressive symptoms. The presence of edentulism and a low score of GOHAI were more frequent in the worse SHR group. After the multivariable logistic regression, all parameters of oral health status were associated with a worse SRH.

Conclusion

In our study, the oral health parameters were associated with self-rated health status. This result supports the inclusion of oral health in comprehensive geriatric assessment.
Empirical Frequency Bound Derivation Reveals Prominent Mid-Frontal Alpha Associated with Neurosensory Dysfunction in Fragile X Syndrome
Authors: Pedapati Ernest V , Sweeney John A. , Schmitt Lauren M. , Ethridge Lauren E. , Miyakoshi Makoto , Liu Rui , Smith Elizabeth , Shaffer Rebecca C. , Wu Steve W. , Gilbert Donald L. , Horn Paul S. , Buckley Aaron , Erickson Craig A.
Published: February 2022

The FMR1 gene is inactive in Fragile X syndrome (FXS), resulting in low levels of FMRP and consequent neurochemical, synaptic and local circuit neurophysiological alterations in the fmr1 KO mouse. In FXS patients, electrophysiological studies of have demonstrated a marked reduction in global alpha activity and regional increases in gamma oscillations that have been associated with intellectual disability and sensory hypersensitivity. Since alpha activity is associated with thalamocortical function that has widely distributed modulatory effects on neocortical excitability, insight into alpha physiology may provide insight into systems-level disease mechanisms. Herein, we took a data driven approach to clarify the temporal and spatial properties of alpha and theta activity in participants with FXS. High-resolution resting-state EEG data was collected from participants affected by FXS (n=65) and matched controls (n=70). We used a multivariate technique to empirically classify neural oscillatory bands based on their coherent spatiotemporal patterns. Participants with FXS demonstrated: 1) a redistribution of lower-frequency boundaries indicating a “slower” dominant alpha rhythm, 2) an anteriorization of alpha frequency activity, and 3) a correlation of increased individualized alpha power measurements with auditory neurosensory dysfunction. These findings suggest an important role for alterations in thalamocortical physiology for the well-established neocortical hyper-excitability in FXS, and thus a role for neural systems level disruption to cortical hyperexcitability that has been studied primarily at the local circuit level in mouse model research.
Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system
Authors: Li Tao , Morselli Marco , Su Trent , Mulugeta Million , Larauche Muriel , Pellegrini Matteo , Taché Yvette , Yuan Pu-Qing
Published: February 2022

The porcine gut is increasingly regarded as a useful translational model. The enteric nerve system (ENS) in the colon coordinates diverse functions. However, knowledge of the molecular profiling of porcine ENS and its similarity to that of human is limited. We identified the distinct transcriptional programs associated with functional characteristics between inner submucosal and myenteric ganglia (ISG, MG) in porcine proximal and distal colon (p-pC, p-dC) using bulk RNA sequencing (RNA-seq) and single-cell RNA-seq. Comparative transcriptomics of MG in corresponding colonic regions of porcine and human revealed highly conserved programs existing in p-pC and p-dC, which explained >90% of their transcriptomic responses to vagal nerve stimulation (VNS), suggesting that p-pC and p-dC could serve as predictors in translational studies. The conserved programs specific for inflammatory modulation were displayed in porcine with VNS. This study provides a valuable transcriptomic resource for understanding of human colonic functions and neuromodulation using porcine model.
A new paradigm of multiheme cytochrome evolution by grafting and pruning protein modules
Authors: Soares Ricardo , Costa Nazua L. , Paquete Catarina M. , Andreini Claudia , Louro Ricardo O.
Published: February 2022

Multiheme cytochromes play key roles in diverse biogeochemical cycles, but understanding the origin and evolution of these proteins is a challenge due to their ancient origin and complex structure. Up until now, the evolution of multiheme cytochromes composed by multiple redox modules in a single polypeptide chain was proposed to occur by gene fusion events. In this context, the pentaheme nitrite reductase NrfA and the tetraheme cytochromec554were previously proposed to be at the origin of the extant octa- and nonaheme cytochromescinvolved in metabolic pathways that contribute to the nitrogen, sulfur and iron biogeochemical cycles by a gene fusion event. Here, we combine structural and character-based phylogenetic analysis with an unbiased root placement method to refine the evolutionary relationships between these multiheme cytochromes. The evidence show that NrfA and cytochromec554belong to different clades, which suggests that these two multiheme cytochromes are products of truncation of ancestral octaheme cytochromes related to extant ONR and MccA, respectively. From our phylogenetic analysis, the last common ancestor is predicted to be an octaheme cytochrome with nitrite reduction ability. Evolution from this octaheme framework led to the great diversity of extant multiheme cytochromes analised here by pruning and grafting of protein modules and hemes. By shedding light into the evolution of multiheme cytochromes that intervene in different biogeochemical cycles, this work contributes to our understanding about the interplay between biology and geochemistry across large time scales in the history of Earth.
Resource requirements for ecotoxicity testing: A comparison of traditional and new approach methods
Authors: Mittal Krittika , Crump Doug , Head Jessica A. , Hecker Markus , Hickey Gordon , Maguire Steve , Hogan Natacha , Xia Jianguo , Basu Niladri
Published: February 2022

Toxicity testing is under transformation as it aims to harness the potential of New Approach Methods (NAMs) as alternative test methods that may be less resource intensive (i.e., fewer animals, cheaper costs, quicker assays) than traditional approaches while also providing more data and information. While many stakeholders are of the opinion that this unfolding transformation holds significant promise as a more efficient and ethical way forward, few studies have compared the resources required for NAMs versus those needed for traditional animal-based toxicity tests, particularly in the field of ecotoxicology. The objective was to compare resources needed for traditional animal-based ecotoxicity tests versus alternative tests using emergent NAMs. From a bibliometric review, we estimate that traditional tests for a single chemical cost $118,000 USD, require 135 animals, and take 8 weeks. In comparison, alternative tests cost $2,600, require 20 animals (or none), and take up to 4 weeks to test 16 (to potentially hundreds of) chemicals. Based on our analysis we conclude that NAMs in ecotoxicology can be more advantageous than traditional methods in terms of resources required (i.e., monetary costs, number of animals needed, and testing times). We note, however, that the evidence underpinning these conclusions is relatively sparse. Moving forward, groups developing and applying NAMs should provide more detailed accounts of the resources required. In addition, there is also a need for carefully designed case studies that demonstrate the domain of applicability of NAMs (and make comparisons to traditional tests) to ultimately build confidence among the user community.
Scrub encroachment promotes biodiversity in wetland restoration under eutrophic conditions
Authors: Brunbjerg Ane Kirstine , Fløjgaard Camilla , Frøslev Tobias Guldberg , Andersen Dagmar Kappel , Bruun Hans Henrik , Dalby Lars , Goldberg Irina , Lehmann Louise Juhl , Moeslund Jesper Erenskjold , Ejrnæs Rasmus
Published: February 2022

Wetlands are important habitats, often threatened by drainage, eutrophication and suppression of ungulate grazing. In many countries, considerable resources are spent combatting scrub encroachment. Here, we hypothesize that encroachment may benefit biodiversity – especially under eutrophic conditions where asymmetric competition among plants compromises conservation targets.

We studied the effects of scrub cover, nutrient levels and soil moisture on richness of vascular plants, bryophytes, soil fungi and microbes in open and overgrown wetlands. We also tested the effect of encroachment, eutrophication and soil moisture on indicators of conservation value (red-listed species, indicator species and uniqueness).

Plant and bryophyte species richness peaked at low soil fertility, whereas soil fertility promoted soil microbes. Soil fungi responded negatively to increasing soil moisture. Lidar-derived variables reflecting degree of scrub cover had predominantly positive effects on species richness measures.

Conservation value indicators had a negative relationship to soil fertility and a positive to encroachment. For plant indicator species, the negative effect of high nutrient levels was offset by encroachment, supporting our hypothesis of competitive release under shade. The positive effect of soil moisture on indicator species was strong in open habitats only.

Nutrient poor mires and meadows host many rare species and require conservation management by grazing and natural hydrology. On former arable lands, where restoration of infertile conditions is unfeasible, we recommend rewilding with opportunities for encroachment towards semi-open willow scrub and swamp forest, with the prospect of high species richness in bryophytes, fungi and soil microbes and competitive release in the herb layer.
Comparing algorithms for assessing upper limb use with inertial measurement units
Authors: Subash Tanya , David Ann , ReetaJanetSurekha StephenSukumaran , Gayathri Sankaralingam , Samuelkamaleshkumar Selvaraj , Magimairaj Henry Prakash , Malesevic Nebojsa , Antfolk Christian , Varadhan SKM , Melendez-Calderon Alejandro , Balasubramanian Sivakumar
Published: February 2022

The various existing measures to quantify upper limb use from wrist-worn inertial measurement units (IMU) can be grouped into three categories: (a) Thresholded activity counting, (b) Gross movement score and (c) machine learning. While machine learning algorithms are a promising approach to detect upper limb use, there is currently no knowledge of the information used by these methods, and the data-related factors that influence their performance. A comparison of existing methods was carried out using data from a previous study which was collected from 10 unimpaired and 5 hemiparetic subjects, with annotation to identify periods of functional and non-functional upper limb use. Intra-subject random forest machine learning measures were found to classify upper limb use more accurately than other measures. The random forest measure uses information about the orientation and the amount of movement of the forearm to detect upper limb use. The types of movements and the proportion of functional data included in training/testing set influences the performance of machine learning measures. This study presents the first step towards understanding and optimizing machine learning methods for upper limb use assessment using wearable sensors.
A novel missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish
Authors: Ellis Jillian L. , Evason Kimberley J. , Zhang Changwen , Fourman Makenzie N. , Liu Jiandong , Ninov Nikolay , Delous Marion , Vanhollebeke Benoit , Fiddes Ian , Otis Jessica P. , Houvras Yariv , Farber Steven A. , Xu Xiaolei , Lin Xueying , Stainier Didier Y.R. , Yin Chunyue
Published: February 2022

Hepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality. Previous studies of patients and rodent models have associated hepatic cyst formation with increased proliferation and fluid secretion in cholangiocytes, which are partially due to impaired primary cilia. Congenital hepatic cysts are thought to originate from faulty bile duct development, but the underlying mechanisms are not fully understood. In a forward genetic screen, we identified a zebrafish mutant that develops hepatic cysts during larval stages. Cyst formation in these mutants is not due to changes in biliary cell proliferation, bile secretion, or impairment of primary cilia. Instead, time-lapse live imaging data showed that the mutant biliary cells failed to form interconnecting bile ducts because of defects in motility and protrusive activity. Accordingly, immunostaining revealed an excessive and disorganized actin and microtubule cytoskeleton in the mutant biliary cells. By whole-genome sequencing, we determined that the cystic phenotype in the mutant was caused by a missense mutation in the furinb gene which encodes a proprotein convertase. The mutation alters Furinb localization and causes endoplasmic reticulum (ER) stress. The cystic phenotype could be suppressed by treatment with the ER stress inhibitor 4-phenylbutyric acid and exacerbated by treatment with the ER stress inducer tunicamycin. The mutant livers also exhibited increased mTOR signaling and treatment with the mTOR inhibitor rapamycin partially blocked cyst formation by reducing ER stress. Our study has established a novel vertebrate model for studying hepatic cystogenesis and illustrated the role of ER stress in the disease pathogenesis.
Identification of HIV-Reservoir Cells with Reduced Susceptibility to Antibody-Dependent Immune Response
Authors: Astorga-Gamaza Antonio , Grau-Expósito Judith , Burgos Joaquín , Navarro Jordi , Curran Adrià , Planas Bibiana , Suanzes Paula , Falcó Vicenç , Genescà Meritxell , Buzon Maria J.
Published: February 2022

HIV establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy, but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.

Graphical Abstract
Active exploration of a novel environment drives the activation of the hippocampus-amygdala complex of domestic chicks
Authors: Morandi-Raikova Anastasia , Mayer Uwe
Published: February 2022

In birds, like in mammals, the hippocampus critically mediates spatial navigation through the formation of a spatial map. This study investigates the impact of active exploration of a novel environment on the hippocampus of young domestic chicks, during formation of a new spatial map. Chicks that were free to actively explore the novel environment exhibited a significantly higher neural activation (measured by c-Fos expression), compared to those that passively observed the novel environment from a restricted area. The difference was limited to the anterior and the dorsolateral parts of the intermediate hippocampus. Furthermore, the nucleus taeniae of the amygdala showed a higher c-Fos expression in the active exploration group than the passive observation group. In both brain regions, brain activation correlated with the number of locations that chicks visited during the test. This suggest that the increase of c-Fos expression in the hippocampus is related to increased firing rates of spatially coding neurons. Furthermore, our study indicates a functional linkage of the hippocampus and nucleus taeniae of the amygdala in processing spatial information. Overall, with the present study, we confirm that, in birds like in mammals, exploration of novel environments activates hippocampus, which is likely related to the formation of new spatial representations.

Summary statement

Active exploration of a novel environment induces stronger activation of hippocampus and taeniae of domestic chicks than pure visual, passive exploration from a restricted area.
Bimodal breeding phenology in the Parsley Frog Pelodytes punctatus as a bet-hedging strategy in an unpredictable environment despite strong priority effects
Authors: Jourdan-Pineau Hélène , Crochet Pierre-André , David Patrice
Published: February 2022

Abstract

When environmental conditions are unpredictable, expressing alternative phenotypes spreads the risk of failure, a mixed strategy called bet-hedging. In the southern part of its range, the Parsley Frog Pelodytes punctatus breeds both in autumn and in spring. Our aim was to study the breeding phenology and reproductive success associated with the use of those two seasonal niches to understand how this breeding strategy can be maintained. Field surveys revealed that breeding phenology was typically bimodal with a higher breeding effort in autumn. More importantly, in spring, the survival rate of offspring was severely reduced by the presence of autumn tadpoles, indicating a clear priority effect. However, the autumn cohort often failed to survive over winter, in which case spring cohorts were often successful. Based on those results, we constructed a model in which females can allocate a variable portion of eggs to each season and added a priority effect. We conclude that the existence of the two breeding seasons may indeed constitute a bet-hedging strategy.
Human HspB1, HspB3, HspB5 and HspB8: Shaping these Disease Factors during Vertebrate Evolution
Authors: Benndorf Rainer , Velazquez Ryan , Zehr Jordan D. , Pond Sergei Kosakovsky , Martin Jody L. , Lucaci Alexander G.
Published: February 2022

Small heat shock proteins (sHSPs) emerged early in evolution and occur in all domains of life and nearly in all species, including humans. Mutations in four sHSPs (HspB1, HspB3, HspB5, HspB8) are associated with neuromuscular disorders. The aim of this study is to investigate the evolutionary forces shaping these sHSPs during vertebrate evolution. We performed comparative evolutionary analyses on a set of orthologous sHSP sequences, based on the ratio of non-synonymous: synonymous substitution rates for each codon. We found that these sHSPs had been historically exposed to different degrees of purifying selection, decreasing in this order: HspB8 > HspB1, HspB5 > HspB3. Within each sHSP, regions with different degrees of purifying selection can be discerned, resulting in characteristic selective pressure profiles. The conserved α-crystallin domains were exposed to the most stringent purifying selection compared to the flanking regions, supporting a ‘dimorphic pattern’ of evolution. Thus, during vertebrate evolution the different sequence partitions were exposed to different and measurable degrees of selective pressures. Among the disease-associated mutations, most are missense mutations primarily in HspB1 and to a minor extent in the other sHSPs. Our data provide an explanation for this disparate incidence. Contrary to the expectation, most missense mutations cause dominant disease phenotypes. Theoretical considerations support a connection between the historic exposure of these sHSP genes to a high degree of purifying selection and the unusual prevalence of genetic dominance of the associated disease phenotypes. Our study puts the genetics of inheritable sHSP-borne diseases into the context of vertebrate evolution.
The evolution of recombination in self-fertilizing organisms
Authors: Stetsenko Roman , Roze Denis
Published: February 2022

Cytological data from flowering plants suggest that the evolution of recombination rates is affected by the mating system of organisms, as higher chiasma frequencies are often observed in self-fertilizing species compared with their outcrossing relatives. Understanding the evolutionary cause of this effect is of particular interest, as it may shed light on the selective forces favoring recombination in natural populations. While previous models showed that inbreeding may have important effects on selection for recombination, existing analytical treatments are restricted to the case of loosely linked loci and weak selfing rates, and ignore the effect of genetic interference (Hill-Robertson effect), known to be an important component of selection for recombination in randomly mating populations. In this article, we derive general expressions quantifying the stochastic and deterministic components of selection acting on a mutation affecting the genetic map length of a whole chromosome along which deleterious mutations occur, valid for arbitrary selfing rates. The results show that selfing generally increases selection for recombination caused by interference among mutations as long as selection against deleterious alleles is sufficiently weak. While interference is often the main driver of selection for recombination under tight linkage or high selfing rates, deterministic effects can play a stronger role under intermediate selfing rates and high recombination, selecting against recombination in the absence of epistasis, but favoring recombination when epistasis is negative. Individual-based simulation results indicate that our analytical model often provides accurate predictions for the strength of selection on recombination under partial selfing.
Western diet unmasks transient low-level vinyl chloride exposure-induced tumorigenesis; potential role of the (epi-)transcriptome
Authors: Liu Silvia , He Liqing , Bannister Olivia B , Schnegelberger Regina D , Tao Junyan , Althouse Andrew D , Schopfer Francisco J , Wahlang Banrida , Cave Matthew C , Monga Satdarshan P , Zhang Xiang , Arteel Gavin E , Beier Juliane I
Published: February 2022

Background & Aims

Vinyl chloride (VC) monomer is a volatile organic compound commonly used in industry to produce polyvinyl chloride (PVC). At high exposure levels, VC causes liver cancer and toxicant-associated steatohepatitis. However, lower exposure levels (i.e., < regulatory exposure limits) that do not directly damage the liver, enhance injury caused by Western diet (WD). Although these lower exposure levels are considered ‘safe,’ it is unknown if the long-term impact of transient low-concentration VC enhances the risk of liver cancer development. Low-concentration VC is especially a concern given that fatty liver disease is in and of itself a risk factor for the development of liver cancer.

Methods

C57Bl/6J mice were fed WD or control diet (CD) for 1 year. During the first 12 weeks of feeding only, mice were also exposed to VC via inhalation at sub-regulatory limit concentrations (<1 ppm) or air for 6 hours/day, 5 days/week.

Results

Feeding WD for 1 year caused significant hepatic injury, including steatohepatitis and moderate fibrosis, which was exacerbated by VC. Additionally, VC increased the number of tumors which ranged from moderately to poorly differentiated hepatocellular carcinoma (HCC). Transcriptomic analysis demonstrated VC-induced changes in metabolic but also ribosomal processes. Epitranscriptomic analysis showed a VC-induced shift of the modification pattern that has been associated with metabolic disease, mitochondrial dysfunction, and cancer.

Conclusions

These data indicate that VC sensitizes the liver to other stressors (e.g., WD), resulting in enhanced tumorigenesis. These data raise concerns about a potential interaction between VC exposure and WD. Furthermore, it also emphasizes that current safety restrictions may be insufficient to account for other factors that can influence hepatotoxicity.
StabMap: Mosaic single cell data integration using non-overlapping features
Authors: Ghazanfar Shila , Guibentif Carolina , Marioni John C.
Published: February 2022

Currently available single cell -omics technologies capture many unique features with different biological information content. Data integration aims to place cells, captured with different technologies, onto a common embedding to facilitate downstream analytical tasks. Current horizontal data integration techniques use a set of common features, thereby ignoring non-overlapping features and losing information. Here we introduce StabMap, a mosaic data integration technique that stabilises mapping of single cell data by exploiting the non-overlapping features. StabMap is a flexible approach that first infers a mosaic data topology, then projects all cells onto supervised or unsupervised reference coordinates by traversing shortest paths along the topology. We show that StabMap performs well in various simulation contexts, facilitates disjoint mosaic data integration, and enables the use of novel spatial gene expression features for mapping dissociated single cell data onto a spatial transcriptomic reference.
An inosine triphosphate pyrophosphatase safeguards plant nucleic acids from aberrant purine nucleotides
Authors: Straube Henryk , Straube Jannis , Rinne Jannis , Niehaus Markus , Witte Claus-Peter , Herde Marco
Published: February 2022

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In plants, inosine is enzymatically introduced in some tRNAs but not in other RNAs or DNA. Nonetheless, our data show that RNA and DNA fromArabidopsis thalianacontain (deoxy)inosine, probably derived from non-enzymatic adenosine deamination in nucleic acids and usage of (deoxy)inosine triphosphate (dITP and ITP) during nucleic acid synthesis.

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We combined biochemical approaches, sample preparation and LC-MS, as well as RNA-Seq to characterize a plant INOSINE TRIPHOSPHATE PYROPHOSPHATASE (ITPA) fromArabidopsis thaliana, which is conserved in many organisms, and investigated the sources of deaminated purine nucleotides in plants.

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ITPA dephosphorylates deaminated nucleoside di- and triphosphates to the respective monophosphates.ITPAloss-of-function causes inosine di- and triphosphate accumulationin vivoand an elevated (deoxy)inosine content in DNA and RNA, as well as salicylic acid (SA) accumulation, early senescence and upregulation of transcripts associated with immunity and senescence. Cadmium-induced oxidative stress leads to more ITP in the wildtype, and this effect is enhanced initpamutants, suggesting that ITP originates from ATP deamination.

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ITPA is part of a molecular protection system, preventing accumulation of (d)ITP, its usage for nucleic acid synthesis, and probably nucleic acid stress leading to SA accumulation, stress gene induction and early senescence.
Brevican, Neurocan, Tenascin-C and Tenascin-R Act as Important Regulators of the Interplay between Perineuronal Nets, Synaptic Integrity, Inhibitory Interneurons and Otx2
Authors: Mueller-Buehl Cornelius , Reinhard Jacqueline , Roll Lars , Bader Verian , Winklhofer Konstanze F. , Faissner Andreas
Published: February 2022

Fast-spiking parvalbumin interneurons are critical for the function of mature cortical inhibitory circuits. Most of these neurons are enwrapped by a specialized extracellular matrix structure (ECM) called perineuronal net (PNN), which can regulate their synaptic input. In this study, we investigated the relationship between PNNs, parvalbumin interneurons and synaptic distribution on these cells in the adult primary visual cortex (V1) of quadruple knockout mice deficient for the ECM molecules brevican, neurocan, tenascin-C and tenascin-R. We used super-resolution structured illumination microscopy (SIM) to analyze PNN structure and associated synapses. Additionally, we examined parvalbumin and calretinin interneuron populations. We observed a reduction in the number of PNN-enwrapped cells and a clear disorganization of the PNN structure in the quadruple knockout V1. This was accompanied by an imbalance of inhibitory and excitatory synapses with a reduction of inhibitory and an increase of excitatory synaptic elements along the PNNs. Also, the number of parvalbumin interneurons was reduced in the quadruple knockout, while calretinin interneurons, which do not wear PNNs did not display differences in number. Interestingly, we found the transcription factor Otx2 homeoprotein positive cell population also reduced. Otx2 is crucial for parvalbumin and PNN maturation and a positive feedback loop between these parameters has been described. Collectively, these data indicate an important role of brevican, neurocan, tenascin-C and tenascin-R in regulating the interplay between PNNs, inhibitory interneurons, synaptic distribution as well as Otx2 in the V1.
Expanding the pulse-reserve paradigm to microorganisms on the basis of differential reserve management strategies
Authors: Garcia-Pichel Ferran , Sala Osvaldo
Published: February 2022

The pulse-reserve paradigm (PRP) is central in dryland ecology, although traits of microorganisms were not explicitly considered in its inception. We asked if the PRP could be reframed to encompass organisms both large and small. We used a synthetic review of recent advances in arid land microbial autoecology combined with a mathematically explicit theoretical model. Preserving the PRPs original core of adaptations by reserve building, the model considers differential organismal strategies to manage these reserves. It proposes a gradient of organisms according to their reserve strategies, from nimble responders (NIRs) to torpid responders (TORs). It predicts how organismal fitness depends on pulse regimes and reserve strategies thus explaining organismal diversification and distribution. After accounting for scaling phenomena and redefining the microscale meaning of aridity, it becomes patent that the PRP is applicable to microbes, and that this modified PRP represents an inclusive theoretical framework working across life-forms.
Cortical compensation for afferent loss in older adults: Associations with GABA and speech recognition in noise
Authors: Harris Kelly C. , Balken Brendan , Dias James W. , McClaskey Carolyn M. , Rumschlag Jeffrey , Prisciandaro James , Dubno Judy R.
Published: February 2022

Age-related deficits in auditory nerve (AN) function reduce afferent input to the auditory cortex. The extent to which the auditory cortex in older adults compensates for this loss of afferent input, also known as central gain, and the mechanisms underlying this compensation are not well understood. We took a neural systems approach to estimate central gain, measuring AN and cortical evoked responses within 50 older and 27 younger adults. Amplitudes were significantly smaller for older than for younger adults for AN responses but not for cortical responses. We used the relationship between AN and cortical response amplitudes in younger adults to predict cortical response amplitudes for older adults from their AN responses. Central gain in older adults was thus defined as the difference between their observed cortical responses and those predicted from the parameter estimates of younger adults. More central gain was associated with decreased cortical levels of GABA measured with 1H-MRS and poorer speech recognition in noise (SIN). Effects of central gain and GABA on SIN occur in addition to, and independent from, effects attributed to elevated hearing thresholds. Our results are consistent with animal models of central gain and suggest that reduced AN afferent input in some older adults may result in changes in cortical encoding and inhibitory neurotransmission, which contribute to reduced SIN. An advancement in our understanding of the changes that occur throughout the auditory system in response to the gradual loss of input with increasing age may provide potential therapeutic targets for intervention.

Significance

Age-related hearing loss is one of the most common chronic conditions of aging, yet little is known about how the cortex compensates for this loss of sensory input. We measured AN and cortical responses to the same stimulus in younger and older adults. In older adults we found an increase in cortical activity following concomitant declines in afferent input that are consistent with central gain. Increased central gain was associated with lower levels of cortical GABA, an inhibitory neurotransmitter, which predicted poorer speech recognition in noise. The results suggest that the cortex in older adults can compensate for attenuated sensory input by reducing inhibition to amplify the cortical response, but this amplification may lead to poorer speech recognition in noise.
Quality assessment and refinement of chromatin accessibility data using a sequence-based predictive model
Authors: Han Seong Kyu , Muto Yoshiharu , Wilson Parker C. , Chakravarti Aravinda , Humphreys Benjamin D. , Sampson Matthew G. , Lee Dongwon
Published: February 2022

Chromatin accessibility assays are central to the genome-wide identification of gene regulatory elements associated with transcriptional regulation. However, the data have highly variable quality arising from several biological and technical factors. To surmount this problem, we use the predictability of open-chromatin peaks from DNA sequence-based machine-learning models to evaluate and refine chromatin accessibility data. Our framework, gapped k-mer SVM quality check (gkmQC), provides the quality metrics for a sample based on the prediction accuracy of the trained models. We tested 886 samples with DNase-seq from the ENCODE/Roadmap projects to demonstrate that gkmQC can effectively identify high-quality samples underperforming owing to marginal read depths. Peaks identified in high-quality samples by gkmQC are more accurately aligned at functional regulatory elements, show greater enrichment of regulatory elements harboring functional variants from genome-wide association studies (GWAS), and explain greater heritability of phenotypes from their relevant tissues. Moreover, gkmQC can optimize the peak-calling threshold to identify additional peaks, especially for single-cell chromatin accessibility data as well as bulk data. Here we provide a standalone open-source toolkit (https://github.com/Dongwon-Lee/gkmQC) for such analyses and share improved regulatory maps using gkmQC. These resources will contribute to the functional interpretation of disease-associated regulatory genetic variation.