bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing sleep behaviors in Latino children and adolescents: what is known, what are we missing, and how do we move forward?
Authors: Blanco Estela , Hyde Eric T. , Martinez Suzanna M.
Published: November 2023

Purpose of review

Sleep health is a commonly overlooked component of pediatric cardiometabolic risk. Disparities in sleep duration and meeting of pediatric sleep guidelines have been well documented among at-risk populations in the United States, including Latinos. However, sleep research often fails to describe or account for contextual and cultural factors impacting the ability for Latino families to meet guidelines. The current review focuses on recent findings related to measurement of sleep duration, understanding of contextual factors that impact sleep hygiene, and interventions designed to increase sleep duration and quality among U.S. Latino families with infants, young children, and adolescents.

Recent findings

Ten studies focusing on sleep health in U.S. Latino children, using different study designs were identified. Overall, cross-sectional studies confirmed inadequate sleep among Latino children, intervention studies demonstrated promise of culturally-sensitive health behavior education for improving sleep in early childhood, and qualitative studies highlighted neighborhood and cultural factors that impact sleep quality.

Implications for clinical practice and research

Rather than new prevalence studies on adherence to sleep recommendations among Latino families, research focusing on adapting clinical guidelines to accommodate the realities of many Latino families (e.g., co-sleeping and bedsharing) will advance our knowledge. A shift towards objective measurement of the 24-h period as well as evaluating specific contextual barriers that make It challenging to meet sleep guidelines for Latino children is needed.
Efficacy and safety of hydrochlorothiazide versus chlorthalidone in patients with hypertension: a systematic review and meta-analysis
Authors: Puri Piyush , Aslam Zaid Muhammad , Danial Muhammad , Sadique Rebecca Sehar , Ahmed Gulzar , Khan Shahzaib , Bhura Zainab Asif , Ansari Mozaena , Patel Dhruvilkumar , Ansari Omema , Shoaib Mudassir , Hoti Muhammad Roshan , Munshi Muhammad Salman , Yusufzai Aazar
Published: November 2023

Background:

Although thiazide diuretics are widely used for treating hypertension (HTN) , the comparative efficacy and safety of hydrochlorothiazide (HCTZ) versus chlorthalidone (CTD) for the management of patients with HTN is not well-established.

Materials and Methods:

A thorough literature search was conducted across two electronic databases (MEDLINE and Cochrane) from inception through May 2023 to identify randomized controlled trials and/or observational double-arm studies evaluating the effects of HCTZ versus CTD on cardiovascular and safety outcomes in patients with HTN. Evaluations were reported as hazard ratios (HRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. A P-value<0.05 was considered significant in all cases.

Results:

From the 409 articles retrieved from initial search, four potentially relevant studies were included in the final analysis. No significant differences were noted for all the cardiovascular outcomes namely MACE, myocardial infarction (MI), stroke, hospitalization for heart failure (HHF), and angina between the HCTZ and CTD arms. However, patients using CTD had significantly higher rates of hypokalemia and hyponatremia when compared with patients using HCTZ. There was no significant difference in the risk of acute kidney injury between the two arms.

Conclusion:

HCTZ and CTD demonstrated similar efficacy profile with respect to cardiovascular outcomes. However, HCTZ appeared to be safer due to lower risk of electrolyte imbalances like hypokalemia and hyponatremia associated with it when compared with CTD.
Unusual Case of Primary Hepatic Squamous Carcinoma on 18F-FDG PET/CT
Authors: Li Wei , Liu Zhidong , Zhang Rusen
Published: November 2023

Primary hepatic squamous carcinoma is an extremely rare liver tumor type with high malignancy and poor prognosis. We present18F-FDG PET/CT findings of primary squamous carcinoma of the liver in a 65-year-old man, who was admitted to the hospital with subxiphoid pain in the epigastric region radiating to the left lower back for 2 months.18F-FDG PET/CT demonstrated a large heterogeneous mild enhancing mass in the left lobe of the liver, with intense circumferential18F-FDG activity.
Surgeon views on firearm safety counseling in clinical practice: A cross-sectional survey
Authors: Kirkendoll Shelbie D. , Silver Casey M. , Stey Anne M. , Nathens Avery B. , Jackson Kathryn , Campbell Brendan T.
Published: November 2023

BACKGROUND

Firearms are commonplace in the United States, and one proposed strategy to decrease risk of firearm injury is to have physicians counsel their patients about safe firearm ownership. Current rates of firearm safety counseling by surgeons who care for injured people are unknown.

METHODS

This study used an anonymous cross-sectional survey derived from previously published survey instruments and was piloted (n = 13) at the annual meeting of the American Association for the Surgery of Trauma (2022). The finalized survey was distributed using a quick response code during two sessions at the 2022 American College of Surgeons Clinical Congress. Eligible participants included the surgeons and surgical trainees who attended these sessions.

RESULTS

One hundred fourteen individuals completed the survey (20% response rate), and a majority were male (n = 71 [62.3%]), attending surgeons (n = 108 [94.7%]), and specialized in acute care surgery (n = 72 [63.2%]). Few participants (n = 43 [37.7%]) reported counseling patients on firearm safety as part of their routine clinical practice; however, the majority (n = 102 [89.5%]) believed that surgeons should provide firearm safety counseling. Counseling rates did not vary significantly by age, sex, surgical specialty, or region of practice, but attitudes toward counseling did differ by firearm safety counseling practices (p = 0.03) and region of practice (0.04). Noted barriers to counseling included lack of time (n = 47 [41.2%]), perceived lack of training (n = 43 [37.7%]), and lack of firearm knowledge/experience (n = 36 [31.6%]).

CONCLUSION

Most surgeon respondents did not provide firearm safety counseling to their patients despite the fact the majority believed they should. This suggests that counseling interventions that do not solely rely on surgeons for implementation could increase the number of patients who receive firearm safety guidance during clinical encounters.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Comparison of Automated Spike Detection Software in Detecting Epileptiform Abnormalities on Scalp-EEG of Genetic Generalized Epilepsy Patients
Authors: Janmohamed Mubeen , Nhu Duong , Shakathreh Lubna , Gonen Ofer , Kuhlman Levin , Gilligan Amanda , Tan Chang Wei , Perucca Piero , O'Brien Terence J. , Kwan Patrick
Published: November 2023

Purpose:

Despite availability of commercial EEG software for automated epileptiform detection, validation on real-world EEG datasets is lacking. Performance evaluation of two software packages on a large EEG dataset of patients with genetic generalized epilepsy was performed.

Methods:

Three epileptologists labelled IEDs manually of EEGs from three centres. All Interictal epileptiform discharge (IED) markings predicted by two commercial software (Encevis 1.11 and Persyst 14) were reviewed individually to assess for suspicious missed markings and were integrated into the reference standard if overlooked during manual annotation during a second phase. Sensitivity, precision, specificity, and F1-score were used to assess the performance of the software packages against the adjusted reference standard.

Results:

One hundred and twenty-five routine scalp EEG recordings from different subjects were included (total recording time, 310.7 hours). The total epileptiform discharge reference count was 5,907 (including spikes and fragments). Encevis demonstrated a mean sensitivity for detection of IEDs of 0.46 (SD 0.32), mean precision of 0.37 (SD 0.31), and mean F1-score of 0.43 (SD 0.23). Using the default medium setting, the sensitivity of Persyst was 0.67 (SD 0.31), with a precision of 0.49 (SD 0.33) and F1-score of 0.51 (SD 0.25). Mean specificity representing non-IED window identification and classification was 0.973 (SD 0.08) for Encevis and 0.968 (SD 0.07) for Persyst.

Conclusions:

Automated software shows a high degree of specificity for detection of nonepileptiform background. Sensitivity and precision for IED detection is lower, but may be acceptable for initial screening in the clinical and research setting. Clinical caution and continuous expert human oversight are recommended with all EEG recordings before a diagnostic interpretation is provided based on the output of the software.
Dynamic gene expression analysis reveals distinct severity phases of immune and cellular dysregulation in COVID-19
Authors: An Andy Y. , Baghela Arjun , Zhang Peter , Blimkie Travis M. , Gauthier Jeff , Kaufmann Daniel E. , Acton Erica , Lee Amy H.Y. , Levesque Roger C. , Hancock Robert E.W.
Published: November 2023

Background

COVID-19 patients experience dynamic changes in immune and cellular function over time with potential clinical implications. However, there is insufficient research investigating, on a gene expression level, the mechanisms that become activated or suppressed over time as patients deteriorate or recover, which can inform use of repurposed and novel drugs as therapies.

Objective

To investigate longitudinal changes in gene expression profiles throughout the COVID-19 disease timeline.

Methods

Three-hundred whole blood samples from 128 adult patients were collected during hospitalization from COVID-19, with up to five samples per patient. Transcriptome sequencing (RNA-Seq), differential gene expression analysis and pathway enrichment was performed. Drug-gene set enrichment analysis was used to identify FDA-approved medications that could inhibit critical genes and proteins at each disease phase. Prognostic gene-expression signatures were generated using machine learning to distinguish 3 disease stages.

Results

Samples were longitudinally grouped by clinical criteria and gene expression into six disease phases: Mild, Moderate, Severe, Critical, Recovery, and Discharge. Distinct mechanisms with differing trajectories during COVID-19 hospitalization were apparent. Antiviral responses peaked early in COVID-19, while heme metabolism pathways became active much later during disease. Adaptive immune dysfunction, inflammation, and metabolic derangements were most pronounced during phases with higher disease severity, while hemostatic abnormalities were elevated early and persisted throughout the disease course. Drug-gene set enrichment analysis predicted repurposed medications for potential use, including platelet inhibitors in early disease, antidiabetic medications for patients with increased disease severity, and dasatinib throughout the disease course. Disease phases could be categorized using specific gene signatures for prognosis and treatment selection. Disease phases were also highly correlated to previously developed sepsis endotypes, indicating that severity and disease timing were significant contributors to heterogeneity observed in sepsis and COVID-19.

Conclusions

Higher temporal resolution of longitudinal mechanisms in COVID-19 revealed multiple immune and cellular changes that were activated at different phases of COVID-19. Understanding how a patient’s gene expression profile changes over time can permit more accurate risk stratification of patients and provide time-dependent personalized treatments with repurposed medications. This creates an opportunity for timely intervention before patients transition to a more severe phase, potentially accelerating patients to recovery.
ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT
Authors: Sekendiz Zennur , Clouston Sean A. P. , Morozova Olga , Carr Melissa A. , Fontana Ashley , Mehta Nikhil , Ali Alina , Jiang Eugene , Luft Benjamin
Published: November 2023

Background

Cognitive impairment is the most common and disabling manifestation of post-acute sequelae of SARS-CoV-2. There is an urgent need for the application of more stringent methods for evaluating cognitive outcomes in research studies.

Objective

To determine whether cognitive decline emerges with the onset of COVID-19 and whether it is more pronounced in patients with Post-Acute Sequelae of SARS-CoV-2 or severe COVID-19.

Methods

This longitudinal cohort study compared the cognitive performance of 276 patients with COVID-19 to that of 217 controls across four neuroinflammation or vascular disease-sensitive domains of cognition using data collected both before and after the pandemic starting in 2015.

Results

The mean age of the COVID-19 group was 56.04±6.6 years, while that of the control group was 58.1±7.3 years. Longitudinal models indicated a significant decline in cognitive throughput ((β=-0.168,P=.001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. The effect sizes were large; the observed changes in throughput were equivalent to 10.6 years of normal aging and a 59.8% increase in the burden of mild cognitive impairment. Cognitive decline worsened with coronavirus disease 2019 severity and was concentrated in participants reporting post-acute sequelae of SARS-CoV-2.

Conclusion

COVID-19 was most likely associated with the observed cognitive decline, which was worse among patients with PASC or severe COVID-19. Monitoring patients with post-acute sequelae of SARS-CoV-2 for declines in the domains of processing speed and visual working memory and determining the long-term prognosis of this decline are therefore warranted.
Lower Physical Activity Modifies the Association between Perceived Fatigability and Executive Function but not Memory: The Study of Muscle, Mobility and Aging (SOMMA)
Authors: Schumacher Benjamin T. , Rosano Caterina , Qiao Yujia (Susanna) , Rosso Andrea L. , Cawthon Peggy M. , Moored Kyle D. , Cummings Steven R. , Kritchevsky Stephen B. , Glynn Nancy W.
Published: November 2023

OBJECTIVE

Emerging evidence shows that perceived fatigability—the quantification of vulnerability to fatigue in relation to specific intensity and duration of activities—may be associated with cognitive function. We sought to quantify associations with multiple domains of cognitive function and the role of physical activity (PA).

METHODS

SOMMA participants completed the Pittsburgh Fatigability Scale (PFS) Physical and Mental subscales (each range 0–50; higher scores=greater fatigability) and three cognitive function assessments [Digit Symbol Substitution Test (DSST), executive function; Montreal Cognitive Assessment (MoCA), general function; and California Verbal Learning Test (CVLT), memory]. Linear regression quantified associations cross-sectionally between each PFS subscale and cognitive assessment scores adjusting for covariates. Effect modification by volume and intensity of accelerometer-measured PA was assessed.

RESULTS

In 873 participants (59.2% women; age 76.3±5.0; 85% White), mean PFS Physical, Mental, and DSST scores were 15.8±8.7, 7.7±7.8, and 55.4±13.7. After adjustments, for each 4-point higher PFS Physical and 3-point higher PFS Mental, participants had nearly one fewer correct DSST items [β coefficient and 95% confidence interval for PFS Physical: -0.69 (-1.09, - 0.29); PFS Mental: -0.64 (-0.97, -0.30)]. Volume and intensity of PA modified the association of PFS Mental and DSST (Pinteractions<0.01). All associations were strongest in those with the lowest volume and intensity of PA. PFS was not associated with MoCA or CVLT.

DISCUSSION

Greater perceived fatigability may be associated with poorer executive function, but not memory. Individuals with greater perceived fatigability, particularly those less active, might benefit from interventions that reduce fatigability and may beneficially influence cognitive function.
Fending for oneself or partnering up: Competition between mixo- and heterotrophic ciliates under dynamic resource supply
Authors: Flöder Sabine , Klauschies Toni , Klaassen Moritz , Stoffers Tjardo , Lambrecht Max , Moorthi Stefanie
Published: November 2023

The outcome of species competition strongly depends on the traits of the competitors and associated trade-offs, as well as on environmental variability. Here we investigate the relevance of consumer trait variation for species coexistence in a ciliate consumer – microalgal prey system under fluctuating regimes of resource supply. We focus on consumer competition and feeding traits, and specifically on the consumer’s ability to overcome periods of resource limitation by mixotrophy, i.e. the ability of photosynthetic carbon fixation via algal symbionts in addition to phagotrophy. In a 48-day chemostat experiment, we investigated competitive interactions of different heterotrophic and mixotrophic ciliates of the generaEuplotesandColepsunder different resource regimes, providing prey either continuously or in pulses under constant or fluctuating light, entailing periods of resource depletion in fluctuating environments, but overall providing the same amount of prey and light. Although ultimate competition results remained unaffected, population dynamics of mixotrophic and heterotrophic ciliates were significantly altered by resource supply mode. However, the effects differed among species combinations and changed over time. Whether mixotrophs or heterotrophs dominated in competition strongly depended on the genera of the competing species and thus species-specific differences in the minimum resource requirements that are associated with feeding on shared prey, nutrient uptake, light harvesting and access to additional resources such as bacteria. Potential differences in the curvature of the species’ resource-dependent growth functions may have further mediated the species-specific responses to the different resource supply modes. In addition, while the presence of a heterotrophic competitor may have a direct negative effect on the growth rate of a mixotrophic species through grazing on a shared prey species, its presence may also have an indirect positive effect on the growth rate of the mixotroph by reducing competition between the autotroph and mixotroph for shared nutrients and light. Our study thus demonstrates that complex trophic interactions determine the outcome of competition, which can only be understood by taking on a multidimensional trait perspective.
Teaching transposon classification as a means to crowd source the curation of repeat annotation – a tardigrade perspective
Authors: Peona Valentina , Martelossi Jacopo , Almojil Dareen , Bocharkina Julia , Brännström Ioana , Brown Max , Cang Alice , Valenzuela Tomas Carrasco , DeVries Jon , Doellman Meredith , Elsner Daniel , Espindola Hernandez Pamela , Friis Montoya Guillermo , Gaspar Bence , Zagorski Danijela , Hałakuc Paweł , Ivanovska Beti , Laumer Christopher , Lehmann Robert , Boštjančić Ljudevit Luka , Mashoodh Rahia , Mazzoleni Sofia , Mouton Alice , Janke Maria Nilsson , Pei Yifan , Potente Giacomo , Provataris Panagiotis , Pardos José Ramón , Raut Ravindra , Sbaffi Tomasa , Schwarz Florian , Stapley Jessica , Stevens Lewis , Sultana Nusrat , Symonova Radka , Tahami Mohadeseh , Urzì Alice , Yang Heidi , Yusuf Abdullah , Pecoraro Carlo , Suh Alexander
Published: November 2023

The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. However, manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd sourcing efforts could offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Here, we present an example of such crowd sourcing effort developed through both in-person and online courses built around a collaborative peer-reviewed teaching process that can be used as teaching reference guide for similar projects. The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs: A hidden treasure awaits discovery within non-model organisms.
Simultaneous analysis of pMHC binding and reactivity unveils virus-specific CD8 T cell immunity to a concise epitope set
Authors: Kristensen Nikolaj Pagh , Dionisio Edoardo , Bentzen Amalie Kai , Tamhane Tripti , Kemming Janine Sophie , Nos Grigorii , Voss Lasse Frank , Hansen Ulla Kring , Lauer Georg Michael , Hadrup Sine Reker
Published: November 2023

Knowledge of widely recognized T-cell epitopes against common virus infections are vital for immune monitoring and characterization of relevant antigen-specific CD8 T cells and their antigen receptors. We therefore aimed to establish a concise and validated epitope panel for monitoring human virus-specific immunity complete with data on both prevalence of recognition and reactivity in humans. To achieve this, we first establish TCR downregulation, and loss of peptide major histocompatibility (pMHC) multimer-binding, as an early and sensitive marker of T cell reactivity after peptide stimulation. We next applied TCR downregulation in a high-throughput assay by monitoring binding, and loss of binding (i.e. reactivity), to libraries of DNA-barcode labelled pMHC multimers in paired unstimulated/stimulated samples. This novel method allowed us to access T-cell responses in 48 donors towards 929 epitopes recorded in the Immune Epitope Database (IEDB) encompassing 29 virus common infections and 25 different HLA alleles. This yielded a concise panel of 137 virus epitopes, many of which were underrepresented in the public domain, recognized by T cells in peripheral blood. 84% of these epitopes exhibited prevalent reactivity to peptide stimulation, which was associated with effector and long-term memory phenotypes. Conversely, non-reactive responses correlated with naïve and immunosenescence phenotypes. This study represents the largest effort to unbiasedly assess T-cell recognition and reactivity to common virus infections in healthy individuals providing a minimal epitope panel for monitoring adaptive immune responses in humans.

Significance Statement

CD8 T-cell epitopes are widely available in public databases yet many are not recognized in the general population. Here we undertook an exhaustive screening process using “state-of-the-art” methods to assess both T-cell recognition and reactivity against common virus infections, which holds significant implications for shaping T-cell immunity and disease protection. We identify 137 commonly recognized epitopes from common virus infections to which T cell responses are expected to occur in human donors. Importantly, several of the verified epitopes were underreported in public databases compared to their observed prevalence of recognition and high cellular frequency making this an important reference dataset and resource for immunologists studying antigen-specific T cells across different immunopathologies and contexts including autoimmunity, infectious disease and cancer immunotherapy.
Can biocrust moss hide from climate change? Fine-scale habitat sheltering improves summer-stress resistance inSyntrichia caninervis
Authors: Clark Theresa A. , Russell Alexander , Greenwood Joshua L. , Devitt Dale , Stanton Daniel , Stark Lloyd R.
Published: November 2023

Premise

Mosses provide many ecosystem functions and are the most vulnerable of biocrust organisms to climate change due to their sensitive water relations stressed by summer aridity. Given their small size, moss stress resistance may be more dependent on fine-scale habitat than macroscale (climate and community), but this sheltering role of habitat (i.e. habitat buffering) has never been compared to macroclimate and may have important implications for predicting critical biocrust refugia in changing climates.

Methods

We located three populations of a keystone biocrust moss,Syntrichia caninervis, spanning 1200-m of altitude comprising three plant communities (elevation-plant zones) in the Mojave Desert. We stratified 96 microsites along three habitat aridity gradients: elevation-zone, topography (aspect), and microhabitat (shrub proximity). We estimated summer photosynthetic stress (Fv/Fm) and aridity exposure (macroclimate, irradiance, and shade).

Results

Microsite aridity exposure varied greatly revealing exposed and buffered microhabitats in all elevation-zones. Moss stress did not differ by elevation zone despite the extensive macroclimate gradient, failing to support the high-elevation refugia hypothesis. Instead, stress was lowest on N-facing slopes and microhabitats with higher shrub shading, while the importance of (and interactions between) topography, irradiance, and shade varied by elevation zone.

Conclusions

We demonstrate fine-scale habitat buffering is physiologically more protective than high-elevation climate, and thus, may allow some mosses to hide from the brunt of climate change in widespread microrefugia throughout their current ranges. Our findings support a scale-focused vulnerability paradigm: microrefugia may be more important than macrorefugia for bolstering biocrust moss resistance to summer climate stress.
Plasma neurofilament light protein provides evidence of accelerated brain ageing in treatment-resistant schizophrenia
Authors: Wannan Cassandra M. J. , Eratne Dhamidhu , Santillo Alexander F. , Malpas Charles , Cilia Brandon , Dean Olivia M. , Walker Adam , Berk Michael , Bousman Chad , Everall Ian , Velakoulis Dennis , Pantelis Christos ,   The MiND Study Group
Published: November 2023

Background

Accelerated brain aging has been observed across multiple psychiatric disorders. Blood markers of neuronal injury such as Neurofilament Light (NfL) protein may therefore represent biomarkers of accelerated brain aging in these disorders. The current study aimed to examine whether relationships between age and plasma NfL were increased in individuals with primary psychiatric disorders compared to healthy individuals.

Methods

Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), a large reference normative healthy control (HC) group (n= 1,926) and a locally-acquired HC sample (n = 59). A general linear model (GLM) was used to examine diagnosis by age interactions on NfL z-scores using the large normative HC sample as a reference group. Significant results were then validated using the locally-acquired HC sample.

Results

a GLM identified a significant age by diagnosis interaction for TRS vs HCs and BPAD vs HCs. Post hoc analyses revealed a positive correlation between NfL levels and age among individuals with TRS, whereas a negative correlation was found among individuals with BPAD. However, only the TRS findings were replicated using the locally-acquired HC sample. Post hoc analyses revealed that individuals with TRS aged <40 had lower NfL levels compared to same-age HCs, whereas individuals with TRS aged >40 had higher NfL levels compared to same-age HCs.

Conclusions

These findings add to the growing literature supporting the notion of accelerated brain ageing in schizophrenia-spectrum disorders.
Intragenomic conflicts with plasmids and chromosomal mobile genetic elements drive the evolution of natural transformation within species
Authors: Mazzamurro Fanny , Chirakadavil Jason Baby , Durieux Isabelle , Poiré Ludovic , Plantade Julie , Ginevra Christophe , Jarraud Sophie , Wilharm Gottfried , Charpentier Xavier , Rocha Eduardo P. C.
Published: November 2023

Natural transformation is the only mechanism of genetic exchange controlled by the recipient bacteria. We quantified its rates in 1282 strains of the human pathogensLegionella pneumophila(Lp) andAcinetobacter baumannii(Ab) and found that transformation rates evolve by large quick changes as a jump process across six orders of magnitude. Close to half of the strains are non-transformable in standard conditions. Transitions to non-transformability were frequent and recent, suggesting that they are deleterious and subsequently purged by natural selection. Accordingly, we find that transformation decreases genetic linkage in both species, which often accelerates adaptation. Intragenomic conflicts with chromosomal mobile genetic elements (MGEs) and plasmids could explain these transitions and a GWAS confirmed systematic negative associations between transformation and MGEs: plasmids and other conjugative elements in Lp, prophages in Ab, and transposable elements in both. In accordance with the modulation of transformation rates by genetic conflicts, transformable strains have fewer MGEs. Defense systems against the latter are associated with lower transformation except the adaptive CRISPR-Cas systems which show the inverse trend. The two species have different lifestyles and gene repertoires, but they exhibit very similar trends in terms of variation of transformation rates and its determinants, suggesting that genetic conflicts could drive the evolution of natural transformation in many bacteria.
Global analysis of the heparin-enriched plasma proteome captures matrisome-associated proteins in Alzheimer’s disease
Authors: Guo Qi , Ping Lingyan , Dammer Eric B. , Duong Duc M. , Yin Luming , Xu Kaiming , Shantaraman Ananth , Fox Edward J. , Johnson Erik C.B. , Roberts Blaine R. , Lah James J. , Levey Allan I. , Seyfried Nicholas T.
Published: November 2023

Matrisome-associated heparin binding proteins (HBPs) with roles in extracellular matrix assembly are strongly correlated to β-amyloid (Aβ) and tau pathology in Alzheimer’s disease (AD) brain and cerebrospinal fluid (CSF). However, it remains challenging to detect these proteins in plasma using standard mass spectrometry (MS)-based proteomic approaches. Here we utilized heparin affinity chromatography for the capture and enrichment of HBPs in plasma from healthy control and individuals with AD. This method was highly reproducible and effectively enriched well-known HBPs like APOE and thrombin, while also efficiently depleting high-abundance proteins such as albumin. To increase the depth of our analysis of the heparin-enriched plasma proteome and compare differences in disease we applied off-line fractionation and tandem mass tag mass spectrometry (TMT-MS) to compare the proteomic profiles between AD and control individuals across two datasets (n= 121 total samples). This led to the identification of 2865 proteins, spanning 10 orders of magnitude in protein abundance within the plasma. Notably, HBPs were some of the most increased proteins in AD plasma compared to controls. This included members of the matrisome-associated module in brain, SMOC1, SMOC2, SPON1, MDK, OLFML3, FRZB, GPNMB and the ɛ4 isoform of APOE. Heparin-enriched plasma proteins also exhibited strong correlations to conventional AD biomarkers including CSF Aβ, total tau (tTau), and phosphorylated tau (pTau) as well as plasma pTau supporting their role as potential surrogate markers of underlying brain pathology. Utilizing a consensus AD brain protein co-expression network, we assessed relationship between the plasma and brain proteomes and observed that specific plasma proteins exhibited consistent direction of change in both brain and plasma, whereas others displayed divergent changes, further highlighting the complex interplay between the two compartments. In summary, these findings provide support for the integration of a heparin enrichment method with MS-based proteomics for identifying a wide spectrum of plasma biomarkers that mirror pathological changes in the AD brain.
DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+T cells
Authors: Yu Zheng , Sasidharan-Nair Varun , Bonifacius Agnes , Khan Fawad , Buchta Thalea , Beckstette Michael , Niemz Jana , Hilgendorf Philipp , Pietzsch Beate , Mausberg Philip , Keller Andreas , Falk Christine , Busch Dirk , Brinkmann Melanie M. , Schober Kilian , Cicin-Sain Luka , Müller Fabian , Eiz-Vesper Britta , Floess Stefan , Huehn Jochen
Published: November 2023

Epigenetic mechanisms stabilize gene expression patterns during CD8+T cell differentiation. However, although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions when compared to bulk memory CD8+T cells. Among them wasTBKBP1, coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8+T cells.TBKBP1demethylation in terminal effector CD8+T cells correlated withTBKBP1expression and was stable upon long-termin vitroculture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8+T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8+T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.
Inference of Locus-Specific Population Mixtures From Linked Genome-Wide Allele Frequencies
Authors: Reyna-Blanco Carlos S. , Caduff Madleina , Galimberti Marco , Leuenberger Christoph , Wegmann Daniel
Published: November 2023

1

Admixture between populations and species is common in nature. Since the influx of new genetic material might be either facilitated or hindered by selection, variation in mixture proportions along the genome is expected in organisms undergoing recombination. Various graph-based models have been developed to better understand these evolutionary dynamics of population splits and mixtures. However, current models assume a single mixture rates for the entire genome and do not explicitly account for linkage. Here, we introduceTreeSwirl, a novel method for inferring branch lengths and locus-specific mixture proportions by using genome-wide allele frequency data, assuming that the admixture graph is known or has been inferred.TreeSwirlbuilds uponTreeMixthat uses Gaussian processes to estimate the presence of gene flow between diverged populations. However, in contrast toTreeMix, our model infers locus-specific mixture proportions employing a Hidden Markov Model that accounts for linkage. Through simulated data, we demonstrate thatTreeSwirlcan accurately estimate locus-specific mixture proportions and handle complex demographic scenarios. It also outperforms related D- and f-statistics in terms of accuracy and sensitivity to detect introgressed loci.
PLK4 homodimerization is required for CEP152 centrosome localization and spindle organization
Authors: Kasera Harshita , Singh Priyanka
Published: November 2023

Polo-Like Kinase 4 (PLK4) is a unique serine/threonine kinase family member that homodimerizes using its cryptic polo-box (CPB) region. Homodimerization of PLK4 causes transphosphorylation, which activates its ubiquitin-mediated degradation. Interestingly, CPB is also involved in interaction with the upstream centrosome recruiters, CEP152 and CEP192 in human cells. However, the effect of PLK4 homodimerization on the CEP192-CEP152 network remains unexplored. In this work, we identified a frequently occurring cancerous PLK4 variant (E774*), which truncated the protein at the 774 position. The truncated PLK4 is unable to homodimerize and interact with CEP152 and CEP192. During the S-phase progression, we show that CEP152 recruits PLK4 to centrosomes. The homodimerization of PLK4, in turn, is needed for maintaining CEP152 centrosome levels. CEP152 levels correlate to pericentrin at S-phase centrosomes, which generate focused spindles by the M-phase. The homodimerization mutant exhibits reduced levels of CEP152 and pericentrin at S-phase centrosomes, which causes unfocused spindles at the M-phase and reduces cell viability. This work shows the requirement of PLK4 homodimerization for proper centrosome and spindle organization, which is disrupted in cancer.
The Arabidopsis Information Resource in 2024
Authors: Reiser Leonore , Bakker Erica , Subramaniam Sabarinath , Chen Xingguo , Sawant Swapnil , Khosa Kartik , Prithvi Trilok , Berardini Tanya Z.
Published: November 2023

Since 1999, The Arabidopsis Information Resource (www.arabidopsis.org) has been curating data about theArabidopsis thalianagenome. Its primary focus is integrating experimental gene function information from the peer-reviewed literature and codifying it as controlled vocabulary annotations. Our goal is to produce a ‘gold standard’ functional annotation set that reflects the current state of knowledge about the Arabidopsis genome. At the same time, the resource serves as a nexus for community-based collaborations aimed at improving data quality, access and reuse. For the past decade, our work has been made possible by subscriptions from our global user base. This update covers our ongoing biocuration work, some of our modernization efforts that contribute to the first major infrastructure overhaul since 2011, the introduction of JBrowse2, and the resource’s role in community activities such as organizing the structural reannotation of the genome. For gene function assessment, we used Gene Ontology annotations as a metric to evaluate: (1) what is currently known about Arabidopsis gene function, and (2) the set of ‘unknown’ genes. Currently, 74% of the proteome has been annotated to at least one Gene Ontology term. Of those loci, half have experimental support for at least one of the following aspects: molecular function, biological process, or cellular component. Our work sheds light on the genes for which we have not yet identified any published experimental data and have no functional annotation. Drawing attention to these unknown genes highlights knowledge gaps and potential sources of novel discoveries.

Article Summary

The Arabidopsis Information Resource (TAIR,www.arabidopsis.org) is a comprehensive website aboutArabidopsis thaliana, a small plant that’s very easy to grow and analyze in the laboratory and is used to understand how many other plants function. We share our progress in data collection and organization, website and tool improvement, and our involvement in community projects.
Tissue-resident alveolar macrophages reduce O3-induced inflammation via MerTK mediated efferocytosis
Authors: Guttenberg M.A. , Vose A.T. , Birukova A. , Lewars K. , Cumming R.I. , Albright M.C. , Mark J.I. , Salazar C.J. , Swaminathan S. , Yu Z. , Sokolenko Yu. V. , Bunyan E. , Yaeger M.J. , Fessler M.B. , Que L.G. , Gowdy K.M. , Misharin A.V. , Tighe R.M.
Published: November 2023

Lung inflammation, caused by acute exposure to ozone (O3) – one of the six criteria air pollutants – is a significant source of morbidity in susceptible individuals. Alveolar macrophages (AMØs) are the most abundant immune cells in the normal lung and their number increases following O3exposure. However, the role of AMØs in promoting or limiting O3-induced lung inflammation has not been clearly defined. Here, we used a mouse model of acute O3exposure, lineage tracing, genetic knockouts, and data from O3-exposed human volunteers to define the role and ontogeny of AMØs during acute O3exposure. Lineage tracing experiments showed that 12, 24, and 72 h after exposure to O3(2 ppm) for 3h all AMØs were tissue-resident origin. Similarly, in humans exposed to FA and O3(200 ppb) for 135 minutes, we did not observe ∼21h post-exposure an increase in monocyte-derived AMØs by flow cytometry. Highlighting a role for tissue-resident AMØs, we demonstrate that depletion of tissue-resident AMØs with clodronate-loaded liposomes led to persistence of neutrophils in the alveolar space after O3exposure, suggesting that impaired neutrophil clearance (i.e., efferocytosis) leads to prolonged lung inflammation. Moreover, depletion of tissue-resident AMØ demonstrated reduced clearance of intratracheally instilled apoptotic Jurkat cells, consistent with reduced efferocytosis. Genetic ablation of MerTK – a key receptor involved in efferocytosis – also resulted in impaired clearance of apoptotic neutrophils followed O3exposure. Overall, these findings underscore the pivotal role of tissue-resident AMØs in resolving O3-induced inflammation via MerTK-mediated efferocytosis.
Mime-seq 2.0: a method to sequence microRNAs from specific mouse cell types
Authors: Mandlbauer Ariane , Sun Qiong , Popitsch Niko , Schwickert Tanja , Spanova Miroslava , Wang Jingkui , Ameres Stefan , Busslinger Meinrad , Cochella Luisa
Published: November 2023

Many microRNAs (miRNAs) are expressed with high spatiotemporal specificity during organismal development, with some being limited to rare cell types, often embedded in complex tissues. Yet most miRNA profiling efforts remain at the tissue and organ levels. To overcome challenges in accessing the microRNomes from tissue-embedded cells, we had previously developed mime-seq (miRNome bymethylation dependent sequencing), a technique in which cell-specific miRNA methylation inC. elegansandDrosophilaenabled chemo-selective sequencing without the need for cell sorting or biochemical purification. Here, we present mime-seq 2.0 for profiling miRNAs from specific mouse cell types. We engineered a chimeric RNA methyltransferase that is tethered to Argonaute and efficiently methylates miRNAs at their 3’-terminal 2’OH in mouse and human cell lines. We also generated a transgenic mouse for conditional expression of this methyltransferase, which can be used to direct methylation of miRNAs in a cell-type of choice. We validated the use of this mouse by profiling miRNAs from B cells and bone marrow plasma cells.
Reputational self-awareness: an innovative career development tool
Authors: Foster Jeff , Stone Thomas , Jawahar I.M. , Steinheider Brigitte , Gray Truit W.
Published: November 2023

Purpose

The authors introduce a new construct, reputational self-awareness (RSA). RSA represents the congruence between how individuals think they are viewed by others (i.e. metaperceptions) versus how they are actually viewed (i.e. other ratings). The authors sought to demonstrate that RSA is a superior predictor of performance indices.

Design/methodology/approach

Personality self-ratings from 381 business students and their ratings by 966 others were collected via online surveys. Other raters rated self-raters' personalities as well as their task performance, organizational citizenship behaviors (OCBs) and counterproductive work behaviors (CWBs).

Findings

Results indicate that RSA predicts variance in performance above and beyond self-report ratings, and performance is highest when metaperceptions and other ratings of performance are aligned. These results support the use of a multi-perspective approach to personality assessment as a useful tool for coaching and career development.

Research limitations/implications

The authors' results support the use of a multi-perspective approach to personality assessment as a useful tool for coaching and career development. A cross-sectional design was used in which personality and performance data were gathered from respondents, and the P 720 is a relatively new personality instrument.

Practical implications

RSA is a valuable tool for employee development, coaching and counseling because, as extant research and the authors' findings demonstrate, awareness of how others view and judge one, one's reputation is essential information to guide work behaviors and career success. Therefore, a key career-development goal for trainers and counselors should be to use a multi-perspective approach to maximize clients' RSA.

Social implications

Use of other ratings as opposed to traditional self-rating of personality provides superior prediction of behavior and is more useful for career development.

Originality/value

This is the first study to demonstrate utility of RSA, i.e. that individuals who more accurately assess their personality are rated as performing better by others. The authors' results offer new insights for personality research and career development and support the use of personality assessment from multiple perspectives, thus enabling the exploration of potentially insightful research questions that cannot be examined by assessing personality from a single perspective.
Who is successful in career development? A person-centered approach to the study of career orientation profiles
Authors: Bazine Nicolas , Chénard-Poirier Léandre Alexis , Battistelli Adalgisa , Lagabrielle Marie-Christine
Published: November 2023

Purpose

This research examined the presence of career orientation profiles by investigating how young workers combined protean career orientation attitudes, motivation to learn to develop one's career and an optimistic future perspective on their career. It explored how a differentiated endorsement of these attitudes and motivation (i.e. career orientation profiles) were associated with the adoption of multiple career-enhancing behaviors, namely proactive career behaviors (i.e. career planning, networking and skill development) and learning behaviors with technologies.

Design/methodology/approach

Latent profile analysis was conducted among young individuals starting their career (N = 767) and found four distinct profiles.

Findings

The first profile revealed that 17.2% of workers in this sample were displaying low levels in protean career orientation, motivation to learn and optimistic future time perspective (profile 1). Two differentiated profiles showed either low levels of protean career orientation and high levels of motivation to learn (profile 2) or high levels of protean career attitudes and low levels of motivation to learn (profile 3). These profiles presented an average level of future time perspective and represented 13.8 and 40.6% of the sample. Finally, 28.4% of the sample showed high levels on all these variables (profile 4).

Originality/value

Only young workers who showed high levels on all these indicators also presented high levels of proactive behaviors and learning with technologies. The other three profiles were associated with suboptimal levels on these outcomes. Taken together, these results offer new insights into the psychological state of mind of workers most adapted to succeed in a modern career.