bluuebunny/crossref_metadata_2025 huggingface dataset:
The hot Neptune WASP-166 b with ESPRESSO – III. A blue-shifted tentative water signal constrains the presence of clouds
Authors: Lafarga M , Brogi M , Gandhi S , Cegla H M , Seidel J V , Doyle L , Allart R , Buchschacher N , Lendl M , Lovis C , Sosnowska D
Published: February 2023

With high-resolution spectroscopy, we can study exoplanet atmospheres and learn about their chemical composition, temperature profiles, and presence of clouds and winds, mainly in hot, giant planets. State-of-the-art instrumentation is pushing these studies towards smaller exoplanets. Of special interest are the few planets in the ‘Neptune desert’, a lack of Neptune-sized planets in close orbits around their hosts. Here, we assess the presence of water in one such planet, the bloated super-Neptune WASP-166 b, which orbits an F9-type star in a short orbit of 5.4 d. Despite its close-in orbit, WASP-166 b preserved its atmosphere, making it a benchmark target for exoplanet atmosphere studies in the desert. We analyse two transits observed in the visible with ESPRESSO. We clean the spectra from the Earth’s telluric absorption via principal component analysis, which is crucial to the search for water in exoplanets. We use a cross-correlation-to-likelihood mapping to simultaneously estimate limits on the abundance of water and the altitude of a cloud layer, which points towards a low water abundance and/or high clouds. We tentatively detect a water signal blue-shifted ∼5 $\mathrm{km\, s^{-1}}$ from the planetary rest frame. Injection and retrieval of model spectra show that a solar-composition, cloud-free atmosphere would be detected at high significance. This is only possible in the visible due to the capabilities of ESPRESSO and the collecting power of the VLT. This work provides further insight on the Neptune desert planet WASP-166 b, which will be observed with JWST.
Accelerated phase-mixing in the stellar halo due to a rotating bar
Authors: Davies Elliot Y , Dillamore Adam M , Vasiliev Eugene , Belokurov Vasily
Published: February 2023

In a galaxy merger, the stars tidally stripped from the satellite and accreted onto the host galaxy undergo phase-mixing and form finely grained structures in the phase space. However, these fragile structures may be destroyed in the subsequent galaxy evolution, in particular, by a rotating bar that appears well after the merger is completed. In this work, we investigate the survivability of phase-space structures in the presence of a bar. We find that a bar with amplitude and pattern speed similar to those of the Milky Way would blur and destroy a substantial amount of the substructure that consists of particles with pericentre radii comparable to the bar length. While this appears to be in tension with the recent discovery of phase-space chevrons in Gaia DR3 data, the most prominent chevrons in our simulations can still be recovered when applying the same analysis procedure as in observations. Moreover, the smoothing effect is less pronounced in the population of stars whose angular momenta have the opposite sign to the bar pattern speed.
Keck, gemini, and palomar 200-inch visible photometry of red and very-red neptunian trojans
Authors: Bolin B T , Fremling C , Morbidelli A , Noll K S , van Roestel J , Deibert E K , Delbo M , Gimeno G , Heo J-E , Lisse C M , Seccull T , Suh H
Published: February 2023

Neptunian Trojans (NTs), trans-Neptunian objects in 1:1 mean-motion resonance with Neptune, are generally thought to have been captured from the original trans-Neptunian protoplanetary disc into co-orbital resonance with the ice giant during its outward migration. It is possible, therefore, that the colour distribution of NTs is a constraint on the location of any colour transition zones that may have been present in the disc. In support of this possible test, we obtained g, r, and i-band observations of 18 NTs, more than doubling the sample of NTs with known visible colours to 31 objects. Out of the combined sample, we found ≈4 objects with g –i colours of >1.2 mags placing them in the very red (VR) category as typically defined. We find, without taking observational selection effects into account, that the NT g – i colour distribution is statistically distinct from other trans-Neptunian dynamical classes. The optical colours of Jovian Trojans and NTs are shown to be less similar than previously claimed with additional VR NTs. The presence of VR objects among the NTs may suggest that the location of the red to VR colour transition zone in the protoplanetary disc was interior to 30 – 35 au.
JWST unveils the brown dwarf sequence of 47 Tucanæ
Authors: Nardiello D , Griggio M , Bedin L R
Published: February 2023

We have developed a technique to restore scientific usage in compromised (publicly available) images collected with the JWST of the Galactic globular cluster NGC 104 (47 Tucanæ). In spite of the degradation and limited data, we were able to recover photometry and astrometry for the coolest stellar objects ever observed within a globular cluster, possibly unveiling the brightest part of the brown dwarf (BD) sequence. This is supported by (i) proper motion membership, derived by the comparison with positions obtained from Hubble Space Telescope archival early epochs, (ii) the predicted location of the BD sequence, and (iii) the mass function for low-mass stars derived from models. Future JWST observations will provide the necessary deep and precise proper motions to confirm the nature of the here-identified BD candidates belonging to this globular cluster.
Role of the histone tails in histone octamer transfer
Authors: Lorch Yahli , Kornberg Roger D , Maier-Davis Barbara
Published: February 2023

The exceptionally high positive charge of the histones, concentrated in the N- and C-terminal tails, is believed to contribute to the stability of the nucleosome by neutralizing the negative charge of the nucleosomal DNA. We find, on the contrary, that the high positive charge contributes to instability, performing an essential function in chromatin remodeling. We show that the tails are required for removal of the histone octamer by the RSC chromatin remodeling complex, and this function is not due to direct RSC–tail interaction. We also show that the tails are required for histone octamer transfer from nucleosomes to DNA, and this activity of the tails is a consequence of their positive charge. Thus, the histone tails, intrinsically disordered protein regions, perform a critical role in chromatin structure and transcription, unrelated to their well-known role in regulation through posttranscriptional modification.
HyperVR: a hybrid deep ensemble learning approach for simultaneously predicting virulence factors and antibiotic resistance genes
Authors: Ji Boya , Pi Wending , Liu Wenjuan , Liu Yannan , Cui Yujun , Zhang Xianglilan , Peng Shaoliang
Published: February 2023

Infectious diseases emerge unprecedentedly, posing serious challenges to public health and the global economy. Virulence factors (VFs) enable pathogens to adhere, reproduce and cause damage to host cells, and antibiotic resistance genes (ARGs) allow pathogens to evade otherwise curable treatments. Simultaneous identification of VFs and ARGs can save pathogen surveillance time, especially in situ epidemic pathogen detection. However, most tools can only predict either VFs or ARGs. Few tools that predict VFs and ARGs simultaneously usually have high false-negative rates, are sensitive to the cutoff thresholds and can only identify conserved genes. For better simultaneous prediction of VFs and ARGs, we propose a hybrid deep ensemble learning approach called HyperVR. By considering both best hit scores and statistical gene sequence patterns, HyperVR combines classical machine learning and deep learning to simultaneously and accurately predict VFs, ARGs and negative genes (neither VFs nor ARGs). For the prediction of individual VFs and ARGs, in silico spike-in experiment (the VFs and ARGs in real metagenomic data), and pseudo-VFs and -ARGs (gene fragments), HyperVR outperforms the current state-of-the-art prediction tools. HyperVR uses only gene sequence information without strict cutoff thresholds, hence making prediction straightforward and reliable.
Therapeutic Role of Tamoxifen for Triple-Negative Breast Cancer: Leveraging the Interaction Between ERβ and Mutant p53
Authors: Scarpetti Lauren , Oturkar Chetan C , Juric Dejan , Shellock Maria , Malvarosa Giuliana , Post Kathryn , Isakoff Steven , Wang Nancy , Nahed Brian , Oh Kevin , Das Gokul M , Bardia Aditya
Published: February 2023

The absence of effective therapeutic targets and aggressive nature of triple-negative breast cancer (TNBC) renders this disease subset difficult to treat. Although estrogen receptor beta (ERβ) is expressed in TNBC, studies on its functional role have yielded inconsistent results. However, recently, our preclinical studies, along with other observations, have shown the potential therapeutic utility of ERβ in the context of mutant p53 expression. The current case study examines the efficacy of the selective estrogen receptor modulator tamoxifen in p53-mutant TNBC with brain metastases. Significant increase in ERβ protein expression and anti-proliferative interaction between mutant p53 and ERβ were observed after cessation of tamoxifen therapy, with significant regression of brain metastases. This case study provides supporting evidence for the use of tamoxifen in p53-mutant, ERβ+TNBC, especially in the setting of brain metastasis.
Blameworthiness and Dependence
Authors: Clarke Randolph , Rawling Piers
Published: February 2023

Some recent accounts of blameworthiness present this property as response-dependent: an agent is blameworthy, they say, if and only if, and (if so) in virtue of the fact that, it is fitting to respond to her with a certain blaming emotion. Given the explanatory aim of these views, the selected emotion cannot be said simply to appraise its object as blameworthy. We argue that articulation of the appraisal in other terms suggested by proponents yields a failure of the coextension required by the accounts. We then address the promise to explain why the conditions that render one blameworthy are as they are. According to proponents, these conditions render one blameworthy because they render fitting the selected emotion. But why do just these conditions do the latter? We find no good answer to this question from proponents of the accounts. While we do not contend that blameworthiness is response-independent, we are unconvinced that it is response-dependent.
Social Positions and Fairness Views on Inequality
Authors: Hvidberg Kristoffer B , Kreiner Claus T , Stantcheva Stefanie
Published: February 2023

We link survey data on Danish people’s perceived income positions and fairness views on inequality within various reference groups to administrative records on their reference groups, income histories, and life events. People are, on average, well-informed about the income levels of their reference groups. Yet, lower-ranked respondents in all groups tend to overestimate their own position among others because they believe others’ incomes are lower than they actually are, whereas the opposite holds true for higher-ranked respondents. Misperceptions of positions in reference groups relate to proximity to other individuals, transparency norms, and visible signals of income. People view inequalities within their co-workers and education groups as significantly more unfair than overall inequality, yet underestimate inequality the most exactly within these groups. Views on the fairness of inequalities are strongly correlated with an individual’s current position, move with shocks like unemployment or promotions, and change when experimentally informing people about their actual positions. However, the higher perceived unfairness of income differences within co-workers and education groups stays unchanged. The theoretical framework shows that this can have important implications for redistribution policy.
A “Surrogate State” for Refugees in Greece
Authors: Moschopoulos Manos
Published: February 2023

The rapid increase in the number of refugees arriving to Greece in 2015 and the subsequent moves by the European Union Member States to limit their secondary movement triggered what has been described as the “most expensive humanitarian response in history.” The European Commission, believing that Greece did not have the capacity to respond to the situation, directly funded international organisations, primarily the United Nations High Commissioner for Refugees (UNHCR), and international non-governmental organisations to do so. The “care and maintenance model” at the core of UNHCR’s response to protracted refugee situations has been described as a “surrogate state,” complete with the territory, services, and citizens. This article aimed to examine whether this refugee response in Greece followed the “surrogate state” model which characterised interventions in other geographies, by studying UNHCR’s service provision, governance functions, perception of legitimacy, territorial presence and influence. This study shows that this refugee response was characterised by a degree of surrogacy that resembles the “surrogate states” observed in other refugee responses. The Greek government was marginalised during the response and abdicated a significant degree of responsibility to UNHCR. This negatively affected the quality of the response itself and the long-term welfare and prospects of refugees.
Identification of flucloxacillin-modified hepatocellular proteins: implications in flucloxacillin-induced liver injury
Authors: Ali Serat-E , Waddington James C , Lister Adam , Sison-Young Rowena , Jones Robert P , Rehman Adeeb H , Goldring Chris E P , Naisbitt Dean J , Meng Xiaoli
Published: February 2023

Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver injury. Although expression of HLA-B*57:01 is associated with increased susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the provision of flucloxacillin-modified peptides that are presented to T-cells by the protein encoded by the risk allele. In this study, we have shown that flucloxacillin binds to multiple proteins within human primary hepatocytes, including major hepatocellular proteins (hemoglobin and albumin) and mitochondrial proteins. Inhibition of membrane transporters multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein (P-gp) appeared to reduce the levels of covalent binding. A diverse range of proteins with different functions was found to be targeted by flucloxacillin, including adaptor proteins (14-3-3), proteins with catalytic activities (liver carboxylesterase 1, tRNA-splicing endonuclease subunit Sen2, All-trans-retinol dehydrogenase ADH1B, Glutamate dehydrogenase 1 mitochondrial, Carbamoyl-phosphate synthase [ammonia] mitochondrial), and transporters (hemoglobin, albumin, and UTP-glucose-1-phosphate uridylyltransferase). These flucloxacillin-modified intracellular proteins could provide a potential source of neoantigens for HLA-B*57:01 presentation by hepatocytes. More importantly, covalent binding to critical cellular proteins could be the molecular initiating events that lead to flucloxacillin-induced cholestasis Data are available via ProteomeXchange with identifier PXD038581.
The Relationship Between Respiratory Complaints and Urine Aluminum Levels in Aluminum Factory Workers
Authors: BilgiN Cahit , Arbak Peri , Güleç Balbay Ege , Balbay Öner , Annakkaya Ali Nihat
Published: February 2023

Objective

This prospective case-control study aimed to investigate the forms and conditions of respiratory effects in workers working in an Aluminum Profile Factory.

Methods

All male (42 person, mean age: 32.2 ± 6.9) workers working in an Aluminum Profile Factory were compared with 33 controls.

Results

The urinary aluminum levels of the workers were significantly higher than the control group. Complaints of cough, sputum, shortness of breath and wheezing were statistically significantly higher than the control group. In aluminum workers, those with dyspnea had a significantly higher urinary Al level than those without dyspnea.

Conclusions

It is thought that primary and secondary prevention are both important in the workplaces with aluminum exposure. Urinary aluminum level monitoring could be key to protecting the respiratory health of the workers.
By Nature, We're Doers and Problem Solvers
Authors: Castro Katherine C. , Fisher Alexandra B. , Geczik Ashley M. , Boyer Stacy L. , Resick Christian J. , Lee Jin , Davis Andrea L. , Taylor Jennifer A. , Allen Joseph A.
Published: February 2023

Objective

The US fire service experienced increased demands due to COVID-19. This qualitative study explored the pandemic's impact on work-life balance and safety.

Methods

Five interviews and 10 focus groups were conducted with 15 fire departments in the COVID-19 RAPID Mental Health Assessment. Coding and multilevel content analysis were conducted in NVivo.

Results

Four department support themes were identified: emotional/social (33.1%), policy (28.4%), instrumental (22.9%), and informational (15.5%). Four work-life balance themes were identified: life (51.2%), children (18.1%), physiological (16.5%), and work (14.2%). We observed more departmental resources to help mitigate job demands within the work environment compared with those for work-life demands.

Conclusions

Job resources are needed to mitigate demands and improve safety culture and mental well-being of the fire service under normal conditions, and for the next pandemic, natural disaster, or long-term emergency.
Impedance Change as an Indicator of Cochlear Implant Failure
Authors: Pisa Justyn F. D. , Almutairi Walleed H. , Mackie Kristy , Stangherlin Daniela , Sulkers Jacob , Hochman Jordan B.
Published: February 2023

Objective

In February 2020, Advanced Bionics initiated a field action notice to remove the MS Ultra (V1) implant from circulation. In this study, we quantify a single site’s incidence with device failure and examine the relationship between impedance change and declining speech perception.

Study Design

Retrospective/cohort study.

Setting

Tertiary healthcare center.

Patients

Forty-nine adult patients (52 devices) were implanted between October 2017 and December 2019, with the following exclusion criteria: <18 years of age, medical/surgical failures, and lack of English-language proficiency.

Interventions

Diagnostic.

Main Outcome Measures

Postoperative speech perception (AzBio sentence test) scores at 12 months postactivation were compared with repeat testing at 6- to 12-month intervals. Degree of change in impedances from 1 month postactivation was analyzed at similar intervals. Device failures were suspected when impedance levels on three or more electrodes dropped to <3.5 kΩ and AzBio scores declined >15%. Device failures were confirmed through analyses completed by the manufacturer.

Results

To date, 21% (11/52) of devices have met all three criteria for a confirmed failure with an average decline in speech perception of 27.7 ± 22%. The average length of time for detection of device failure was 21.9 ± 5 months postimplantation. An additional 7 devices (13%) are currently being monitored for failure but have not yet met full criteria. There was no predictive relationship between degree of impedance change and speech perception scores. Electrodes along the entire array (channels 1–16) can be affected.

Conclusions

Impedance values can be used as a reliable indicator of device malfunction, thus facilitating patient counseling and early intervention. No correlation was identified between impedance changes and speech perception scores.
Totally Implantable Hearing Implant Revision Surgery Indications and Outcomes
Authors: Shohet Jack , Bibee Jacqueline , Gende Deanna
Published: February 2023

Objective

Analyze indications, findings, and outcomes of revision procedures for a totally implantable active middle ear implant (AMEI) over the past 17 years.

Study Design

Retrospective review.

Setting

Single institution, private practice setting.

Subjects

Adult patients using a totally implantable AMEI called the Esteem middle ear implant by Envoy Medical who needed revision to their original implant between 2005 and 2022. Thirty-nine patients had 60 revision procedures.

Intervention

History of a totally implantable AMEI revision procedure. Indications for revision were related to either surgical wound issues or reduced device function.

Outcome Measures

Device diagnostics, audiometric outcomes, and documented subjective report.

Results

Surgical site wound issues were readily corrected in the majority of patients; most had risk factors for wound breakdown. For sterile wound dehiscence, it was not always necessary to remove the sound processor for an extended time to promote healing. Outcomes for revision procedures because of device issues ranged from 31 to 100% success rate, depending on the cause of issue. The most common indication for revision was reduced device function caused by scar band and/or fibrotic tissue accumulation in the middle ear.

Conclusion

Revision of fully implantable AMEI can be successful for many indications. Appropriate preoperative device troubleshooting and medical evaluation is helpful in identifying the issue and determining surgical approach. Suboptimal device function and feedback can sometimes be improved by removing tissue around the implant, although permanency of this procedure varies among patients.
Recurrent Benign Paroxysmal Positional Vertigo in DFNB16 Patients with Biallelic STRC Gene Deletions
Authors: Achard Sophie , Campion Margaux , Parodi Marine , MacAskill Melissa , Hochet Baptiste , Simon François , Rouillon Isabelle , Jonard Laurence , Serey-Gaut Margaux , Denoyelle Françoise , Loundon Natalie , Marlin Sandrine
Published: February 2023

Objective

Deletions of STRC gene (DFNB16) account for 12% of isolated congenital mild to moderate hearing loss (HL). In mice, the stereocilin protein, encoded by STRC, is present in the vestibular kinocilium embedded in the otoconial membrane of the utricular macula. Despite this, effects on vestibular function have not been widely investigated. The aim of this study was to investigate the prevalence of benign paroxysmal positional vertigo (BPPV) in a cohort of DFNB16 patients.

Study Design

Observational descriptive epidemiological study.

Setting

Single-center study, in a tertiary referral center.

Patients

Older than 5 years, with a genetic diagnosis of HL related to biallelic STRC gene deletions, diagnosed between 2015 and 2021

Intervention

Patients or their parents were interviewed to determine whether they had experienced vertigo or episodes of BPPV.

Main Outcome Measure

Criteria were at least five acute episodes of rotatory vertigo, each lasting less than 1 minute, episodes triggered by changes in specific head position, and an absence of neurological symptoms.

Results

Sixty-four patients having mild (33%) to moderate (66%) HL were included. Median age was 15 years (range, 6–48 yr). Prevalence of BPPV was 39% (25 of 64). Median age of first onset was 13 years (range, 3–18 yr).

Conclusions

This study showed recurrent BPPV and early age of onset in patients with biallelic STRC gene deletions. BPPV may be associated with the HL phenotype in patients with STRC gene deletions. It is important to inform patients and families of this potential risk such that appropriate management can be proposed.
Oxidized phospholipid oxPAPC induces a Th1-like phenotype in regulatory T cells and inhibits their protective function in atherosclerosis
Authors: Appleton Brenna D. , Palmer Sydney A. , Smith Harrison P. , Stephens Lilly E. , Major Amy S.
Published: February 2023

Background

Regulatory T cells (Tregs) are protective in atherosclerosis but reduced during disease progression due to cell death and loss of stability. However, the mechanisms of Tregdysfunction remain unknown. Oxidized phospholipids (oxPLs) are abundant in atherosclerosis and can activate innate immune cells, but there is limited information regarding their impact on T cells. Given Tregloss during atherosclerosis progression and oxPL levels in the plaque microenvironment, we sought to determine whether oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), an oxPL associated with atherosclerotic plaques, alters Tregdifferentiation and function.

Methods

Naïve CD4+T cells were cultured under Treg,Th1, and Th17 polarizing conditions with or without oxPAPC and assessed by flow cytometry. Gene expression in oxPAPC-treated Tregswas analyzed by bulk RNA sequencing. Functional studies of oxPAPC-induced Tregswere performed by co-culturing Tregswith CTV-labeled CD8+cellsin vitro. In vivosuppression of atherosclerosis was evaluated by adoptively transferring control or oxPAPC-treated Tregsto hyperlipidemicLdlr-/-mice.

Results

Compared to controls, oxPAPC-treated Tregswere less viable but expressed higher levels of the Th1-associated markers T-bet, CXCR3, and IFN-γ. Th1 and Th17 skewing cultures were unaltered by oxPAPC. IFN-γ is linked to Treginstability, thus Tregpolarization experiments were repeated usingIfngr1-/-CD4+T cells. IFNγR1 deficiency did not improve cell viability in oxPAPC-treated Tregs, however, T-bet and IFN-γ expression was not increased suggesting a role for IFN-γ signaling. OxPAPC-treated Tregswere less suppressivein vitro, and adoptive transfer studies in hyperlipidemicLdlr-/-mice showed that oxPAPC-induced Tregspossessed altered tissue homing and were insufficient to inhibit atherosclerosis progression.

Conclusions

OxPAPC elicits Treg-specific changes that induce a Th1-like phenotype dependent on IFN-γ signaling. This is biologically relevant as oxPAPC-treated Tregsare unable to reduce atherosclerosis progression inLdlr-/-mice. This study supports a role for oxPLs in negatively impacting Tregdifferentiation and atheroprotective function.
Industrial chicory genome gives insights into the molecular timetable of anther development and male sterility
Authors: Waegneer Evelien , Rombauts Stephane , Baert Joost , Dauchot Nicolas , De Keyser Annick , Eeckhaut Tom , Haegeman Annelies , Liu Chang , Maudoux Olivier , Notté Christine , Staelens Ariane , Van der Veken Jeroen , Van Laere Katrijn , Ruttink Tom
Published: February 2023

Industrial chicory (Cichorium intybusvar.sativum) is a biannual crop mostly cultivated for extraction of inulin, a fructose polymer used as a dietary fiber. F1hybrid breeding is a promising breeding strategy in chicory but crucially relies on stable self-incompatibility. Here, we report the assembly and annotation of a new industrial chicory reference genome. Additionally, we performed RNA-Seq on subsequent stages of flower bud development of a fertile line and two cytoplasmic male sterile (CMS) clones. Comparison of fertile and CMS flower bud transcriptomes combined with morphological microscopic analysis of anthers, provided a molecular understanding of anther development and identified key genes in a range of underlying processes, including tapetum development, sink establishment, pollen wall development and anther dehiscence. We also described the role of phytohormones in the regulation of these processes under normal fertile flower bud development. In parallel, we evaluated which processes are disturbed in CMS clones and could contribute to the male sterile phenotype. Taken together, this study provides a state-of-the-art industrial chicory reference genome, an annotated and curated candidate gene set related to anther development and male sterility as well as a detailed molecular timetable of flower bud development in fertile and CMS lines.
The clustering of multiple health and lifestyle behaviours among Swedish adolescents: A person-oriented analysis
Authors: Jonsson Kenisha Russell , Corell Maria , Löfstedt Petra , Adjei Nicholas Kofi
Published: February 2023

Background

Knowledge of the distribution, prevalence, and clustering of multiple health and lifestyle related behaviours (HLBs) among adolescents can inform the development of more effective health-promoting policies and interventions. We therefore assessed the clustering of multiple HLBs among 11, 13 and 15-year-old Swedish adolescents and examined the socioeconomic and demographic correlates of each cluster.

Methods

We used data from the 2017/2018 Swedish Health Behaviour in School-aged Children (HBSC) study to conduct sex and age-stratified latent class analysis (LCA). The LCA was based on five HLBs: eating behaviour and habits (EBH), physical activity (PA), tobacco usage (TU), alcohol consumption (AC) and sleeping habits and patterns (SHPs). Multinomial logistic regression models were used to assess the associations between the identified clusters and the socioeconomic and demographic characteristics of adolescents and their parents.

Results

Health behaviours varied by age and sex. Four distinct clusters were identified based on sex: cluster 1 (Mixed eating behaviours and habits, physical activity and low alcohol consumption), cluster 2 Healthy lifestyle behaviours), cluster 3 (Unhealthy lifestyle behaviours), and cluster 4 (Breakfast, low alcohol consumption and tobacco usage). In the age-stratified analyses, three clusters were identified: cluster 1 (Unhealthy lifestyle behaviours), cluster 2 (Moderately healthy lifestyle behaviours) and cluster 3 (Healthy lifestyle behaviours). The multinomial analysis showed that sex, age, family situation and perceived family wealth were strong predictors of health behaviours. In particular, unhealthy behaviours showed the most frequent associations with socioeconomic disadvantage, having a migrant background and living in reconstructed families or single parent households.

Conclusions

Health behaviours vary significantly based on socioeconomic and demographic factors. Targeted policy and interventions programmes can effectively improve HLBs among vulnerable and at-risk adolescents.
Improved cognition after high-intensity exercise paired with motor practice in individuals with stroke and older adults: A randomized controlled trial
Authors: Greeley Brian , Larssen Beverley C. , Ferris Jennifer , Yeganeh Negin Motamed , Andrushko Justin W. , Chau Briana , Jones Christina B. , Peters Sue , Campbell Kristin L. , Neva Jason L. , Boyd Lara A.
Published: February 2023

Introduction

Stroke is a leading cause of long-term disability resulting in cognitive and motor impairments. Exercise may improve cognition and motor function. We paired multiple bouts of high-intensity interval training (HIIT) exercise with motor practice to positively affect cognitive and motor function after stroke and age-matched controls.

Methods

Using a randomized controlled parallel group design, 31 individuals with chronic stroke and 41 older adult controls were randomized to either 23 minutes of HIIT exercise or rest prior to completing motor task practice using their paretic/non-dominant arm across five days. Primary outcomes were reaction time and motor function. Assessors were blinded to the intervention group. Trail Making Test-A and B (TMT-A, TMT-B), and object hit and avoid (OHA) were used to assess processing speed and inhibitory control.

Results

All participants showed evidence of motor learning; HIIT exercise did not confer an additional benefit. For stroke participants, motor function (p= .047), but not motor impairment, improved. The stroke exercise group displayed significant reductions in TMT-A completion time (p= .026). Exercise with motor practice also led to a reduced number of distractors hit (p =.035) in the OHA task for both participant groups. There were no adverse events.

Conclusions

Five days of HIIT exercise paired with motor practice led to improved processing speed for individuals with stroke. Both participant, exercise groups showed improved visuospatial skills and inhibitory control. Together, HIIT exercise paired with motor practice appears to be a safe and effective means of enhancing cognitive-motor skills after stroke and in older adults.

Trial Registry

ClinicalTrials.gov, ID:NCT02980796

Trial registry name

The Influence of Exercise on Neuroplasticity and Motor Learning After Stroke (EX-ML3)
CDK5 activity in retinal pigment epithelium contributes to gap junction dynamics during phagocytosis
Authors: Fadjukov Julia , Wienbar Sophia , Milićević Nemanja , Hakanen Satu , Vihinen-Ranta Maija , Ihalainen Teemu O. , Schwartz Gregory W. , Nymark Soile
Published: February 2023

Retinal pigment epithelium (RPE) at the back of the eye is a monolayer of cells with an extensive network of gap junctions that contributes to retinal health in a multitude of ways. One of those roles is the phagocytosis of photoreceptor outer segments. This renewal is under circadian regulation and peaks after light onset. Connexin 43 (Cx43) is the most predominantly expressed gap junction protein in RPE. In this study, we examine how gap junctions and specifically, Cx43 phosphorylation, contribute to phagocytosis in both human embryonic stem cell derived RPE and mouse RPE monolayers. We show that both Rac1 and CDK5 have differences in protein localization at different points in phagocytosis, and that by using their effectors, the capability of RPE for phagocytosis changes. CDK5 has not yet been reported in RPE tissue, and here we show that it likely regulates Cx43 localization and resulting electrical coupling. We find that gap junctions in RPE are temporally highly dynamic during phagocytosis and that regulation of gap junctions via phosphorylation is likely critical for maintaining eye health.
Population genetics in the early emergence of the Omicron SARS-CoV-2 variant in the provinces of South Africa
Authors: Contreras-González María Fernanda , Castelán-Sánchez Hugo G. , Diaz-Valenzuela Erik , Cibrián-Jaramillo Angélica
Published: February 2023

Population genetic analyses of viral genome populations provide insight into the emergence and evolution of new variants of SARS-CoV-2. In this study, we use a population genetic approach to examine the evolution of the Omicron variant of SARS-CoV-2 in four provinces of South Africa (Eastern Cape, Gauteng, KwaZulu-Natal, and Mpumalanga) during the first months before emergence and after early spread. Our results show that Omicron polymorphisms increase sharply from September to November. We found differences between SARS-CoV-2 populations from Gauteng and Kwazulu-Natal and viruses from the Eastern Cape, where allele frequencies were higher, suggesting that natural selection may have contributed to the increase in frequency or that this was the site of origin. We found that the frequency of variants N501Y, T478K, and D614G increased in the spike in November compared with other mutations, some of which are also present in other animal hosts. Gauteng province was the most isolated, and most genetic variation was found within populations. Our population genomic approach is useful for small-scale genomic surveillance and identification of novel allele-level variants that can help us understand how SARS-CoV-2 will continue to adapt to humans and other hosts.
Defining the Burden of Disease of RSV in Europe: estimates of RSV-associated hospitalisations in children under 5 years of age. A systematic review and modelling study
Authors: Del Riccio Marco , Spreeuwenberg Peter , Osei-Yeboah Richard , Johannesen Caroline K. , Fernandez Liliana Vazquez , Teirlinck Anne C. , Wang Xin , Heikkinen Terho , Bangert Mathieu , Caini Saverio , Campbell Harry , Paget John
Published: February 2023

Background

Respiratory syncytial virus (RSV) infections cause an estimated 22-50 million episodes of acute lower respiratory infections (ALRI) every year in children younger than 5 years. To date, no overall estimate of RSV-associated hospitalisations in children under 5 years has been published for the European Union (EU). Through statistical modelling, we estimated the RSV hospitalisation burden in children under 5 years of age in EU countries and Norway, by age group and country.

Methods

We collated national RSV-associated hospitalisation estimates calculated using linear regression models in children under 5 years via the RESCEU project for Denmark, England, Finland, Norway, the Netherlands and Scotland during 2006-2018. A systematic literature review was conducted to collect additional estimates. Using the multiple imputation and nearest neighbour matching extrapolation methods, we estimated RSV-associated hospitalisation rates in all EU countries.

Results

Additional estimates for Spain and France were found in the literature and added to the analysis. We estimated that an average of 245,244 (95%CI 224,688-265,799) hospital admissions with a respiratory infection per year were associated with RSV in children under the age of 5, with most cases occurring among children aged less than 1 year (75%). Infants aged less than 2 months represented the most affected group (71.6 per 1,000 children; 95%CI: 66.6-76.6). The hospitalisation rates varied widely across countries: for example, estimated rates in the 0-2 months age group ranged from 47.4 (37.5-57.3) per 1,000 in the Netherlands to 98.3 (88.5-108.1) per 1,000 in France.

Conclusion

To our knowledge, this is the first attempt to estimate the overall RSV hospitalisation burden in children under the age of 5 years in the EU. Our findings will help support decisions regarding prevention efforts, and they will also represent an important benchmark to understand changes in the RSV burden following the introduction of RSV immunisation programs in Europe.
Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2
Authors: Lee Ding-Chin , Tai Jui-Hung , Lin Hsin-Fu , Chao Tai-Ling , Ruan Yongsen , Cheng Ya-Wen , Chou Yu-Chi , Lin You-Yu , Chang Sui-Yuan , Chen Pei-Jer , Yeh Shiou-Hwei , Wang Hurng-Yi
Published: February 2023

Analyses of the genomic diversity of SARS-CoV-2 found that some sites across the genome appear to have mutated independently multiple times with frequency significantly higher than four-fold sites, which can be either due to mutational bias, i.e., elevated mutation rate in some sites of the genome, or selection of the variants due to antagonistic pleiotropy, a condition where mutations increase some components of fitness at a cost to others. To examine how different forces shaped evolution of SARS-CoV-2 in 2020–2021, we analyzed a large set of genome sequences (~ 2 million). Here we show that while evolution of SARS-CoV-2 during the pandemic was largely mutation-driven, a group of nonsynonymous changes is probably maintained by antagonistic pleiotropy. To test this hypothesis, we studied the function of one such mutation, spike M1237I. Spike I1237 increases viral assembly and secretion, but decreases efficiency of transmissionin vitro. Therefore, while the frequency of spike M1237I may increase within hosts, viruses carrying this mutation would be outcompeted at the population level. We also discuss how the antagonistic pleiotropy might facilitate positive epistasis to promote virus adaptation and reconcile discordant estimates of SARS-CoV-2 transmission bottleneck sizes in previous studies.
The genomic landscape of swine influenza A viruses in Southeast Asia
Authors: Zeller Michael A , Ma Jordan , Wong Foong Ying , Tum Sothrya , Hidano Arata , Holt Hannah , Chhay Ty , San Sorn , Koeut Dina , Seng Bunnary , Chao Sovanncheypo , Ng Giselle GK , Yan Zhuang , Chou Monidarin , Rudge James W , Smith Gavin JD , Su Yvonne CF
Published: February 2023

Swine are a primary source for the emergence of pandemic influenza A viruses. The intensification of swine production, along with global trade, has amplified the transmission and zoonotic risk of swine influenza virus (swIAV). Effective surveillance is essential to uncover emerging virus strains, however gaps remain in our understanding of the swIAV genomic landscape in Southeast Asia. By collecting more than 4,000 nasal swabs and 4,000 sera from pigs in Cambodia, we unmasked the co-circulation of multiple lineages of genetically diverse swIAV of pandemic concern. Genomic analyses revealed a novel European avian-like H1N2 swine reassortant variant with North American triple reassortant internal genes, that emerged approximately seven years before its first detection in pigs in 2021. Using phylogeographic reconstruction, we identified south central China as the dominant source of swine viruses disseminated to other regions in China and Southeast Asia. We also identified nine distinct swIAV lineages in Cambodia, which diverged from their closest ancestors between two to 15 years ago, indicating significant undetected diversity in the region, including reverse zoonoses of human H1N1/2009 pandemic and H3N2 viruses. A similar period of cryptic circulation of swIAVs occurred in the decades before the H1N1/2009 pandemic. The hidden diversity of swIAV observed here further emphasizes the complex underlying evolutionary processes present in this region, reinforcing the importance of genomic surveillance at the human-swine interface for early warning of disease emergence to avoid future pandemics.
Improving cell-free expression of membrane proteins by tuning ribosome co-translational membrane association and nascent chain aggregation
Authors: Steinküher Jan , Peruzzi Justin A. , Krüger Antje , Jacobs Miranda L. , Jewett Michael C. , Kamat Neha P.
Published: February 2023

Cell-free gene expression (CFE) systems are powerful tools for transcribing and translating genes outside of a living cell. Given their diverse roles in nature, synthesis of membrane proteins is of particular interest, but their yield in CFE is substantially lower than for soluble protein. In this paper, we study factors that affect the cell-free synthesis of membrane proteins and develop a quantitative kinetic model of their production. We identify that stalling of membrane protein translation on the ribosome is a strong predictor of membrane protein synthesis and creates a negative feedback loop in which stalled peptide sequences quench ribosome activity through aggregation between the ribosome nascent chains. Synthesis can be improved by the addition of lipid membranes which incorporate protein nascent chains and, therefore, kinetically competes with aggregation. Using both quantitative modeling and experiment, we show that the balance between peptide-membrane association and peptide aggregation rates determines the total yield of synthesized membrane protein. We then demonstrate that this balance can be shifted by altering membrane composition or the protein N-terminal domain sequence. Based on these findings, we define a membrane protein expression score that can be used to rationalize the engineering of N-terminal domain sequences both of a native and computationally designed membrane proteins produced through CFE.
Sema7A and Sema4D Heterodimerization is Essential for Membrane Targeting and Neocortical Wiring
Authors: Bessa Paraskevi , Newman Andrew G. , Yan Kuo , Schaub Theres , Dannenberg Rike , Lajkó Denis , Eilenberger Julia , Brunet Theresa , Textoris-Taube Kathrin , Kemmler Emanuel , Banerjee Priyanka , Ravindran Ethiraj , Mülleder Michael , Preissner Robert , Grosschedl Rudolf , Rosário Marta , Tarabykin Victor
Published: February 2023

Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving intellectual disability, speech delay, epilepsy and craniofacial defects. We show that Satb2 controls neuronal migration and axonal outgrowth by inducing the expression of the GPI-anchored protein, Sema7A. We find that heterodimerization with Sema4D increases targeting of Sema4D to the membrane and is required for Sema7A function. Finally, we report that membrane localization and pos- translational modification of the Sema7A-Sema4D complex is disrupted by a novel de novo mutation in Sema4D (Q497P) that is associated with epilepsy in humans.

GRAPHICAL ABSTRACT

HIGHLIGHTS

Sema7A is a direct Satb2 target that drives neuronal migration and axon outgrowth

Sema7A exerts its effect by heterodimerizing with Sema4D at neurites and growth cones

Sema7A increases cell surface localization of Sema4D

De novohuman Sema4D-Q497P mutation causes epilepsy, inhibits post-translational processing & surface localization

eTOC

Sema7A is a direct target of the transcription factor Satb2. Sema7A promotes normal migration and axon outgrowth in cortical neurons by modulating reverse signaling via Sema4D. These processes are dependent on Sema7A-Sema4D heterodimerization and membrane localization; insufficient transcription of Sema7A or incomplete glycosylation of Sema4D inhibit this progression.
The yeast RNA methylation complex consists of conserved yet reconfigured components with m6A-dependent and independent roles
Authors: Ensinck Imke , Maman Alexander , Albihlal Waleed S. , Lassandro Michelangelo , Salzano Giulia , Sideri Theodora , Howell Steven , Calvani Enrica , Patel Harshil , Bushkin G. Guy , Ralser Markus , Snijders Ambrosius P. , Skehel Mark , Casañal Ana , Schwartz Schraga , van Werven Folkert J.
Published: February 2023

N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis and was known to comprise three proteins, of which two were conserved. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian MTC orthologs. Unlike the mammalian bipartite MTC, the yeast MTC is unipartite, yet multifunctional. The mRNA interacting module, comprising Ime4, Mum2, Vir1, and Kar4, exerts the MTC’s m6A-independent function, while Slz1 enables the MTC catalytic function in m6A deposition. Both functions are critical for meiotic progression. Kar4 also has a mechanistically separate role from the MTC during mating. The yeast MTC constituents play distinguishable m6A-dependent, MTC-dependent and MTC-independent functions, highlighting their complexity and paving the path towards dissecting multi-layered MTC functions in mammals.