bluuebunny/crossref_metadata_2025 huggingface dataset:
Martian global current systems and related solar wind energy transfer: hybrid simulation under nominal conditions
Authors: Wang Xiao-Dong , Fatemi Shahab , Holmström Mats , Nilsson Hans , Futaana Yoshifumi , Barabash Stas
Published: December 2023

The magnetized solar wind drives a current system around Mars that maintains its induced magnetosphere. The solar wind also transfers its energy to the atmospheric ions, causing continuous atmospheric erosion, which has a profound impact on the planet’s evolution history. Here, we use Amitis, a Graphics Processing Unit (GPU)-based hybrid plasma model to first reproduce the global pattern of the net electric current and ion currents under an interplanetary magnetic field perpendicular to the solar wind flow direction. The resultant current distribution matches the observations and reveals more details. Using the electric field distribution characterized earlier with the same model, we calculate for the first time the spatial distribution of energy transfer rate to the plasmas in general and to different ion species at Mars. We find out that (1) the solar wind kinetic energy is the dominant energy source that drives Martian induced magnetosphere, (2) the energy flux of the shocked solar wind flows from the magnetic equatorial plane towards the plasma sheet in the induced magnetotail, (3) both the bow shock and the induced magnetospheric boundary are dynamos where plasma energy is transferred to the electromagnetic field, and (4) the planetary ions act as loads and gain energy from the electromagnetic field. The most intense load region is the planetary ion plume. The general pattern of the energy transfer rate revealed in this study is common for induced magnetospheres. Its variabilities with the upstream conditions can provide physical insight into the observed ion escape variabilities.
A Bayesian method to mitigate the effects of unmodelled time-varying systematics for 21-cm cosmology experiments
Authors: Kirkham Christian J , Anstey Dominic J , de Lera Acedo Eloy
Published: December 2023

Radio observations of the neutral hydrogen signal from the Cosmic Dawn and Epoch of Reionization have helped to provide constraints on the properties of the first stars and galaxies. Since this global 21-cm cosmological signal from the Cosmic Dawn is effectively constant on observing time-scales and since effects resulting from systematics will vary with time, the effects of these systematics can be mitigated without the need for a model of the systematic. We present a method to account for unmodelled time-varying systematics in 21-cm radio cosmology experiments using a squared exponential Gaussian process kernel to account for correlations between time bins in a fully Bayesian way. We find by varying the model parameters of a simulated systematic that the Gaussian process method improves our ability to recover the signal parameters by widening the posterior in the presence of a systematic and reducing the bias in the mean fit parameters. When varying the amplitude of a model sinusoidal systematic between 0.25 and 2.00 times the 21-cm signal amplitude and the period between 0.5 and 4.0 times the signal width, we find on average a 5  per cent improvement in the root mean squared error of the fitted signal. We can use the fitted Gaussian process hyperparameters to identify the presence of a systematic in the data, demonstrating the method’s utility as a diagnostic tool. Furthermore, we can use Gaussian process regression to calculate a mean fit to the residuals over time, providing a basis for producing a model of the time-varying systematic.
Interaction of histone H4 with Cse4 facilitates conformational changes in Cse4 for its sumoylation and mislocalization
Authors: Ohkuni Kentaro , Au Wei-Chun , Kazi Amira Z , Villamil Mark , Kaiser Peter , Basrai Munira A
Published: December 2023

Mislocalization of overexpressed CENP-A (Cse4 in budding yeast, Cnp1 in fission yeast, CID in flies) contributes to chromosomal instability (CIN) in yeasts, flies, and human cells. Mislocalization of CENP-A is observed in many cancers and this correlates with poor prognosis. Structural mechanisms that contribute to mislocalization of CENP-A are poorly defined. Here, we show that interaction of histone H4 with Cse4 facilitates an in vivo conformational change in Cse4 promoting its mislocalization in budding yeast. We determined that Cse4 Y193A mutant exhibits reduced sumoylation, mislocalization, interaction with histone H4, and lethality in psh1Δ and cdc48-3 strains; all these phenotypes are suppressed by increased gene dosage of histone H4. We developed a new in vivo approach, antibody accessibility (AA) assay, to examine the conformation of Cse4. AA assay showed that wild-type Cse4 with histone H4 is in an ‘open’ state, while Cse4 Y193A predominantly exhibits a ‘closed’ state. Increased gene dosage of histone H4 contributes to a shift of Cse4 Y193A to an ‘open’ state with enhanced sumoylation and mislocalization. We provide molecular insights into how Cse4-H4 interaction changes the conformational state of Cse4 in vivo. These studies advance our understanding for mechanisms that promote mislocalization of CENP-A in human cancers.
DAXX promotes centromeric stability independently of ATRX by preventing the accumulation of R-loop-induced DNA double-stranded breaks
Authors: Pinto Lia M , Pailas Alexandros , Bondarchenko Max , Sharma Abhishek Bharadwaj , Neumann Katrin , Rizzo Anthony J , Jeanty Céline , Nicot Nathalie , Racca Carine , Graham Mindy K , Naughton Catherine , Liu Yaqun , Chen Chun-Long , Meakin Paul J , Gilbert Nick , Britton Sébastien , Meeker Alan K , Heaphy Christopher M , Larminat Florence , Van Dyck Eric
Published: December 2023

Maintaining chromatin integrity at the repetitive non-coding DNA sequences underlying centromeres is crucial to prevent replicative stress, DNA breaks and genomic instability. The concerted action of transcriptional repressors, chromatin remodelling complexes and epigenetic factors controls transcription and chromatin structure in these regions. The histone chaperone complex ATRX/DAXX is involved in the establishment and maintenance of centromeric chromatin through the deposition of the histone variant H3.3. ATRX and DAXX have also evolved mutually-independent functions in transcription and chromatin dynamics. Here, using paediatric glioma and pancreatic neuroendocrine tumor cell lines, we identify a novel ATRX-independent function for DAXX in promoting genome stability by preventing transcription-associated R-loop accumulation and DNA double-strand break formation at centromeres. This function of DAXX required its interaction with histone H3.3 but was independent of H3.3 deposition and did not reflect a role in the repression of centromeric transcription. DAXX depletion mobilized BRCA1 at centromeres, in line with BRCA1 role in counteracting centromeric R-loop accumulation. Our results provide novel insights into the mechanisms protecting the human genome from chromosomal instability, as well as potential perspectives in the treatment of cancers with DAXX alterations.
Protist ubiquitin ligase effector PbE3-2 targets cysteine protease RD21A to impede plant immunity
Authors: Li Chao , Luo Shaofeng , Feng Lu , Wang Qianqian , Cheng Jiasen , Xie Jiatao , Lin Yang , Fu Yanping , Jiang Daohong , Chen Tao
Published: December 2023

Clubroot, caused by the soil-borne protist pathogen Plasmodiophora brassicae, is one of the most devastating diseases of Brassica oil and vegetable crops worldwide. Understanding the pathogen infection strategy is crucial for the development of disease control. However, because of its obligate biotrophic nature, the molecular mechanism by which this pathogen promotes infection remains largely unknown. P. brassicae E3 ubiquitin ligase 2 (PbE3-2) is a Really Interesting New Gene (RING)-type E3 ubiquitin ligase in P. brassicae with E3 ligase activity in vitro. Yeast (Saccharomyces cerevisiae) invertase assay and apoplast washing fluid extraction showed that PbE3-2 harbors a functional signal peptide. Overexpression of PbE3-2 in Arabidopsis (Arabidopsis thaliana) resulted in higher susceptibility to P. brassicae and decreases in chitin-triggered reactive oxygen species burst and expression of marker genes in salicylic acid signaling. PbE3-2 interacted with and ubiquitinated host cysteine protease RESPONSIVE TO DEHYDRATION 21A (RD21A) in vitro and in vivo. Mutant plants deficient in RD21A exhibited similar susceptibility and compromised immune responses as in PbE3-2 overexpression plants. We show that PbE3-2, which targets RD21A, is an important virulence factor for P. brassicae. Two other secretory RING-type E3 ubiquitin ligases in P. brassicae performed the same function as PbE3-2 and ubiquitinated RD21A. This study reveals a substantial virulence functional role of protist E3 ubiquitin ligases and demonstrates a mechanism by which protist E3 ubiquitin ligases degrade host immune-associated cysteine proteases to impede host immunity.
Immunophilin FKB20-2 participates in oligomerization of Photosystem I in Chlamydomonas
Authors: Guo Jia , Yao Qiang , Dong Jie , Hou Jinrong , Jia Pulian , Chen Xueying , Li Guoyang , Zhao Qi , Wang Jingyi , Liu Fang , Wang Ziyu , Shan Yuying , Zhang Tengyue , Fu Aigen , Wang Fei
Published: December 2023

PSI is a sophisticated photosynthesis protein complex that fuels the light reaction of photosynthesis in algae and vascular plants. While the structure and function of PSI have been studied extensively, the dynamic regulation on PSI oligomerization and high light response is less understood. In this work, we characterized a high light-responsive immunophilin gene FKB20-2 (FK506-binding protein 20-2) required for PSI oligomerization and high light tolerance in Chlamydomonas (Chlamydomonas reinhardtii). Biochemical assays and 77-K fluorescence measurement showed that loss of FKB20-2 led to the reduced accumulation of PSI core subunits and abnormal oligomerization of PSI complexes and, particularly, reduced PSI intermediate complexes in fkb20-2. It is noteworthy that the abnormal PSI oligomerization was observed in fkb20-2 even under dark and dim light growth conditions. Coimmunoprecipitation, MS, and yeast 2-hybrid assay revealed that FKB20-2 directly interacted with the low molecular weight PSI subunit PsaG, which might be involved in the dynamic regulation of PSI-light-harvesting complex I supercomplexes. Moreover, abnormal PSI oligomerization caused accelerated photodamage to PSII in fkb20-2 under high light stress. Together, we demonstrated that immunophilin FKB20-2 affects PSI oligomerization probably by interacting with PsaG and plays pivotal roles during Chlamydomonas tolerance to high light.
Dimensions of Emotional Fit
Authors: Mason Sam
Published: December 2023

Emotions are open to various kinds of normative assessment. For example, we can assess emotions for their prudential or moral value. Recently, philosophers have increasingly attended to a distinct form of normative assessment of emotions—fittingness assessment. An emotion is fitting when it is merited by its object. For example, admiration is fitting when it is felt towards the admirable, and shame towards the shameful. This paper defends a hybrid account of emotional fittingness. Emotions are complex, and typically involve various elements. As well as involving representations that can be assessed for accuracy, emotions typically motivate their subjects in characteristically urgent ways. The fittingness of an emotion as a whole is a function of the fittingness of both its representational and motivational aspects.
The Psychological Externalities of Investing: Evidence from Stock Returns and Crime
Authors: Huck John R
Published: December 2023

This paper investigates the psychological effects from stock market returns. Using an FBI database of over 55 million daily reported crime incidents across the United States, crime is proposed as a measure of psychological well-being. The evidence suggests that stock returns affect the well-being of not only investors but also noninvestors. Specifically, a contemporaneous negative (positive) relationship between daily stock market returns and violent crime rates is found for investors (noninvestors). A similar relationship is also found between local earnings surprises and violent crime. The contrasting relationships for investors and noninvestors suggests that relative wealth may influence well-being.
A new proposed procedure for calibrating personal dosemeters for X and gamma radiations, based on Hp(30)water
Authors: Bouzegzi Kamal , Amroun-Frahi Akila , Medjadj Toufik , Herrati Ammar
Published: December 2023

Recently, a new operational quantity Hp(30)water has been proposed to replace Hp(10). This paper describes a new proposed procedure for calibrating personal dosemeters, for X and gamma radiations, in terms of this new quantity Hp(30)water. Compared to the current procedure based on Hp(10), the proposed procedure requires fewer steps and it is easier to implement. Indeed, this new procedure is based on the direct measurement of the quantity of interest, unlike the current one that necessitates the measurement of an intermediate quantity, the air kerma and then the use of conversion coefficients. Some of the advantages of the proposed procedure, such as no need of conversion coefficients to determine the value of the quantity of interest, and no need of additional material to ensure the conditions of electronic equilibrium of the secondary electrons, are highlighted. The feasibility of the proposed procedure is verified. The fluence-to-Hp(30)water conversion coefficients are measured for Cs-137 and Co-60 radiation qualities, and are found in good agreement with those available in the literature.
Upper and lower airway interactions in children
Authors: de Benedictis Fernando M.
Published: December 2023

Purpose of review

The aim of the present review was to highlight the interactions between rhinitis, rhinosinusitis and asthma in children and to discuss the most relevant scientific progresses in the pathophysiology and treatment of these combined conditions.

Recent findings

Advances in understanding the mechanisms underlying the relationship between upper and lower airways have provided valuable insights into the role of eosinophils in the pathophysiology of inflammatory events and have further delineated the concept of united airway disease. Studies addressed to evaluate the burden of sinonasal system on asthma outcomes showed a parallel severity of upper and lower airway diseases. Histopathology of sinonasal tissue in patients with chronic rhinosinusitis is different in adults and children. Targeted administration of biological agents represents an effective treatment in patients with severe uncontrolled asthma, but specific trials are awaited in children with chronic sinonasal disease.

Allergic rhinitis and rhinosinusitis are important comorbidities in patients with asthma. Improved knowledge of pathogenic mechanisms of inflammation and remodelling in the sinonasal system and the lung has led to new therapeutic approaches in patients with united airway disease and opened interesting perspectives for personalized drug therapies.
Expert Views on State Policies to Improve Engagement and Retention in Treatment for Opioid Use Disorder: A Qualitative Analysis of an Online Modified Delphi Process
Authors: Grant Sean , Smart Rosanna , Gordon Adam J. , Pacula Rosalie Liccardo , Stein Bradley D.
Published: December 2023

Objectives

The aim of this study was to examine expert views on the effectiveness and implementability of state policies to improve engagement and retention in treatment for opioid use disorder (OUD).

Methods

We conducted a 3-round modified Delphi process using the online ExpertLens platform. Participants included 66 experts on OUD treatment policies. Experts commented on 14 hypothetical state policies targeting treatment engagement and quality of care. Using the GRADE Evidence-to-Decision framework, we conducted reflexive thematic analysis to develop patterns of meaning from the dataset.

Results

Only policies for providing continued access to evidence-based treatment for highly at-risk populations, settings, and periods were seen as effective in meaningfully reducing population-level opioid-related overdose mortality. Experts commented that, although the general public increasingly supports policies expanding medications for OUD and evidence-based care, ongoing stigma about OUD encourages public acceptance of punitive and paternalistic policies. Experts viewed all policies as at least moderately feasible given the current infrastructure and resources, with affordability reliant on long-term cost savings from reduced opioid-related harms. Equitability depended on whether experts perceived a policy as inherently equitable in its design as well as concerns about the potential for inequitable implementation due to structural oppression and interpersonal biases in criminal-legal, healthcare, and other systems.

Conclusions

Experts believe that supportive (rather than punitive) policies improve engagement and retention in OUD treatment. States could prioritize implementing supportive policies that are patient-centered and take a harm-reduction approach to enhance medications for OUD access and utilization. States could consider deimplementing punitive policies that are coercive, take an abstinence-only approach, and use punitive and restrictive measures.
Association between outdoor temperature and fatal police shootings in the United States, 2015–2021
Authors: Martinson Ellen , Chang Howard H. , D’Souza Rohan R. , Ebelt Stefanie , Scovronick Noah
Published: December 2023

Background:

Here, we investigate the association between outdoor temperature and fatal police shootings in the United States between 2015 and 2021.

Methods:

We conducted a time-stratified case-crossover study. Data on fatal police shootings were from the Washington Post’s Fatal Force database and temperature data were from Daymet.

Results:

A 5°C increase in maximum same-day temperature was associated with a 1.033 (95% CI = 1.002, 1.065) increased odds of a fatal police shooting. In stratified analyses, the strongest associations were observed in victims who were armed (OR, 1.052 [95% CI = 1.017, 1.088), White (OR, 1.052 [95% CI = 1.006, 1.100), or aged 45+ (OR, 1.110 [95% CI = 1.044, 1.181]). In additional subgroup analyses, relative risks were also generally higher among those who were armed.

Conclusions:

There is evidence of an association between outdoor temperature and fatal police shootings in the United States, particularly when the victims were reported as armed. This study cannot determine if the associations are a result of any specific causes (e.g., increased police aggression or other factors).
EUS coil and glue for gastric varices-prevent, treat and rescue, one therapy to rule them all?
Authors: Puri Rajesh , Sharma Zubin Dev , Patle Saurabh , Bhagat Suraj , Kathuria Abhishek
Published: December 2023

Background and Objectives

In portal hypertension, gastric varix–associated bleeding is known to have higher transfusion requirements, uncontrolled bleeding, rebleeding, intensive care unit requirements, and death. EUS–guided coil insertion is now an acceptable modality for endoscopic management in cases of gastric varices. With this study, we discuss our large single-center experience in the use of EUS for coil and glue injection in gastric varices. We also look into adverse events associated with and possibilities of using this modality as both primary prophylaxis and a rescue therapy.

Methods

The study was conducted in a tertiary care center in India. A total of 86 patients were included in the study. The indication for EUS-guided coil and glue was divided into 3 clinical situations, namely, rebleed, rescue, and primary. The technical success and clinical success, that is, control of bleed in patients, were confirmed by absence of Doppler signal on EUS, endoscopic view, and stabilized hemoglobin with no need of blood product transfusion to maintain hemoglobin.

Results

The mean Child-Turcotte-Pugh score and Model for End-Stage Liver Disease–Na score were 9.2 and 14.6, respectively. The mean size of the gastric varices was 18.9 mm. The mean number of coils used was 2.9, and the average quantity of glue required was 1.6 mL. The technical success was 100% across the patient group. Clinical success was seen in 90% of the patient group. Mean follow-up was seen for 175.2 days.

Conclusions

EUS-guided coil and glue therapy has a role in different clinical settings, as primary therapy, rebleed, and rescue therapy. It has significant technical and clinical success. Its role in treatment algorithms needs to be further studied in prospective studies. It may offer a cost advantage in comparison to interventional radiology-led interventions.
Anti-Xa Assay Monitoring Improves the Precision of Anticoagulation in Venovenous Extracorporeal Membrane Oxygenation
Authors: Hla Teddy Tun Win , Christou Silvana , Sanderson Barnaby , Hanks Fraser , Cameron Lynda , Camporota Luigi , Doyle Andrew J. , Retter Andrew
Published: December 2023

Unfractionated heparin (UFH) is the most used anticoagulant in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO). Its therapeutic levels are monitored using activated partial thromboplastin time ratio (aPTTr) or antifactor Xa (anti-Xa) assay. This was a retrospective, single-center, cohort study where all adult patients with viral etiology respiratory failure requiring VV-ECMO from January 2, 2015 to January 31, 2022 were included. Anticoagulation was monitored using aPTTr (until November 1, 2019) or anti-Xa assay (after November 1, 2019). We compared the accuracy and precision of anticoagulation monitoring tests using time in therapeutic range (TTR) and variance growth rate (VGR), respectively, and their impact on bleeding and thrombotic events (BTEs). A total of 254 patients, 74 in aPTTr and 180 in anti-Xa monitoring groups, were included with a total of 4,992 ECMO-person days. Accuracy was comparable: mean TTR of 47% in aPTTr and 51% in anti-Xa groups (p = 0.28). Antifactor Xa monitoring group demonstrated improved precision with a lower variance (median VGR 0.21 vs. 1.61 in aPTTr, p < 0.05). Secondary outcome of less heparin prescription changes (adjusted rate ratio [RR] = 1.01, p = 0.01), fewer blood transfusions (adjusted RR = 0.78, p < 0.05), and ECMO circuit changes (adjusted RR = 0.68, p < 0.05) were seen with anti-Xa monitoring.
Cognitive, Functional, and Quality of Life Outcomes 6 Months After Mechanical Ventilation for Bronchiolitis: A Secondary Analysis of Data From the Randomized Evaluation of Sedation Titration for Respiratory Failure Trial (RESTORE)
Authors: Fischer Meredith , Ngendahimana David K. , Watson R. Scott , Schwarz Adam J. , Shein Steven L.
Published: December 2023

OBJECTIVES:

To describe rates and associated risk factors for functional decline 6 months after critical bronchiolitis in a large, multicenter dataset.

DESIGN:

Nonprespecified secondary analysis of existing 6-month follow-up data of patients in the Randomized Evaluation of Sedation Titration for Respiratory Failure trial (RESTORE, NCT00814099).

SETTING:

Patients recruited to RESTORE in any of 31 PICUs in the United States, 2009–2013.

PATIENTS:

Mechanically ventilated PICU patients under 2 years at admission with a primary diagnosis of bronchiolitis.

INTERVENTIONS:

There were no interventions in this secondary analysis; in the RESTORE trial, PICUs were randomized to protocolized sedation versus usual care.

MEASUREMENTS AND MAIN RESULTS:

“Functional decline,” defined as worsened Pediatric Overall Performance Category and/or Pediatric Cerebral Performance Category (PCPC) scores at 6 months post-PICU discharge as compared with preillness baseline. Quality of life was assessed using Infant Toddler Quality of Life Questionnaire (ITQOL; children < 2 yr old at follow-up) or Pediatric Quality of Life Inventory (PedsQL) at 6 months post-PICU discharge. In a cohort of 232 bronchiolitis patients, 28 (12%) had functional decline 6 months postdischarge, which was associated with unfavorable quality of life in several ITQOL and PedsQL domains. Among 209 patients with normal baseline functional status, 19 (9%) had functional decline. In a multivariable model including all subjects, decline was associated with greater odds of worse baseline PCPC score and longer PICU length of stay (LOS). In patients with normal baseline status, decline was also associated with greater odds of longer PICU LOS.

CONCLUSIONS:

In a random sampling of RESTORE subjects, 12% of bronchiolitis patients had functional decline at 6 months. Given the high volume of mechanically ventilated patients with bronchiolitis, this observation suggests many young children may be at risk of new morbidities after PICU admission, including functional and/or cognitive morbidity and reduced quality of life.
COVID-19 Vaccine Information Seeking Patterns and Vaccine Hesitancy: A Latent Class Analysis to Inform Practice
Authors: Piltch-Loeb Rachael , Silver Diana , Kim Yeerae , Abramson David
Published: December 2023

Context:

Throughout the COVID-19 pandemic, state and local health departments served as risk communicators to the public; however, public health practitioners have limited resources at their disposal when trying to communicate information, especially when guidance is rapidly changing. Identifying how the population gathers information across channels and which subsets of the population utilize which channels can help practitioners make the best use of these limited resources.

Objective:

To identify how individuals utilized different information channels to get COVID-19–related information and determine its effect on one COVID-19–related action: vaccine intentions.

Design:

This study applies latent class analysis to utilization of information channels to characterize information consumption patterns during the COVID-19 infodemic and then explores the relationship between these patterns and vaccine hesitancy.

Setting:

The data were collected from the COVID-19 Vaccine Hesitancy Survey, which is a nationally representative sample of US adults 18 years and older recruited from Social Science Research Solutions (SSRS)'s Opinion Panel.

Participants:

The online survey was conducted between April 7 and April 11, 2021, after the COVID-19 vaccine was available to all adults and enrolled more than 3000 respondents (n = 3014).

Main Outcome Measure(s):

Respondents were asked about their frequency of information seeking related to the COVID-19 vaccine, sociodemographics, and vaccine perceptions.

Results:

Based on fit statistics and prior research, we identified 6 latent classes that characterize information seeking: Nonseekers, Legacy, Legacy + Facebook/Instagram, Traditional Omnivore, Omnivore + Broad Social Media, and Twitter. Sociodemographics, political, economic, and COVID-19 exposure variables are associated with different patterns of seeking information about COVID-19. Membership in 3 of these classes was associated with higher rates of vaccine refusal and vaccine hesitancy.

Discussion:

The study has implications for public health officials and policymakers who use media channels to share news and health information with the public. Information should be tailored to the sociodemographic profiles of those users who are likely consuming information across multiple different channels.
Rho and a riboswitch regulatemntPexpression evading manganese stress and membrane toxicity
Authors: Prakash Anand , Kalita Arunima , Bhardwaj Kanika , Mishra Rajesh Kumar , Ghose Debarghya , Kaur Gursharan , Pani Bibhusita , Nudler Evgeny , Dutta Dipak
Published: December 2023

The trace metal ion manganese in excess is toxic. Therefore, a small subset of factors tightly maintains its cellular level, among which an efflux protein MntP is the champion. Multiple transcriptional regulators and a manganese-dependent translational riboswitch regulate the MntP expression. As riboswitches are untranslated RNAs, they are often associated with the Rho-dependent transcription termination in bacteria. Here we demonstrate that Rho efficiently terminates transcription at themntPriboswitch region. The addition of manganese activates the riboswitch, thereby restoring the coupling between transcription and translation to evade Rho-dependent transcription termination partially. Deletion of the riboswitch abolishes Rho-dependent termination and renders bacteria sensitive to manganese due to overexpression ofmntP. The highmntPexpression is associated with reactive oxygen species (ROS) production, slow growth, and cell filamentation phenotypes. We posit that manganese-dependent transcriptional activation in the absence of Rho-dependent termination leads to the observed toxicity arising from excessive MntP expression, a membrane protein. Thus, we identified a novel regulatory role of Rho in preventing membrane protein toxicity by terminating at the riboswitch element.
Gut Microbiome Dynamics and Predictive Value in Hospitalized COVID-19 Patients: A Comparative Analysis of Shallow and Deep Shotgun Sequencing
Authors: Kopera Katarzyna , Gromowski Tomasz , Wydmański Witold , Skonieczna-Żydecka Karolina , Muszyńska Agata , Zielińska Kinga , Wierzbicka-Woś Anna , Kaczmarczyk Mariusz , Kadaj-Lipka Roland , Cembrowska-Lech Danuta , Januszkiewicz Kornelia , Kotfis Katarzyna , Witkiewicz Wojciech , Nalewajska Magdalena , Feret Wiktoria , Marlicz Wojciech , Łoniewski Igor , Łabaj Paweł P. , Rydzewska Grażyna , Kosciolek Tomasz
Published: December 2023

The COVID-19 pandemic caused by SARS-CoV-2 has led to a wide range of clinical presentations, with respiratory symptoms being common. However, emerging evidence suggests that the gastrointestinal (GI) tract is also affected, with angiotensin-converting enzyme 2, a key receptor for SARS-CoV-2, abundantly expressed in the ileum and colon. The virus has been detected in GI tissues and fecal samples, even in cases with negative respiratory results. GI symptoms have been associated with an increased risk of ICU admission and mortality. The gut microbiome, a complex ecosystem of around 40 trillion bacteria, plays a crucial role in immunological and metabolic pathways. Dysbiosis of the gut microbiota, characterized by a loss of beneficial microbes and decreased microbial diversity, has been observed in COVID-19 patients, potentially contributing to disease severity. We conducted a comprehensive gut microbiome study in 204 hospitalized COVID-19 patients using both shallow and deep shotgun sequencing methods. We aimed to track microbiota composition changes induced by hospitalization, link these alterations to clinical procedures (antibiotics administration) and outcomes (ICU referral, survival), and assess the predictive potential of the gut microbiome for COVID-19 prognosis. Shallow shotgun sequencing was evaluated as a cost-effective diagnostic alternative for clinical settings.
Graph-KIR: Graph-based KIR Copy Number Estimation and Allele Calling Using Short-read Sequencing Data
Authors: Lin Hong-Ye , Chuang Hui-Wen , Hung Tsung-Kai , Wang Ting-Jian , Lin Ching-Jim , Hsu Jacob Shujui , Hsu Chia-Lang , Yang Ya-Chien , Chen Pei-Lung , Chen Chien-Yu
Published: December 2023

Motivation: The Killer-cell Immunoglobulin-like Receptor (KIR) is a highly polymorphic region in the human genome, associated with autoimmune diseases and organ transplantation. The sequences of KIR genes are highly similar among star alleles as well as in between individual genes, with the copy number of each KIR gene typically ranging from 0 to 4. In this study, we introduce a tool Graph-KIR that aims to estimate the copy number of genes and calls full-resolution (7 digits) KIR alleles from a whole genome sequencing (WGS) sample. Results: Graph-KIR, unlike most KIR tools, is capable of independently typing KIR alleles per sample with no reliance on the distribution of any framework gene in a cohort. In a set of 100 simulated samples, Graph-KIR demonstrated 100% accuracy in copy number estimation and high accuracy of allele typing: 91.2% at 7-digit resolution, 97.0% at 5-digit resolution, 97.2% at 3-digit resolution, and 99.6% at gene-level resolution. Graph-KIR outperforms existing tools such as PING's WGS version (91.9% accuracy) and T1K (84.6% accuracy) at 5-digit resolution. By analyzing the results on 44 HPRC samples, Graph-KIR achieves an accuracy of 85.0%, better than PING's WGS version (75.5% accuracy) at 5-digit resolution.
Imitating the ‘breeder’s eye’: predicting grain yield from measurements of non-yield traits
Authors: Jin Hongyu , Tross Michael C. , Tan Ruijuan , Newton Linsey , Mural Ravi V. , Yang Jinliang , Thompson Addie M. , Schnable James C.
Published: December 2023

Plant breeding relies on information gathered from field trials to select promising new crop varieties for release to farmers and to develop genomic prediction models that can enhance the efficiency and rate of genetic improvement in future breeding cycles. However, field trials conducted in one environment provide limited insight into how well crop varieties will perform in other environments. As the pace of climate change intensifies, the time lag of developing and deploying new crop varieties indicates that plant breeders will need to make decisions about new crop varieties without knowing the future environments those crop varieties will encounter in farmers’ fields. Therefore, significant improvements in cross-environment prediction of crop performance are essential for creating and maintaining resilient agricultural systems in the latter half of the twenty-first century. To address this challenge, we conducted linked yield trials of 752 public maize genotypes in two distinct environments: Lincoln, Nebraska, and East Lansing, Michigan. Our findings confirmed that genomic predictions of yield can outperform direct yield measurements used to train the genomic prediction model in predicting yield in a second environment. Additionally, we developed and trained another trait-based yield prediction model, which we refer to as the Silicon Breeder’s Eye (SBE). Our results demonstrate that SBE prediction has comparable predictive power to genomic prediction models. SBE prediction has the potential to be applied to a wider range of breeding programs, including those that lack the resources to genotype large populations of individuals, such as programs in the developing world, breeding programs for specialty crops, and public sector programs.
Tradeoffs in the Design of RNA Thermometers
Authors: Gola Krishan Kumar , Patel Abhilash , Sen Shaunak
Published: December 2023

The synthesis of RNA thermometers is aimed at achieving temperature responses with desired thresholds and sensitivities. Although previous works have generated thermometers with a variety of thresholds and sensitivities as well as guidelines for design, possible constraints in the achievable thresholds and sensitivities remain unclear. We addressed this issue using a two-state model and its variants, as well as melt profiles generated from thermodynamic computations. In the two-state model, we found that the threshold was inversely proportional to the sensitivity, in the case of a fixed energy difference between the two states. Notably, this constraint could persist in variations of the two-state model with sequentially unfolding states and branched parallel pathways. Furthermore, the melt profiles generated from a library of thermometers exhibited a similar constraint. These results should inform the design of RNA thermometers as well as other responses that are mediated in a similar fashion.
Perivascular Excitation Tunnelling: a Novel and Preventable Cause of Cardiac Reperfusion Arrhythmias
Authors: Chleilat Enaam , Walz Teo Puig , Han Bo , Quinn T Alexander , Kohl Peter , Zgierski-Johnston Callum M
Published: December 2023

Background

Reperfusion after myocardial ischaemia can lead to deadly arrhythmias, in part due to heterogeneities in electrophysiology (EP) across affected tissue. There is a need to understand the spatiotemporal dynamics of ischaemia-reperfusion arrhythmias (IRA), so that reperfusion strategies to prevent them can be found.

Methods

Langendorff-perfused rabbit isolated hearts were loaded with a voltage-sensitive dye. Epifluorescence imaging was used to track action potential propagation across the cardiac surface. The heart was simultaneously perfused ‘globally’ (viathe aorta) and ‘locally’ (viacannulation of a single coronary artery) with an oxygenated physiological saline solution. Local perfusion was subsequently switched to and from solutions that mimic aspects of ischaemia (acidosis, hypoxia, hyperkalaemia, or a simulated ischaemia solution combining all three) or to no-flow. Subsequently, different reperfusion strategies were tested to reduce IRA re-entries. The most successful strategy for preventing re-entry was tested in Langendorff-perfused isolated pig hearts to assess the clinical relevance of the observed mechanism and treatment strategy.

Results

Upon sudden reperfusion of the cannulated coronary artery in rabbit hearts we observed a preferential recovery of electrical excitability along the vessel’s main branch (‘perivascular excitation tunnelling’, PVET). This resulted in re-entry in roughly half of the hearts. Hyperkalaemia and hypoxia, but not acidosis, were sufficient to lead to conduction block, PVET, and re-entry, with both PVET and re-entry more frequently observed after hyperkalaemia than hypoxia.

PVET was also present in pigs and PVET-based re-entries were successfully prevented in rabbit and pig hearts by two-step reperfusion, first of the distal majority of the previously ischaemic region, and then of the remaining tissue from the proximal point. With this strategy, any PVET that developed in the distal tissue was blocked by the still inexcitable proximal tissue. Upon reperfusion of the proximal tissue, there was a reduced path length for PVET. As a consequence, the associated excitable gap was too short for re-entrant excitation.

Conclusions

We observed a novel arrhythmia mechanism upon coronary reperfusion (PVET), which suggests that preferential recovery of myocardial excitability along the reperfused vessel is an important mechanism underlying IRA formation. PVET-induced re-entry reliably occurred in both rabbit and pig hearts and could be prevented by two-step reperfusion.

Graphical Abstract
Investigation of astrocytes’ morphological changes in response to laser-induced shockwave
Authors: Pouladian Pegah , Ho Janelle , Perez Nicolas , Wakida Nicole M. , Gomez-Godinez Veronica , Preece Daryl
Published: December 2023

Traumatic Brain Injury (TBI) arises from an external force affecting the brain, leading to a range of outcomes from mild to severe. Despite continuous scientific advancements, it continues to pose a persistent threat and remains a significant cause of physical impairment and mortality.

Various models, including blast-induced TBI (bTBI), have been proposed to simulate TBI. Laser-induced shockwaves (LIS) us emerging as an effective method. LIS generates shockwaves via pulsed laser-induced plasma formation, offering a controlled means to study TBI at the cellular level. Astrocytes, pivotal in maintaining brain function post-injury, undergo dynamic morphological changes, contributing to the understanding of injury responses and neurodegenerative diseases.

This study introduces a system combining Laser-Induced Shockwaves (LIS) and Quantitative Phase Microscopy (QPM) to quantify morphological changes in astrocytes during and after LIS exposure. QPM, a label-free method, facilitates 3D imaging and captures real-time cellular dynamics. The integration of LIS and QPM enables the assessment of astrocyte responses to shear stress caused by LIS, revealing immediate and sustained morphological transformations.

Analysis post-LIS exposure indicates significant alterations in circularity, volume, surface area, and other features. Statistical tests affirm of observed trends, providing insights into astrocyte responses to mechanical forces. The findings contribute to understanding how mechanical stimuli impact astrocyte morphology, holding promise for targeted therapeutic strategies in traumatic brain injuries and related neurological disorders. The integrated LIS and QPM approach serves as a powerful tool for 3D imaging and quantitative measurement of astrocyte morphological changes, offering deeper insights into cellular dynamics and potential therapeutic interventions.
miRVim: Three-dimensional miRNA Structure Data Server
Authors: Sahu Vishal Kumar , Parida Ankita Subhadarsani , Ranjan Amit , Basu Soumya
Published: December 2023

MicroRNAs (miRNAs), a distinct category of non-coding RNAs, exert multifaceted regulatory functions in a variety of organisms, including humans, animals, and plants. The inventory of identified miRNAs stands at approximately 60,000 among all species and 1,926 inHomo sapiensmanifests miRNA expression. Their theranostic role has been explored by researchers over the last few decades, positioning them as prominent therapeutic targets as our understanding of RNA targeting advances. However, the limited availability of experimentally determined miRNA structures has constrained drug discovery efforts relying on virtual screening or computational methods, including machine learning. To address this limitation, miRVim has been developed, providing a repository of human miRNA structures derived from both two-dimensional (MXFold2, CentroidFold, and RNAFold) and three-dimensional (RNAComposer and 3dRNA) structure prediction algorithms, in addition to experimentally available structures from the RCSB PDB repository. This data server aims to facilitate computational data analysis for drug discovery, opening new avenues for advancing technologies such as machine learning-based predictions in the field. The publicly accessible structures provided by miRVim, available athttps://mirna.in/miRVim, offer a valuable resource for the research community, advancing the field of miRNA-related computational analysis and drug discovery.
Patterns of physical activity in hunter-gatherer children compared with US and UK children
Authors: Kretschmer Luke , Dyble Mark , Chaudhary Nikhil , Bann David , Salali Gul Deniz
Published: December 2023

Sedentary lifestyles, mismatched with our active foraging history, contribute to escalating rates of non-communicable diseases. Contemporary hunter-gatherers appear to be highly active, but little is known about physical activity levels in hunter-gatherer children. We analysed 150 days of accelerometer data from 51 BaYaka hunter-gatherer children (aged 3-18) in the Republic of Congo, comparing it with British and American children (MCS and NHANES). BaYaka children were highly active, engaging in over 3 hours of moderate-to-vigorous physical activity (MVPA) daily, surpassing British adolescents by over 70 minutes. In US children activity declined with age; while in BaYaka children activity increased with age, unaffected by gender. Reflecting their foraging lifestyle, activity patterns varied within and between days, yet all children consistently rose with the sun. These findings highlight the impact of a foraging upbringing on children’s activity levels, providing a benchmark for understanding childhood physical activity and wellbeing.
Strawberry phenotypic plasticity in flowering time is driven by interaction between genetic loci and temperature
Authors: Prohaska Alexandre , Petit Aurélie , Lesemann Silke , Rey-Serra Pol , Mazzoni Luca , Masny Agnieszka , Sánchez-Sevilla José F. , Potier Aline , Gaston Amèlia , Klamkowski Krzysztof , Rothan Christophe , Mezzetti Bruno , Amaya Iraida , Olbricht Klaus , Denoyes Béatrice
Published: December 2023

The flowering time, which determines when the fruits or seeds can be harvested, is known to be sensitive to plasticity, i.e. the ability of a genotype to display different phenotypes in response to environmental variations. In the context of climate change, strawberry breeding can take advantage of phenotypic plasticity to create high-performing varieties adapted either to local conditions or to a wide range of climates. To decipher how the environment affects the genetic architecture of flowering time in cultivated strawberry (Fragaria ×ananassa) and modify its QTL effects, we used a bi-parental segregating population grown for two years at widely divergent latitudes (5 European countries) and combined climatic variables with genomic data (Affymetrix® SNP array). We detected 10 unique flowering time QTL and demonstrated that temperature modulates the effect of plasticity-related QTL. We propose candidate genes for the three main plasticity QTL, includingFaTFL1which is the most relevant candidate in the interval of the major temperature-sensitive QTL (6D_M). We further designed and validated a genetic marker for the 6D_M QTL which offers great potential for breeding programs, for example for selecting of early-flowering strawberry varieties well adapted to different environmental conditions.

Highlights

A GXE study of a segregating strawberry population in Europe showed that temperature is the main driver of flowering time plasticity. A genetic marker was designed for the main QTL.
Synthetic mucus barrier arrays as a nanoparticle formulation screening platform
Authors: Zou Harry , Boboltz Allison , Cheema Yahya , Song Daniel , Duncan Gregg A.
Published: December 2023

A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug delivery systems delivered to these sites may become trapped in mucus and subsequently cleared before they can reach target cells. As such, optimizing the properties of nanoparticle delivery vehicles, such as their surface chemistry and size, is essential to improving their penetration through the mucus barrier. In previous work, we developed a mucin-based hydrogel that has viscoelastic properties like that of native mucus which can be further tailored to mimic specific mucosal tissues and disease states. Using this biomimetic hydrogel system, a 3D-printed array containing synthetic mucus barriers was created that is compatible with a 96-well plate enabling its use as a high-throughput screening platform for nanoparticle drug delivery applications. To validate this system, we evaluated several established design parameters to determine their impact on nanoparticle penetration through synthetic mucus barriers. Consistent with the literature, we found nanoparticles of smaller size and coated with a protective PEG layer more efficiently penetrated through synthetic mucus barriers. In addition, we evaluated a mucolytic (tris (2-carboxyethyl) phosphine, TCEP) for use as a permeation enhancer for mucosal drug delivery. In comparison to N-acetyl cysteine (NAC), we found TCEP significantly improved nanoparticle penetration through a disease-like synthetic mucus barrier. Overall, our results establish a new high-throughput screening approach using synthetic mucus barrier arrays to identify promising nanoparticle formulation strategies for drug delivery to mucosal tissues.
Top-down perceptual inference shaping the activity of early visual cortex
Authors: Csikor Ferenc , Meszéna Balázs , Ócsai Katalin , Orbán Gergő
Published: December 2023

Deep discriminative models provide remarkable insights into hierarchical processing in the brain by predicting neural activity along the visual pathway. However, these models differ from biological systems in their computational and architectural properties. Unlike biological systems, they require teaching signals for supervised learning. Moreover, they rely on feed-forward processing of stimuli, which contrasts with the extensive top-down connections in the ventral pathway. Here, we address both issues by developing a hierarchical deep generative model and show that it predicts an extensive set of experimental results in the primary and secondary visual cortices (V1 and V2). We show that the widely documented sensitivity of V2 neurons to textures is a consequence of learning a hierarchical representation of natural images. Further, we show that top-down influences are inherent to hierarchical inference. Hierarchical inference explains neural signatures of top-down interactions and reveals how higher-level representation shapes low-level representations through modulation of response mean and noise correlations in V1.