bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cell division protein FzlA performs a conserved function in diverse alphaproteobacteria
Authors: Payne Isaac P. , Aubry Brody , Barrows Jordan M. , Brown Pamela J. B. , Goley Erin D. 
Published: September 2024

ABSTRACT

In almost all bacteria, the tubulin-like GTPase FtsZ polymerizes to form a “Z-ring” that marks the site of division. FtsZ recruits other proteins, collectively known as the divisome, that together remodel and constrict the envelope. Constriction is driven by peptidoglycan (PG) cell wall synthesis by the glycosyltransferase FtsW and the transpeptidase FtsI (FtsWI), but these enzymes require activation to function. How recruitment of FtsZ to the division site leads to FtsWI activation and constriction remains largely unknown. Previous work in our laboratory demonstrated that an FtsZ-binding protein, FzlA, is essential for activation of FtsWI in the alphaproteobacterium
Caulobacter crescentus
. Additionally, we found that FzlA binds to a DNA translocase called FtsK, suggesting that it may link constriction activation to chromosome segregation. FzlA is conserved throughout Alphaproteobacteria but has only been examined in detail in
C. crescentus
. Here, we explored whether FzlA function is conserved in diverse Alphaproteobacteria. We assessed FzlA homologs from
Rickettsia parkeri
and
Agrobacterium tumefaciens
, and found that, similar to
C. crescentus
FzlA, they bind directly to FtsZ and localize to midcell. The FtsZ-FzlA interaction interface is conserved, as we demonstrated that FzlA from each of the three species examined can bind to FtsZ from any of the three
in vitro
. Finally, we determined that
A. tumefaciens
FzlA can fulfill the essential function of FzlA when produced in
C. crescentus
, indicating conservation of function. These results suggest that FzlA serves as an important regulator that coordinates chromosome segregation with envelope constriction across diverse Alphaproteobacteria.

IMPORTANCE

Cell division is essential for bacterial replication and must be highly regulated to ensure robust remodeling of the cell wall in coordination with segregation of the genome to daughter cells. In
Caulobacter crescentus
, FzlA plays a major role in regulating this process by activating cell wall synthesis in a manner that couples constriction to chromosome segregation. FzlA is broadly conserved in Alphaproteobacteria, suggesting that it plays a similar function across this class of bacteria. Here, we have shown that, indeed, FzlA biochemical interactions and function are conserved in diverse Alphaproteobacteria. Because FzlA is conserved in Alphaproteobacterial human pathogens, understanding this protein and its interactome could present therapeutic benefits by identifying potential antibiotic targets to treat infections.
How structural biology has changed our understanding of icosahedral viruses
Authors: Comas-Garcia Mauricio 
Published: September 2024

ABSTRACT

Cryo-electron microscopy and tomography have allowed us to unveil the remarkable structure of icosahedral viruses. However, in the past few years, the idea that these viruses must have perfectly symmetric virions, but in some cases, it might not be true. This has opened the door to challenging paradigms in structural virology and raised new questions about the biological implications of “unusual” or “defective” symmetries and structures. Also, the continual improvement of these technologies, coupled with more rigorous sample purification protocols, improvements in data processing, and the use of artificial intelligence, has allowed solving the structure of sub-viral particles in highly heterogeneous samples and finding novel symmetries or structural defects. In this review, I initially analyzed the case of the symmetry and composition of hepatitis B virus-produced spherical sub-viral particles. Then, I focused on Alphaviruses as an example of “imperfect” icosahedrons and analyzed how structural biology has changed our understanding of the Alphavirus assembly and some biological implications arising from these discoveries.
Supplemental Material: Late Quaternary slip rate of the strike-slip faults on the eastern margin of the Qaidam Basin on the Tibetan Plateau and its implication on regional strain partitioning
Authors: Bao Guodong , al. et 
Published: September 2024

<p>Text S1 (the process of the Photoscan software), Text S2 (optically stimulated luminescence dating), and Figures S1–S26. </p>
Generative artificial intelligence in primary care: an online survey of UK general practitioners
Authors: Blease Charlotte R , Locher Cosima , Gaab Jens , Hägglund Maria , Mandl Kenneth D 
Published: September 2024

ObjectivesFollowing the launch of ChatGPT in November 2022, interest in large language model-powered chatbots has soared with increasing focus on the clinical potential of these tools. We sought to measure general practitioners’ (GPs) current use of this new generation of chatbots to assist with any aspect of clinical practice in the UK.MethodsAn online survey was distributed to a non-probability sample of GPs registered with the clinician marketing service Doctors.net.uk. The study was launched as a monthly ‘omnibus survey’ which has a predetermined sample size of 1000 participants.Results531 (53%) respondents were men, 544 (54%) were 46 years or older. 20% (205) reported using generative artificial intelligence (AI) tools in clinical practice; of those who answered affirmatively and were invited to clarify further, 29% (47) reported using these tools to generate documentation after patient appointments and 28% (45) to suggest a differential diagnosis.DiscussionAdministered a year after ChatGPT was launched, this is the largest survey we know of conducted into doctors’ use of generative AI in clinical practice. Findings suggest that GPs may derive value from these tools, particularly with administrative tasks and to support clinical reasoning.ConclusionDespite a lack of guidance about these tools and unclear work policies, GPs report using generative AI to assist with their job. The medical community will need to find ways to both educate physicians and trainees and guide patients about the safe adoption of these tools.
Characteristics of positive feedback provided by UK health service users: content analysis of examples from two databases
Authors: Lloyd Rebecca , Slade Mike , Byng Richard , Russell Alex , Ng Fiona , Stirzaker Alex , Rennick-Egglestone Stefan 
Published: September 2024

BackgroundMost feedback received by health services is positive. Our systematic scoping review mapped all available empirical evidence for how positive patient feedback creates healthcare change. Most included papers did not provide specific details on positive feedback characteristics.ObjectivesDescribe positive feedback characteristics by (1) developing heuristics for identifying positive feedback; (2) sharing annotated feedback examples; (3) describing their positive content.Methods200 items were selected from two contrasting databases: (1)https://careopinion.org.uk/; (2) National Health Service (NHS) Friends and Family Test data collected by an NHS trust. Preliminary heuristics and positive feedback categories were developed from a small convenience sample, and iteratively refined.ResultsCategories were identified: positive-only; mixed; narrative; factual; grateful. We propose a typology describing tone (positive-only, mixed), form (factual, narrative) and intent (grateful). Separating positive and negative elements in mixed feedback was sometimes impossible due to ambiguity. Narrative feedback often described the cumulative impact of interactions with healthcare providers, healthcare professionals, influential individuals and community organisations. Grateful feedback was targeted at individual staff or entire units, but the target was sometimes ambiguous.ConclusionPeople commissioning feedback collection systems should consider mechanisms to maximise utility by limiting ambiguity. Since being enabled to provide narrative feedback can allow contributors to make contextualised statements about what worked for them and why, then there may be trade-offs to negotiate between limiting ambiguity, and encouraging rich narratives. Groups tasked with using feedback should plan the human resources needed for careful inspection, and consider providing narrative analysis training.
Relationship between plantar pressure distribution and sagittal spinal curvatures among handball players: A cross-sectional study
Authors: Abdel-aziem Amr A. , Ameer Mariam A. , Al Abbad Ammar M. , Mahdi Maher A. 
Published: September 2024

Background: Handball affects the spinal anterior–posterior curvatures and disturbs the foot plantar pressure which provides insights into alterations in an individual’s posture. However, little is known about how the mal-alignment affects the distribution of plantar pressure. Objective: To investigate the relationship between the thoracic kyphosis angle, and plantar pressure distribution among handball players. Methods: Sixty male handball players were distributed into two groups based on their thoracic kyphosis angles. Group A: 28 handball players with an angle greater than 44∘ (kyphotic group), and group B: 32 handball players with an angle equal to or less than 44∘ (normal group). The Formetric III 4D spine and DIERS Pedoscan devices were used to measure the trunk anthropometry and plantar pressure distribution. The Pearson correlation test was used to explore the relationship between the kyphosis angle and plantar pressure distribution. Results: Group A was significantly taller, had longer trunk length, greater lumbar lordosis angles, and forefoot plantar pressure (FPP), and less rearfoot plantar pressure (RPP) than group B ([Formula: see text]). They showed a highly significant positive correlation between the thoracic kyphosis angle and FPP, and a highly significant negative correlation with the RPP ([Formula: see text], [Formula: see text], respectively). There was no correlation between the lumbar lordosis angle and FPP or RPP ([Formula: see text], [Formula: see text], respectively). Conclusion: Handball players with greater thoracic kyphosis angle have greater lumbar lordosis angle. Increasing the thoracic kyphosis angle is strongly associated with increased FPP and decreased RPP. While there is no relationship between the lumbar lordosis angle and FPP or RPP.
Processing of Zirconium Oxide Raw Materials to Produce Zirconium Silicides via Electrolysis of KCl-K2SiF6-ZrO2 Melt
Authors: Gorshkov Leonid , Suzdaltsev Andrey , Gevel Timofey , Zaikov Yury 
Published: September 2024

The possibility of electrochemical synthesis of zirconium silicides by electrolysis of KCl-K2SiF6 melt with ZrO2 additives at 790 °C has been studied. To determine the synthesis parameters, the kinetics and some features of the mechanism of the cathodic process in the investigated melt on glassy carbon were studied by cyclic chronovoltammetry and chronoamperometry. It was shown that the electroreduction of silicon ions in the KCl-K2SiF6 melt takes place at potentials from 0 to −0.2 V. Additional peaks at more negative potentials were obtained on the voltametric dependences, presumably related to the reduction of zirconium ions and the co-reduction of silicon and zirconium ions. Electrolysis of KCl-K2SiF6 melt with additions of 0.33 and 0.66 wt% ZrO2 in galvanostatic mode at cathodic current density of 20 mA cm−2 was performed in order to check assumptions. Cathode deposits were obtained, which were analyzed by X-ray diffraction and scanning electron microscopy after separation of salt residues. It is shown that the precipitates were represented by zirconium silicides (ZrSi2, ZrSi) as well as oxides (SiO2, ZrO2).
Peroxisome Proliferator–Activated Receptor δ Suppresses the Cytotoxicity of CD8+ T Cells by Inhibiting RelA DNA-Binding Activity
Authors: Cen Bo , Wei Jie , Wang Dingzhi , DuBois Raymond N. 
Published: September 2024

Abstract
The molecular mechanisms regulating CD8+ cytotoxic T lymphocytes (CTL) are not fully understood. Here, we show that the peroxisome proliferator–activated receptor δ (PPARδ) suppresses CTL cytotoxicity by inhibiting RelA DNA binding. Treatment of ApcMin/+ mice with the PPARδ agonist GW501516 reduced the activation of normal and tumor-associated intestinal CD8+ T cells and increased intestinal adenoma burden. PPARδ knockout or knockdown in CTLs increased their cytotoxicity against colorectal cancer cells, whereas overexpression of PPARδ or agonist treatment decreased it. Correspondingly, perforin, granzyme B, and IFNγ protein and mRNA levels were higher in PPARδ knockout or knockdown CTLs and lower in PPARδ overexpressing or agonist-treated CTLs. Mechanistically, we found that PPARδ binds to RelA, interfering with RelA–p50 heterodimer formation in the nucleus, thereby inhibiting its DNA binding in CTLs. Thus, PPARδ is a critical regulator of CTL effector function.
Significance: Here, we provide the first direct evidence that PPARδ plays a critical role in suppressing the immune response against tumors by downregulating RelA DNA-binding activity. This results in decreased expression of perforin, granzyme B, and IFNγ. Thus, PPARδ may serve as a valuable target for developing future cancer immunotherapies.
Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial
Authors: Verhaar Barbara J.H. , Wijdeveld Madelief , Wortelboer Koen , Rampanelli Elena , Levels Johannes H.M. , Collard Didier , Cammenga Marianne , Nageswaran Vanasa , Haghikia Arash , Landmesser Ulf , Li Xinmin S. , DiDonato Joseph A. , Hazen Stanley L. , Garrelds Ingrid M. , Danser A.H. Jan , van den Born Bert-Jan H. , Nieuwdorp Max , Muller Majon 
Published: September 2024

BACKGROUND:
The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension.

METHODS:
We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction).

RESULTS:
Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mm Hg and diastolic BP of 93.0±8.3 mm Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02–17.20) mm Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34–8.78) mm Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption.

CONCLUSIONS:
Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies.

REGISTRATION:

URL:
https://onderzoekmetmensen.nl/
; Unique identifier: NL8924.
Automated segmentation of midbrain nuclei using deep learning and multisequence MRI: A longitudinal study on iron accumulation with age
Authors: Falahati Farshad , Gustavsson Jonatan , Kalpouzos Grégoria 
Published: September 2024

Abstract
Elevated levels of brain iron, particularly within the basal ganglia, have been associated with cognitive and motor impairment in normal aging and neurodegenerative conditions. The subthalamic nucleus (STN), substantia nigra (SN), and red nucleus (RN), despite their high iron content and contribution to motor and cognitive processes, are less frequently studied. This oversight can largely be attributed to the challenges posed by in-vivo assessments of these small, deep-seated midbrain structures. We developed and validated an automated tool for the segmentation of the STN, SN, and RN. Multi-sequence magnetic resonance imaging (MRI) data, including T1-weighted, FLAIR, Quantitative Susceptibility Mapping (QSM) and R2* alongside manual delineation on QSM images of 40 individuals, were used to train segmentation models based on the nnU-Net deep-learning framework. A combination of QSM and FLAIR sequences was found to be optimal for structure segmentation (mean Dice scores of 0.84, 0.91, and 0.94 for STN, SN, and RN, respectively). We next applied the automated segmentation method to an independent 3-year longitudinal dataset, including 175 healthy adults (age range at baseline: 20–79 years old). Structural equation modelling was used to assess iron accumulation over time using age, sex, baseline iron, and regional volume as factors of interest. Cross-sectionally, older age was linearly associated with higher iron load in SN and STN; the association was non-linear in RN. Longitudinally, results indicated significant iron accumulation in the STN (Mean increase = 0.02, p = 0.005) and SN (Mean increase = 0.035, p = 0.001), but not in the RN (Mean increase = 0.015, p = 0.2). Our findings demonstrated high performance of nnU-Net in automated segmentation, and advanced our understanding of iron accumulation in midbrain nuclei in aging.
The Verb in Classical Hebrew
Authors: Isaksson Bo 
Published: September 2024

The consecutive tenses are fundamental in all descriptions of Classical Hebrew grammar. They are even basic to the textbooks on Biblical Hebrew. Being fundamental in the verbal system, and part of any beginner’s grammar, they pose a serious problem to a linguistic understanding of the verbal system, since grammars describe an alternation of ‘forms’ or ‘tenses’ in double pairs: wayyiqṭol alternates with its ‘equivalent’ qaṭal, and wə-qaṭal alternates with its ‘equivalent’ yiqṭol.
This ‘enigma’ in the verbal system is handled in the book by recognising that the alternation of the consecutive tenses with other tenses, in the reality of the text, represents a linking of clauses. The ‘consecutive tenses’ are clause-types with a natural language connective wa- directly followed by a finite verbal morpheme, a type of clause that expressed continuity in the earliest stage of Semitic. The commonly held assumption that there is a special ‘consecutive waw’ is unwarranted. The use of the ‘consecutive’ clause-types in order to express discourse continuity indicates that Classical Hebrew has retained the old unmarked declarative word order of Semitic syntax. Seen in the light of recent research on the Tiberian reading tradition, the ‘consecutive’ wayyiqṭol can be analysed as a retention of the old Semitic past perfective *wa-yaqtul, which was pronounced wa-yiqṭol in Classical Hebrew. The ‘consecutive’ wə-qāṭal (pronounced wa-qaṭal in the classical language) constitutes the result of an internal Hebrew development into a construction (in the sense of Joan Bybee) already foreshadowed in the earliest Northwest Semitic languages.
The book understands the ‘consecutive tenses’ as discourse continuity clauses, which typically form chains of main line clauses. Such chains can be interrupted by other types of clauses. This interruption is a clause linking that receives special attention in the interpretation of the Classical Hebrew verbal system. Chapter six presents a regenerated text linguistics founded on the new terminology. A clause linking approach is the central methodological procedure in this book. To this must be added diachronic typology in a comparative Semitic setting. The linguistic examples of clause linking are gathered from a large Classical Hebrew corpus, the Pentateuch and the Book of Judges, and made searchable in a database of 6559 non-archaic text records.
The Influence of Anomalous Biomass Emissions on ENSO in CESM2
Authors: Fasullo John T. , Rosenbloom Nan , Buchholz Rebecca 
Published: September 2024

Abstract
The influence of biomass burning (BB) aerosols arising from wildfires and agricultural fires on the transient coupled evolution of El Niño–Southern Oscillation (ENSO) is explored in Community Earth System Model, version 2 (CESM2). For both El Niño and La Niña, two 20-member ensembles are generated from initial states that are predisposed to evolve into ENSO events. For each ENSO phase, one ensemble is forced with the observed BB emissions during satellite-era ENSO events while the other is forced with a climatological annual cycle, with the responses to anomalous BB emissions estimated from interensemble differences. It is found that the regional responses to anomalous BB emissions occur mainly during boreal fall, which is also the time of the climatological seasonal maximum in emissions. Transient responses are identified in precipitation, clouds, and radiation in both the tropics and extratropics. At the onset of El Niño, these include increased precipitation in the northern branch of the intertropical convergence zone (ITCZ) and an enhancement of cloud albedo and amount across the Maritime Continent and eastern subtropical Pacific Ocean. Additional responses are identified through the course of El Niño and successive La Niña events, the net effect of which is to strengthen sea surface temperature (SST) anomalies in the eastern Pacific Ocean during El Niño and warm the tropical Pacific Ocean during La Niña. These responses improve the simulation of ENSO power, diversity, and asymmetry in CESM2.

Significance Statement
Biomass burning emissions from both wildfires and agricultural fires during ENSO act as a climate feedback, as they are both driven by fire weather anomalies tied to ENSO and influence clouds, radiation, and precipitation on a global scale. While the largest biomass burning (BB) emissions emanate mainly from Indonesia, other regions also exhibit systematic responses. When simulated in CESM2, the emissions collectively impact the flows of energy across the tropical Pacific Ocean in a spatially and temporally complex fashion, with the net effect of improving CESM2’s simulation of ENSO events.