bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial regulation of DNA damage tolerance protein Rad5 interconnects genome stability maintenance and proteostasis networks
Authors: Lehmann Carl P , González-Fernández Paula , Tercero José Antonio 
Published: December 2023

Abstract
The Rad5/HLTF protein has a central role in the tolerance to DNA damage by mediating an error-free mode of bypassing unrepaired DNA lesions, and is therefore critical for the maintenance of genome stability. We show in this work that, following cellular stress, Rad5 is regulated by relocalization into two types of nuclear foci that coexist within the same cell, which we termed ‘S’ and ‘I’. Rad5 S-foci form in response to genotoxic stress and are associated with Rad5’s function in maintaining genome stability, whereas I-foci form in the presence of proteotoxic stress and are related to Rad5’s own proteostasis. Rad5 accumulates into S-foci at DNA damage tolerance sites by liquid-liquid phase separation, while I-foci constitute sites of chaperone-mediated sequestration of Rad5 at the intranuclear quality control compartment (INQ). Relocalization of Rad5 into each type of foci involves different pathways and recruitment mechanisms, but in both cases is driven by the evolutionarily conserved E2 ubiquitin-conjugating enzyme Rad6. This coordinated differential relocalization of Rad5 interconnects DNA damage response and proteostasis networks, highlighting the importance of studying these homeostasis mechanisms in tandem. Spatial regulation of Rad5 under cellular stress conditions thus provides a useful biological model to study cellular homeostasis as a whole.
A Multinational Case Series Describing Successful Treatment of Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection Caused by Omicron Sublineages With Prolonged Courses of Nirmatrelvir/Ritonavir
Authors: Snell Luke B , McGreal-Bellone Aimee , Nye Clemency , Gage Sarah , Bakrania Prijay , Williams Tom G S , Aarons Emma , Botgros Alina , Douthwaite Samuel T , Mallon Patrick , Milligan Iain , Moore Catherine , O’Kelly Brendan , Underwood Jonathan , de Barra Eoghan , Nebbia Gaia 
Published: December 2023

Abstract
The optimum treatment for persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not known. Our case series, across 5 hospitals in 3 countries, describes 11 cases where persistent SARS-CoV-2 infection was successfully treated with prolonged courses (median, 10 days [range, 10–18 days]) of nirmatrelvir/ritonavir (Paxlovid). Most cases (9/11) had hematological malignancy and 10 (10/11) had received CD20-depleting therapy. The median duration of infection was 103 days (interquartile range, 85–138 days). The majority (10/11) were hospitalized, and 7 (7/11) had severe/critical disease. All survived and 9 of 11 demonstrated viral clearance, almost half (4/9) of whom received nirmatrelvir/ritonavir as monotherapy. This case series suggests that prolonged nirmatrelvir/ritonavir has a role in treating persistent infection.
Higher Sensitivity of Xpert MTB/RIF Ultra Over Tuberculosis Culture for the Diagnosis of Spinal Tuberculosis With Open or Computed Tomography–Guided Biopsies
Authors: Waters Robyn , Laubscher Maritz , Dunn Robert N , Adikary Nawaal , Coussens Anna K , Held Michael 
Published: December 2023

Abstract

Background
Diagnostic specimens for spinal tuberculosis (STB) are mostly collected via open surgery. Percutaneous computed tomography (CT)–guided biopsies are used in times of limited surgical availability. However, poor diagnostic accuracy of Mycobacterium tuberculosis (Mtb) culture has been reported with this method, due to limited sample volume and the paucibacillary nature of STB. We evaluated Xpert MTB/RIF Ultra on open and CT-guided biopsies as compared with the gold standard Mtb culture and histopathology.

Methods
We conducted a prospective diagnostic accuracy study of Xpert Ultra, as compared with tuberculosis culture and histopathology, in adults with signs and symptoms of STB at a tertiary academic hospital in South Africa from November 2020 to December 2021. Diagnostic testing was performed on 31 patients with available samples.

Results
Xpert Ultra had a sensitivity of 94.7% (95% CI, 75.3%–99.7%) and specificity of 100% (95% CI, 75.7%–100.0%) against a reference standard of Mtb culture and histopathology. Xpert Ultra had high diagnostic accuracy in open and CT-guided biopsy samples with sensitivity and specificity of 100% and 100% (open) and 89% and 100% (CT), respectively. Mtb culture had limited specificity for CT-guided biopsies (43%; 95% CI, 15.8%–74.9%). HIV-1 coinfection did not affect Mtb abundance measures by Xpert Ultra or culture. Xpert Ultra was also superior to culture for STB diagnosis in patients concurrently treated for pulmonary tuberculosis.

Conclusions
Xpert Ultra detected more STB cases than culture for CT-guided biopsy samples. There was also no difference in sensitivity for open biopsies, irrespective of HIV-1 status, making it an important tool for rapid diagnosis, especially during times or in locations where open surgery is not possible or concurrent pulmonary tuberculosis treatment is initiated.
KAgoshima Galactic Object survey with Nobeyama 45 m telescope by Mapping in Ammonia lines (KAGONMA): Discovery of parsec-scale CO depletion in the Canis Major star-forming region
Authors: Hirata Yushi , Murase Takeru , Nishi Junya , Shimajiri Yoshito , Omodaka Toshihiro , Nakano Makoto , Sunada Kazuyoshi , Ito Takumi , Handa Toshihiro 
Published: December 2023

Abstract
In observational studies of infrared dark clouds, the number of detections of CO freeze-out on to dust grains (CO depletion) at the pc scale is extremely limited, and the conditions for its occurrence are, therefore, still unknown. We report a new object where pc-scale CO depletion is expected. As part of the Kagoshima Galactic Object survey with Nobeyama 45 m telescope by Mapping in Ammonia lines (KAGONMA), we have made mapping observations of NH3 inversion transition lines towards the star-forming region associated with Canis Major OB1, including IRAS 07077−1026, IRAS 07081−1028, and PGCC G224.28−0.82. By comparing the spatial distributions of NH3 (1,1) and C18O (J = 1–0), an intensity anti-correlation was found in IRAS 07077−1026 and IRAS 07081−1028 on the ∼1 pc scale. Furthermore, we obtained a lower abundance of C18O at least in IRAS 07077−1026 than in the other parts of the star-forming region. After examining high-density gas dissipation, photodissociation, and CO depletion, we concluded that the intensity anti-correlation in IRAS 07077−1026 is due to CO depletion. On the other hand, in the vicinity of the center of PGCC G224.28−0.82, the emission line intensities of both NH3 (1,1) and C18O (J = 1–0) were strongly detected, although the gas temperature and density were similar to IRAS 07077−1026. This indicates that there are situations where C18O (J = 1–0) cannot trace dense gas on the pc scale and implies that the conditional differences in which C18O (J = 1–0) can and cannot trace dense gas are unclear.
HISTONE DEACETYLASE19 Controls Ovule Number Determination and Transmitting Tract Differentiation
Authors: Manrique Silvia , Cavalleri Alex , Guazzotti Andrea , Villarino Gonzalo H , Simonini Sara , Bombarely Aureliano , Higashiyama Tetsuya , Grossniklaus Ueli , Mizzotti Chiara , Pereira Ana Marta , Coimbra Silvia , Sankaranarayanan Subramanian , Onelli Elisabetta , Masiero Simona , Franks Robert G , Colombo Lucia 
Published: December 2023

Abstract
The gynoecium is critical for the reproduction of flowering plants as it contains the ovules and the tissues that foster pollen germination, growth, and guidance. These tissues, known as the reproductive tract (ReT), comprise the stigma, style, and transmitting tract (TT). The ReT and ovules originate from the carpel margin meristem (CMM) within the pistil. SHOOT MERISTEMLESS (STM) is a key transcription factor for meristem formation and maintenance. In all above-ground meristems, including the CMM, local STM downregulation is required for organ formation. However, how this downregulation is achieved in the CMM is unknown. Here, we have studied the role of HISTONE DEACETYLASE 19 (HDA19) in Arabidopsis (Arabidopsis thaliana) during ovule and ReT differentiation based on the observation that the hda19-3 mutant displays a reduced ovule number and fails to differentiate the TT properly. Fluorescence-activated cell sorting coupled with RNA-sequencing revealed that in the CMM of hda19-3 mutants, genes promoting organ development are downregulated while meristematic markers, including STM, are upregulated. HDA19 was essential to downregulate STM in the CMM, thereby allowing ovule formation and TT differentiation. STM is ectopically expressed in hda19-3 at intermediate stages of pistil development, and its downregulation by RNA interference alleviated the hda19-3 phenotype. Chromatin immunoprecipitation assays indicated that STM is a direct target of HDA19 during pistil development and that the transcription factor SEEDSTICK is also required to regulate STM via histone acetylation. Thus, we identified factors required for the downregulation of STM in the CMM, which is necessary for organogenesis and tissue differentiation.
mRNA cleavage by 21-nucleotide phasiRNAs determines temperature-sensitive male sterility in rice
Authors: Shi Chuanlin , Zou Wenli , Zhu Yiwang , Zhang Jie , Teng Chong , Wei Hua , He Huiying , He Wenchuang , Liu Xiangpei , Zhang Bin , Zhang Hong , Leng Yue , Guo Mingliang , Wang Xianmeng , Chen Wu , Zhang Zhipeng , Qian Hongge , Cui Yan , Jiang Hongshuang , Chen Ying , Fei Qili , Meyers Blake C , Liang Wanqi , Qian Qian , Shang Lianguang 
Published: December 2023

Abstract
Temperature-sensitive male sterility is one of the core components for hybrid rice (Oryza sativa) breeding based on the 2-line system. We previously found that knockout of ARGONAUTE 1d (AGO1d) causes temperature-sensitive male sterility in rice by influencing phased small interfering RNA (phasiRNA) biogenesis and function. However, the specific phasiRNAs and their targets underlying the temperature-sensitive male sterility in the ago1d mutant remain unknown. Here, we demonstrate that the ago1d mutant displays normal female fertility but complete male sterility at low temperature. Through a multiomics analysis of small RNA (sRNA), degradome, and transcriptome, we found that 21-nt phasiRNAs account for the greatest proportion of the 21-nt sRNA species in rice anthers and are sensitive to low temperature and markedly downregulated in the ago1d mutant. Moreover, we found that 21-nt phasiRNAs are essential for the mRNA cleavage of a set of fertility- and cold tolerance–associated genes, such as Earlier Degraded Tapetum 1 (EDT1), Tapetum Degeneration Retardation (TDR), OsPCF5, and OsTCP21, directly or indirectly determined by AGO1d-mediated gene silencing. The loss of function of 21-nt phasiRNAs can result in upregulation of their targets and causes varying degrees of defects in male fertility and grain setting. Our results highlight the essential functions of 21-nt phasiRNAs in temperature-sensitive male sterility in rice and suggest their promising application in 2-line hybrid rice breeding in the future.
Deep proteomics reveals incorporation of unedited proteins into mitochondrial protein complexes in Arabidopsis
Authors: Rugen Nils , Senkler Michael , Braun Hans-Peter 
Published: December 2023

Abstract
The mitochondrial proteome consists of numerous types of proteins which either are encoded and synthesized in the mitochondria, or encoded in the cell nucleus, synthesized in the cytoplasm and imported into the mitochondria. Their synthesis in the mitochondria, but not in the nucleus, relies on the editing of the primary transcripts of their genes at defined sites. Here, we present an in-depth investigation of the mitochondrial proteome of Arabidopsis (Arabidopsis thaliana) and a public online platform for the exploration of the data. For the analysis of our shotgun proteomic data, an Arabidopsis sequence database was created comprising all available protein sequences from the TAIR10 and Araport11 databases, supplemented with sequences of proteins translated from edited and nonedited transcripts of mitochondria. Amino acid sequences derived from partially edited transcripts were also added to analyze proteins encoded by the mitochondrial genome. Proteins were digested in parallel with six different endoproteases to obtain maximum proteome coverage. The resulting peptide fractions were finally analyzed using liquid chromatography coupled to ion mobility spectrometry and tandem mass spectrometry. We generated a “deep mitochondrial proteome” of 4,692 proteins. 1,339 proteins assigned to mitochondria by the SUBA5 database (https://suba.live) accounted for &gt;80% of the total protein mass of our fractions. The coverage of proteins by identified peptides was particularly high compared to single-protease digests, allowing the exploration of differential splicing and RNA editing events at the protein level. We show that proteins translated from nonedited transcripts can be incorporated into native mitoribosomes and the ATP synthase complex. We present a portal for the use of our data, based on “proteomaps” with directly linked protein data. The portal is available at www.proteomeexplorer.de.
Distance to vaccine sites is tied to decreased COVID-19 vaccine uptake
Authors: Mazar Asaf , Jaro Daniel , Tomaino Geoff , Carmon Ziv , Wood Wendy 
Published: December 2023

Abstract
COVID-19 remains a leading cause of mortality in the United States, despite the widespread availability of vaccines. Conventional wisdom ties failure to vaccinate primarily to vaccine-skeptic beliefs (e.g. conspiracy theories, partisanship). Yet in this research, we find that vaccination is also hindered by travel distance to vaccine sites (a form of friction, or structural barriers). In study 1, Californians living farther from vaccine sites had lower vaccination rates, and this effect held regardless of partisanship. In study 2, Chicago zip codes saw an uptick in vaccination following vaccine site opening. These results proved robust in multiverse analyses accounting for a wide range of covariates, outcomes, and distance indicators. COVID-19 vaccination is hampered not only by vaccine hesitancy but also by structural barriers like distance. Efforts to boost vaccination could benefit from minimizing friction.
Policy sequencing can increase public support for ambitious climate policy
Authors: Montfort Simon , Fesenfeld Lukas , Stadelmann-Steffen Isabelle , Ingold Karin 
Published: December 2023

Abstract
Public support for ambitious climate policies and carbon prices that have direct costs for voters may depend on policy sequencing. Policy sequencing theory suggests that the strategic ordering of policies into sequences that initially create benefits can subsequently increase support for higher carbon prices. However, systematic quantitative evidence about the effects of sequencing on public support is lacking. We provide novel theoretical and empirical insights on the mechanisms through which strategic policy sequencing affects public support for climate policies. We generated these insights using geospatial data and a representative conjoint experiment with Swiss voters conducted just before the popular vote on an amendment to the Federal Act on the Reduction of Greenhouse Gas Emissions in June 2021. Our evidence shows that the perceived effectiveness of prior policy-induced benefits is related to more public support for higher carbon prices across sectors. Moreover, we find that more opportunity structures for low-emission alternatives—like higher EV charging station density—are associated with increased public support for carbon prices in the sector where the former material benefits occur. Our results also imply that positive policy perceptions of prior climate policies are related to increased support, particularly among conservative voters and those who do not regard climate change as a salient issue. Thus, strategic policy sequencing could be an effective strategy for broadening public support for ambitious climate policies.
Renal outcomes after contrast exposure in patients with diabetes who use sodium–glucose cotransporter 2 inhibitors
Authors: Chen Chih-Wei , Su Fu-You , Wang Ping-Ping , Chuang Ming-Tsang , Lin Yi-Cheng , Kao Chih-Chin , Huang Chun-Yao 
Published: December 2023

Abstract

Background
Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear.

Methods
Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders.

Results
This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs.

Conclusions
SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.
Hip dysplasia as risk factor for clinically relevant and radiographic hip osteoarthritis: 10-year results from the CHECK cohort
Authors: Vinge Rebecka , Riedstra Noortje , Tiderius Carl Johan , Bierma-Zeinstra Sita , Agricola Rintje , Runhaar Jos 
Published: December 2023

Abstract

Objectives
To investigate hip dysplasia as a risk factor for clinically relevant and incident radiographic hip OA.

Methods
From a prospective cohort (CHECK) of 1002 middle-aged, new consulters for hip and/or knee pain, 468 hips (251 individuals) were selected based on hip pain, available lateral center edge angle (LCEA) and absence of definite radiographic hip OA (Kellgren and Lawrence [KL] grade &lt;2) at baseline, as well as available follow-up measures. Clinically relevant hip OA was defined by an expert diagnosis based on clinical and radiographic data obtained between years 5 and 10 from baseline. Incident radiographic hip OA was defined by KL grade ≥2 or a total hip replacement at the 10-year follow-up. Associations between hip dysplasia (LCEA ≤20°) and outcomes were expressed as an odds ratio (OR) adjusted for age, sex and BMI.

Results
At baseline, participants had a mean age of 55.5 (5.4) years, 88% were female and, on hip level, the prevalence of hip dysplasia was 3.6% (n = 17). After 10 years, hip dysplasia was associated with an increased risk for clinically relevant hip OA (OR 2.80; 95% CI: 1.15, 6.79), but not for incident radiographic hip OA (OR 0.78; 95% CI: 0.26, 2.30).

Conclusion
In the long term, baseline hip dysplasia was associated with an increased risk for clinically relevant hip OA, but not for incident radiographic hip OA. With this in mind, we suggest that future research investigating the link between hip dysplasia and OA strives to include a definition for OA that is clinically relevant.
Investigation of the protective activity of baicalein on the lungs via regulation of various cellular responses in rats exposed to experimental sepsis
Authors: Dicle Yalcin , Aydin Elif , Seker Ugur 
Published: December 2023

Abstract

Backgrounds
In the present study, a cecal ligation and puncture (CLP)-induced experimental sepsis rat model was used to explore the effects of baicalein on inflammatory cytokine levels and oxidative stress as well as the possible regulatory role of nuclear factor-kappa B (NF-κB).

Methods
For that purpose, 42 Wistar albino rats were equally divided into control, sham, sepsis, B50 + S, B100 + S, S + B50, and S + B100 groups. The B50 + S and B100 + S groups received baicalein before the induction of sepsis, while the S + B50 and S + B100 groups received baicalein afterwards. Experimental sepsis in related groups is generated through ligation of cecum and a puncture in cecal wall. Serum samples were used for tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) analyses, and tissue Malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione (GSH), IL-6, and NF-κB levels were measured.

Results
Compared to the control group, there were significantly increases in the serum TNF-α, IL-6, tissue MDA, and NF-κB levels and decreases in the tissue SOD and GSH levels in the septic group (P &lt; 0.05). Compared to the septic group, inflammation and oxidative stress were reduced in the baicalein-treated groups. Although all of the pre- and post-treatment protocols alleviated inflammation and oxidative stress to varying degrees, pre-treatment with 100 mg/kg was the most successful.

Conclusions
Findings of this study indicated that baicalein has the potential to reduce sepsis-related oxidative stress and inflammation in the lungs and that pathological outcomes could be regulated via NF-κB transcription factor activity.
Selective elimination of younger erythrocytes in blood circulation and associated molecular changes in benzo (a) pyrene induced mouse model of lung cancer
Authors: Chauhan Pooja , Bhardwaj Nitin , Rajaura Sumit , Gupta Neelujain 
Published: December 2023

Abstract

Background
Anemia is a common feature in cancer patients. The present research was conducted to explore the mechanisms of induction of anemia in a mouse model of lung cancer.

Methods
The lung cancer was induced by treating orally with BaP (50 mg/kg body weight, twice a week for four weeks). The erythrocyte kinetics were studied using a double in vivo biotinylation (DIB) technique. ROS production and apoptosis analysis were done by staining with the CMH2DCFDA stain and anti-mouse Annexin V antibody, followed by flow cytometry. The expression of antioxidant, apoptotic, anti-apoptotic and inflammatory genes was analyzed by quantitative PCR (RT-qPCR).

Results
BaP-induced tumour reduced body weight and induced persistent haemolytic anaemia. The kinetics data suggest that, though reticulocyte production was enhanced, the proportion of young erythrocytes did not increase in the same proportion. The young aged erythrocytes were selectively eliminated from blood circulation, but intermediate and old aged erythrocytes persisted for a longer duration. The tumour progression leads to a significant increase in ROS production and apoptosis in the erythrocytes. The molecular data suggests that the expression levels of antioxidants (SOD1, catalase, and GPX1) and erythropoietin (Epo) were significantly increased. The anti-inflammatory genes Interleukin-6 (IL-6), Interleukin-10 (IL-10) were significantly decreased.Apoptotic genes Bax, and caspase 3 were significantly decreased while Bcl 2 was significantly increased in the blood of tumour-bearing mice.

Conclusions
The overall data suggest that erythrocyte turnover is severely modulated with the progression of tumor. The apoptosis, ROS levels, antioxidant, anti-apoptotic, and Epo gene expressions were increased, but proapoptotic and anti-inflammatory gene expression were suppressed.