bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deacetylation of MTHFD2 by SIRT4 senses stress signal to inhibit cancer cell growth by remodeling folate metabolism
Authors: Zhang Fan , Wang Di , Li Jintao , Su Ying , Liu Suling , Lei Qun-Ying , Yin Miao 
Published: March 2022

Abstract
Folate metabolism plays an essential role in tumor development. Various cancers display therapeutic response to reagents targeting key enzymes of the folate cycle, but obtain chemoresistance later. Therefore, novel targets in folate metabolism are highly demanded. Methylenetetrahydrofolate dehydrogenase/methylenetetrahydrofolate cyclohydrolase 2 (MTHFD2) is one of the key enzymes in folate metabolism and its expression is highly increased in multiple human cancers. However, the underlying mechanism that regulates MTHFD2 expression remains unknown. Here, we elucidate that SIRT4 deacetylates the conserved lysine 50 (K50) residue in MTHFD2. K50 deacetylation destabilizes MTHFD2 by elevating cullin 3 E3 ligase-mediated proteasomal degradation in response to stressful stimuli of folate deprivation, leading to suppression of nicotinamide adenine dinucleotide phosphate production in tumor cells and accumulation of intracellular reactive oxygen species, which in turn inhibits the growth of breast cancer cells. Collectively, our study reveals that SIRT4 senses folate availability to control MTHFD2 K50 acetylation and its protein stability, bridging nutrient/folate stress and cellular redox to act on cancer cell growth.
Effects of aging on basement membrane of tibialis anterior muscle during recovery following muscle injury in rats
Authors: Kanazawa Yuji , Nagano Mamoru , Koinuma Satoshi , Sugiyo Shinichi , Shigeyoshi Yasufumi 
Published: March 2022

Abstract
We investigated the effect of aging on the basement membrane (BM) during postinjury muscle recovery. Using a rat model, we found that aging delayed muscle fiber and BM recovery. In addition, expression of BM-related factors peaked 7 days after muscle injury among both young and older rats. Peak expression of collagen IV synthetic factors decreased with age, whereas expression of the degradative factor was unaffected by age. These results suggest that age-related delays in postinjury muscle fiber and BM recovery may be related to the suppression of collagen IV synthetic factors.
SEED LIPID DROPLET PROTEIN1, SEED LIPID DROPLET PROTEIN2, and LIPID DROPLET PLASMA MEMBRANE ADAPTOR mediate lipid droplet–plasma membrane tethering
Authors: Krawczyk Hannah Elisa , Sun Siqi , Doner Nathan M , Yan Qiqi , Lim Magdiel Sheng Satha , Scholz Patricia , Niemeyer Philipp William , Schmitt Kerstin , Valerius Oliver , Pleskot Roman , Hillmer Stefan , Braus Gerhard H , Wiermer Marcel , Mullen Robert T , Ischebeck Till 
Published: March 2022

AbstractMembrane contact sites (MCSs) are interorganellar connections that allow for the direct exchange of molecules, such as lipids or Ca2+ between organelles, but can also serve to tether organelles at specific locations within cells. Here, we identified and characterized three proteins of Arabidopsis thaliana that form a lipid droplet (LD)–plasma membrane (PM) tethering complex in plant cells, namely LD-localized SEED LD PROTEIN (SLDP) 1 and SLDP2 and PM-localized LD-PLASMA MEMBRANE ADAPTOR (LIPA). Using proteomics and different protein–protein interaction assays, we show that both SLDPs associate with LIPA. Disruption of either SLDP1 and SLDP2 expression, or that of LIPA, leads to an aberrant clustering of LDs in Arabidopsis seedlings. Ectopic co-expression of one of the SLDPs with LIPA is sufficient to reconstitute LD–PM tethering in Nicotiana tabacum pollen tubes, a cell type characterized by dynamically moving LDs in the cytosolic streaming. Furthermore, confocal laser scanning microscopy revealed both SLDP2.1 and LIPA to be enriched at LD–PM contact sites in seedlings. These and other results suggest that SLDP and LIPA interact to form a tethering complex that anchors a subset of LDs to the PM during post-germinative seedling growth in Arabidopsis.
SNARE SYP132 mediates divergent traffic of plasma membrane H+-ATPase AHA1 and antimicrobial PR1 during bacterial pathogenesis
Authors: Baena Guillermo , Xia Lingfeng , Waghmare Sakharam , Karnik Rucha 
Published: March 2022

AbstractThe vesicle trafficking SYNTAXIN OF PLANTS132 (SYP132) drives hormone-regulated endocytic traffic to suppress the density and function of plasma membrane (PM) H+-ATPases. In response to bacterial pathogens, it also promotes secretory traffic of antimicrobial pathogenesis-related (PR) proteins. These seemingly opposite actions of SYP132 raise questions about the mechanistic connections between the two, likely independent, membrane trafficking pathways intersecting plant growth and immunity. To study SYP132 and associated trafficking of PM H+-ATPase 1 (AHA1) and PATHOGENESIS-RELATED PROTEIN1 (PR1) during pathogenesis, we used the virulent Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) bacteria for infection of Arabidopsis (Arabidopsis thaliana) plants. SYP132 overexpression suppressed bacterial infection in plants through the stomatal route. However, bacterial infection was enhanced when bacteria were infiltrated into leaf tissue to bypass stomatal defenses. Tracking time-dependent changes in native AHA1 and SYP132 abundance, cellular distribution, and function, we discovered that bacterial pathogen infection triggers AHA1 and SYP132 internalization from the plasma membrane. AHA1 bound to SYP132 through its regulatory SNARE Habc domain, and these interactions affected PM H+-ATPase traffic. Remarkably, using the Arabidopsis aha1 mutant, we discovered that AHA1 is essential for moderating SYP132 abundance and associated secretion of PR1 at the plasma membrane for pathogen defense. Thus, we show that during pathogenesis SYP132 coordinates AHA1 with opposing effects on the traffic of AHA1 and PR1.
Scurvy in Children: The Silent Masquerader
Authors: Subhash Swathy , Santosh Sanuja Titus 
Published: March 2022

Abstract
In modern society, scurvy is well known in its historical perspective rather than clinical relevance. Scurvy is classically thought to manifest with signs of ‘bleeding painful gums’ in the undernourished. Little is known regarding its ability to mimic a wide range of rheumatological, orthopaedic, neurological and haematological illnesses. Due to the rarity of its occurrence, there is a poor understanding among present-day clinicians, and so scurvy can easily deceive the uninitiated. We report a school-aged boy with normal neurodevelopment who presented with lower limb pain and difficulty in walking. He was seen by multiple specialist doctors before the clinical diagnosis of scurvy was made by a general paediatrician. Investigations showed that this child had X-ray changes typical of scurvy with low serum ascorbic acid levels. On supplementation with vitamin C, he showed dramatic improvement in symptoms and gradually achieved complete recovery.
Involvement ofArabidopsisAcyl Carrier Protein 1 in PAMP-Triggered Immunity
Authors: Zhao Zhenzhen , Fan Jiangbo , Yang Piao , Wang Zonghua , Opiyo Stephen Obol , Mackey David , Xia Ye 
Published: March 2022

Plant fatty acids (FAs) and lipids are essential in storing energy and act as structural components for cell membranes and signaling molecules for plant growth and stress responses. Acyl carrier proteins (ACPs) are small acidic proteins that covalently bind the fatty acyl intermediates during the elongation of FAs. The Arabidopsis thaliana ACP family has eight members. Through reverse genetic, molecular, and biochemical approaches, we have discovered that ACP1 localizes to the chloroplast and limits the magnitude of pattern-triggered immunity (PTI) against the bacterial pathogen Pseudomonas syringae pv. tomato. Mutant acp1 plants have reduced levels of linolenic acid (18:3), which is the primary precursor for biosynthesis of the phytohormone jasmonic acid (JA), and a corresponding decrease in the abundance of JA. Consistent with the known antagonistic relationship between JA and salicylic acid (SA), acp1 mutant plants also accumulate a higher level of SA and display corresponding shifts in JA- and SA-regulated transcriptional outputs. Moreover, methyl JA and linolenic acid treatments cause an apparently enhanced decrease of resistance against P. syringae pv. tomato in acp1 mutants than that in WT plants. The ability of ACP1 to prevent this hormone imbalance likely underlies its negative impact on PTI in plant defense. Thus, ACP1 links FA metabolism to stress hormone homeostasis to be negatively involved in PTI in Arabidopsis plant defense.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The CYCLOPS Response Element in the NIN Promoter Is Important but Not Essential for Infection Thread Formation During Lotus japonicus–Rhizobia Symbiosis
Authors: Akamatsu Akira , Nagae Miwa , Takeda Naoya 
Published: March 2022

The establishment of the legume-rhizobia symbiosis, termed the root-nodule symbiosis (RNS), requires elaborate interactions at the molecular level. The host plant–derived transcription factor NODULE INCEPTION (NIN) is known to be crucial for RNS, regulating associated processes such as alteration of root hair morphology, infection thread formation, and cell division during nodulation. This emphasizes the importance of the precise spatiotemporal regulation of NIN expression for the establishment of RNS; however, the detailed role of NIN promoter sequences in this process remains unclear. The daphne mutant, a nin mutant allele containing a chromosomal translocation approximately 7 kb upstream of the start codon, does not form nodules but does form infection threads, indicating that the region within 7 kb of the NIN start codon contributes to NIN expression during infection thread formation. CYCLOPS binds to a CYCLOPS response element ( CYC-RE) in the NIN promoter, and cyclops mutants are defective in infection thread formation. Here, we performed complementation analysis in nin mutants, using various truncated forms of the NIN promoter, and found that the CYC-RE is important for infection thread formation. Additionally, the CYC-RE deletion mutant, generated through CRISPR/Cas9 technology, displayed a significant reduction in infection thread formation, indicating that the CYC-RE is important for the fine-tuning of NIN expression during this process. However, the fact that infection thread formation is not completely abolished in the CYC-RE deletion mutant suggests that cis and trans factors other than CYCLOPS and the CYC-RE may cooperatively regulate NIN expression for the induction of infection thread formation. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Optimized infection control practices augment the robust protective effect of vaccination for ESRD patients during a hemodialysis facility SARS-CoV-2 outbreak
Authors: Meller Megan E. , Pfaff Bridget L. , Borgert Andrew J. , Richmond Craig S. , Athas Deena M. , Kenny Paraic A. , Sabin Arick P. 
Published: March 2022

ABSTRACTBackgroundWhile dialysis patients are at greater risk of serious SARS-CoV-2 complications, stringent infection prevention measures can help mitigate the risk of infection and transmission within dialysis facilities. We describe an outbreak of 14 cases diagnosed in a 13-day period in the second quarter of 2021 in a hospital-based ESRD facility, and our coordinated use of epidemiology, viral genome sequencing, and infection control practices to quickly end the cycle of transmission.MethodsSymptomatic patients and staff members were diagnosed via RT-PCR tests. Facility-wide screening was conducted using rapid SARS-CoV-2 antigen tests. SARS-CoV-2 genome sequences were obtained from residual diagnostic PCR specimens.ResultsOf the 106 patients who received dialysis in the facility, 10 were diagnosed with SARS-CoV-2 infection, as was one patient support person. Of three positive staff members, two were unvaccinated and had provided care for six and four of the affected patients, respectively. Sequencing demonstrated that all the cases in the cluster shared an identical B.1.1.7./Alpha substrain. Attack rates were greatest among unvaccinated patients and staff. Vaccine effectiveness was 88% among patients.ConclusionsPrompt recognition of an infection cluster and rapid intervention efforts successfully ended the outbreak. Alongside consistent adherence to core infection prevention measures, vaccination was highly effective in reducing disease incidence and morbidity in this vulnerable population.
Trivalent NDV-HXP-S vaccine protects against phylogenetically distant SARS-CoV-2 variants of concern in mice
Authors: González-Domínguez Irene , Martínez Jose Luis , Slamanig Stefan , Lemus Nicholas , Liu Yonghong , Lai Tsoi Ying , Carreño Juan Manuel , Singh Gagandeep , Singh Gagandeep , Schotsaert Michael , Mena Ignacio , McCroskery Stephen , Coughlan Lynda , Krammer Florian , García-Sastre Adolfo , Palese Peter , Sun Weina 
Published: March 2022

AbstractEquitable access to vaccines is necessary to limit the global impact of the coronavirus disease 2019 (COVID-19) pandemic and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. In previous studies, we described the development of a low-cost vaccine based on a Newcastle Disease virus (NDV) expressing the prefusion stabilized spike protein from SARS-CoV-2, named NDV-HXP-S. Here, we present the development of next-generation NDV-HXP-S variant vaccines, which express the stabilized spike protein of the Beta, Gamma and Delta variants of concerns (VOC). Combinations of variant vaccines in bivalent, trivalent and tetravalent formulations were tested for immunogenicity and protection in mice. We show that the trivalent preparation, composed of the ancestral Wuhan, Beta and Delta vaccines, substantially increases the levels of protection and of cross-neutralizing antibodies against mismatched, phylogenetically distant variants, including the currently circulating Omicron variant.
Acupuncture with or without acupoint application for primary dysmenorrhea: protocol for a systematic review and meta-analysis
Authors: Zhao Xuewei , Tian Yu , Zhao Jinying , Jiang Hailin , Sun Jiabao , Zhi Xiaoyu , Liu Baiyan , Liu Wu , Liu Yanze , Li Tie , Wang Fuchun 
Published: March 2022

AbstractIntroductionDysmenorrhea is the most common gynaecological symptom reported by women. Ninety percent of women presenting for primary care experience some menstrual pain. Population surveys suggest that, although prevalence rates vary considerably by geographic al location, complaints of dysmenorrhea are widespread in diverse populations. This study will evaluate the results of randomized controlled trials to determine the efficacy and safety of acupuncture with or without acupoint application for the treatment of dysmenorrhea.MethodsEight databases, including China National Knowledge Infrastructure, Chinese Scientific Journal Database, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, PubMed, Wanfang Database, and Web of Science, will be searched using English and Chinese search strategies. In addition, manual retrieval of research papers, conference papers, ongoing experiments, and internal reports, among others, will supplement electronic retrieval. All eligible studies published on or before December 12, 2021 will be selected. To enhance the effectiveness of the study, only clinical randomized controlled trials related to the use of acupuncture with or without acupoint application for the treatment of dysmenorrhea will be included.AnalysisThe Visual Analog Scale will be the primary outcome measure, whereas the McGill pain questionnaire, SF-36 Scale, Self-Rating Anxiety, and Self-Rating Depression scale will be the secondary outcomes. Side effects and adverse events will be included as safety evaluations. To ensure the quality of the systematic evaluation, study selection, data extraction, and quality assessment will be independently performed by two authors, and a third author will resolve any disagreement.Ethics and disseminationThis systematic review will evaluate the efficacy and safety of acupuncture with or without acupoint application for the treatment of dysmenorrhea. Since all included data will be obtained from published articles, it does not require ethical approval and will be published in a peer-reviewed journal.INPLASY registration numberINPLASY202230051.
Inference of B cell clonal families using heavy/light chain pairing information
Authors: Ralph Duncan K. , Matsen Frederick A. 
Published: March 2022

AbstractNext generation sequencing of B cell receptor (BCR) repertoires has become a ubiquitous tool for understanding the antibody-mediated immune response: it is now common to have large volumes of sequence data coding for both the heavy and light chain subunits of the BCR. However, until the recent development of high throughput methods of preserving heavy/light chain pairing information, these samples contained no explicit information on which heavy chain sequence pairs with which light chain sequence. One of the first steps in analyzing such BCR repertoire samples is grouping sequences into clonally related families, where each stems from a single rearrangement event. Many methods of accomplishing this have been developed, however, none so far has taken full advantage of the newly-available pairing information. This information can dramatically im-prove clustering performance, especially for the light chain. The light chain has traditionally been challenging for clonal family inference because of its low diversity and consequent abundance of non-clonal families with indistinguishable naive rearrangements. Here we present a method of incorporating this pairing information into the clustering process in order to arrive at a more accurate partition of the data into clonally related families. We also demonstrate two methods of fixing imperfect pairing information, which may allow for simplified sample preparation and increased sequencing depth. Finally, we describe several other improvements to thepartissoftware package (https://github.com/psathyrella/partis).AuthorSummaryAntibodies form part of the adaptive immune response, and are critical to immunity acquired by both vaccination and infection. Next generation sequencing of the B cell receptor (BCR) repertoire provides a broad and highly informative view of the DNA sequences from which antibodies arise. Until recently, however, this sequencing data was not able to pair together the two domains (from separate chromosomes) that make up a functional antibody. In this paper we present several methods to improve analysis of the newpaireddata that does pair together sequence data for complete antibodies. We first show a method that better groups together sequences stemming from the same ancestral cell, solving a problem called “clonal family inference.” We then show two methods that can correct for various imperfections in the data’s identification of which sequences pair together to form complete antibodies, which together may allow for significantly simplified experimental methods.
An integrative analysis of the biological clock hypothesis in human gut microbiome
Authors: Moss Anh D. , Sun Shan , Blakley Ivory C. , Fodor Anthony A. 
Published: March 2022

AbstractBackgroundWhile previous studies have explored the relationship between aging and the gut microbiome, it remains unclear how consistent and reproducible this association is across different cultures and groups. We performed an integrative analysis with 11 independent datasets from nine different countries to test the idea that the aging gut microbiome can be viewed as a biological clock, in which microbial changes associated with age are consistent and measurable across distinct datasets.ResultsAs expected, our Principal Coordinate Analysis found strong batch effects with study ID by far the strongest signal across datasets. Despite this large batch effect, we found a consistent signal across studies that was largely driven by sample size with only our larger cohorts showing taxa in common associated with age. Likewise, Shannon diversity and richness were not consistently associated with age across the 11 datasets, but some positive correlations with richness and host age were observed among the four largest cohorts. The taxon with the most potential as a biomarker for the aging human gut microbiome is genus Bifidobacterium, with significantly negative associations with host age in three out of the four datasets that had more than 200 samples.ConclusionThe driving force behind low reproducibility of association of age with the microbiome in previous studies appears to be inadequate sample size rather than structural differences in the microbial community based on cohort characteristics. Results from a power analysis suggest that future studies on the aging human gut microbiome consider on the order of 100-300 samples to consistently observe an age signal. With these larger sample sizes, parametric and non-parametric model yield broadly similar power.
Sensory neuron-associated macrophages proliferate in the sensory ganglia after peripheral nerve injury in a CX3CR1 signaling dependent manner
Authors: Guimarães Rafaela M. , da Silva Conceição E. A. , Davoli-Ferreira Marcela , Gomes Francisco Isaac F. , Mendes Atlante , Fonseca Miriam M. , Damasceno Samara , Andrade Larissa P. , Cunha Fernando Q. , Alves-Filho José C. , Cunha Thiago M. 
Published: March 2022

AbstractResident macrophages are distributed across all tissues and are highly heterogeneous as a consequence of adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia which have been involved in different conditions, especially in neuropathic pain development and nerve regeneration. However, it is still under debate whether macrophages accumulation in the sensor ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or as a result of blood monocytes infiltration. Here, we confirmed that the number of macrophages increased in the DRGs after spared nerve injury (SNI) model in mice. By using different approaches, we found that the increase in the number of macrophages in the DRGs after SNI is mainly in consequence of the proliferation of resident CX3CR1+ macrophages but not due to infiltration of CCR2+ blood monocytes. These proliferating macrophages are the source of the production of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain and/or nerve regeneration.