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Microbiology Spectrum Jun 2024All sulfur transfer pathways have generally a l-cysteine desulfurase as an initial sulfur-mobilizing enzyme in common, which serves as a sulfur donor for the...
All sulfur transfer pathways have generally a l-cysteine desulfurase as an initial sulfur-mobilizing enzyme in common, which serves as a sulfur donor for the biosynthesis of numerous sulfur-containing biomolecules in the cell. In , the housekeeping l-cysteine desulfurase IscS has several interaction partners, which bind at different sites of the protein. So far, the interaction sites of IscU, Fdx, CyaY, and IscX involved in iron-sulfur (Fe-S) cluster assembly have been mapped, in addition to TusA, which is required for molybdenum cofactor biosynthesis and mnmsU34 tRNA modifications, and ThiI, which is involved in thiamine biosynthesis and sU8 tRNA modifications. Previous studies predicted that the sulfur acceptor proteins bind to IscS one at a time. TusA has, however, been suggested to be involved in Fe-S cluster assembly, as fewer Fe-S clusters were detected in a mutant. The basis for this reduction in Fe-S cluster content is unknown. In this work, we investigated the role of TusA in iron-sulfur cluster assembly and iron homeostasis. We show that the absence of TusA reduces the translation of , thereby leading to pleiotropic cellular effects, which we dissect in detail in this study.IMPORTANCEIron-sulfur clusters are evolutionarily ancient prosthetic groups. The ferric uptake regulator plays a major role in controlling the expression of iron homeostasis genes in bacteria. We show that a mutant is impaired in the assembly of Fe-S clusters and accumulates iron. TusA, therefore, reduces mRNA translation leading to pleiotropic cellular effects.
PubMed: 38916309
DOI: 10.1128/spectrum.00556-24 -
Anatomy & Cell Biology Jun 2024The 7th cervical vertebra (C7) is described as having the most prominent spinous process (SP) and is characterized as the "vertebra prominens" (VP) of the cervical spine...
The 7th cervical vertebra (C7) is described as having the most prominent spinous process (SP) and is characterized as the "vertebra prominens" (VP) of the cervical spine in anatomy textbooks. The VP is an important anatomical landmark of the neck for clinical examination and therapeutic intervention. The present study identifies the level of the most prominent SP of the cervical and uppermost thoracic vertebrae in a cadaveric cohort. Thirty-nine (23 female and 16 male) cadavers of a mean age of 77.5 years were investigated in a prone position and a certain cervical kyphotic bending. The most prominent SP, at the base of the neck, was palpated and marked with a wedging nail into the SP of the vertebra. The cervical region was dissected, and a blind investigator examined whether the nail was placed into the SP of C7 or the SP of another upper or lower vertebra. In 19 out of 39 cadavers (48.7%), the C7 was identified as the VP (typical anatomy), followed by the C6 (in 14 cadavers, 35.9%), C5 (in 4 cadavers, 10.3%). In 2 cadavers (5.1%) the first thoracic vertebra was identified as having the most prominent SP. Although C7 is described as the VP, in the present study the SP of C7 was the most prominent in less than 50%. The high variable projection level of the most prominent SP of the cervical vertebra holds great clinical significance for spine examination, neck surgery, and spinal anesthesia.
PubMed: 38916082
DOI: 10.5115/acb.24.061 -
Cureus May 2024Background Thyroidectomy is a routinely performed surgical procedure used to treat benign, malignant, and some hormonal disorders of the thyroid that are not responsive...
Background Thyroidectomy is a routinely performed surgical procedure used to treat benign, malignant, and some hormonal disorders of the thyroid that are not responsive to medical therapy. Voice alterations following thyroid surgery are well-documented and often attributed to recurrent laryngeal nerve dysfunction. However, subtle changes in voice quality can persist despite anatomically intact laryngeal nerves. This study aimed to quantify post-thyroidectomy voice changes in patients with intact laryngeal nerves, focusing on fundamental frequency, first formant frequency, shimmer intensity, and maximum phonation duration. Methodology This cross-sectional study was conducted at a tertiary referral center in central India and focused on post-thyroidectomy patients with normal vocal cord function. Preoperative assessments included laryngeal endoscopy and voice recording using a computer program, with evaluations repeated at one and three months post-surgery. Patients with normal laryngeal endoscopic findings underwent voice analysis and provided feedback on subjective voice changes. The PRAAT version 6.2 software was utilized for voice analysis. Results The study included 41 patients with normal laryngoscopic findings after thyroid surgery, with the majority being female (85.4%) and the average age being 42.4 years. Hemithyroidectomy was performed in 41.4% of patients and total thyroidectomy in 58.6%, with eight patients undergoing central compartment neck dissection. Except for one patient, the majority reported no subjective change in voice following surgery. Objective voice analysis showed statistically significant changes in the one-month postoperative period compared to preoperative values, including a 5.87% decrease in fundamental frequency, a 1.37% decrease in shimmer intensity, and a 6.24% decrease in first formant frequency, along with a 4.35% decrease in maximum phonatory duration. These trends persisted at the three-month postoperative period, although values approached close to preoperative levels. Results revealed statistically significant alterations in voice parameters, particularly fundamental frequency and first formant frequency, with greater values observed in total thyroidectomy patients. Shimmer intensity also exhibited slight changes. Comparison between hemithyroidectomy and total thyroidectomy groups revealed no significant differences in fundamental frequency, first formant frequency, and shimmer. However, maximum phonation duration showed a significantly greater change in the hemithyroidectomy group at both one-month and three-month postoperative intervals. Conclusions This study on post-thyroidectomy patients with normal vocal cord movement revealed significant changes in voice parameters postoperatively, with most patients reporting no subjective voice changes. The findings highlight the importance of objective voice analysis in assessing post-thyroidectomy voice outcomes.
PubMed: 38916010
DOI: 10.7759/cureus.60873 -
JACC. Advances Mar 2024
PubMed: 38915882
DOI: 10.1016/j.jacadv.2023.100824 -
DEN Open Apr 2025Endoscopic submucosal dissection (ESD) is a transformative advancement in the endoscopic management of superficial gastrointestinal lesions. Initially conceived for the... (Review)
Review
Endoscopic submucosal dissection (ESD) is a transformative advancement in the endoscopic management of superficial gastrointestinal lesions. Initially conceived for the treatment of early gastric cancer, ESD has demonstrated proficiency in achieving en-bloc resection of superficial gastrointestinal lesions. ESD has experienced widespread acceptance in Japan and East Asia; however, its adoption in the USA remains delayed. This initial hesitancy could be attributed to procedural complexity and training demands; nonetheless, recently, ESD has been gaining popularity in the USA. This is due to the advancements in endoscopic technology, tailored training programs, and cumulative evidence regarding the efficacy and safety of ESDs. This review aimed to deliberate the historical progress, current implementation, and prospective trajectory of ESDs in the USA. With ongoing clinical research, technological integration, and educational efforts, ESD is likely to become the gold standard for managing large gastrointesitinal lesions. This progress marks an imperative step toward less invasive, more precise, and patient-centric approaches regarding advanced therapeutic endoscopy in the USA.
PubMed: 38915785
DOI: 10.1002/deo2.394 -
BioRxiv : the Preprint Server For... Jun 2024Memory CD8 T cells (T ) can be activated into innate-like killers by cytokines like IL-12, IL-15, and/or IL-18; but mechanisms regulating this phenomenon (termed...
Memory CD8 T cells (T ) can be activated into innate-like killers by cytokines like IL-12, IL-15, and/or IL-18; but mechanisms regulating this phenomenon (termed bystander activation) are not fully resolved. We found strain-intrinsic deficiencies in bystander activation using specific pathogen-free mice, whereby basal IL-4 signals antagonize IL-18 sensing. We show that therapeutic and helminth-induced IL-4 impairs protective bystander-mediated responses against pathogens. However, this IL-4/IL-18 axis does not completely abolish bystander activation but rather tunes the expression of direct versus indirect mediators of cytotoxicity (granzymes and interferon-γ, respectively). We show that antigen-experience overrides strain-specific deficiencies in bystander activation, leading to uniform IL-18 receptor expression and enhanced capacity for bystander activation/cytotoxicity. Our data highlight that bystander activation is not a binary process but tuned/deregulated by other cytokines that are elevated by contemporaneous infections. Further, our findings underscore the importance of antigen-experienced T to dissect the contributions of bystander T in health and disease.
PubMed: 38915668
DOI: 10.1101/2024.06.10.598293 -
BioRxiv : the Preprint Server For... Jun 2024The microbiome is increasingly recognized to shape many aspects of its host biology and is a key determinant of health and disease. The microbiome may influence...
BACKGROUND
The microbiome is increasingly recognized to shape many aspects of its host biology and is a key determinant of health and disease. The microbiome may influence transmission of pathogens by their vectors, such as mosquitoes or aquatic snails. We previously sequenced the bacterial 16S V4 ribosomal DNA of the hemolymph (blood) of spp. snails, one of the vectors of the human blood fluke schistosome. We showed that snail hemolymph harbored an abundant and diverse microbiome. This microbiome is distinct from the water environment and can discriminate snail species and populations. As hemolymph bathes snail organs, we then investigated the heterogeneity of the microbiome in these organs.
RESULTS
We dissected ten snails for each of two different species ( and ) and collected their organs (ovotestis, hepatopancreas, gut, and stomach). We also ground in liquid nitrogen four whole snails of each species. We sampled the water in which the snails were living (environmental controls). Sequencing the 16S V4 rDNA revealed organ- specific microbiomes. These microbiomes harbored a lower diversity than the hemolymph microbiome, and the whole-snail microbiome. The organ microbiomes tend to cluster by physiological function. In addition, we showed that the whole-snail microbiome is more similar to hemolymph microbiome.
CONCLUSIONS
These results are critical for future work on snail microbiomes and show the necessity of sampling individual organ microbiomes to provide a complete description of snail microbiomes.
PubMed: 38915569
DOI: 10.1101/2024.06.11.598555 -
BioRxiv : the Preprint Server For... Jun 2024The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented...
The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented the phenotypic changes by gene or protein expression, less is known about the role of blood flow pattern on the endothelial cell (EC) lipidome. In this study, shotgun lipidomics was conducted on human aortic ECs (HAECs) exposed to unidirectional laminar flow (UF), disturbed flow (DF), or static conditions for 48 hrs. A total of 520 individual lipid species from 17 lipid subclasses were detected. Total lipid abundance was significantly increased for HAECs exposed to DF compared to UF conditions. Despite the increase in the total lipid abundance, HAECs maintained equivalent composition of each lipid subclass (% of total lipid) under both DF and UF. However, by lipid composition (% of total subclass), 28 lipid species were significantly altered between DF and UF. Complimentary RNA sequencing of HAECs exposed to UF or DF revealed changes in transcripts involved in lipid metabolism. Shotgun lipidomics was also performed on HAECs exposed to pro-inflammatory agonists lipopolysaccharide (LPS) or Pam3CSK4 (Pam3) for 48 hrs. Exposure to LPS or Pam3 reshaped the EC lipidome in both unique and overlapping ways. In conclusion, exposure to flow alters the EC lipidome and ECs undergo stimulus-specific lipid reprogramming in response to pro-inflammatory agonist exposure. Ultimately, this work provides a resource to profile the transcriptional and lipidomic changes that occur in response to applied flow that can be accessed by the vascular biology community to further dissect and extend our understanding of endothelial lipid biology.
PubMed: 38915541
DOI: 10.1101/2024.06.13.598934 -
BioRxiv : the Preprint Server For... Jun 2024Inactivating mutations in the melanocortin 4 receptor ( ) gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive...
Inactivating mutations in the melanocortin 4 receptor ( ) gene cause monogenic obesity. Interestingly, female patients also display various degrees of reproductive disorders, in line with the subfertile phenotype of MC4RKO female mice. However, the cellular mechanisms by which MC4R regulates reproduction are unknown. Kiss1 neurons directly stimulate gonadotropin-releasing hormone (GnRH) release through two distinct populations; the Kiss1 neurons, controlling GnRH pulses, and the sexually dimorphic Kiss1 neurons controlling the preovulatory LH surge. Here, we show that expressed in Kiss1 neurons is required for fertility in females. , deletion of from Kiss1 neurons in female mice replicates the reproductive impairments of MC4RKO mice without inducing obesity. Conversely, reinsertion of in Kiss1 neurons of MC4R null mice restores estrous cyclicity and LH pulsatility without reducing their obese phenotype. , we dissect the specific action of MC4R on Kiss1 vs Kiss1 neurons and show that MC4R activation excites Kiss1 neurons through direct synaptic actions. In contrast, Kiss1 neurons are normally inhibited by MC4R activation except under elevated estradiol levels, thus facilitating the activation of Kiss1 neurons to induce the LH surge driving ovulation in females. Our findings demonstrate that POMC neurons acting through MC4R, directly regulate reproductive function in females by stimulating the "pulse generator" activity of Kiss1 neurons and restricting the activation of Kiss1 neurons to the time of the estradiol-dependent LH surge, and thus unveil a novel pathway of the metabolic regulation of fertility by the melanocortin system.
PubMed: 38915534
DOI: 10.1101/2024.02.18.580873 -
BioRxiv : the Preprint Server For... Jun 2024Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating...
Stress has been shown to promote the development and persistence of binge eating behaviors. However, the neural circuit mechanisms for stress-induced binge-eating behaviors are largely unreported. The endogenous dynorphin (dyn)/kappa opioid receptor (KOR) opioid neuropeptide system has been well-established to be a crucial mediator of the anhedonic component of stress. Here, we aimed to dissect the basis of dynorphinergic control of stress-induced binge-like eating behavior. We first established a mouse behavioral model for stress-induced binge-like eating behaviors. We found that mice exposed to stress increased their food intake of familiar palatable food (high fat, high sugar, HPD) compared to non-stressed mice. Following a brain-wide analysis, we isolated robust cFos-positive cells in the Claustrum (CLA), a subcortical structure with highly abundant KOR expression, following stress-induced binge-eating behavior. We report that KOR signaling in CLA is necessary for this elevated stress-induced binge eating behavior using local pharmacology and local deletion of KOR. In vivo calcium recordings using fiber photometry revealed a disinhibition circuit structure in the CLA during the initiation of HPD feeding bouts. We further established the dynamics of endogenous dynorphinergic control of this behavior using a genetically encoded dynorphin biosensor, Klight. Combined with 1-photon single-cell calcium imaging, we report significant heterogeneity with the CLA population during stress-induced binge eating and such behavior attenuates local dynorphin tone. Furthermore, we isolate the anterior Insular cortex (aIC) as the potential source of endogenous dynorphin afferents in the CLA. By characterizing neural circuits and peptidergic mechanisms within the CLA, we uncover a pathway that implicates endogenous opioid regulation stress-induced binge eating.
PubMed: 38915527
DOI: 10.1101/2024.06.10.598168