Search Results (17)

Adipose tissue exhibits dynamic metabolic and structural changes in response to environmental stimuli, including temperature fluctuations. While continuous cold exposure has been extensively studied, the molecular effects of prolonged intermittent cold exposure (ICE) remain poorly characterized. Here, we present a proteomic analysis of inguinal white adipose tissue (IWAT) from mice subjected to a 16-week regimen of short-term daily ICE (6 °C for 6 h, 5 days per week) without compensatory caloric intake. Mass spectrometry identified 1108 proteins, with 140 differentially expressed between experimental and control groups. ICE significantly upregulated mitochondrial proteins associated with lipid and carbohydrate catabolism, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipogenesis, including LETM1, AIFM1, PHB, PHB2, ACOT2, NDUA9, and ATP5J. These changes reflect enhanced metabolic activity and mitochondrial remodeling. In contrast, proteins linked to oxidative stress, insulin resistance, inflammation, and extracellular matrix remodeling were downregulated, such as HMGB1, FETUA, SERPH1, RPN1, and AOC3. Notably, gamma-synuclein (SYUG), which inhibits lipolysis, was undetectable in ICE-treated samples. Our findings support the hypothesis that ICE promotes thermogenic reprogramming and metabolic rejuvenation in subcutaneous fat through activation of futile cycles and mitochondrial restructuring. This study offers molecular insights into adaptive thermogenesis and presents intermittent cold exposure as a potential strategy to mitigate adipose tissue aging. Full article

Introduction: Downbeat nystagmus (DBN) is an ocular motor disorder characterized by persistent to-and-fro eye movements with a slow phase directed upwards and a corrective fast phase downwards. DBN in the context of myelin oligodendrocyte glycoprotein-associated disorder (MOGAD) represents a rare clinical presentation. Case Presentation: A 24-year-old male with MOGAD presented with DBN, status epilepticus, and longitudinally extensive transverse myelitis (LETM). Intervention: The clinical course, diagnostic findings, and management approach are described in detail within the full report. Outcomes: The patient at follow-up was able to ambulate independently, and his nystagmus had improved. He continued to demonstrate transient DBN on supine positioning and head-shaking test. Conclusions: This case report contributes to the understanding of DBN as a manifestation of MOGAD. The accompanying literature review examines the neuroanatomy, pathophysiology, and emerging therapeutic approaches for DBN, providing context for this unusual presentation. Full article

Background/Objectives: Finding single nucleotide polymorphisms (SNPs) and candidate genes that influence the expression of key traits is essential for genomic selection and helps improve the efficiency of poultry production. Here, we aimed to conduct a genome-wide association study (GWAS) for egg production traits in an F₂ resource population of chickens (Gallus gallus). Methods: The examined F₂ population was produced by crossing two divergently selected breeds with contrasting phenotypes for egg performance traits, namely Russian White (of higher egg production) and Cornish White (of lower egg production). Sampled birds (n = 142) were genotyped using the Illumina Chicken 60K SNP iSelect BeadChip. Results: In the course of the GWAS analysis, we were able to clarify significant associations with phenotypic traits of interest and economic value by using 47,432 SNPs after the genotype dataset was filtered. At the threshold p < 1.06 × 10⁻⁶, we found 23 prioritized candidate genes (PCGs) associated with egg weight at the age of 42–52 weeks (FGF14, GCK), duration of egg laying (CNTN4), egg laying cycle (SAMD12) and egg laying interval (PHF5A, AKR1B1, CALD1, ATP7B, PIK3R4, PTK2, PRKCE, FAT1, PCM1, CC2D2A, BMS1, SEMA6D, CDH13, SLIT3, ATP10B, ISCU, LRRC75A, LETM2, ANKRD24). Moreover, two SNPs were co-localized within the FGF14 gene. Conclusions: Based on our GWAS findings, the revealed SNPs and candidate genes can be used as genetic markers for egg weight and other performance characteristics in chickens to attain genetic enhancement in production and for further genomic selection. Full article

Background/Objectives: Transverse myelitis (TM) is a rare, acute inflammatory disorder affecting the spinal cord, with severe potential consequences, particularly in pediatric patients. Therapeutic plasma exchange (TPE) has emerged as a possible intervention for children unresponsive to high-dose corticosteroids. This study explores the efficacy of early TPE in pediatric TM through a case report and scoping review aiming to clarify the therapeutic benefits of TPE when used in conjunction with corticosteroids in children. Methods: We present a scoping review of existing literature on the early administration of TPE in pediatric patients with TM, supplemented by a case report of a 5-year-old boy with Longitudinally Extensive Transverse Myelitis (LETM), who received early TPE and corticosteroid therapy. Clinical progression, response to TPE, and functional outcomes were documented over a 9-month follow-up period. Results: Among the reviewed cases, early TPE demonstrated potential to expedite neurological recovery and improve functional outcomes. In our case report, the patient showed rapid recovery, achieving unassisted ambulation by day four of TPE. No adverse effects were observed. MRI findings revealed substantial resolution of spinal cord lesions by three months, with near-complete symptom resolution at nine months. Conclusions: Early initiation of TPE, in conjunction with corticosteroids, may offer significant therapeutic benefit in pediatric TM, potentially accelerating recovery and improving outcomes. This case highlights the need for further controlled studies to establish evidence-based guidelines for TPE use in pediatric TM. Full article

Background: Copy number alterations are common genetic lesions in cancer. In squamous non-small cell lung carcinomas, the most common copy-number-altered loci are at chromosomes 3q26-27 and 8p11.23. The genes that may be drivers in squamous lung cancers with 8p11.23 amplifications are unclear. Methods: Data pertaining to copy number alterations, mRNA expression and protein expression of genes located in the 8p11.23 amplified region were extracted from various sources including The Cancer Genome Atlas, the Human Protein Atlas and the Kaplan Meier Plotter. Genomic data were analyzed using the cBioportal platform. Survival analysis of cases with amplifications compared to nonamplified cases was performed using the Kaplan Meier Plotter platform. Results: The 8p11.23 locus is amplified in 11.5% to 17.7% of squamous lung carcinomas. The most frequently amplified genes include NSD3, FGFR1 and LETM2. Only some of the amplified genes present concomitant overexpression at the mRNA level. These include NSD3, PLPP5, DDHD2, LSM1 and ASH2L, while other genes display lower levels of correlation, and still, some genes in the locus show no mRNA overexpression compared with copy-neutral samples. The protein products of most locus genes are expressed in squamous lung cancers. No significant difference in overall survival in 8p11.23-amplified squamous cell lung cancers versus nonamplified cancers is observed. In addition, there is no adverse effect of mRNA overexpression for relapse-free survival of any of the amplified genes. Conclusion: Several genes that are part of the commonly amplified locus 8p11.23 in squamous lung carcinomas are putative oncogenic candidates. A subset of genes of the centromeric part of the locus, which is amplified more commonly than the telomeric part, show high concomitant mRNA expression. Full article

The availability of sustainable, efficient electricity access is critical for rural communities as it can facilitate economic development and improve the quality of life for residents. Isolated microgrids can provide a solution for rural electrification, as they can generate electricity from local renewable energy sources and can operate independently from the central grid. Residential load scheduling is also an important aspect of energy management in isolated microgrids. However, effective management of the microgrid’s energy resources and load scheduling is essential for ensuring the reliability and cost-effectiveness of the system. To cope with the stochastic nature of RERs, the idea of an optimal energy management system (EMS) with a local energy transactive market (LETM) in an isolated multi-microgrid system is proposed in this work. Nature-inspired algorithms such as JAYA (Sanskrit word meaning victory) and teaching–learning based optimization algorithm (TLBO) can get stuck in local optima, thus reducing the effectiveness of EMS. For this purpose, a modified hybrid version of the JAYA and TLBO algorithm, namely, the modified JAYA learning-based optimization (MJLBO), is proposed in this work. The prosumers can sell their surplus power or buy power to meet their load demand from LETM enabling a higher load serving as compared to a single isolated microgrid with multi-objectives, resulting in a reduced electricity bill, increased revenue, peak-average ratio, and user discomfort. The proposed system is evaluated against three other algorithms TLBO, JAYA, and JAYA learning-based optimization (JLBO). The result of this work shows that MJLBO outperforms other algorithms in achieving the best numerical value for all objectives. The simulation results validate that MJLBO achieves a peak-to-average ratio (PAR) reduction of 65.38% while there is a PAR reduction of 51.4%, 52.53%, and 51.2% for TLBO, JLBO, and JAYA as compared to the unscheduled load. Full article

Pancreatic ductal adenocarcinoma (PDAC) is one of the highest mortalities malignant tumors, which is characterized by difficult diagnosis, rapid progression and high recurrence rate. Nevertheless, PDAC responds poorly to conventional therapies, which highlights the urgency to identify novel prognostic and therapeutic targets. LEMT2 was a newly discovered protein-encoding gene with little cancer research and an unclear mechanism. Thus, this study aimed to illustrate LETM2 as the crucial oncogene for tumor progression in PDAC. In this study, we analyzed the expression level and prognostic value of LETM2 in multiple cancers using pan-cancer analysis. The analyses based on the TCGA-GTEx dataset indicated that the LETM2 expression was obviously elevated in several cancers, and it was the most significantly related to the dismal prognosis of PDAC. Subsequently, we demonstrated the functional role and mechanism of LETM2 by clinical sample evaluation, and in in vitro and in vivo experiments. Immunohistochemical analyses showed that high expression of LETM2 was correlated with poor outcomes of PDAC. Moreover, we demonstrated that LETM2 knockdown significantly inhibited tumor proliferation and metastasis, and promoted cell apoptosis, while LETM2 overexpression exerted the opposite effects. Finally, the impairment caused by LETM2-knockdown could be recovered via excitation of the PI3k-Akt pathway in vitro and in vivo animal models, which suggested that LETM2 could activate the downstream PI3K-Akt pathway to participate in PDAC progression. In conclusion, the study enhanced our understanding of LETM2 as an oncogene hallmark of PDAC. LETM2 may facilitate tumor progression by activating the PI3K-Akt signaling pathway, which provides potential targets for the diagnosis, treatment, and prognosis of pancreatic cancer. Full article

Longitudinally extensive transverse myelitis (LETM) associated with cytomegalovirus infection is extremely rare and is, mainly observed in immunocompetent people. A 55-year-old woman with no evidence of immunosuppression was admitted with paresthesia in the lower limbs for 15 days, difficulty walking, fecal incontinence, and acute urinary retention. Magnetic resonance imaging (MRI) in the T2 sequence showed signs of hyperintensity in the cervical and thoracic cord. The serological study showed IgM antibodies to cytomegalovirus, and the result of the FilmArray meningitis/encephalitis panel showed the presence of cytomegalovirus. She received treatment with methylprednisolone and ganciclovir with a favorable outcome. This case highlights the importance of investigating treatable causes in patients with longitudinally extensive transverse myelitis with acute presentation. Full article

Previous work showed a role of BNIP3 in myocardial remodeling and progression to HFrEF. We utilized a multiomics approach to unravel BNIP3-related molecular mechanisms in the pathogenesis of HFrEF. BNIP3 knockdown in HFrEF improved glycolysis, pyruvate metabolism, branched-chain amino acid catabolism, and oxidative phosphorylation, and restored endoplasmic reticulum (ER)–mitochondrial (mt) calcium and ion homeostasis. These effects of BNIP3 on cardiac metabolism were related to its interaction and downregulation, and/or phosphorylation, of specific mt-proteins involved in the aforementioned metabolic pathways, including the MICOS and SLC25A families of carrier proteins. BNIP3 affected ER–mt-calcium and ion homeostasis via its interaction-induced VDAC1 dimerization and modulation of VDAC1 phosphorylation at Ser104 and Ser241, and the downregulation of LETM1. At the ER level, BNIP3 interacted with the enzyme SERCA2a and the PKA signaling complex, leading to the downregulation of SERCA2a and PKA-mediated Ser16 phospholamban phosphorylation. Additionally, BNIP3 attenuated AMPK and PRKCE activity by modulating AMPK phosphorylation at Ser485/491 and Ser377 residues, and PRKCE phosphorylation at Thr521 and Thr710 residues. BNIP3 also interacted with sarcomeric, cytoskeletal, and cellular transcription and translation proteins, and affected their expression and/or phosphorylation. In conclusion, BNIP3 modulates multiple pathobiological processes and constitutes an attractive therapeutic target in HFrEF. Full article

An increasing number of people are undergoing vaccination for COVID-19 because of the ongoing pandemic. The newly developed, genetically engineered mRNA vaccines are critical for controlling the epidemic disease. However, major adverse effects, including neuroimmunological disorders, are being attributed to this vaccine. For instance, several cases of acute transverse myelitis (ATM) after COVID-19 vaccination have been reported in clinical trials. Here, we report an exceedingly rare case of longitudinally extensive transverse myelitis (LETM), a rare subtype of ATM involving three or more vertebral segments, that occurred shortly after vaccination with the Moderna COVID-19 (mRNA-1273) vaccine, with a comorbidity of vitamin B12 deficiency. The findings of subsequent investigations suggest the possibility that autoimmune responses are triggered by the reactions between anti-SARS-CoV-2 spike protein antibodies and tissue proteins, as well as the interaction between spike proteins and angiotensin-converting enzyme 2 receptors. Full article

In ‘Tsuda’ turnip, the swollen root peel accumulates anthocyanin pigments in a light-dependent manner, but the mechanism is unclear. Here, mutant g120w which accumulated extremely low levels of anthocyanin after light exposure was identified. Segregation analysis showed that the anthocyanin-deficient phenotype was controlled by a single recessive gene. By using bulked-segregant analysis sequencing and CAPS marker-based genetic mapping analyses, a 21.6-kb region on chromosome A07 was mapped, in which a calcium-binding EF hand family protein named BrLETM2 was identified as the causal gene. RNA sequencing analysis showed that differentially expressed genes (DEGs) between wild type and g120w in light-exposed swollen root peels were enriched in anthocyanin biosynthetic process and reactive oxygen species (ROS) biosynthetic process GO term. Furthermore, nitroblue tetrazolium (NBT) staining showed that the ROS level decreased in g120w mutant. Anthocyanins induced by UV-A were abolished by the pre-treatment of seedlings with DPI (an inhibitor of nicotinamide adenine nucleoside phosphorylase (NADPH) oxidase) and decreased in g120w mutant. These results indicate that BrLETM2 modulates ROS signaling to promote anthocyanin accumulation in turnip under UV-A and provides new insight into the mechanism of how ROS and light regulate anthocyanin production. Full article

The prognosis of diffuse large B-cell lymphoma (DLBCL) is heterogeneous. Therefore, we aimed to highlight predictive biomarkers. First, artificial intelligence was applied into a discovery series of gene expression of 414 patients (GSE10846). A dimension reduction algorithm aimed to correlate with the overall survival and other clinicopathological variables; and included a combination of Multilayer Perceptron (MLP) and Radial Basis Function (RBF) artificial neural networks, gene-set enrichment analysis (GSEA), Cox regression and other machine learning and predictive analytics modeling [C5.0 algorithm, logistic regression, Bayesian Network, discriminant analysis, random trees, tree-AS, Chi-squared Automatic Interaction Detection CHAID tree, Quest, classification and regression (C&R) tree and neural net)]. From an initial 54,613 gene-probes, a set of 488 genes and a final set of 16 genes were defined. Secondly, two identified markers of the immune checkpoint, PD-L1 (CD274) and IKAROS (IKZF4), were validated in an independent series from Tokai University, and the immunohistochemical expression was quantified, using a machine-learning-based Weka segmentation. High PD-L1 associated with poor overall and progression-free survival, non-GCB phenotype, Epstein–Barr virus infection (EBER+), high RGS1 expression and several clinicopathological variables, such as high IPI and absence of clinical response. Conversely, high expression of IKAROS was associated with a good overall and progression-free survival, GCB phenotype and a positive clinical response to treatment. Finally, the set of 16 genes (PAF1, USP28, SORT1, MAP7D3, FITM2, CENPO, PRCC, ALDH6A1, CSNK2A1, TOR1AIP1, NUP98, UBE2H, UBXN7, SLC44A2, NR2C2AP and LETM1), in combination with PD-L1, IKAROS, BCL2, MYC, CD163 and TNFAIP8, predicted the survival outcome of DLBCL with an overall accuracy of 82.1%. In conclusion, building predictive models of DLBCL is a feasible analytical strategy. Full article

Mitochondrial carriers facilitate the transfer of small molecules across the inner mitochondrial membrane (IMM) to support mitochondrial function and core cellular processes. In addition to the classical SLC25 (solute carrier family 25) mitochondrial carriers, the past decade has led to the discovery of additional protein families with numerous members that exhibit IMM localization and transporter-like properties. These include mitochondrial pyruvate carriers, sideroflexins, and mitochondrial cation/H⁺ exchangers. These transport proteins were linked to vital physiological functions and disease. Their structures and transport mechanisms are, however, still largely unknown and understudied. Protein sequence analysis per se can often pinpoint hotspots that are of functional or structural importance. In this review, we summarize current knowledge about the sequence features of mitochondrial transporters with a special focus on the newly included SLC54, SLC55 and SLC56 families of the SLC solute carrier superfamily. Taking a step further, we combine sequence conservation analysis with transmembrane segment and secondary structure prediction methods to extract residue positions and sequence motifs that likely play a role in substrate binding, binding site gating or structural stability. We hope that our review will help guide future experimental efforts by the scientific community to unravel the transport mechanisms and structures of these novel mitochondrial carriers. Full article

The homologous leucine zipper/EF-hand-containing transmembranes (LETMs) are highly conserved across a broad range of eukaryotic organisms. The LETM functional characteristics involved in biological process have been identified primarily in animals, but little is known about the LETM biological function mode in plants. Based on the results of the current investigation, the GhLETM1 gene crucially affects filament elongation and anther dehiscence of the stamen in cotton. Both excessive and lower expression of the GhLETM1 gene lead to defective stamen development, resulting in shortened filaments and indehiscent anthers with pollen abortion. The results also showed that the phenotype of the shortened filaments was negatively correlated with anther defects in the seesaw model under the ectopic expression of GhLETM1. Moreover, our results notably indicated that the gene requires accurate expression and exhibits a sensitive dose effect for its proper function. This report has important fundamental and practical significance in crop science, and has crucial prospects for genetic engineering of new cytoplasmic male sterility lines and breeding of crop hybrid varieties. Full article

Intracellular calcium (Ca²⁺) homeostasis plays a vital role in the preservation of skeletal muscle. In view of the well-maintained skeletal muscle found in Daurian ground squirrels (Spermophilus dauricus) during hibernation, we hypothesized that hibernators possess unique strategies of intracellular Ca²⁺ homeostasis. Here, cytoplasmic, sarcoplasmic reticulum (SR), and mitochondrial Ca²⁺ levels, as well as the potential Ca²⁺ regulatory mechanisms, were investigated in skeletal muscle fibers of Daurian ground squirrels at different stages of hibernation. The results showed that cytoplasmic Ca²⁺ levels increased in the skeletal muscle fibers during late torpor (LT) and inter-bout arousal (IBA), and partially recovered when the animals re-entered torpor (early torpor, ET). Furthermore, compared with levels in the summer active or pre-hibernation state, the activity and protein expression levels of six major Ca²⁺ channels/proteins were up-regulated during hibernation, including the store-operated Ca²⁺ entry (SOCE), ryanodine receptor 1 (RyR1), leucine zipper-EF-hand containing transmembrane protein 1 (LETM1), SR Ca²⁺ ATPase 1 (SERCA1), mitochondrial calcium uniporter complex (MCU complex), and calmodulin (CALM). Among these, the increased extracellular Ca²⁺ influx mediated by SOCE, SR Ca²⁺ release mediated by RyR1, and mitochondrial Ca²⁺ extrusion mediated by LETM1 may be triggers for the periodic elevation in cytoplasmic Ca²⁺ levels observed during hibernation. Furthermore, the increased SR Ca²⁺ uptake through SERCA1, mitochondrial Ca²⁺ uptake induced by MCU, and elevated free Ca²⁺ binding capacity mediated by CALM may be vital strategies in hibernating ground squirrels to attenuate cytoplasmic Ca²⁺ levels and restore Ca²⁺ homeostasis during hibernation. Compared with that in LT or IBA, the decreased extracellular Ca²⁺ influx mediated by SOCE and elevated mitochondrial Ca²⁺ uptake induced by MCU may be important mechanisms for the partial cytoplasmic Ca²⁺ recovery in ET. Overall, under extreme conditions, hibernating ground squirrels still possess the ability to maintain intracellular Ca²⁺ homeostasis. Full article