Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize ...molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation.
Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks.
Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family.
This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation.
Carbon fibers are materials of paramount importance for composites applied in fields such as aerospace engineering, medicine, and renewable energy. Currently, most of the production of carbon fibers ...uses polyacrylonitrile, which incurs significant greenhouse gas emissions and high production costs. Therefore, carbon fiber manufacturing from asphaltene-enriched feedstocks is attractive as it could add value to extra-heavy fossil fuels and cut down precursor costs by ∼90%. Recent studies indicate that some asphaltene-rich samples feature rheological properties that make them optimal for melt-spinning and carbon fiber production; in other cases, the spun asphaltene feedstocks are unsuitable for such applications. In this work, bitumen asphaltenes were subjected to upgrading processes under three distinctive conditions to tweak their rheological properties in order to produce carbon fibers. The treated samples were comprehensively studied by separations based on solubility and extrography, and subsequently characterized by ultrahigh-resolution mass spectrometry, gas-phase fragmentation, and thermogravimetric analysis. The results indicate that upon thermal processing, asphaltene-rich feedstocks produced a mixture with diverse solubility, i.e., maltenes, asphaltenes, and toluene-insoluble material. The molecular composition of remnant asphaltenes suggests that thermal treatment dramatically decreased molecular polydispersity in terms of the content of heteroatoms, alkyl chains, and structural motifs, i.e., single-core vs multicore, also known as island vs archipelago. The processed asphaltenes revealed high abundances of alkyl-depleted island species. Such thermally treated samples produced no stable carbon fibers. Conversely, a feedstock treated with molten sodium in a proprietary process designed to remove sulfur, revealed increased content of alkyl-side chains and archipelago structural motifs. This sample produced stable carbon fibers. Furthermore, thermal analysis coupled with mass spectrometry (TGA-HRMS) was conducted to understand thermal desorption and pyrolysis profiles for the samples, as well as the presence of occluded compounds and carbon residue formation. The TGA-HRMS results are consistent with extrography and IRMPD FT-ICR MS studies and confirmed the ultrahigh abundance of multicore compounds in the desulfurized sample. Although the sample size is limited, and thus, correlations between molecular composition and rheology properties are not achieved, this is the first study that aims to understand the role of feed composition in the ability to generate carbon fibers from asphaltene-enriched feedstocks. Collectively, the results indicate that samples comprised of abundant highly aromatic asphaltenes, dominant in alkyl-depleted single-core structures, are unlikely optimal for carbon fiber applications. Conversely, a sample with a marked increase in H/C, a significant decrease in S content, and abundant multicore species could generate stable carbon fibers. More studies are underway to find correlations between molecular features and carbon fiber production.
Hypoxia is known to modify skeletal muscle biological functions and muscle regeneration. However, the mechanisms underlying the effects of hypoxia on human myoblast differentiation remain unclear. ...The hypoxic response pathway is of particular interest in patients with hereditary muscular dystrophies since many present respiratory impairment and muscle regeneration defects. For example, an altered hypoxia response characterizes the muscles of patients with facioscapulohumeral dystrophy (FSHD).
We examined the impact of hypoxia on the differentiation of human immortalized myoblasts (LHCN-M2) cultured in normoxia (PO
: 21%) or hypoxia (PO
: 1%). Cells were grown in proliferation (myoblasts) or differentiation medium for 2 (myocytes) or 4 days (myotubes). We evaluated proliferation rate by EdU incorporation, used myogenin-positive nuclei as a differentiation marker for myocytes, and determined the fusion index and myosin heavy chain-positive area in myotubes. The contribution of HIF1α was studied by gain (CoCl
) and loss (siRNAs) of function experiments. We further examined hypoxia in LHCN-M2-iDUX4 myoblasts with inducible expression of DUX4, the transcription factor underlying FSHD pathology.
We found that the hypoxic response did not impact myoblast proliferation but activated precocious myogenic differentiation and that HIF1α was critical for this process. Hypoxia also enhanced the late differentiation of human myocytes, but in an HIF1α-independent manner. Interestingly, the impact of hypoxia on muscle cell proliferation was influenced by dexamethasone. In the FSHD pathological context, DUX4 suppressed HIF1α-mediated precocious muscle differentiation.
Hypoxia stimulates myogenic differentiation in healthy myoblasts, with HIF1α-dependent early steps. In FSHD, DUX4-HIF1α interplay indicates a novel mechanism by which DUX4 could interfere with HIF1α function in the myogenic program and therefore with FSHD muscle performance and regeneration.
Increasing evidence points toward epigenetic variants as a risk factor for developing obesity. We analyzed DNA methylation of the
(pro-opiomelanocortin) gene, which is pivotal for satiety regulation. ...We identified sex-specific and nongenetically determined
hypermethylation associated with a 1.4-fold (confidence interval, 1.03 to 2.04) increased individual risk of developing obesity. To investigate the early embryonic establishment of
methylation states, we established a human embryonic stem cell (hESC) model. Here, hESCs (WA01) were transferred into a naïve state, which was associated with a reduction of DNA methylation. Naïve hESCs were differentiated via a formative state into POMC-expressing hypothalamic neurons, which was accompanied by re-establishment of DNA methylation patterning. We observed that reduced
gene expression was associated with increased
methylation in
-expressing neurons. On the basis of these findings, we treated
-hypermethylated obese individuals (
= 5) with an MC4R agonist and observed a body weight reduction of 4.66 ± 2.16% (means ± SD) over a mean treatment duration of 38.4 ± 26.0 weeks. In summary, we identified an epigenetic obesity risk variant at the
gene fulfilling the criteria for a metastable epiallele established in early embryonic development that may be addressable by MC4R agonist treatment to reduce body weight.
Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing ...integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
To investigate electric scooter (e-scooter)-associated radiological injury incidence and distribution of injuries.
Retrospective cross-sectional study of radiological examinations related to ...e-scooter injuries at a major trauma centre in a small university city. The hospital radiology information system was searched for terms related to e-scooters between January 1, 2015, and October 31, 2022. E-scooter use was confirmed by review of the patients' electronic medical records. Specific injuries were divided based on site of injury using the Injury Severity Scale categorized groups.
A total of 568 radiological studies related to e-scooter injuries were identified on 340 distinct patients (56% male, with an average age of 28 years). Peak incidence of e-scooter-related injuries was seen in the summer months, after a local scooter sharing system was introduced in October 2020. A total of 149 patients had radiologically diagnosed injuries, with extremity injuries being most frequent (80%). Facial (8%), head/neck (8%), and thorax/abdomen (4%) were less common. Radial head fractures were the most common injury (n = 27). Thirteen patients had multiple sites of injury, four of which had both upper limb and facial bone fractures described.
We report a significant increase in radiological investigations and injuries in the context of e-scooter injuries, particularly since the introduction of an e-scooter sharing scheme. This study informs radiologists on common locations of injuries when reporting studies of patients that have had e-scooter-related injuries.
This is the first UK-based study providing a comprehensive radiological perspective of the impact of e-scooter use and associated distribution of injuries, adding important data for many cities that are currently undertaking review of their e-scooter sharing schemes.
Middle meningeal artery embolization (MMAE) is an emerging endovascular treatment technique with proven promising results for chronic subdural hematomas (cSDHs). MMAE as an adjunct to open surgery is ...being utilized with the goal of preventing the recurrence of cSDH. However, the efficacy of MMAE following surgical evacuation of cSDH has not been clearly demonstrated. The authors sought to compare the outcomes of open surgery followed by MMAE versus open surgery alone.
Patients who underwent surgical evacuation alone (open surgery-alone group) or MMAE along with open surgery for cSDH (adjunctive MMAE group) were identified at the authors' institution. Two balanced groups were obtained through propensity score matching. Primary outcomes included recurrence risk and reintervention rate. Secondary outcomes included decrease in hematoma size and modified Rankin Scale (mRS) score at last follow-up. Variables in the two groups were compared by use of the Mann-Whitney U-test, paired-sample t-test, and Fisher's exact test.
A total of 345 cases of open surgery alone and 52 cases of open surgery with adjunctive MMAE were identified. After control for subjective confounders, 146 patients treated with open surgery alone and 41 with adjunctive MMAE following open surgery with drain placement were included in the analysis. Before matching, the rebleeding risk and reintervention rate for open surgery trended higher in the open surgery alone than the open surgery plus MMAE group (14.4% vs 7.3%, p = 0.18; and 11.6% vs 4.9%, p = 0.17, respectively). No significant differences were seen in duration of radiographic or clinical follow-ups or decreases in hematoma size and mRS score at last follow-up. After one-to-one nearest neighbor propensity score matching, 26 pairs of cases were compared for outcomes. Rates of recurrence (7.7% vs 30.8%, p = 0.038) and overall reintervention (3.8% vs 23.1%, p = 0.049) after open surgery were found to be significantly lower in the adjunctive MMAE group than the open surgery-alone group. With one-to-many propensity score matching, 76 versus 37 cases were compared for open surgery alone versus adjunctive MMAE following open surgery. Similarly, the adjunctive MMAE group had significantly lower rates of recurrence (5.4% vs 19.7%, p = 0.037) and overall reintervention (2.7% vs 14.5%, p = 0.049).
Adjunctive MMAE following open surgery can lower the recurrence risks and reintervention rates for cSDH.
N-phosphino-functionalized N-heterocyclic carbene (NHCP) ligands have been evaluated as potential supporting ligands in ruthenium-catalyzed olefin metathesis. Initial density functional theory (DFT) ...calculations suggested that these NHCP ligands may allow access to neutral 14 valence electron (VE) speciesequivalents of the active 14 VE species formed by phosphine dissociation from Grubbs II precatalystsvia facile decoordination of the NHCP phosphino donor of the strained four-membered RuPNC chelate systems. Their attempted synthesis from NHCPs and Grubbs-type Ru carbenes revealed addition of an NHCP donor atom (P or C) to the alkylidene fragment, forming a new C–P or C–C bond in five-membered chelate structures. DFT investigations showed that these reactions are controlled kinetically and must not be neglected as important possible deactivation routes in olefin metathesis.
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