Notes

Biofouling impacts on polyethylene occurrence along with tragedy throughout coastal oceans: A new macro/micro showing level?
The de novo 370Kb hemizygous deletion of 5'-UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3gene.
The de novo 370Kb hemizygous deletion of 5'-UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3 gene.Butyrophilin 3A1 (BTN3A1), a major histocompatibility complex-associated gene that encodes a membrane protein with two extracellular immunoglobulin domains and an intracellular B30.2 domain, is critical in T-cell activation and adaptive immune response. Here, the expression of BTN3A1 in cancers was analyzed in eight databases comprising 86 733 patients of 33 cancers, and the findings were validated in patient samples and cell models. We showed that BTN3A1 was expressed in most cancers, and its expression level was strongly correlated with clinical outcome of 13 cancers. Mutations of BTN3A1 were detected, and the mutations were distributed throughout the entire gene. Gene set enrichment analysis showed that BTN3A1 co-expression genes and interacting proteins were enriched in immune regulation-related pathways. BTN3A1 was associated with tumor-infiltrating immune cells and was co-expressed with multiple immune checkpoints in patients with breast cancer (BRCA) and non-small cell lung cancer (NSCLC). We reported that BTN3A1 was downregulated in 46 of 65 (70.8%) NSCLCs, and its expression level was inversely associated with clinical outcome of the patients. BTN3A1 in tumor samples was lower than in counterpart normal tissues in 31 of 38 (81.6%) BRCAs. Bioinformatics analyses showed that BTN3A1 could be a target gene of transcription factor Spi-1 proto-oncogene (SPI1), and our 'wet' experiments showed that ectopic expression of SPI1 upregulated, whereas silencing of SPI1 downregulated, BTN3A1 expression in cells. These results suggest that BTN3A1 may function as a tumor suppressor and may serve as a potential prognostic biomarker in NSCLCs and BRCAs.
The severity of early brain edema (EBE) after aneurysm rupture was reported to be strongly associated with the risk of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Using the recently developed Subarachnoid Hemorrhage Early Brain Edema Score (SEBES), we analyzed the predictors of EBE and its impact on complications related to intracranial pressure (ICP) increase after SAH and on poor outcome.

All consecutive SAH cases treated between January 2003 and June 2016 with assessable SEBES were included (n=745). Data on demographic characteristics, medical history, initial severity of SAH, need for conservative ICP treatment and decompressive craniectomy, occurrence of cerebral infarctions and unfavorable outcome at 6months (modified Rankin scale score>2) were collected. Univariable and multivariable analyses were performed.

Younger age (<55years; adjusted odds ratio [aOR]3.16, 95% confidence interval [CI]2.28-4.38), female sex (aOR1.64, 95% CI1.16-2.31), poor initial clinical condition (Wocomorbidities on the severity of EBE after SAH.Diabetes is a common condition that is increasing in incidence all over the world. Even though the skin manifestations of this condition are well described, there is scant literature of its nail changes. In this review, we allude to the various clinical features of nail changes in those with diabetes. They can be broadly divided into infections, vascular changes, neuropathic manifestations, and miscellaneous changes. There is no pathognomonic nail alteration, but it is important to be aware of the potential nail manifestations in diabetes as it facilitates investigations and thereby early diagnosis of diabetes, resulting in holistic management of the patient.
Comorbidities are common in multiple sclerosis (MS), and have been associated with worse outcomes and increased health care resource usage. We studied the frequency of comorbidities and adverse health behaviors (AHBs) in MS patients in the Mediterranean region of Catalonia.

This population-based, case-control study used primary health care information covering 80% of Catalonia's population. Cases were matched by age/sex with randomly chosen controls (ratio = 15). Demographic information, comorbidities, AHBs, annual visits, sick leave days, and medication dispensing were studied. The association of comorbidities with MS and the profile of comorbidities according to sex within MS cases were assessed with multivariate logistic regression models, after adjusting for confounding variables. Health care resource usage was analyzed in MS cases compared to controls, and within MS cases in those with compared to those without comorbidities.

Five thousand five hundred forty-eight MS cases and 27,710 controls (70% idities increases the health care resource usage in MS patients.Kainate (KA) receptors (KARs) are important modulators of synaptic transmission. We studied here the role of KARs on glutamatergic synaptic transmission in the CA2 region of the hippocampus where the actions of these receptors are unknown. We observed that KA depresses glutamatergic synaptic transmission at Schaffer collateral-CA2 synapses; an effect that was antagonized by NBQX (a KA/AMPA receptors antagonist) under condition where AMPA receptors were previously blocked. The study of paired-pulse facilitation ratio, miniature responses, and fluctuation analysis indicated a presynaptic locus of action for KAR. Additionally, we determined the action mechanism for this depression of glutamate release mediated by the activation of KARs. We found that inhibition of protein kinase A suppressed the effect of KAR activation on evoked excitatory post-synaptic current, an effect that was not suppressed by protein kinase C inhibitors. Furthermore, in the presence of Pertussis toxin, the depression of glutamate release mediated by KAR activation was not present, invoking the participation of a Gi/o protein in this modulation. Finally, the KAR-mediated depression of glutamate release was not suppressed by treatments that affect calcium entry trough voltage-dependent calcium channels or calcium release from intracellular stores. We conclude that KARs present at these synapses mediate a depression of glutamate release through a mechanism that involves the activation of G protein and protein kinase A.Extracellular vesicles (EVs) either as endocytic or plasma membrane-emerged vesicles play pivotal role in cell-to-cell communication. Due to the bioactive molecules transformation, lymphoma cell-derived vesicles can alter a recipient cell's function and contribute to signal transduction and drug resistance. These vesicles by acting not only in tumor cells but also in tumor-associated cells have important roles in tumor growth and invasion. On the other hand, the total protein level of circulating exosomes reveals the disease stage, tumor burden, response to therapy, and survival. In residual disease, leukemic blasts are undetectable in the bone marrow by conventional methods but exosomal proteins are elevated significantly. In this manner, new methods for measuring exosomes and exosomal components are required. In this review, we try to reveal the concealed role of EVs in hematological malignancies besides therapeutic potentials.Testicular germ cell tumors (GCTs) are stratified into seminomas and nonseminomas. check details Seminomas share many histological and molecular features with primordial germ cells, whereas the nonseminoma stem cell population-embryonal carcinoma (EC)-is pluripotent and thus able to differentiate into cells of all three germ layers (teratomas). Furthermore, ECs are capable of differentiating into extra-embryonic lineages (yolk sac tumors, choriocarcinomas). In this study, we deciphered the molecular and (epi)genetic mechanisms regulating expression of CD24, a highly glycosylated signaling molecule upregulated in many cancers. CD24 is overexpressed in ECs compared with other GCT entities and can be associated with an undifferentiated pluripotent cell fate. We demonstrate that CD24 can be transactivated by the pluripotency factor SOX2, which binds in proximity to the CD24 promoter. In GCTs, CD24 expression is controlled by epigenetic mechanisms, that is, histone acetylation, since CD24 can be induced by the application histone deacetylase inhibitors. Vice versa, CD24 expression is downregulated upon inhibition of histone methyltransferases, E3 ubiquitin ligases, or bromodomain (BRD) proteins. Additionally, three-dimensional (3D) co-cultivation of EC cells with microenvironmental cells, such as fibroblasts, and endothelial or immune cells, reduced CD24 expression, suggesting that crosstalk with the somatic microenvironment influences CD24 expression. In a CRISPR/Cas9 deficiency model, we demonstrate that CD24 fulfills a bivalent role in differentiation via regulation of homeobox, and phospho- and glycoproteins; that is, it is involved in suppressing the germ cell/spermatogenesis program and mesodermal/endodermal differentiation, while poising the cells for ectodermal differentiation. Finally, blocking CD24 by a monoclonal antibody enhanced sensitivity toward cisplatin in EC cells, including cisplatin-resistant subclones, highlighting CD24 as a putative target in combination with cisplatin.Previous studies have suggested that phosphorylation of translation elongation factor 1A (eEF1A) can alter its function, and large-scale phospho-proteomic analyses in Saccharomyces cerevisiae have identified 14 eEF1A residues phosphorylated under various conditions. Here, a series of eEF1A mutations at these proposed sites were created and the effects on eEF1A activity were analyzed. The eEF1A-S53D and eEF1A-T430D phosphomimetic mutant strains were inviable, while corresponding alanine mutants survived but displayed defects in growth and protein synthesis. The activity of an eEF1A-S289D mutant was significantly reduced in the absence of the guanine nucleotide exchange factor eEF1Bα and could be restored by an exchange-deficient form of the protein, suggesting that eEF1Bα promotes eEF1A activity by a mechanism other than nucleotide exchange. Our data show that several of the phosphorylation sites identified by high-throughput analysis are critical for eEF1A function.
Whereas intravenous administration of Toll-like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies.

Eighteen healthy male volunteers received 2 or 4 intradermal 10ng LPS injections and 1 saline injection on the forearms. The LPS response was evaluated by noninvasive (perfusion, skin temperature and erythema) and invasive assessments (cellular and cytokine responses) in skin biopsy and blister exudate.

LPS elicited a visible response and returned to baseline at 48 hours. Erythema, perfusion and temperature were statistically significant (P< .0001) over a 24-hour time course compared to saline. The protein response was dominated by an acute interleukin (IL)-6, IL-8 and tumour necrosis factor response followed by IL-1β, IL-10 and interferon-γ.
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