Evolutionary significance of a middle Cambrian (Series 3) in situ occurrence of the pedunculate rhynchonelliform brachiopod Nisusia sulcata

Exceptionally preserved, silicified and articulated complete shells of the rhynchonelliform kutorginate brachiopod Nisusia sulcata are redescribed from the middle Cambrian (Series 3) Marjum Limestone, Utah. Cylindroid sausage‐like protrusions, emerging posteriorly between the valves, were originally interpreted as faecal in origin, but restudy under the SEM shows that these features represent silicified pedicles as they are attached in situ to other Nisusia. The Nisusia host most likely was alive at the time of attachment. Restudy of the pedicles of Nisusia provides new phylogenetic information on the anatomy of the earliest rhynchonelliforms. The silicified pedicles differ considerably from the pedicles of living crown group rhynchonelliforms in being strongly annulated, distally tapering, and were likely to have been rather more flexible. The Nisusia pedicles are more similar to the exceptionally preserved pedicles from other Cambrian rhynchonelliform brachiopods, including Kutorgina, Longtancunella and Alisina, but these emerge from the ventral apical foramen rather than from between the valves as in Nisusia. Although generally similar, these two types of pedicles are unlikely to represent homologous structures as Nisusia is provided with both an apical foramen (possibly larval attachment) and a posterior adult pedicle. The similarities may be explained by similar type of accretionary growth from two different types of epithelia. The Nisusia‐like pedicle appeared early within the kutorginates and rhynchonellates. The discovery of hollow spines in Nisusia sulcata further supports the generic assignation of the species.     

Severe pulmonary hypertension in aging female apolipoprotein E-deficient mice is rescued by estrogen replacement therapy

Corticotropin-releasing factor overexpressing (CRF-OE) male mice showed an inhibited feeding response to a fast, and lower plasma acyl ghrelin and Fos expression in the arcuate nucleus compared to wild-type (WT) mice. We investigated whether hormones and hypothalamic feeding signals are impaired in CRF-OE mice and the influence of sex. Male and female CRF-OE mice and WT littermates (4–6 months old) fed ad libitum or overnight fasted were assessed for body, adrenal glands and perigonadal fat weights, food intake, plasma hormones, blood glucose, and mRNA hypothalamic signals. Under fed conditions, compared to WT, CRF-OE mice have increased adrenal glands and perigonadal fat weight, plasma corticosterone, leptin and insulin, and hypothalamic leptin receptor and decreased plasma acyl ghrelin. Compared to male, female WT mice have lower body and perigonadal fat and plasma leptin but higher adrenal glands weights. CRF-OE mice lost these sex differences except for the adrenals. Male CRF-OE and WT mice did not differ in hypothalamic expression of neuropeptide Y (NPY) and proopiomelanocortin (POMC), while female CRF-OE compared to female WT and male CRF-OE had higher NPY mRNA levels. After fasting, female WT mice lost more body weight and ate more food than male WT, while CRF-OE mice had reduced body weight loss and inhibited food intake without sex difference. In male WT mice, fasting reduced plasma insulin and leptin and increased acyl ghrelin and corticosterone while female WT showed only a rise in corticosterone. In CRF-OE mice, fasting reduced insulin while leptin, acyl ghrelin and corticosterone were unchanged with no sex difference. Fasting blood glucose was higher in CRF-OE with female > male. In WT mice, fasting increased hypothalamic NPY expression in both sexes and decreased POMC only in males, while in CRF-OE mice, NPY did not change, and POMC decreased in males and increased in females. These data indicate that CRF-OE mice have abnormal basal and fasting circulating hormones and hypothalamic feeding-related signals. CRF-OE also abolishes the sex difference in body weight, abdominal fat, and fasting-induced feeding and changes in plasma levels of leptin and acyl ghrelin.     

Non-carcinogenic risk assessment to human health due to intake of fluoride in the groundwater in rural areas of Gonabad and Bajestan,Iran: A case study

In this study, a field research regarding groundwater contamination with fluoride and its related health risks to human health was carried out in 39 rural areas of Gonabad and Bajestan, Iran, in 2017. The results indicated that fluoride levels in two rural areas exceeded the WHO guideline. A total of 55% and 4.7% of the studied rural areas in Gonabad and Bajestan, respectively, had fluoride levels below the minimum recommended value of WHO for fluoride (0.5 mg/L). In this article, chronic non-cancer risks to three different groups of people, adults, children, and infants, for exposure to the fluoride were assessed. Health risk index values for fluoride contamination for 44% and 90% of children and infants in rural areas of Gonabad and Bajestan, respectively, were more than unity (>1), which clearly reveals that these age groups at the studied areas are at the chronic health risk due to the intake of fluoride-containing water. The order of fluoride contribution to non-carcinogenic health risk among the studied age groups was infants > children > adults. Therefore, from a public health viewpoint, it would be prudent and important that risk reduction measures be implemented to diminish the total body burden of fluoride in residents.     

Determination of cathepsin B expression may offer additional prognostic information for ovarian cancer patients

The lysosomal cysteine proteinase cathepsin B has been implicated in the progression of various human tumors including ovarian cancer. Included in this study were 63 patients with epithelial ovarian carcinoma. Follow-up information (median follow-up period 7 years) was available for all patients, among whom 42 (66.7%) had relapsed and 32 (50.8%) had died. The immunohistochemistry method was adopted for the detection of cathepsin B using paraffin embedded specimens. Results were compared to clinico-pathological data. Statistical analysis showed cathepsin B expression to be significantly associated with the stage of disease, debulking success and interestingly, with progesterone receptors. It was also inversely related to progression-free survival (PFS) and overall survival (OS). Accordingly, cathepsin B can be regarded as unfavorable and as an independent tumor marker for progression-free survival and overall survival in ovarian cancer patients with long follow-up.     

Investigation on the effect of static magnetic field up to 15 mT on the viability and proliferation rate of rat bone marrow stem cells

This investigation was performed to evaluate the influence of the static magnetic field up to 15 mT on the viability and proliferation rate of rat bone marrow stem cells. Cells from passage 5 were trypsinized, and a cell suspension was prepared. The cells were counted and cultured in 25-cm² flasks. They were incubated for 1 d, washed with phosphate-buffered saline, and then exposed with different intensities of static magnetic field (4, 7, and 15 mT) at different exposure times (24, 48, 72, and 96 h). Cells were then washed with phosphate-buffered saline, trypsinized, and a cell suspension was prepared separately from each flask. To investigate the viability and proliferation rates of treated cells, staining with Trypan blue and counting were performed with an optical microscope. The mean number of whole cells and living cells was considered as proliferation and survival rates, respectively. Increasing of intensity and time of static magnetic field exposure decreased the viability percent and proliferation rate in treated groups compared with corresponded control. However, reduced cell viability, where this occurred, is exclusively due to apoptosis since necrosis is never observed by others.     

Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase

Voltage-gated K(+) (Kv) channels are key determinants of cardiac and neuronal excitability. A substantial body of evidence has accumulated in support of a role for Src family tyrosine kinases in the regulation of Kv channels. In this study, we examined the possibility that c-Src tyrosine kinase participates in the modulation of the transient voltage-dependent K(+) channel Kv4.3. Supporting a mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293 cells stably transfected with Kv4.3 showed high degree of co-localization of the two proteins at the plasma membrane. Our results further demonstrate an association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down assays, this interaction being mediated by the SH2 and SH3 domains of c-Src. Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal conditions. The functional relevance of the observed interaction between Kv4.3 and c-Src was established in patch-clamp experiments, where application of the Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the inactive structural analogue PP3. Conversely, intracellular application of recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen) increased Kv4.3 peak current amplitude. In conclusion, our findings provide evidence that c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in regulating cardiac and neuronal excitability.