GPER-induced signaling is essential for the survival of breast cancer stem cells.

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

DISTRIBUTION OF GRIP PRESSURE THROUGHOUT THE PHASES OF PUTTING IN ELITE GOLF COLLEGE PLAYERS

The purpose of this study is to investigate the distribution of grip pressure, force and the peak pressure of different phases during the putting stroke. Five elite college players with handicaps of 2-8 participated in the study. The Novel Pliance-x System and 150Hz 8- camera Motion Analysis Corporation System were used to collect grip pressure and identify each phase of the putting stroke. At each phase of the putting stroke, average grip pressure, peak pressure and grip force were investigated. Results indicated that lowest grip pressure occurred at address up to the top of backswing (2.41±1.36 Kpa). Grip pressure started to increase during the downswing and reached its peak, 0.02±0.05s, before impact (4.70±1.97 Kpa). The pressure reduced again after impact (4.36±2.06 Kpa). Results indicate that grip pressure does not remain the same throughout the stroke

THE CORRELATION OF GOLF PUTTING CLUB HEAD VELOCITY AND GRIP FORCE FOR EACH PHASE

We investigate the correlation of golf putting club head velocity and grip force in different phases during the putting stroke. Five elite college players (handicap: 2~8) executed a putt as accurately as possible to reach a target distance of 12ft. The Novel System and were used to measure the grip force and club head velocity. The lowest club head velocity and grip force both occurred at address up to the top of backswing (phase I). The club head velocity and grip force started increasing during the downswing and reached its peak before impact (phase II), and decreased after impact to finish (phase III). The mean club head velocity and grip force for Phase I, II, III in order are 0.33m/s, 0.92m/s, 0.87m/s; 28.09N, 54.77N, 50.76N. Club head velocity was significantly correlated to grip force in phase II and III (r=0.937; r=0.866). The similar variation pattern of club head speed and grip force may give better control to the putter during the impact and produce more consistent putting stroke

Follicular Oocytes Better Support Development in Rabbit Cloning Than Oviductal Oocytes

This study was conducted to determine the effect of rabbit oocytes collected from ovaries or oviducts on the developmental potential of nuclear transplant embryos. Donor nuclei were obtained from adult skin fibroblasts, cumulus cells, and embryonic blastomeres. Rabbit oocytes were flushed from the oviducts (oviductal oocytes) or aspirated from the ovaries (follicular oocytes) of superovulated does at 10, 11, or 12-h post-hCG injection. The majority of collected oocytes were still attached to the sites of ovulation on the ovaries. We found that follicular oocytes had a significantly higher rate of fusion with nuclear donor cells than oviductal oocytes. There was no difference in the cleavage rate between follicular and oviductal groups, but morula and blastocyst development was significantly higher in the follicular group than in the oviductal group. Two live clones were produced in follicular group using blastomere and cumulus nuclear donors, whereas one live clone was produced in the oviductal group using a cumulus nuclear donor. These results demonstrate that cloned rabbit embryos derived from follicular oocytes have better developmental competence than those derived from oviductal oocytes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90481/1/cell-2E2011-2E0030.pd

Multi-omics analysis reveals the efficacy of two probiotic strains in managing feline chronic kidney disease through gut microbiome and host metabolome

Gut dysbiosis has been implicated in the progression of chronic kidney disease (CKD), yet the functional alterations of the microbiome and their links to host metabolism in feline CKD pathophysiology remain unclear. Our previous findings suggested that Lactobacillus mix (Lm) may mitigate CKD progression by modulating gut microbiota composition and restoring microbial balance. In this pilot study, we aimed to evaluate the potential effects of an 8-week Lm intervention in cats with stage 2–3 CKD and to investigate the underlying host-microbiota interactions through integrated multi-omics analysis. We performed full-length 16S rRNA amplicon sequencing and untargeted metabolomics to characterize the intricate interactions between the gut microbiome and host metabolome, and further investigate the modulation of microbial function and its related gut-derived metabolites before and after the intervention. During this period, creatinine and blood urea nitrogen levels were stabilized or reduced in most cats, and gut-derived uremic toxins (GDUTs) showed modest numerical reductions without statistically significant changes. Lm intervention was also associated with increased gut microbial diversity, alterations in specific bacterial taxa, and upregulation of microbial functions involved in GDUTs and short-chain fatty acid (SCFAs) biosynthesis pathways. To further explore individual variations in response, we conducted a post hoc exploratory subgroup analysis based on changes in microbial-derived metabolites. Cats classified as high responders, defined as those with reductions in three GDUTs and increases in SCFAs, exhibited distinct microbiome compositions, microbial functional profiles, and metabolite shifts compared to moderate responders. Among high responders, modulation of microbial pathways involved in GDUTs (tyrosine, tryptophan, and phenylalanine metabolism) and SCFAs (pyruvate, propanoate, and butanoate metabolism) biosynthesis was particularly evident. Notably, the relative abundance of Lm strains was higher in high responders, suggesting a potential association between colonization efficiency and microbial metabolic outcomes. This study demonstrates an Lm-mediated interconnection between the modulation of microbial composition, metabolic functions, and systemic metabolite profiles. Overall, our findings suggest that Lm intervention may influence the gut-kidney axis in cats with CKD. These preliminary, hypothesis-generating results highlight the value of multi-omics approaches for understanding host-microbe interactions and support further investigation into personalized probiotic strategies as potential adjuvant therapies in feline CKD

Pre-Emptive Treatment of Lidocaine Attenuates Neuropathic Pain and Reduces Pain-Related Biochemical Markers in the Rat Cuneate Nucleus in Median Nerve Chronic Constriction Injury Model

This study investigates the effects of lidocaine pre-emptive treatment on neuropathic pain behavior, injury discharges of nerves, neuropeptide Y (NPY) and c-Fos expression in the cuneate nucleus (CN) after median nerve chronic constriction injury (CCI). Behavior tests demonstrated that the pre-emptive lidocaine treatment dose dependently delayed and attenuated the development of mechanical allodynia within a 28-day period. Electrophysiological recording was used to examine the changes in injury discharges of the nerves. An increase in frequency of injury discharges was observed and peaked at postelectrical stimulation stage in the presaline group, which was suppressed by lidocaine pre-emptive treatment in a dose-dependent manner. Lidocaine pretreatment also reduced the number of injury-induced NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI neurons within the CN in a dose-dependent manner. Furthermore, the mean number of c-Fos-LI neurons in the CN was significantly correlated to the NPY reduction level and the sign of mechanical allodynia following CCI

Differential correlation analysis of glioblastoma reveals immune ceRNA interactions predictive of patient survival

BACKGROUND: Recent studies illuminated a novel role of microRNA (miRNA) in the competing endogenous RNA (ceRNA) interaction: two genes (ceRNAs) can achieve coexpression by competing for a pool of common targeting miRNAs. Individual biological investigations implied ceRNA interaction performs crucial oncogenic/tumor suppressive functions in glioblastoma multiforme (GBM). Yet, a systematic analysis has not been conducted to explore the functional landscape and prognostic significance of ceRNA interaction. RESULTS: Incorporating the knowledge that ceRNA interaction is highly condition-specific and modulated by the expressional abundance of miRNAs, we devised a ceRNA inference by differential correlation analysis to identify the miRNA-modulated ceRNA pairs. Analyzing sample-paired miRNA and gene expression profiles of GBM, our data showed that this alternative layer of gene interaction is essential in global information flow. Functional annotation analysis revealed its involvement in activated processes in brain, such as synaptic transmission, as well as critical tumor-associated functions. Notably, a systematic survival analysis suggested the strength of ceRNA-ceRNA interactions, rather than expressional abundance of individual ceRNAs, among three immune response genes (CCL22, IL2RB, and IRF4) is predictive of patient survival. The prognostic value was validated in two independent cohorts. CONCLUSIONS: This work addresses the lack of a comprehensive exploration into the functional and prognostic relevance of ceRNA interaction in GBM. The proposed efficient and reliable method revealed its significance in GBM-related functions and prognosis. The highlighted roles of ceRNA interaction provide a basis for further biological and clinical investigations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-017-1557-4) contains supplementary material, which is available to authorized users