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2%). If we used proportional rank instead of alpha versus non-alpha status in the model, we observed a weak effect of rank such that fGCs rose 4.2% from the highest- to lowest-ranking female in the hierarchy. Models using ordinal rank, Elo rating, or high-middle-low categories alone failed to explain variation in female fGCs. Our findings shed new light on the association between dominance rank and the stress response, the competitive landscape of female baboons as compared to males, and the assumptions inherent in a researcher's choice of rank metric.During the transition to parenthood (TTP), both women and men report declines in sexual desire, which are thought to reflect an evolutionarily adaptive focus on parenting over mating. New parents also show changes in testosterone, a steroid hormone implicated in both parenting and mating, suggesting that changes in sexual desire may be associated with changes in testosterone. To test these associations, we followed a sample of heterosexual couples expecting their first child across the prenatal period. We examined prenatal changes in testosterone and two forms of sexual desire (solitary, dyadic). Expectant mothers showed prenatal increases in testosterone, and women's higher testosterone was associated with lower dyadic desire. Expectant fathers showed prenatal decreases in testosterone, and declines in men's testosterone were associated with lower dyadic desire. Testosterone was unrelated to men's or women's solitary desire. Our findings provide support for the idea that prenatal changes in testosterone contribute to an evolutionarily adaptive focus on parenting over mating during the TTP.TsIIIA, the first μ-conotoxin from Conus tessulatus, can selectively inhibit rat tetrodotoxin-resistant sodium channels. TsIIIA also shows potent analgesic activity in a mice hotplate analgesic assay, but its effect on human sodium channels remains unknown. In this study, eight human sodium channel subtypes, hNav1.1- hNav1.8, were expressed in HEK293 or ND7/23 cells and tested on the chemically synthesized TsIIIA. Patch clamp experiments showed that 10 μM TsIIIA had no effects on the tetrodotoxin-sensitive hNav1.1, hNav1.2, hNav1.3, hNav1.4, hNav1.6 and hNav1.7, as well as tetrodotoxin-resistant hNav1.5. For tetrodotoxin-resistant hNav1.8, concentrations of 1, 5 and 10 μM TsIIIA reduced the hNav1.8 currents to 59.26%, 36.21% and 24.93% respectively. Further detailed dose-effect experiments showed that TsIIIA inhibited hNav1.8 currents with an IC50 value of 2.11 μM. In addition, 2 μM TsIIIA did not induce a shift in the current-voltage relationship of hNav1.8. Taken together, the hNav1.8 peptide inhibitor TsIIIA provides a pharmacological probe for sodium channels and a potential therapeutic agent for pain.Neoantigen-based cancer immunotherapies hold the promise of being a truly personalized, effective treatment for diverse cancer types. ELISPOT assays, as a powerful experimental technique, can verify the existence of antigen specific T cells to support basic clinical research and monitor clinical trials. However, despite the high sensitivity of ELISPOT assays, detecting immune responses of neoantigen specific T cells in a patient or healthy donor's PBMCs is still extremely difficult, since the frequency of these T cells can be very low. We developed a novel experimental method, by co-stimulation of T cells with anti-CD28 and IL-2 at the beginning of ELISPOT, to further increase the sensitivity of ELISPOT and mitigate the challenge introduced by low frequency T cells. Under the optimal concentration of 1 μg/ml for anti-CD28 and 1 U/ml for IL-2, an 11.7-fold increase of T cell response against CMV peptide was observed by using our method, and it outperforms other cytokine stimulation alternatives (5-10 folds). We also showed that this method can be effectively applied to detect neoantigen-specific T cells in healthy donors' and a melanoma patient's PBMCs. To the best of our knowledge, this is the first report that the co-stimulation of anti-CD28 and IL-2 is able to significantly improve the sensitivity of ELISPOT assays, indicating that anti-CD28 and IL-2 signaling can act in synergy to lower the T cell activation threshold and trigger more neoantigen-specific T cells.Leishmaniasis is an important infectious disease in Iran. Rudbar County of Guilan Province is introduced as a new focus of cutaneous leishmaniasis. The present study is going to investigate the sand flies fauna in the province and their seasonality and ecology in Rudbar County. To study the sand flies fauna, the sampling was carried out in ten localities of Guilan Province using light traps, sticky traps and manual aspirators during 2016. For the determination of seasonality, the sampling was carried out every two weeks in the fixed site of Pareh Village of Rudbar County during April-October 2016. Sand Flies were removed from sticky traps, rinsed in acetone and then conserved in 80% ethanol as well as the samples of light traps and hand catch. #link# In total, 4430 specimens of sand flies of the genera Phlebotomus and Sergentomyia were collected and identified including Ph. kandelakii, Ph. neglectus, Ph. perfiliewi, Ph. sergenti, Ph. tobbi and Se. link2 dentata. Sergentomyia dentata was found for the first time in Guilan sing specific tests in the province is suggested.Cryo-electron microscopy (cryoEM) has become one of the most important approach for structural biology. However, barriers are still there for an increased successful rate, a better resolution and improved efficiency from sample preparation, data collection to image processing. CryoEM sample preparation is one of the bottlenecks with many efforts made recently, including the optimization of supporting substrate (e.g. ultra-thin carbon, graphene, pure gold, 2d crystal of streptavidin, and affinity modification), which was aimed to solve air-water interface problem, or reduce beam induced motion (BIM), or change particle distribution in the grid hole. Here, we report another effort of developing a new supporting substrate, the amorphous nickel-titanium alloy (ANTA) film, for cryoEM sample preparation as a layer of holey supporting film covering on TEM grid. Our investigations showed advantages of ANTA film in comparison with conventional carbon film, including much better electron conductivity and trace non-specific interaction with protein. These advantages yield less BIM and significantly improved particle distribution during cryoEM experiment of human apo-ferritn, thus resulting an improved reconstruction resolution from a reduced number of micrographs and particles. Unlike the pure gold film, the usage of the ANTA film is just same with the carbon film, compatible to conventional automatic cryoEM data collection procedure.Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P less then 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P less then 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.Traumatic optic neuropathy (TON) can occur following blunt trauma to the orbit and can lead to permanent vision loss. In this study, we investigated the effectiveness of elamipretide (MTP-131), a small mitochondrially-targeted tetrapeptide, in conjunction with etanercept, a tumor necrosis factor (TNF) inhibitor, as neuroprotective agents of retinal ganglion cells (RGCs) after optic nerve trauma with sonication-induced TON (SI-TON) in mice. Treatment with intravitreal MTP-131 and subcutaneous etanercept and MTP-131 showed a 21% increase (p less then 0.01) in RGC survival rate compared to PBS-treated control eyes. Subcutaneous etanercept and MTP-131 had an 11% increase (p less then 0.05) in RGC survival compared to controls. Subcutaneous etanercept only group showed 20% increase (p less then 0.01) in RGC survival compared to controls, while subcutaneous MTP-131 alone showed a 17% increase (p less then 0.01). Surprisingly, we did not observe a synergistic effect between the two drugs in the group receiving both etanercept and MTP-131. One possible explanation for the absence of a synergistic effect is that MTP-131 and etanercept may be acting on different portions of the same pathway.Accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE) is one of the main events involved in age-related macular degeneration and its increase together with RPE dysfunction, blood retinal barrier disruption and photoreceptors death progressively leads to blindness. Lipofuscin is the main autofluorescent (AF) component of the retina and therapies to counteract its deposition are a main goal to be achieved, since effective treatments have not yet been identified. Here, we first investigated the spatio-temporal pattern of AF deposits accumulation in the light-damage model of age-related macular degeneration. Afterward, we tested the ability of cerium oxide nanoparticles, a well known anti-oxidant agent, to counteract AF granules accumulation. learn more was performed both before and after the induction of the degeneration. AF granules were quantified by confocal microscopy on whole mounted retinas. link3 We demonstrated that the acute light-damage increases the accumulation of AF deposits in the hot spot retina in terms of number of granules and percentage of occupied area, with a peak 7 days after the exposure. Remarkably, cerium oxide nanoparticles showed a strong efficacy in preventing the formation of AF deposits when they were injected 3 days before light exposure. Moreover, when the treatment was performed 7 days after light exposure, nanoceria activity was found to be effective also in reducing the amount of the AF granules still deposited up to 60 days. These important results represent the very first evidence about the ability of cerium oxide nanoparticles to counteract AF deposits accumulation in retinal degeneration, laying the foundations for the development of a new therapy possibly targeting lipofuscin in AMD.