Expression of Tas1 Taste Receptors in Mammalian Spermatozoa: Functional Role of Tas1r1 in Regulating Basal Ca2+ and cAMP Concentrations in Spermatozoa

Background: During their transit through the female genital tract, sperm have to recognize and discriminate numerous chemical compounds. However, our current knowledge of the molecular identity of appropriate chemosensory receptor proteins in sperm is still rudimentary. Considering that members of the Tas1r family of taste receptors are able to discriminate between a broad diversity of hydrophilic chemosensory substances, the expression of taste receptors in mammalian spermatozoa was examined. Methodology/Principal Findings: The present manuscript documents that Tas1r1 and Tas1r3, which form the functional receptor for monosodium glutamate (umami) in taste buds on the tongue, are expressed in murine and human spermatozoa, where their localization is restricted to distinct segments of the flagellum and the acrosomal cap of the sperm head. Employing a Tas1r1-deficient mCherry reporter mouse strain, we found that Tas1r1 gene deletion resulted in spermatogenic abnormalities. In addition, a significant increase in spontaneous acrosomal reaction was observed in Tas1r1 null mutant sperm whereas acrosomal secretion triggered by isolated zona pellucida or the Ca2+ ionophore A23187 was not different from wild-type spermatozoa. Remarkably, cytosolic Ca2+ levels in freshly isolated Tas1r1-deficient sperm were significantly higher compared to wild-type cells. Moreover, a significantly higher basal cAMP concentration was detected in freshly isolated Tas1r1-deficient epididymal spermatozoa, whereas upon inhibition of phosphodiesterase or sperm capacitation, the amount of cAMP was not different between both genotypes. Conclusions/Significance: Since Ca2+ and cAMP control fundamental processes during the sequential process of fertilization, we propose that the identified taste receptors and coupled signaling cascades keep sperm in a chronically quiescent state until they arrive in the vicinity of the egg - either by constitutive receptor activity and/or by tonic receptor activation by gradients of diverse chemical compounds in different compartments of the female reproductive tract

Concomitant constitutive LNK and NFE2 mutation with loss of sum9oylation in a case of hereditary thrombocythemia

The vast majority of patients with myeloproliferative neoplasms (MPN), polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis, acquire driver mutations in the JAK2, MPL or CALR gene. Clustering of MPN is seen in select families, but in most pedigrees the MPN-predisposing change has not been determined and affected individuals somatically acquire one of the three above mentioned driver mutations. In contrast, a small number of individuals with hereditary thrombocythemia (HT) carry constitutive alterations, for example in the TPO or the LNK (SH2B3) gene.1–4 Acquired mutations in LNK, a negative regulator of JAK2 signaling, rarely occur in both sporadic and familial MPN cases.1,2 In the latter, they do not segregate with disease phenotype and diseased individuals acquire a concomitant MPN driver mutation.2 It, therefore, appears unlikely that mutant LNK acts as a driver in MPN

Profile and needs of primary informal caregivers of older patients in Belgian geriatric day hospitals: a multicentric cross-sectional study.

With the improvement of life expectancy, the world faces increasing demands for care of older persons. In this manuscript, we define the characteristics of primary informal caregivers (PIC) of patients aged 75 years and older admitted to geriatric day hospitals (GDH) in Belgium. A PIC is defined as the person who most often provides care and assistance to persons who need to be cared for. We describe PIC socio-demographic characteristics, satisfaction, burden and wishes about caring; the type of assistance provided and received, their self-rated health, socio-demographic and medical characteristics of proxies, in particular the presence of behavioural disorders. We conducted a cross-sectional study in 25 GDH. Four hundred seventy-five PIC of patients ≥75 years and their proxies. PIC completed a questionnaire at the GDH assessing burden by Zarit Burden Index-12 (ZBI-12), self-rated health, social restriction due to caregiving and financial participation. We compared the characteristics of PIC with high and low burden, and the characteristics of spouses and adult children PIC. We also analyzed factors associated with a high burden in a multivariable logistic regression model. PIC were mainly women (72%), adult children (53.8%) and spouses (30.6%). The mean age was 64 ± 14 years for PIC and 84 ± 5 years for care recipients. PIC helped for most of Activities in Daily Living (ADL) and Instrumental ADL (iADL). The median ZBI-12 score was 10 [IQR 5-18]. In multivariable regression analysis, a high burden was positively associated in the total group with living with the relative (p = 0.045), the difficulty to take leisure time or vacation (p <  0.001), behavioral and mood disorders (p <  0.001;p = 0.005), and was negatively associated with bathing the relative (p = 0.017) and a better subjective health status estimation (p <  0.001). Primary informal caregivers, who were predominantly women, were involved in care for ADL and iADL. A high burden was associated with living with the relative, the difficulty to take leisure time or vacation and the relative's behavioral and mood disorders. Bathing the relative and a subjective health status estimated as good as or better than people the same age, were protective factors against a high burden