TRPV4 is the temperature-sensitive ion channel of human sperm.

Ion channels control the ability of human sperm to fertilize the egg by triggering hyperactivated motility, which is regulated by membrane potential, intracellular pH, and cytosolic calcium. Previous studies unraveled three essential ion channels that regulate these parameters: (1) the Ca2+ channel CatSper, (2) the K+ channel KSper, and (3) the H+ channel Hv1. However, the molecular identity of the sperm Na+ conductance that mediates initial membrane depolarization and, thus, triggers downstream signaling events is yet to be defined. Here, we functionally characterize DSper, the Depolarizing Channel of Sperm, as the temperature-activated channel TRPV4. It is functionally expressed at both mRNA and protein levels, while other temperature-sensitive TRPV channels are not functional in human sperm. DSper currents are activated by warm temperatures and mediate cation conductance, that shares a pharmacological profile reminiscent of TRPV4. Together, these results suggest that TRPV4 activation triggers initial membrane depolarization, facilitating both CatSper and Hv1 gating and, consequently, sperm hyperactivation

Sensory adaptation to chemical cues by vomeronasal sensory neurons

Sensory adaptation is a source of experience-dependent feedback that impacts responses to environmental cues. In the mammalian main olfactory system (MOS), adaptation influences sensory coding at its earliest processing stages. Sensory adaptation in the accessory olfactory system (AOS) remains incompletely explored, leaving many aspects of the phenomenon unclear. We investigated sensory adaptation in vomeronasal sensory neurons (VSNs) using a combination of in situ Ca2+ imaging and electrophysiology. Parallel studies revealed prominent short-term sensory adaptation in VSNs upon repeated stimulation with mouse urine and monomolecular bile acid ligands at interstimulus intervals (ISIs) less than 30 s. In such conditions, Ca2+ signals and spike rates were often reduced by more than 50%, leading to dramatically reduced chemosensory sensitivity. Short-term adaptation was reversible over the course of minutes. Population Ca2+ imaging experiments revealed the presence of a slower form of VSN adaptation that accumulated over dozens of stimulus presentations delivered over tens of minutes. Most VSNs showed strong adaptation, but in a substantial VSN subpopulation adaptation was diminished or absent. Investigation of same-and opposite-sex urine responses in male and female VSNs revealed that adaptation to same-sex cues occurred at ISIs up to 180 s, conditions that did not induce adaptation to opposite-sex cues. This result suggests that VSN sensory adaptation can be modulated by sensory experience. These studies comprehensively establish the presence of VSN sensory adaptation and provide a foundation for future inquiries into the molecular and cellular mechanisms of this phenomenon and its impact on mammalian behavior

Beamforming for measurements under disturbed propagation conditions using numerically calculated Green’s functions

Beamforming methods for sound source localization are usually based on free-field Green’s functions to model the sound propagation between source and microphones. This assumption is known to be incorrect for many industrial applications and the beamforming results can suffer from this inconsistency regarding both, main lobe width and dynamic range. The aim of this paper is to investigate whether the use of numerically calculated Green’s functions, which include the diffraction and reflection of the sound path between source and microphones, can improve the results of beamforming measurements. The current test cases of numerical and experimental investigations consist of a source placed in a short rectangular duct. The measurements are performed outside the duct in a semi-anechoic chamber. A typical example for this kind of installation is a fan with a heat exchanger. The Green’s functions for this test case are calculated numerically using the boundary element method. These tailored Green’s functions are used to calculate the corresponding beamforming steering vectors. Beamforming measurements are performed in this paper using a loudspeaker mounted in a disc as a reference source in the heat exchanger duct. The measurements are performed both with stationary and rotating disc. The stationary measurements are evaluated in the frequency domain. For the evaluation of the rotating measurements, a new beamforming method in the time domain is presented. This method also uses the stationary Green’s functions, which were calculated numerically in the frequency domain. It is also shown how the weighting of these tailored Green’s functions can be done for time domain beamforming. By means of different validation criteria it can be shown that the results with the numerical calculated Green’s functions are improved compared to free field beamforming. This is true both in the stationary and rotating case

TMEM16A and TMEM16B modulate pheromone-evoked action potential firing in mouse vomeronasal sensory neurons

The mouse vomeronasal system controls several social behaviors. Pheromones and other social cues are detected by sensory neurons in the vomeronasal organ (VNO). Stimuli activate a transduction cascade that leads to membrane potential depolarization, increase in cytosolic Ca2+ level, and increased firing. The Ca2+-activated chloride channels TMEM16A and TMEM16B are co-expressed within microvilli of vomeronasal neurons, but their physiological role remains elusive. Here, we investigate the contribution of each of these channels to vomeronasal neuron firing activity by comparing wild-type (WT) and knock-out (KO) mice. Performing loosepatch recordings from neurons in acute VNO slices, we show that spontaneous activity is modified by Tmem16a KO, indicating that TMEM16A, but not TMEM16B, is active under basal conditions. Upon exposure to diluted urine, a rich source of mouse pheromones, we observe significant changes in activity. Vomeronasal sensory neurons (VSNs) from Tmem16a cKO and Tmem16b KO mice show shorter interspike intervals (ISIs) compared with WT mice, indicating that both TMEM16A and TMEM16B modulate the firing pattern of pheromone-evoked activity in VSNs

Телемедицина: перспективы развития

Необходимость развития в условиях цифровой экономики такого направления как телемедицина кажется необходимостью, однако существует противоречие между существующими проблемами в системе организации здравоохранения Российской Федерации и возможностями доступности к услугам телемедицины. Анализ показал, что данное направление востребовано, необходимо, существует ряд сервисов, предлагающих услуги по телемедицине, однако нормативно-правовая база не позволяет в полной мере организовать полноценную работу по предоставлению телемедицинских услуг, в том числе, бесплатных

Transcription at the proximity of the nuclear pore: A role for the THP1-SAC3-SUS1-CDC31 (THSC) complex

4 páginas, 1 figura.A key aspect of eukaryotic gene expression is the coupling of transcription with RNA processing, polyadenylation and export. The use of new techniques based on tandem affinity purification (TAP) and chromatin immunoprecipitation (ChIP), and of genetic and cell biology approaches has contributed to the beginning of deciphering the network of protein-mRNA interactions accompanying this coupling. Although an extensive amount of work has shed light on this matter, the order of participation and precise role of the different proteins remain to be deciphered. It seems that different and sequential protein interactions must converge to finally promote the anchoring of genes to the nuclear periphery. Here we discuss the new data on the coupling of gene expression and RNA export, with emphasis on the THP1-SAC3-SUS1-CDC31 complex and the possible implications of these results on transcription at the nuclear pore.Research in A.A.’s lab is funded by grants from the Spanish Ministry of Science and Education and the Junta de Andalucía.Peer reviewe

GAR22β regulates cell migration, sperm motility, and axoneme structure

© 2016 Gamper et al. Spatiotemporal cytoskeleton remodeling is pivotal for cell adhesion and migration. Here we investigated the function of Gas2-related protein on chromosome 22 (GAR22β), a poorly characterized protein that interacts with actin and microtubules. Primary and immortalized GAR22β-/- Sertoli cells moved faster than wild-type cells. In addition, GAR22β-/- cells showed a more prominent focal adhesion turnover. GAR22β overexpression or its reexpression in GAR22β-/- cells reduced cell motility and focal adhesion turnover. GAR22β-actin interaction was stronger than GAR22β-microtubule interaction, resulting in GAR22β localization and dynamics that mirrored those of the actin cytoskeleton. Mechanistically, GAR22β interacted with the regulator of microtubule dynamics end-binding protein 1 (EB1) via a novel noncanonical amino acid sequence, and this GAR22β-EB1 interaction was required for the ability of GAR22β to modulate cell motility. We found that GAR22β is highly expressed in mouse testes, and its absence resulted in reduced spermatozoa generation, lower actin levels in testes, and impaired motility and ultrastructural disorganization of spermatozoa. Collectively our findings identify GAR22β as a novel regulator of cell adhesion and migration and provide a foundation for understanding the molecular basis of diverse cytoskeleton-dependent processes