BTDAzo: A Photoswitchable TRPC5 Channel Activator

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally-resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5-modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two-colour photoswitching. BTDAzo ' s ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel

Assembly of the Mitochondrial Protein Import Channel: Role of Tom5 in Two-Stage Interaction of Tom40 with the SAM Complex

Tom40 forms the channel of the mitochondrial preprotein translocase. This beta-barrel protein assembles with alpha-helical proteins, however little is known about the mechanism of assembly. Becker et al identified a new intermediate in Tom40 assembly and show that small alpha-helical Tom proteins associate with Tom40 directly at the SAM complex

The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins

The Mim1 complex imports α-helical mitochondrial outer membrane proteins with multiple transmembrane segments

BTDAzo - a photoswitchable TRPC5 channel activator

Photoswitchable reagents to modulate protein activity are powerful tools for high-spatiotemporal-precision control over endogenous biological functions. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, ranging from synaptic function to hormone regulation. Achieving spatially-resolved control over TRPC5 activity in particular cells or tissues, and temporal regulation in targeted cells, are therefore crucial milestones towards understanding and harnessing the biology of TRPC5. Here we develop the first photoswitchable TRPC5-modulating reagent, BTDAzo, towards reaching this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene that features excellent two-colour photoswitching. BTDAzo\u27s TRPC5 control across relevant channel biology settings makes it appropriate for a range of dynamically reversible photoswitching studies in TRP channel biology, aiming to decipher the various biological roles of this centrally important ion channel

Systematic Review of Psychological Interventions for Quality of Life, Mental Health, and Hair Growth in Alopecia Areata and Scarring Alopecia

Alopecia is associated with significant psychological burden. There is limited evidence on the use of psychological interventions in conditions of hair loss. This manuscript systematically reviews the current state of literature on psychological treatments for quality of life, mental health, and hair growth in various forms of alopecia. PubMed and Embase were searched with predefined inclusion and exclusion criteria. Reference lists were also examined for relevant studies. Nine articles met our criteria and are included in this review. Eight of the articles related to alopecia areata and one related to scarring alopecia. Mindfulness-based stress reduction (MBSR) was found to improve quality of life-related subjective symptoms, relationship impacts, anxiety, phobia, distress, and psychological symptom intensity. Alopecia-specific collocated behavioral health (CLBH) treatment showed a trend for psychosocial improvement in areas such as appearance shame, activity avoidance, negative emotions, and coping. Hypnotherapy was found to improve anxiety and depression, quality of life measures, and alexithymia. There was also some evidence for significant hair growth with hypnosis, but the data are mixed. Psychotherapy combined with immunotherapy led to more hair growth, and supported self-confidence. Finally, coping strategies modulated the subjective burden of alopecia, and were associated with disease improvement. Further research will be necessary to better establish the efficacy and optimal administration of these interventions in alopecia

Systematic Review of Psychological Interventions for Quality of Life, Mental Health, and Hair Growth in Alopecia Areata and Scarring Alopecia.

Alopecia is associated with significant psychological burden. There is limited evidence on the use of psychological interventions in conditions of hair loss. This manuscript systematically reviews the current state of literature on psychological treatments for quality of life, mental health, and hair growth in various forms of alopecia. PubMed and Embase were searched with predefined inclusion and exclusion criteria. Reference lists were also examined for relevant studies. Nine articles met our criteria and are included in this review. Eight of the articles related to alopecia areata and one related to scarring alopecia. Mindfulness-based stress reduction (MBSR) was found to improve quality of life-related subjective symptoms, relationship impacts, anxiety, phobia, distress, and psychological symptom intensity. Alopecia-specific collocated behavioral health (CLBH) treatment showed a trend for psychosocial improvement in areas such as appearance shame, activity avoidance, negative emotions, and coping. Hypnotherapy was found to improve anxiety and depression, quality of life measures, and alexithymia. There was also some evidence for significant hair growth with hypnosis, but the data are mixed. Psychotherapy combined with immunotherapy led to more hair growth, and supported self-confidence. Finally, coping strategies modulated the subjective burden of alopecia, and were associated with disease improvement. Further research will be necessary to better establish the efficacy and optimal administration of these interventions in alopecia

Systematic Review of Psychological Interventions for Quality of Life, Mental Health, and Hair Growth in Alopecia Areata and Scarring Alopecia

Alopecia is associated with significant psychological burden. There is limited evidence on the use of psychological interventions in conditions of hair loss. This manuscript systematically reviews the current state of literature on psychological treatments for quality of life, mental health, and hair growth in various forms of alopecia. PubMed and Embase were searched with predefined inclusion and exclusion criteria. Reference lists were also examined for relevant studies. Nine articles met our criteria and are included in this review. Eight of the articles related to alopecia areata and one related to scarring alopecia. Mindfulness-based stress reduction (MBSR) was found to improve quality of life-related subjective symptoms, relationship impacts, anxiety, phobia, distress, and psychological symptom intensity. Alopecia-specific collocated behavioral health (CLBH) treatment showed a trend for psychosocial improvement in areas such as appearance shame, activity avoidance, negative emotions, and coping. Hypnotherapy was found to improve anxiety and depression, quality of life measures, and alexithymia. There was also some evidence for significant hair growth with hypnosis, but the data are mixed. Psychotherapy combined with immunotherapy led to more hair growth, and supported self-confidence. Finally, coping strategies modulated the subjective burden of alopecia, and were associated with disease improvement. Further research will be necessary to better establish the efficacy and optimal administration of these interventions in alopecia

Pregnancy and estrogen enhance neural progenitor-cell proliferation in the vomeronasal sensory epithelium

International audienceThe hormonal state during the estrus cycle or pregnancy produces alterations on female olfactory perception that are accompanied by specific maternal behaviors, but it is unclear how sex hormones act on the olfactory system to enable these sensory changes. Herein, we show that the production of neuronal progenitors is stimulated in the vomeronasal organ (VNO) epithelium of female mice during a late phase of pregnancy. Using a wide range of molecular markers that cover the whole VNO cell maturation process in combination with Ca(2+) imaging in early postmitotic neurons, we show that newly generated VNO cells adopt morphological and functional properties of mature sensory neurons. A fraction of these newly generated cells project their axons to the olfactory forebrain, extend dendrites that contact the VNO lumen, and can detect peptides and urinary proteins shown to contain pheromone activity. High-throughput RNA-sequencing reveals concomitant differences in gene expression in the VNO transcriptomes of pregnant females. These include relative increases in expression of 20 vomeronasal receptors, of which 17 belong to the V1R subfamily, and may therefore be considered as candidate receptors for mediating maternal behaviors. We identify the expression of several hormone receptors in the VNO of which estrogen receptor α (Esr1) is directly localized to neural progenitors. Administration of sustained high levels of estrogen, but not progesterone, is sufficient to stimulate vomeronasal progenitor cell proliferation in the VNO epithelium. Peripheral olfactory neurogenesis driven by estrogen may contribute to modulate sensory perception and adaptive VNO-dependent behaviors during pregnancy and early motherhood

Proteomic Analysis of the Yeast Mitochondrial Outer Membrane Reveals Accumulation of a Subclass of Preproteins

Mitochondria consist of four compartments–outer membrane, intermembrane space, inner membrane, and matrix—with crucial but distinct functions for numerous cellular processes. A comprehensive characterization of the proteome of an individual mitochondrial compartment has not been reported so far. We used a eukaryotic model organism, the yeast Saccharomyces cerevisiae, to determine the proteome of highly purified mitochondrial outer membranes. We obtained a coverage of ∼85% based on the known outer membrane proteins. The proteome represents a rich source for the analysis of new functions of the outer membrane, including the yeast homologue (Hfd1/Ymr110c) of the human protein causing Sjögren–Larsson syndrome. Surprisingly, a subclass of proteins known to reside in internal mitochondrial compartments were found in the outer membrane proteome. These seemingly mislocalized proteins included most top scorers of a recent genome-wide analysis for mRNAs that were targeted to mitochondria and coded for proteins of prokaryotic origin. Together with the enrichment of the precursor form of a matrix protein in the outer membrane, we conclude that the mitochondrial outer membrane not only contains resident proteins but also accumulates a conserved subclass of preproteins destined for internal mitochondrial compartments