Envisioning a future for transgender and gender-diverse people beyond the DSM

SummaryThis editorial describes current considerations regarding psychiatric diagnoses for transgender and gender-diverse (TGD) people. In addition to offering an assessment of the limitations in current diagnostic standards, the authors articulate a vision for psychiatric practice marked by renewed commitment to an affirmative framework that reduces stigma.</jats:p

“It’s how we get to know each other”: Substance use, connectedness, and sexual activity among men who have sex with men who are living with HIV

Abstract Background Among MSM, substance use increases risk for acquiring HIV and is associated with sub-optimal engagement in HIV-related care. Most research related to substance use and sexual activity among MSM focuses on identifying and reducing risk of HIV acquisition and transmission rather than pleasure and agency. However, substance use may also facilitate sexual pleasure and build community, which could be particularly meaningful for individuals who cope with intersecting stigmas related to the disease, sexual identity, and drug use. Methods To explore the ways in which substance use both promotes and hinders positive sexual expression and healthy sexual relationships, we conducted a secondary analysis of 33 semi-structured qualitative interviews with MSM living with HIV who were poorly engaged in care and reported recent substance use. Results Thematic analysis revealed that substance use was perceived as: (1) a potential pathway to intimacy and enhanced sexual experiences; (2) a tool to help access partners and gain entry to a community; and (3) a source of empowerment, though some noted that it sometimes came at the cost of sexual disempowerment and unbalanced relationships. Conclusions Clinically, our results suggest that the complex motivations for substance use during sexual activity need to be carefully considered and discussed with patients, especially when attempting to decrease problematic use as a pathway to improved HIV self-care. </jats:sec

Additional file 1 of “It’s how we get to know each other”: Substance use, connectedness, and sexual activity among men who have sex with men who are living with HIV

Additional file 1. Intersecting Stigmatized Identities & Engagement in HIV Treatment (INSIGHT) Study

Dynein Interacts with the Neural Cell Adhesion Molecule (NCAM180) to Tether Dynamic Microtubules and Maintain Synaptic Density in Cortical Neurons

Cytoplasmic dynein is well characterized as an organelle motor, but dynein also acts to tether and stabilize dynamic microtubule plus-ends in vitro. Here we identify a novel and direct interaction between dynein and the 180-kDa isoform of the neural cell adhesion molecule (NCAM). Optical trapping experiments indicate that dynein bound to beads via the NCAM180 interaction domain can tether projecting microtubule plus-ends. Live cell assays indicate that the NCAM180-dependent recruitment of dynein to the cortex leads to the selective stabilization of microtubules projecting to NCAM180 patches at the cell periphery. The dynein-NCAM180 interaction also enhances cell-cell adhesion in heterologous cell assays. Dynein and NCAM180 co-precipitate from mouse brain extract and from synaptosomal fractions, consistent with an endogenous interaction in neurons. Thus, we examined microtubule dynamics and synaptic density in primary cortical neurons. We find that depletion of NCAM, inhibition of the dynein-NCAM180 interaction, or dampening of microtubule dynamics with low dose nocodazole all result in significantly decreased in synaptic density. Based on these observations, we propose a working model for the role of dynein at the synapse, in which the anchoring of the motor to the cortex via binding to an adhesion molecule mediates the tethering of dynamic microtubule plus-ends to potentiate synaptic stabilization

Dynein Tethers and Stabilizes Dynamic Microtubule Plus Ends

SummaryMicrotubules undergo alternating periods of growth and shortening, known as dynamic instability. These dynamics allow microtubule plus ends to explore cellular space. The “search and capture” model posits that selective anchoring of microtubule plus ends at the cell cortex may contribute to cell polarization, spindle orientation, or targeted trafficking to specific cellular domains [1–3]. Whereas cytoplasmic dynein is primarily known as a minus-end-directed microtubule motor for organelle transport, cortically localized dynein has been shown to capture and tether microtubules at the cell periphery in both dividing and interphase cells [3–7]. To explore the mechanism involved, we developed a minimal in vitro system, with dynein-bound beads positioned near microtubule plus ends using an optical trap. Dynein induced a significant reduction in the lateral diffusion of microtubule ends, distinct from the effects of other microtubule-associated proteins such as kinesin-1 and EB1. In assays with dynamic microtubules, dynein delayed barrier-induced catastrophe of microtubules. This effect was ATP dependent, indicating that dynein motor activity was required. Computational modeling suggests that dynein delays catastrophe by exerting tension on individual protofilaments, leading to microtubule stabilization. Thus, dynein-mediated capture and tethering of microtubules at the cortex can lead to enhanced stability of dynamic plus ends