Hair cells in the cochlea must tune resonant modes to the edge of instability without destabilizing collective modes.

Sound produces surface waves along the cochlea's basilar membrane. To achieve the ear's astonishing frequency resolution and sensitivity to faint sounds, dissipation in the cochlea must be canceled via active processes in hair cells, effectively bringing the cochlea to the edge of instability. But how can the cochlea be globally tuned to the edge of instability with only local feedback? To address this question, we use a discretized version of a standard model of basilar membrane dynamics, but with an explicit contribution from active processes in hair cells. Surprisingly, we find the basilar membrane supports two qualitatively distinct sets of modes: a continuum of localized modes and a small number of collective extended modes. Localized modes sharply peak at their resonant position and are largely uncoupled. As a result, they can be amplified almost independently from each other by local hair cells via feedback reminiscent of self-organized criticality. However, this amplification can destabilize the collective extended modes; avoiding such instabilities places limits on possible molecular mechanisms for active feedback in hair cells. Our work illuminates how and under what conditions individual hair cells can collectively create a critical cochlea.

Hair cells in the cochlea must tune resonant modes to the edge of instability without destabilizing collective modes.

Sound produces surface waves along the cochlea's basilar membrane. To achieve the ear's astonishing frequency resolution and sensitivity to faint sounds, dissipation in the cochlea must be canceled via active processes in hair cells, effectively bringing the cochlea to the edge of instability. But how can the cochlea be globally tuned to the edge of instability with only local feedback? To address this question, we use a discretized version of a standard model of basilar membrane dynamics, but with an explicit contribution from active processes in hair cells. Surprisingly, we find the basilar membrane supports two qualitatively distinct sets of modes: a continuum of localized modes and a small number of collective extended modes. Localized modes sharply peak at their resonant position and are largely uncoupled. As a result, they can be amplified almost independently from each other by local hair cells via feedback reminiscent of self-organized criticality. However, this amplification can destabilize the collective extended modes; avoiding such instabilities places limits on possible molecular mechanisms for active feedback in hair cells. Our work illuminates how and under what conditions individual hair cells can collectively create a critical cochlea.

Nucleic acid detection aboard the International Space Station by colorimetric loop-mediated isothermal amplification (LAMP).

Human spaceflight endeavors present an opportunity to expand our presence beyond Earth. To this end, it is crucial to understand and diagnose effects of long-term space travel on the human body. Developing tools for targeted, on-site detection of specific DNA sequences will allow us to establish research and diagnostics platforms that will benefit space programs. We describe a simple DNA diagnostic method that utilizes colorimetric loop-mediated isothermal amplification (LAMP) to enable detection of a repetitive telomeric DNA sequence in as little as 30 minutes. A proof of concept assay for this method was carried out using existing hardware on the International Space Station and the results were read instantly by an astronaut through a simple color change of the reaction mixture. LAMP offers a novel platform for on-orbit DNA-based diagnostics that can be deployed on the International Space Station and to the broader benefit of space programs.

A GPR174-CCL21 module imparts sexual dimorphism to humoral immunity.

Humoral immune responses to immunization and infection and susceptibilities to antibody-mediated autoimmunity are generally lower in males1-3. However, the mechanisms underlying such sexual dimorphism are not well understood. Here we show that there are intrinsic differences between the B cells that produce germinal centres in male and female mice. We find that antigen-activated male B cells do not position themselves as efficiently as female B cells in the centre of follicles in secondary lymphoid organs, in which germinal centres normally develop. Moreover, GPR174-an X-chromosome-encoded G-protein-coupled receptor-suppresses the formation of germinal centres in male, but not female, mice. This effect is intrinsic to B cells, and correlates with the GPR174-enhanced positioning of B cells towards the T-cell-B-cell border of follicles, and the distraction of male, but not female, B cells from S1PR2-driven follicle-centre localization. Biochemical fractionation of conditioned media that induce B-cell migration in a GPR174-dependent manner identifies CCL21 as a GPR174 ligand. In response to CCL21, GPR174 triggers a calcium flux and preferentially induces the migration of male B cells; GPR174 also becomes associated with more Gαi protein in male than in female B cells. Male B cells from orchidectomized mice exhibit impaired GPR174-mediated migration to CCL21, and testosterone treatment rescues this defect. Female B cells from testosterone-treated mice exhibit male-like GPR174-Gαi association and GPR174-mediated migration. Deleting GPR174 from male B cells causes more efficient positioning towards the follicular centre, the formation of more germinal centres and an increased susceptibility to B-cell-dependent experimental autoimmune encephalomyelitis. By identifying GPR174 as a receptor for CCL21 and demonstrating its sex-dependent control of B-cell positioning and participation in germinal centres, we have revealed a mechanism by which B-cell physiology is fine-tuned to impart sexual dimorphism to humoral immunity.