Two structural switches in HIV-1 capsid regulate capsid curvature and host factor binding.

The mature HIV-1 capsid protects the viral genome and interacts with host proteins to travel from the cell periphery into the nucleus. To achieve this, the capsid protein, CA, constructs conical capsids from a lattice of hexamers and pentamers, and engages in and then relinquishes multiple interactions with cellular proteins in an orchestrated fashion. Cellular host factors including Nup153, CPSF6, and Sec24C engage the same pocket within CA hexamers. How CA assembles pentamers and hexamers of different curvatures, how CA oligomerization states or curvature might modulate host-protein interactions, and how binding of multiple cofactors to a single site is coordinated, all remain to be elucidated. Here, using single-particle cryoEM, we have determined the structure of the mature HIV-1 CA pentamer and hexamer from conical CA-IP6 polyhedra to ~3 Å resolution. We also determined structures of hexamers in the context of multiple lattice curvatures and number of pentamer contacts. Comparison of these structures, bound or not to host protein peptides, revealed two structural switches within HIV-1 CA that modulate peptide binding according to CA lattice curvature and whether CA is hexameric or pentameric. These observations suggest that the conical HIV-1 capsid has different host-protein binding properties at different positions on its surface, which may facilitate cell entry and represent an evolutionary advantage of conical morphology.

Patients treated for acute headache with intranasal droperidol spend less time in the emergency department: A retrospective observational study.

OBJECTIVE: Headache is a common presenting complaint to the ED. Using time from the first provider to discharge as a surrogate for effectiveness, we aimed to determine if intranasal (IN) droperidol is as beneficial as usual treatment for acute headache in the ED. METHODS: There were 1213 consecutive presentations of adults with acute headache over a 42-month period. Electronic records for each event were interrogated, 406 events met pre-determined exclusion criteria. Of the remaining 805 eligible patient events, 139 received IN droperidol, whereas 666 were given usual therapy. RESULTS: There was a 20 min reduction of mean and median ED length of stay (LOS) for the group that got treated with IN droperidol. CONCLUSIONS: IN droperidol reduced LOS in the ED. There are potential cost savings of this effective treatment via this novel route. A prospective multi-centre study of the use of IN droperidol for the treatment of acute headache in the ED is recommended.

Parenting an Autistic Child: Experiences of Parents with Significant Autistic Traits.

Despite autism being highly heritable, this study is the first to investigate the experiences of parents of autistic children who have significant autistic traits themselves. Eight parents of autistic children with significant autistic traits themselves were interviewed regarding their parenting experiences. In line with what has previously been reported by parents of autistic children, participants described difficulties with parental mental health and navigating professional services. Novel participant experiences included the interaction between parental and child autistic traits helping and hindering their parenting; parents learning to manage their own autistic traits, and parents finding the home to be an accepting place of autism. The need for adequately funded, tailored and accessible services for these families is emphasised.

Autistic Cognition: Charting Routes to Anxiety.

Autism Spectrum Conditions are typified by a divergence in cognitive style from that of the non-autistic population. Cognitive differences in autism may underlie significant strengths, but also increase vulnerability to psychopathology such as anxiety, which is a major problem for many autistic people. Many autistic people also do not respond to typical psychotherapeutic interventions, suggesting that autism-specific models and interventions are needed. We advance a theoretical model explaining how three constructs, attenuated predictions, intolerance of uncertainty, and 'black and white thinking', may interact to lead to anxiety in autism. We hope to start a dialogue surrounding how we can best address specific autistic cognitive differences that may lead to distress by developing appropriate models, measurements, and psychotherapeutic interventions.