WDR62 is associated with the spindle pole and is mutated in human microcephaly

Autosomal recessive primary microcephaly (MCPH) is a disorder of neurodevelopment resulting in a small brain. We identified WDR62 as the second most common cause of MCPH after finding homozygous missense and frame-shifting mutations in seven MCPH families. In human cell lines, we found that WDR62 is a spindle pole protein, as are ASPM and STIL, the MCPH7 and MCHP7 proteins. Mutant WDR62 proteins failed to localize to the mitotic spindle pole. In human and mouse embryonic brain, we found that WDR62 expression was restricted to neural precursors undergoing mitosis. These data lend support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis, controlled in great part by the centrosomes and spindle poles, is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain.     

Historicity and explanation

Some scientific explanations are distinctively historical. The aim of this paper is to say what gives such explanations their historical character. A secondary aim is to describe what makes an explanation a stronger or weaker historical explanation. We begin with a critical discussion of John Beatty's and Eric Desjardins' work on historicity and historical narrative. We then offer an alternative account of historical explanation that draws on the work of earlier philosophers (Gallie, Danto, Mink, and Hull). In that alternative account, we highlight four features of narrative explanation that Beatty and Desjardins underemphasize: central subjects; historical trajectories; the idea that historical narratives are known retrospectively; and criteria for determining what is a stronger or weaker historical narrative.     

Adherens junction protein nectin-4 is the epithelial receptor for measles virus

Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor. These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously. How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. 8; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing measles-virus-based clinical trials of oncolysis.     

Humans integrate visual and haptic information in a statistically optimal fashion.

When a person looks at an object while exploring it with their hand, vision and touch both provide information for estimating the properties of the object. Vision frequently dominates the integrated visual-haptic percept, for example when judging size, shape or position, but in some circumstances the percept is clearly affected by haptics. Here we propose that a general principle, which minimizes variance in the final estimate, determines the degree to which vision or haptics dominates. This principle is realized by using maximum-likelihood estimation to combine the inputs. To investigate cue combination quantitatively, we first measured the variances associated with visual and haptic estimation of height. We then used these measurements to construct a maximum-likelihood integrator. This model behaved very similarly to humans in a visual-haptic task. Thus, the nervous system seems to combine visual and haptic information in a fashion that is similar to a maximum-likelihood integrator. Visual dominance occurs when the variance associated with visual estimation is lower than that associated with haptic estimation.