Conjunctions of social categories considered from different points of view

Conjunctions of divergent social categories may elicit emergent attributes to render the composite concept more coherent. Following Kunda, Miller & Clare, (1990) participants listed and rated attributes for people who belong to unexpected conjunctions of social categories. In order to explore the flexibility in such constructions, they were also asked to adopt the point of view of a person in one of the two categories. Experiment 1 found that when adopting the point of view of one constituent category, people tended to combine the concepts antagonistically, meaning that they attributed to members of the conjunction the more negative aspects of the opposing category. Experiment 2 showed that this polarizing effect was reduced when the point of view category was itself unusual. Strong gender stereotype differences were also found in the degree to which combinations were antagonistic. Female stereotypes as points of view generated a greater degree of integration in the conceptual combination

Is spoken language all-or-nothing? Implications for future speech-based human-machine interaction

Recent years have seen significant market penetration for voice-based personal assistants such as Apple’s Siri. However, despite this success, user take-up is frustratingly low. This article argues that there is a habitability gap caused by the inevitablemismatch between the capabilities and expectations of human users and the features and benefits provided by contemporary technology. Suggestions aremade as to how such problems might be mitigated, but a more worrisome question emerges: “is spoken language all-or-nothing”? The answer, based on contemporary views on the special nature of (spoken) language, is that there may indeed be a fundamental limit to the interaction that can take place between mismatched interlocutors (such as humans and machines). However, it is concluded that interactions between native and non-native speakers, or between adults and children, or even between humans and dogs, might provide critical inspiration for the design of future speech-based human-machine interaction

The p.M292T NDUFS2 mutation causes complex I-deficient Leigh syndrome in multiple families

Isolated complex I deficiency is the most frequently observed oxidative phosphorylation defect in children with mitochondrial disease, leading to a diverse range of clinical presentations, including Leigh syndrome. For most patients the genetic cause of the biochemical defect remains unknown due to incomplete understanding of the complex I assembly process. Nonetheless, a plethora of pathogenic mutations have been described to date in the seven mitochondrial-encoded subunits of complex I as well as in 12 of the nuclear-encoded subunits and in six assembly factors. Whilst several mitochondrial DNA mutations are recurrent, the majority of these mutations are reported in single families. We have sequenced core structural and functional nuclear-encoded subunits of complex I in a cohort of 34 paediatric patients with isolated complex I deficiency, identifying pathogenic mutations in 6 patients. These included a novel homozygous NDUFS1 mutation in an Asian child with Leigh syndrome, a previously identified NDUFS8 mutation (c.236C>T, p.P79L) in a second Asian child with Leigh-like syndrome and six novel, compound heterozygous NDUFS2 mutations in four white Caucasian patients with Leigh or Leigh-like syndrome. Three of these children harboured an identical NDUFS2 mutation (c.875T>C, p.M292T), which was also identified in conjunction with a novel NDUFS2 splice site mutation (c.866+4A>G) in a fourth Caucasian child who presented to a different diagnostic centre, with microsatellite and single nucleotide polymorphism analyses indicating that this was due to an ancient common founder event. Our results confirm that NDUFS2 is a mutational hotspot in Caucasian children with isolated complex I deficiency and recommend the routine diagnostic investigation of this gene in patients with Leigh or Leigh-like phenotypes

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution.

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations

Bi-allelic variants in SPATA5L1 lead to intellectual disability, spastic-dystonic cerebral palsy, epilepsy, and hearing loss

Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype

Phenotypic expansion and further characterization of the 17q21.31 microdeletion syndrome (Journal of Medical Genetics (2009) 46 (480-489))

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Rumen fermentation and microbial yield of high- or low-protein diets containing ground soybean seeds or homemade rapeseed expellers evaluated with RUSITEC

This experiment aimed to compare diets containing two crude protein (CP) concentrations [147 or 109 g kg-1 in dry matter (DM)] and two protein sources containing ground soybean seed (GSS) or rapeseed expeller (RSE). Diets were compared in terms of digestibility, volatile fatty acids (VFA) and ammonia concentrations, and N flows, using rumen simulation fermenters (RUSITEC). Home-made RSE (CP=287 g kg-1 dry matter and ether extract=199 g kg-1 DM) was produced using equipment adopted by small farms. Reduction of dietary CP content did not affect digestibility, except for a reduction of N apparent digestibility (P<0.01), but increased efficiency of N utilization (P-0.001) without affecting microbial N production (P=0.82). Total VFA concentration was not (P=0.56) influenced by CP content. Compared with GSS, RSE exhibited a greater neutral detergent fibre digestibility (P<0.01), it did not influence total volatile fatty acids (VFA; P=0.10) but decreased the proportions of acetate and propionate on total VFA (P<0.001) and increased those of butyrate and branched-chain VFA (P<0.001). Microbial efficiency was comparable for GSS and RSE. Results suggest that reduction of dietary CP concentration in DM did not impair in vitro digestibility and microbial growth. The protein mixture containing homemade RSE showed in vitro fermentative properties and microbial growth comparable with those of GSS