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Directional migration during embryogenesis and tumor progression faces the challenge that numerous external signals need to converge to precisely control cell movement. The Rho guanine exchange factor (GEF) Trio is especially well suited to relay signals as it features distinct catalytic domains to activate Rho GTPases. Here we show that Trio is required for Xenopus cranial neural crest (NC) cell migration and cartilage formation. Trio cell-autonomously controls protrusion formation of NC cells and Trio morphant NC cells show a blebbing phenotype. Interestingly, the Trio GEF2 domain is sufficient to rescue protrusion formation and migration of Trio morphant NC cells. We show that this domain interacts with the DEP/C-terminus of Dishevelled (DVL). DVL - but not a deletion construct lacking the DEP domain – is able to rescue protrusion formation and migration of Trio morphant NC cells. This is likely mediated by activation of Rac1, as we find that DVL rescues Rac1 activity in Trio morphant embryos. Thus, our data provide evidence for a novel signaling pathway, whereby Trio controls protrusion formation of cranial NC cells by interacting with DVL to activate Rac1.

Background Hidradenitis suppurativa (HS) is a rare, debilitating neutrophilic dermatosis characterized by chronic inflammation of hair follicles. Many inflammatory conditions may accompany HS. Objectives To investigate the association of variants of the MEFV gene with a complex HS phenotype. Methods Firstly, we identified the clinical characteristics of 119 patients with HS with a complex phenotype (Hurley stage III disease and/or additional inflammatory symptoms). Then, we searched for MEFV variants among these patients. The odds ratios (ORs) for pathogenic MEFV mutations were calculated using data from these patients with HS and 191 healthy controls. Results The male/female ratio was higher, and the mean age of onset was earlier, in our complex HS group compared with patients with HS in general. Five of the patients with HS (4 center dot 2%) had a diagnosis of familial Mediterranean fever (FMF) with a standardized morbidity ratio of 45 [95% confidence interval (CI) 16 center dot 50-99 center dot 84, P < 0 center dot 001] when compared with the frequency of FMF in the general Turkish population. Of the patients with complex HS, 38% were positive for pathogenic variants of MEFV. The OR for carrying a pathogenic MEFV allele was 2 center dot 80 (95% CI 1 center dot 31-5 center dot 97, P < 0 center dot 001). Conclusions The frequency of MEFV mutations in the group of patients with complex HS was higher than that in healthy controls, suggesting that MEFV mutations may contribute to the pathogenesis of HS. Understanding the role of autoinflammation in HS is of fundamental importance for the development of novel therapies.

Effort can be perceived both cognitively and physically, but the computational mechanisms underlying the motivation to invest effort in each domain remain unclear. In particular, it is unknown whether intensive physical training is associated with higher motivation specific to that domain, or whether it is accompanied by corresponding changes in cognitive motivation. Here, we tested a group of elite Oxford University rowers, and compared their behaviour to matched non-athletic controls. We trained participants on two tasks involving cognitive or physical effort. They then decided between a baseline low level of effort for low reward, versus higher levels of effort for higher rewards. Separate choices were made for the cognitive and physical tasks, which allowed us to computationally model motivation in each domain independently. As expected, athletes were willing to exert greater amounts of physical effort than non-athletes. Critically, however, the nature of cognitive effort-based decisions was different between groups, with a concave pattern of effort discounting for athletes but a convex pattern for non-athletes. These data suggest that the greater physical drive in athletes is accompanied by fundamentally different patterns of cognitive effort discounting, and suggests a complex relationship between motivation in the two domains.

In everyday life, we have to decide whether it is worth exerting effort to obtain rewards. Effort can be experienced in different domains, with some tasks requiring significant cognitive demand, and others being more physically effortful. The motivation to exert effort for reward is highly subjective, and varies considerably across the different domains of behaviour. However, very little is known about the computational or neural basis of how different effort costs are subjectively weighed against rewards. Is there a common, domain-general system of brain areas that evaluates all costs and benefits? Here, we used computational modelling and functional magnetic resonance imaging (fMRI) to examine the mechanisms underlying value processing in both the cognitive and physical domains. Participants were trained on two novel tasks which parametrically varied either cognitive or physical effort. During fMRI, participants indicated their preferences between a fixed loweffort/ low-reward option and a variable higher-effort/higher-reward offer for each effort domain. Critically, reward devaluation by both cognitive and physical effort was subserved by a common network of areas including dorsomedial and dorsolateral prefrontal cortex, intraparietal sulcus and anterior insula. Activity within these domain-general areas also covaried negatively with reward and positively with effort, suggesting an integration of these parameters within these areas. Additionally, the amygdala appeared to play a unique, domain-specific role in processing the value of rewards associated with cognitive effort. These results are the first to reveal the neurocomputational mechanisms underlying subjective cost-benefit valuation across different domains of effort, and provide insight into the multidimensional nature of motivation.

Patients suffering from hair loss or undesirable excessive hair growth are a challenge for dermatologists because the pathogenesis of most hair diseases is not well understood and therapeutic options are limited. This particularly holds true for genetic hair disorders, in which all current treatment attempts are unsuccessful. Furthermore, these diseases also pose a diagnostic challenge due to a broad range of clinical and genetic heterogeneity. However, the enormous progress in molecular biology over the past 20 years, in particular the availability of different new techniques such as whole exome and genome sequencing, has enabled us to elucidate the genetic basis of most monogenic hair disorders, given the availability of suitable index patients and families as well as adequate technical equipment and sufficient financial resources. In this review we provide an update on clinical and genetic aspects of selected monogenic and polygenic hair diseases manifesting with hypertrichosis and hypotrichosis.

The 2008 annual meeting of the Signal Transduction Society covered a broad spectrum of topics, with signaling in immune cells as the special focus of the meeting. Many of the immune signaling talks concerned B and T lymphocytes in particular; the role of inflammatory cytokines in cancer progression was also addressed. Neoplastic development was also discussed with regard to aspects of cell cycle control, aging, and transformation. Topics extended to signaling pathways induced by bacteria, viruses, and environmental toxins, as well as those involved in differentiation, morphogenesis, and cell death. This international and interdisciplinary scientific gathering induced lively discussions and close interactions between participants.

Individuals with REM sleep behaviour disorder are at significantly higher risk of developing Parkinson's disease. Here we examined visual short-term memory deficits--long associated with Parkinson's disease--in patients with REM sleep behaviour disorder without Parkinson's disease using a novel task that measures recall precision. Visual short-term memory for sequentially presented coloured bars of different orientation was assessed in 21 patients with polysomnography-proven idiopathic REM sleep behaviour disorder, 26 cases with early Parkinson's disease and 26 healthy controls. Three tasks using the same stimuli controlled for attentional filtering ability, sensorimotor and temporal decay factors. Both patients with REM sleep behaviour disorder and Parkinson's disease demonstrated a deficit in visual short-term memory, with recall precision significantly worse than in healthy controls with no deficit observed in any of the control tasks. Importantly, the pattern of memory deficit in both patient groups was specifically explained by an increase in random responses. These results demonstrate that it is possible to detect the signature of memory impairment associated with Parkinson's disease in individuals with REM sleep behaviour disorder, a condition associated with a high risk of developing Parkinson's disease. The pattern of visual short-term memory deficit potentially provides a cognitive marker of 'prodromal' Parkinson's disease that might be useful in tracking disease progression and for disease-modifying intervention trials.

Ontogeny of Blood Parameters in the Domestic Fowl Gallus gallus domesticus: I. Blood Cells and Haemoglobin The paper presents the ontogeny of 8 (from 27 investigated) haematological parameters in the precocial fowl Gallus gallus from hatching through the beginning of sexual maturity (week 18) to week 22: We found significant increases in the parameters responsible for O2-transport, immune defence, protein metabolism, and muscle growth (e.g. number of erythrocytes RBC, haemoglobin Hb, mean corpuscular haemoglobin concentration MCHC), but also in total protein, calcium, creatine kinase, aspartate aminotransferase (see introduction). Increases in mean cell volume of erythrocytes (MCV), glucose, triglycerides, uric acid, lactate dehydrogenase, and alkaline phosphatase are presumably due to growth requirements and tissue development. No marked ontogenetic changes were found in mean corpuscular haemoglobin (MCH), and haematocrit (PCV). The number of white blood cells (WBC) does not show constant increases or decreases but a very high flexibility (especially in lymphocytes).

Ontogeny of Blood Parameters in the Domestic Fowl Gallus gallus domesticus: II. Plasma Parameter Ontogenetic development of 11 (from 19 continuously measured) haematological plasma parameters in the precocial fowl Gallus gallus from hatching through the start of sexual maturity (week 18) and through week 22 were measured daily (data of blood cells and haemoglobin values were already published in a preceding paper Prinzinger R, Misovic A, Giehl K, Sennert F (2015) Ontogeny of Blood Parameters in the Domestic Fowl Gallus gallus domesticus: I. Blood Cells and Haemoglobin. J Vet Sci Med Diagn 4:5).