Autism-Associated Neuroligin-3 Mutations Commonly Impair Striatal Circuits to Boost Repetitive Behaviors

In humans, neuroligin-3 mutations are associated with autism, while in mice the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum, but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse, and thereby provide a plausible circuit substrate for autism pathophysiology

Autism-Associated Neuroligin-3 Mutations Commonly Impair Striatal Circuits to Boost Repetitive Behaviors

In humans, neuroligin-3 mutations are associated with autism, while in mice the corresponding mutations produce robust synaptic and behavioral changes. However, different neuroligin-3 mutations cause largely distinct phenotypes in mice, and no causal relationship links a specific synaptic dysfunction to a behavioral change. Using rotarod motor learning as a proxy for acquired repetitive behaviors in mice, we found that different neuroligin-3 mutations uniformly enhanced formation of repetitive motor routines. Surprisingly, neuroligin-3 mutations caused this phenotype not via changes in the cerebellum or dorsal striatum, but via a selective synaptic impairment in the nucleus accumbens/ventral striatum. Here, neuroligin-3 mutations increased rotarod learning by specifically impeding synaptic inhibition onto D1-dopamine receptor-expressing but not D2-dopamine receptor-expressing medium spiny neurons. Our data thus suggest that different autism-associated neuroligin-3 mutations cause a common increase in acquired repetitive behaviors by impairing a specific striatal synapse, and thereby provide a plausible circuit substrate for autism pathophysiology

Leadership Styles and Innovative Entrepreneurship: An International Study

This research attempts to empirically examine the relationship between leadership styles and innovative entrepreneurship through regression analysis, using a sample of 43 countries and data from Global Entrepreneurship Monitor and Global Leadership and Organizational Behavior Effectiveness. In light of institutional approaches and specifically based on the normative dimension, the main findings of the study indicate that participative leadership and higher education represent the strongest explanatory factor in the variance of the current rates of innovative entrepreneurship. This study has contributions for both researchers and policymakers on new firm creation (entrepreneurship) and on the generation of innovation within organizations (intrapreneurship).Stefan van Hemmen acknowledges the financial resources from ECO2013-48496-C4-4-R (Spanish Ministry of Economy & Competitiveness) and 2014-SGR-1259 (Economy & Knowledge Department -Catalan Government-). Marta Peris-Ortiz acknowledges support from the Universitat Politecnica de Valencia through the project Paid-06-12 (Sp 20120792). Claudia Alvarez and David Urbano acknowledge the financial support from the Projects ECO2013-44027-P (Spanish Ministry of Economy & Competitiveness) and 2014-SGR-1626)Economy & Knowledge Department -Catalan Government-).Van Hemmen, S.; Alvarez, C.; Peris-Ortiz, M.; Urbano, D. (2015). Leadership Styles and Innovative Entrepreneurship: An International Study. Cybernetics and Systems. 46(3-4):271-286. https://doi.org/10.1080/01969722.2015.1012896S271286463-

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Shift in the Intrinsic Excitability of Medial Prefrontal Cortex Neurons following Training in Impulse Control and Cued-Responding Tasks

Impulse control is an executive process that allows animals to inhibit their actions until an appropriate time. Previously, we reported that learning a simple response inhibition task increases AMPA currents at excitatory synapses in the prelimbic region of the medial prefrontal cortex (mPFC). Here, we examined whether modifications to intrinsic excitability occurred alongside the synaptic changes. To that end, we trained rats to obtain a food reward in a response inhibition task by withhold responding on a lever until they were signaled to respond. We then measured excitability, using whole-cell patch clamp recordings in brain slices, by quantifying action potentials generated by the injection of depolarizing current steps. Training in this task depressed the excitability of layer V pyramidal neurons of the prelimbic, but not infralimbic, region of the mPFC relative to behavioral controls. This decrease in maximum spiking frequency was significantly correlated with performance on the final session of the task. This change in intrinsic excitability may represent a homeostatic mechanism counterbalancing increased excitatory synaptic inputs onto those neurons in trained rats. Interestingly, subjects trained with a cue that predicted imminent reward availability had increased excitability in infralimbic, but not the prelimbic, pyramidal neurons. This dissociation suggests that both prelimbic and infralimbic neurons are involved in directing action, but specialized for different types of information, inhibitory or anticipatory, respectively

'Let the Right Ones In!': Widening Participation, Academic Writing and the Standards Debate in Higher Education

This paper challenges the frequently expressed concern, post-1992, that widening participation (WP) has contributed to a general ‘dumbing down’ of higher education in English universities *(Burke, 2005; Leathwood, 2010). In particular, it explores the implications of a long-standing ‘moral panic’ (Cohen, 1972) about the poor quality of students’ academic writing, particularly in the ‘new’ universities, which have been raised in various academic reports and countless media articles. A vampire metaphor is used throughout the paper to highlight ways in which assumptions about these falling standards in undergraduates’ academic writing feed on the foundations of a longstanding, albeit implicit, distrust of the growth in the sector on elitist, ideological grounds. The second half of the paper investigates how academic writing practices, whilst difficult to define, nonetheless wield a ‘disciplinary power’ (Foucault, 1980), over lecturers and students in the academy. This includes a discussion about how a situated, New Literacy Studies (NLS) approach to academic writing development challenges the view that students’ academic writing standards are falling. In contrast, the paper suggests that all universities have a responsibility to acknowledge and develop the different literacies that students, especially widening participation students, bring with them to university. (193

Angel investor's selection criteria: a comparative institutional perspective

Despite the important role of angel investors as critical financial providers for new ventures, little is known regarding how institutions make their investment decisions. While angels make decisions based on selection criteria during the first stage, they are also embedded within and affected by different institutional settings and as a result weight these criteria differently than other investors. We compare angel investors' selection criteria in China and Denmark using the comparative institutional perspective. We use a policy capturing approach and hierarchy linear modeling, revealing that since Chinese angels are embedded within relationship-based institutional settings they tend to reply more on strong ties such as family and friends in management team, as well as weighting risks less compared to Danish angels operating within more rule-based institutional contexts

Characteristics of infralimbic neurons.

<p>*: p<0.05 vs all groups.</p

Training in the Cue condition had no effect on the intrinsic excitability of prelimbic neurons.

<p><b>A.</b> Action potentials were produced by increasing current steps (800 ms, 50 pA steps). <b>B.</b> Learning the cue had no effect the maximum number of action potentials evoked. Sample sizes for subjects (above) and cells (below) are indicated within the bars. <b>C.</b> Representative traces show action potentials generated by 500 pA (left) and 1500 pA (right) current steps for differing behavioral conditions. (Calibration Bars: 20 mV/0.1 s; *: p<0.05 vs. all groups).</p