Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

Reward processing in autism: a thematic series

This thematic series presents theoretical and empirical papers focused on understanding autism from the perspective of reward processing deficits. Although the core symptoms of autism have not traditionally been conceptualized with respect to altered reward-based processes, it is clear that brain reward circuitry plays a critical role in guiding social and nonsocial learning and behavior throughout development. Additionally, brain reward circuitry may respond to social sources of information in ways that are similar to responses to primary rewards, and recent clinical data consistently suggest abnormal behavioral and neurobiologic responses to rewards in autism. This thematic series presents empirical data and review papers that highlight the utility of considering autism from the perspective of reward processing deficits. Our hope is that this novel framework may further elucidate autism pathophysiology, with the ultimate goal of yielding novel insights with potential therapeutic implications

The Molecular Clockwork of the Fire Ant Solenopsis invicta

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

Use of Vesicular - Arbuscular Mycorrhiza (VAM) as Biofertilizer for Horticultural Plants in Developing Countries

Mycorrhiza is the product of an association between a fungus and plant root. Vesicular-arbuscular mycorrhiza (VAM) is formed by the symbiotic association between certain phycomycetous fungi and angiosperm roots. The fungus colonizes the root cortex forming a mycelial network and characteristic vesicles (bladder-like structures) and arbuscules (branched finger-like hyphae). The mycelia are aseptate or septate ramifying intercellularly thus causing little damage to tissues. The arbuscules are the most characteristic structures, formed intracellularly and probably having an absorptive function. The vesicles are terminal swellings of hyphae formed inter and intracellularly having a storage function. There are six genera of fungi belonging to Endogonaceae which have been shown to form mycorrhizal associations: Glomus, Gigaspora, Acaulospora, Entrophospora Sclerocystis and Scutellospora. These are mainly identified by their characteristic spores and sporocarps which are formed mostly in the soil surrounding the roots and rarely inside the roots. The identification of VAM fungi directly from roots has been difficult. One of the striking features of VAM fungi is their very wide host range which includes angiosperm species belonging to almost all the families. Even the roots of some aquatic plants are colonized by VAM fungi

Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity

Satellite cells (SCs) represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible. Even though the pool of SCs is accepted as the major, and possibly the only, source of myonuclei in postnatal muscle, it is likely that SCs are not all multipotent stem cells and evidences for diversities within the myogenic compartment have been described both in vitro and in vivo. Here, by isolating single fibers from rat flexor digitorum brevis (FDB) muscle we were able to identify and clonally characterize two main subpopulations of SCs: the low proliferative clones (LPC) present in major proportion (∼75%) and the high proliferative clones (HPC), present instead in minor amount (∼25%). LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if co-cultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (ΔΨm), ATP balance and Reactive Oxygen Species (ROS) generation underlying diversities in metabolism that precede differentiation. Notably, SCs heterogeneity is retained in vivo. SCs may therefore be comprised of two distinct, though not irreversibly committed, populations of cells distinguishable for prominent differences in basal biological features such as proliferation, metabolism and differentiation. By these means, novel insights on SCs heterogeneity are provided and evidences for biological readouts potentially relevant for diagnostic purposes described

Does individual learning styles influence the choice to use a web-based ECG learning programme in a blended learning setting?

<p>Abstract</p> <p>Background</p> <p>The compressed curriculum in modern knowledge-intensive medicine demands useful tools to achieve approved learning aims in a limited space of time. Web-based learning can be used in different ways to enhance learning. Little is however known regarding its optimal utilisation. Our aim was to investigate if the individual learning styles of medical students influence the choice to use a web-based ECG learning programme in a blended learning setting.</p> <p>Methods</p> <p>The programme, with three types of modules (learning content, self-assessment questions and interactive ECG interpretation training), was offered on a voluntary basis during a face to face ECG learning course for undergraduate medical students. The Index of Learning Styles (ILS) and a general questionnaire including questions about computer and Internet usage, preferred future speciality and prior experience of E-learning were used to explore different factors related to the choice of using the programme or not.</p> <p>Results</p> <p>93 (76%) out of 123 students answered the ILS instrument and 91 the general questionnaire. 55 students (59%) were defined as users of the web-based ECG-interpretation programme. Cronbach's alpha was analysed with coefficients above 0.7 in all of the four dimensions of ILS. There were no significant differences with regard to learning styles, as assessed by ILS, between the user and non-user groups; Active/Reflective; Visual/Verbal; Sensing/Intuitive; and Sequential/Global (p = 0.56-0.96). Neither did gender, prior experience of E-learning or preference for future speciality differ between groups.</p> <p>Conclusion</p> <p>Among medical students, neither learning styles according to ILS, nor a number of other characteristics seem to influence the choice to use a web-based ECG programme. This finding was consistent also when the usage of the different modules in the programme were considered. Thus, the findings suggest that web-based learning may attract a broad variety of medical students.</p

Measuring the value of social engagement in adults with and without autism

Differences in social communication are commonly reported in autism spectrum condition (ASC). A recent theory attributes this to a reduced motivation to engage with others, that is, deficits in social motivation. However, there are currently few simple, direct, behavioural ways to test this claim. This study uses a new behavioural measure of social motivation to test if preferences for direct gaze and face stimuli are linked to autistic traits or an ASC diagnosis. Our novel choose-a-movie (CAM) paradigm measures the effort participants invest to see particular stimuli. This aspect of social motivation is also known as social seeking. Methods In experiment 1, 80 typical adults completed the CAM task and a measure of autistic traits. In experiment 2, 30 adults with ASC and 24 age/IQ-matched typical adults completed the CAM paradigm. Results The results from study one showed that typical adults prefer social stimuli over non-social, but this preference is weaker in those with higher levels of autistic traits. In study two, adults with ASC showed a significant reduction in their preference for direct gaze but little difference in their preference for faces without direct gaze. Conclusions These data show that social motivation can be measured in a simple, direct, behavioural paradigm. Furthermore, adults with ASC prefer direct gaze less than typical adults but may not avoid faces without direct gaze. This data advance our understanding of how social motivation may differ between those with and without autism