Neurotrophin and Wnt signaling cooperatively regulate dendritic spine formation

Dendritic spines are major sites of excitatory synaptic transmission and changes in their numbers and morphology have been associated with neurodevelopmental and neurodegenerative disorders. Brain-derived Neurotrophic Factor (BDNF) is a secreted growth factor that influences hippocampal, striatal and neocortical pyramidal neuron dendritic spine density. However, the mechanisms by which BDNF regulates dendritic spines and how BDNF interacts with other regulators of spines remain unclear. We propose that one mechanism by which BDNF promotes dendritic spine formation is through an interaction with Wnt signaling. Here, we show that Wnt signaling inhibition in cultured cortical neurons disrupts dendritic spine development, reduces dendritic arbor size and complexity, and blocks BDNF-induced dendritic spine formation and maturation. Additionally, we show that BDNF regulates expression of Wnt2, and that Wnt2 is sufficient to promote cortical dendrite growth and dendritic spine formation. Together, these data suggest that BDNF and Wnt signaling cooperatively regulate dendritic spine formation

Penicillin-resistant isolates of Neisseria-lactamica produce altered forms of penicillin-binding protein-2 that arose by interspecies horizontal gene-transfer

Isolates of Neisseria lactamica that have increased resistance to penicillin have emerged in recent years. Resistance to penicillin was shown to be due to the production of altered forms of penicillin-binding protein 2 (PBP 2) that have reduced affinity for the antibiotic. The sequences of the PBP 2 genes (penA) from two penicillin-resistant isolates were almost identical (less than or equal to 1% sequence divergence) to that of a penicillin-susceptible isolate, except in a 175-bp region where the resistant and susceptible isolates differed by 27%. The nucleotide sequences of these divergent regions were identical (or almost identical) to the sequence of the corresponding region of the penA gene of N. flavescens NCTC 8263. Altered forms of PBP 2 with decreased affinity for penicillin in the two penicillin-resistant isolates of N. lactamica appear, therefore, to have arisen by the replacement of part of the N. lactamica penA gene with the corresponding region from the penA gene of N. flavescens

Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis

Non-beta-lactamase-producing, penicillin-resistant strains of Neisseria meningitidis produce altered forms of penicillin-binding protein 2 that have decreased affinity for penicillin. The sequence of the penicillin-binding protein 2 gene (penA) from a penicillin-resistant strain of N. meningitidis was compared to the sequence of the same gene from penicillin-sensitive strains and from penicillin-sensitive and penicillin-resistant strains of Neisseria gonorrhoeae. The penA genes from penicillin-sensitive strains of N. gonorrhoeae and N. meningitidis were 98% identical. The gene from the penicillin-resistant strain of N. meningitidis consisted of regions that were almost identical to the corresponding regions in the penicillin-sensitive strains (less than 0.2% divergence) and two regions that were very different from them (approximately 22% divergence). The two blocks of altered sequence have arisen by the replacement of meningococcal sequences with the corresponding regions from the penA gene of Neisseria flavescens and result in an altered form of penicillin-binding protein 2 that contains 44 amino acid substitutions and 1 amino acid insertion compared to penicillin-binding protein 2 of penicillin-sensitive strains of N. meningitidis. A similar introduction of part of the penA gene of N. flavescens, or a very similar commensal Neisseria species, appears to have occurred independently during the development of altered penA genes in non-beta-lactamase-producing penicillin-resistant strains of N. gonorrhoeae

A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Amplified ambivalence: having a sibling with juvenile idiopathic arthritis

Despite increased awareness of family responses to chronic illness and disability, there is still a need to understand experiences of well siblings. We begin to address this by asking “What is it like to have a sibling with juvenile idiopathic arthritis?” (JIA).Eight families with an adolescent diagnosed with JIA participated. Four members of each family, including one healthy sibling, were interviewed and transcripts analyzed using grounded theory. Analysis suggests healthy siblings see their family as different to ‘normal’ families, forfeit time with peers, share vicariously adverse experiences of their ill sibling, and feel inadequately informed. Such experiences amplify the ambivalent nature of sibling relationships and are possibly felt most strongly during late childhood and early adolescence. Support from extended family can reduce these negative experiences and facilitate social and emotional adjustment which also occurs over time as the children mature. These findings have implications for healthcare professionals and voluntary organizations

Examining the Relationships among the Coaching Climate, Life Skills Development and Well-Being in Sport

Using Benson and Saito's framework for positive youth development, we investigated the relationships between the coaching climate, young people's perceived life skills development within sport, and their psychological well-being. British youth sport participants (N=326, Mage=13.81, range=11–18 years) completed a survey assessing the coaching climate, participants' perceived life skills development (teamwork, goal setting, time management, emotional skills, interpersonal communication, social skills, leadership, and problem solving and decision making) and psychological well-being (self-esteem, positive affect, and satisfaction with life). In all analyses, the coaching climate was positively related to young peoples' perceived development of life skills within sport and their psychological well-being. Total life skills development (a summative score of all eight life skills scores) was positively related to all three psychological well-being indicators – providing support for the "pile-up" effect – and partially mediated the relationships between the coaching climate and participants' psychological well-being. Interpretation of the results indicated that coaches should foster the development of multiple life skills in youth sport participants, as they are associated with participants' psychological well-being. One way this can be achieved is through autonomy-supportive coaching behaviours

High star formation rates as the origin of turbulence in early and modern disk galaxies

High spatial and spectral resolution observations of star formation and kinematics in early galaxies have shown that two-thirds are massive rotating disk galaxies with the remainder being less massive non-rotating objects. The line of sight averaged velocity dispersions are typically five times higher than in today's disk galaxies. This has suggested that gravitationally-unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. However these accreting flows have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report on a new sample of rare high-velocity-dispersion disk galaxies we have discovered in the nearby Universe where cold accretion is unlikely to drive their high star-formation rates. We find that the velocity dispersion is most fundamentally correlated with their star-formation rates, and not their mass nor gas fraction, which leads to a new picture where star formation itself is the energetic driver of galaxy disk turbulence at all cosmic epochs.Comment: 9 pages, 2 figures, Supplimentary Info available at: http://pulsar.swin.edu.au/~agreen/nature/sigma_mean_arXiv.pdf. Accepted for publication in Natur

The effects of an afterschool STEM program on students’ motivation and engagement

Background: One significant factor in facilitating students’ career intentions and persistence in STEM (science, technology, engineering, and mathematics) fields is targeting their interests and motivation before eighth grade. To reach students at this critical stage, a design-based afterschool STEM program, titled Studio STEM, was implemented to foster motivation and engagement in STEM topics and activities. The purpose of this study is twofold: (a) to investigate how Studio STEM affected students’ beliefs about science and whether these beliefs differed from their peers who did not participate in the program, and (b) to examine a case study of one Studio STEM implementation to investigate elements of the curriculum that motivated students to engage in the program. Results: After completing two Studio STEM programs, participants’ ratings of their values for science and science competence were higher than those of non participants. In addition, the Studio STEM participants’ motivational beliefs about science and intentions to pursue a college degree were more resilient over time than their peers. We also found that students could be motivated in a voluntary afterschool program (Studio STEM) in which they grappled with STEM concepts and activities, and could verbalize specific program elements that motivated them. Conclusions: Through this study, we found that students could be motivated in Studio STEM and that the experience had a positive impact on their perceptions about science as a field. Importantly, Studio STEM appeared to halt the decline in these students’ motivational beliefs about science that typically occurs during the middle school years, indicating that after school programs can be one way to help students maintain their motivation in science. Studying the program features that the students found motivating may help educators to make connections between research and theory, and their classroom instruction to motivate their students.ECU Open Access Publishing Support Fun

Defining goal terms in development and health

YesMost academic literature uses ‘goal’, ‘aim’, ‘objective’ and ‘target’ as synonymous terms, but development and healthcare sectors define them as distinct etymological entities with varied and confusing interpretations. This review sought to constructively harmonise and differentiate each definition using a thematic framework. An inductive synthesis of definitions of the goal terms collected from 22 literature sources selected through a systematic internet search. Thirty-three specific definitions were reduced through serial category-building to single general definitions, and a set of theoretical themes generated as characteristic framework of each goal. Seven conceptual themes evolved from the synthesis, including the object, scope, hierarchy, timeframe, measurability, significance and expression of each goal term. Two terms, ‘goal’ and ‘aim’ are thematically similar as broad objects of immeasurable terminal impact, with a long-term timeframe. They signify organisational success, expressed as general purpose statements. ‘Objective’ is differentiated as a specific object of measurable intermediate outcome, with short-term timeframe. It signifies intervention effectiveness, expressed as a SMART statement. ‘Target’ is simply a specific quantifiable level of an indicator. Goal, aim, objective and target are conceptually different. New frameworks for writing complete goal statements are proposed, including impact and timeframe; and outcome, indicator and timeframe frameworks for aim and objective respectivel

Redating the earliest evidence of the mid-Holocene relative sea-level highstand in Australia and implications for global sea-level rise.

Reconstructing past sea levels can help constrain uncertainties surrounding the rate of change, magnitude, and impacts of the projected increase through the 21st century. Of significance is the mid-Holocene relative sea-level highstand in tectonically stable and remote (far-field) locations from major ice sheets. The east coast of Australia provides an excellent arena in which to investigate changes in relative sea level during the Holocene. Considerable debate surrounds both the peak level and timing of the east coast highstand. The southeast Australian site of Bulli Beach provides the earliest evidence for the establishment of a highstand in the Southern Hemisphere, although questions have been raised about the pretreatment and type of material that was radiocarbon dated for the development of the regional sea-level curve. Here we undertake a detailed morpho- and chronostratigraphic study at Bulli Beach to better constrain the timing of the Holocene highstand in eastern Australia. In contrast to wood and charcoal samples that may provide anomalously old ages, probably due to inbuilt age, we find that short-lived terrestrial plant macrofossils provide a robust chronological framework. Bayesian modelling of the ages provide improved dating of the earliest evidence for a highstand at 6,880±50 cal BP, approximately a millennium later than previously reported. Our results from Bulli now closely align with other sea-level reconstructions along the east coast of Australia, and provide evidence for a synchronous relative sea-level highstand that extends from the Gulf of Carpentaria to Tasmania. Our refined age appears to be coincident with major ice mass loss from Northern Hemisphere and Antarctic ice sheets, supporting previous studies that suggest these may have played a role in the relative sea-level highstand. Further work is now needed to investigate the environmental impacts of regional sea levels, and refine the timing of the subsequent sea-level fall in the Holocene and its influence on coastal evolution