Structural studies of hydrated samples of amorphous calcium phosphate and phosphoprotein nanoclusters

There are abundant examples of nanoclusters and inorganic microcrystals in biology. Their study under physiologically relevant conditions remains challenging due to their heterogeneity, instability, and the requirements of sample preparation. Advantages of using neutron diffraction and contrast matching to characterize biomaterials are highlighted in this article. We have applied these and complementary techniques to search for nanocrystals within clusters of calcium phosphate sequestered by bovine phosphopeptides, derived from osteopontin or casein. The neutron diffraction patterns show broad features that could be consistent with hexagonal hydroxyapatite crystallites smaller than 18.9 Å. Such nanocrystallites are, however, undetected by the complementary X-ray and FTIR data, collected on the same samples. The absence of a distinct diffraction pattern from the nanoclusters supports the generally accepted amorphous calcium phosphate structure of the mineral core

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction

The structures of enzymes catalyzing the reactions in central metabolic pathways are generally well conserved as are their catalytic mechanisms. The two types of 3-dehydroquinate dehydratase (DHQase) are therefore most unusual since they are unrelated at the sequence level and they utilize completely different mechanisms to catalyze the same overall reaction. The type I enzymes catalyze a cis-dehydration of 3-dehydroquinate via a covalent imine intermediate, while the type II enzymes catalyze a trans-dehydration via an enolate intermediate. Here we report the three-dimensional structures of a representative member of each type of biosynthetic DHQase.Both enzymes function as part of the shikimate pathway, which is essential in microorganisms and plants for the biosynthesis of aromatic compounds including folate, ubiquinone and the aromatic amino acids. An explanation for the presence of two different enzymes catalyzing the same reaction is presented. The absence of the shikimate pathway in animals makes it an attractive target for antimicrobial agents. The availability of these two structures opens the way for the design of highly specific enzyme inhibitors with potential importance as selective therapeutic agents

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

<b>Background</b> In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.<p></p> <b>Discussion</b> As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.<p></p> <b>Summary</b> Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts

Redefining the role of urban studies Early Career Academics in the post-COVID-19 university

We are an international collective of Early Career Academics (ECAs) who met throughout 2020 to explore the implications of COVID-19 on precarious academics. With this intervention, our aims are to voice commonly shared experiences and concerns and to reflect on the extent to which the pandemic offers opportunities to redefine Higher Education and research institutions, in a context of ongoing precarity and funding cuts. Specifically, we explore avenues to build solidarity across institutions and geographies, to ensure that the conduct of urban research, and support offered to ECAs, allows for more inclusivity, diversity, security and equitability. *The Urban ECA Collective emerged from a workshop series described in this article which intended to foster international solidarity among self-defined early career academics working within urban research.ITESO, A.C

Video game intervention for sexual risk reduction in minority adolescents : randomized controlled trial

BACKGROUND : Human immunodeficiency virus (HIV) disproportionately impacts minority youth. Interventions to decrease HIV sexual risk are needed. OBJECTIVE : We hypothesized that an engaging theory-based digital health intervention in the form of an interactive video game would improve sexual health outcomes in adolescents. METHODS : Participants aged 11 to 14 years from 12 community afterschool, school, and summer programs were randomized 1:1 to play up to 16 hours of an experimental video game or control video games over 6 weeks. Assessments were conducted at 6 weeks and at 3, 6, and 12 months. Primary outcome was delay of initiation of vaginal/anal intercourse. Secondary outcomes included sexual health attitudes, knowledge, and intentions. We examined outcomes by gender and age. RESULTS : A total of 333 participants were randomized to play the intervention (n=166) or control games (n=167): 295 (88.6%) were racial/ethnic minorities, 177 (53.2%) were boys, and the mean age was 12.9 (1.1) years. At 12 months, for the 258 (84.6%) participants with available data, 94.6% (122/129) in the intervention group versus 95.4% (123/129) in the control group delayed initiation of intercourse (relative risk=0.99, 95% CI 0.94-1.05, P=.77). Over 12 months, the intervention group demonstrated improved sexual health attitudes overall compared to the control group (least squares means [LS means] difference 0.37, 95% CI 0.01-0.72, P=.04). This improvement was observed in boys (LS means difference 0.67, P=.008), but not girls (LS means difference 0.06, P=.81), and in younger (LS means difference 0.71, P=.005), but not older participants (LS means difference 0.03, P=.92). The intervention group also demonstrated increased sexual health knowledge overall (LS means difference 1.13, 95% CI 0.64-1.61, P<.001), in girls (LS means difference 1.16, P=.001), boys (LS means difference 1.10, P=.001), younger (LS means difference 1.18, P=.001), and older (LS means difference=1.08, P=.002) participants. There were no differences in intentions to delay the initiation of intercourse between the two groups (LS means difference 0.10, P=.56). CONCLUSIONS : An interactive video game intervention improves sexual health attitudes and knowledge in minority adolescents for at least 12 months.Grant R01HD062080 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.http://www.jmir.orgam2017Psycholog