Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen

The survival of all microbes depends upon their ability to respond to environmental challenges. To establish infection, pathogens such as Candida albicans must mount effective stress responses to counter host defences while adapting to dynamic changes in nutrient status within host niches. Studies of C. albicans stress adaptation have generally been performed on glucose-grown cells, leaving the effects of alternative carbon sources upon stress resistance largely unexplored. We have shown that growth on alternative carbon sources, such as lactate, strongly influence the resistance of C. albicans to antifungal drugs, osmotic and cell wall stresses. Similar trends were observed in clinical isolates and other pathogenic Candida species. The increased stress resistance of C. albicans was not dependent on key stress (Hog1) and cell integrity (Mkc1) signalling pathways. Instead, increased stress resistance was promoted by major changes in the architecture and biophysical properties of the cell wall. Glucose- and lactate-grown cells displayed significant differences in cell wall mass, ultrastructure, elasticity and adhesion. Changes in carbon source also altered the virulence of C. albicans in models of systemic candidiasis and vaginitis, confirming the importance of alternative carbon sources within host niches during C. albicans infection

Brief mindfulness training enhances cognitive control in socioemotional contexts: Behavioral and neural evidence.

In social contexts, the dynamic nature of others' emotions places unique demands on attention and emotion regulation. Mindfulness, characterized by heightened and receptive moment-to-moment attending, may be well-suited to meet these demands. In particular, mindfulness may support more effective cognitive control in social situations via efficient deployment of top-down attention. To test this, a randomized controlled study examined effects of mindfulness training (MT) on behavioral and neural (event-related potentials [ERPs]) responses during an emotional go/no-go task that tested cognitive control in the context of emotional facial expressions that tend to elicit approach or avoidance behavior. Participants (N = 66) were randomly assigned to four brief (20 min) MT sessions or to structurally equivalent book learning control sessions. Relative to the control group, MT led to improved discrimination of facial expressions, as indexed by d-prime, as well as more efficient cognitive control, as indexed by response time and accuracy, and particularly for those evidencing poorer discrimination and cognitive control at baseline. MT also produced better conflict monitoring of behavioral goal-prepotent response tendencies, as indexed by larger No-Go N200 ERP amplitudes, and particularly so for those with smaller No-Go amplitude at baseline. Overall, findings are consistent with MT's potential to enhance deployment of early top-down attention to better meet the unique cognitive and emotional demands of socioemotional contexts, particularly for those with greater opportunity for change. Findings also suggest that early top-down attention deployment could be a cognitive mechanism correspondent to the present-oriented attention commonly used to explain regulatory benefits of mindfulness more broadly

Antibody responses to a Cryptosporidium parvum rCP15/60 vaccine

Cryptosporidium parvum is a zoonotic apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhoea in mammals worldwide. The organism is transmitted by ingestion of oocysts, which are shed in faeces, and completes its lifecycle in a single host.^1^ C. parvum is ubiquitous on dairy operations worldwide and is one of the leading causes of diarrhoea in calves on these farms.^2,3^ Here, for the first time, we describe the antibody response in a large group of cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine and the antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. Results of recent genotype surveys indicate that calves are the only major reservoir for C. parvum infections in humans.^4^ Human C. parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDs patients.^4^ Drug therapy against cryptosporidiosis is limited and not wholly efficacious in either humans or calves^5^, making development of an effective vaccine of paramount importance. To date, there is no commercially available effective vaccine against C. parvum, although passive immunization utilizing different zoite surface (glyco)proteins has showed promise.^6-9^ All cows we vaccinated produced an antibody response to the rCP15/60 vaccine and the magnitude of response correlated strongly with the subsequent level of antibody in their colostrum. All calves fed rCP15/60-immune colostrum showed a dose-dependent absorption of antibody. Our results demonstrate that vaccination of cows with rCP15/60 successfully induces antibodies against CP15/60 in their serum and colostrum and that these antibodies are then well absorbed when fed to neonatal calves. With further research, this C. parvum vaccine may well be a practical method of conferring passive protection to calves against cryptosporidiosis. Furthermore, a specifically targeted immune-colostrum may be valuable in protection and treatment of immunocompromised human patients with cryptosporidiosis

Residential school placements for children and young people with intellectual disabilities: their use and implications for adult social care

Out of area residential placements are associated with a range of poor outcomes for adults with intellectual disabilities and behaviours that challenge. In recent years there has been an increased drive to reduce such placements at as early a stage as possible. In this context the current review collates research and policy regarding use of residential schools for children and young people with intellectual disabilities and transition from these settings to adult services. The review highlights that relatively little is known about both use of, and transition from, residential schooling for children and young people with intellectual disabilities in the UK. Thirteen articles are identified: 7 examining the child or families’ experiences before placement, 4 examining outcomes during the placement, and 4 examining the process of transitioning from the placement and longer term outcomes. The methodological quality of articles was often limited. A lack of control groups, independent samples, or adequate sample sizes was particularly notable. Results are discussed in relation to factors that lead to a child’s placement in a residential school, children and families’ experiences of the placement, and outcomes following placement, including the transition process. A number of research priorities are highlighted based on gaps in the literature. Examples of alternative forms of support from clinical practice are provided, with recognition that a multi-element model is likely to be needed to provide high quality support to this group of young people

Quantitative analysis of regulatory flexibility under changing environmental conditions

The circadian clock controls 24-h rhythms in many biological processes, allowing appropriate timing of biological rhythms relative to dawn and dusk. Known clock circuits include multiple, interlocked feedback loops. Theory suggested that multiple loops contribute the flexibility for molecular rhythms to track multiple phases of the external cycle. Clear dawn- and dusk-tracking rhythms illustrate the flexibility of timing in Ipomoea nil. Molecular clock components in Arabidopsis thaliana showed complex, photoperiod-dependent regulation, which was analysed by comparison with three contrasting models. A simple, quantitative measure, Dusk Sensitivity, was introduced to compare the behaviour of clock models with varying loop complexity. Evening-expressed clock genes showed photoperiod-dependent dusk sensitivity, as predicted by the three-loop model, whereas the one- and two-loop models tracked dawn and dusk, respectively. Output genes for starch degradation achieved dusk-tracking expression through light regulation, rather than a dusk-tracking rhythm. Model analysis predicted which biochemical processes could be manipulated to extend dusk tracking. Our results reveal how an operating principle of biological regulators applies specifically to the plant circadian clock

Rational design of a (S)-selective-transaminase for asymmetric synthesis of (1S)-1-(1,1′-biphenyl-2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production of pure chiral amines. However, their catalytic efficiency toward bulky ketone substrates is greatly limited by steric hindrance and therefore presents a great challenge for industrial synthetic applications. We hereby report an example of rational transaminase enzyme design to help alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has no detectable catalytic activity toward the bulky aromatic ketone 2-acetylbiphenyl, we employed a rational design strategy combining in silico and in vitro studies to engineer the transaminase enzyme with a minimal number of mutations, achieving an high catalytic activity and high enantioselectivity. We found that, by introducing two mutations W57G/R415A, detectable enzyme activity was achieved. The rationally designed variant, W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rate by more than 1716-fold toward the bulky ketone under study, producing the corresponding enantiomeric pure (S)-amine (enantiomeric excess (ee) value of >99%)

Nest location preferences in zoo-housed orangutans

Nest building is an advanced and complex activity that wild orangutans engage in, yet they do so on a daily basis and with potential safety consequences. Like their wild counterparts, zoo-housed orangutans also make nests when given adequate materials, yet comparatively little research has documented the nesting habits of captive orangutans, including potential social and environmental influences of nest site selections. We documented the night nesting behavior of six adult orangutans housed at the Smithsonian's National Zoological Park (NZP), identifying preferred nest locations and proximity to conspecifics, comparing observed patterns to those reported in a nest behavior survey of orangutan facilities throughout the Association of Zoos and Aquariums (AZA). Survey results reveal that in addition to several universal patterns of nesting behaviors, as in the wild, the sharing of night nests by captive adult orangutans occurs only rarely (2 of 31 surveyed facilities). Data collected at NZP indicate that night nearest neighbor associations among nesting conspecifics may be a useful proxy for actual nearest neighbor data taken during daytime social interactions and may offer a more feasible alternative for determining social relationships among large groups of socially housed orangutans

Clustering of Dust-Obscured Galaxies at z ~ 2

We present the angular autocorrelation function of 2603 dust-obscured galaxies (DOGs) in the Bootes field of the NOAO Deep Wide-Field Survey. DOGs are red, obscured galaxies, defined as having R-[24] \ge 14 (F_24/F_R \ga 1000). Spectroscopy indicates that they are located at 1.5 \la z \la 2.5. We find strong clustering, with r_0 = 7.40^{+1.27}_{-0.84} Mpc/h for the full F_24 > 0.3 mJy sample. The clustering and space density of the DOGs are consistent with those of submillimeter galaxies, suggestive of a connection between these populations. We find evidence for luminosity-dependent clustering, with the correlation length increasing to r_0 = 12.97^{+4.26}_{-2.64} Mpc/h for brighter (F_24 > 0.6 mJy) DOGs. Bright DOGs also reside in richer environments than fainter ones, suggesting these subsamples may not be drawn from the same parent population. The clustering amplitudes imply average halo masses of log M = 12.2^{+0.3}_{-0.2} Msun for the full DOG sample, rising to log M = 13.0^{+0.4}_{-0.3} Msun for brighter DOGs. In a biased structure formation scenario, the full DOG sample will, on average, evolve into ~ 3 L* present-day galaxies, whereas the most luminous DOGs may evolve into brightest cluster galaxies.Comment: ApJL in press; 4 pages, 3 figures, 1 tabl

The Legal Needs of People Living with a Sexually Transmissible Infection or Blood-Borne Virus: Perspectives From a Sample of the Australian Sexual Health and Blood Borne Virus Workforce

Law and the legal environment are important factors in the epidemiology and prevention of sexually transmissible infections (STIs) and blood-borne viruses (BBVs). However, there has been no sustained effort to monitor the legal environment surrounding STIs and BBVs. This article presents the first data on the incidence and impacts of unmet legal needs for those affected by an STI or BBV in Australia using a survey administered to a sample of the Australian sexual health and BBV workforce. Migration, Housing, Money/Debt, Health (including complaints about health services), and Crime (accused/offender) were reported as the five most common legal need areas, with 60% of respondents describing these legal problems as generating a “severe” impact on health. These results indicate that unmet legal needs generate significant negative impacts in terms of individual health, on public health, and the ability to provide sustainable services such as testing and treatment to those facing unmet legal needs