Cell biology:Collagen secretion explained

Cells package proteins into vesicles for secretion to the extracellular milieu. A study shows that an enzyme modifies the packaging machinery to encapsulate unusually large proteins such as collagen

Bifidobacterial Dominance of the Gut in Early Life and Acquisition of Antimicrobial Resistance.

Bifidobacterium species are important commensals capable of dominating the infant gut microbiome, in part by producing acids that suppress growth of other taxa. Bifidobacterium species are less prone to possessing antimicrobial resistance (AMR) genes (ARGs) than other taxa that may colonize infants. Given that AMR is a growing public health crisis and ARGs are present in the gut microbiome of humans from early life, this study examines the correlation between a Bifidobacterium-dominated infant gut microbiome and AMR levels, measured by a culture-independent metagenomic approach both in early life and as infants become toddlers. In general, Bifidobacterium dominance is associated with a significant reduction in AMR in a Bangladeshi cohort, both in the number of acquired AMR genes present and in the abundance of AMR genes. However, by year 2, Bangladeshi infants had no significant differences in AMR related to their early-life Bifidobacterium levels. A generalized linear model including all infants in a previously published Swedish cohort found a significant negative association between log-transformed total AMR and Bifidobacterium levels, thus confirming the relationship between Bifidobacterium levels and AMR. In both cohorts, there was no change between early-life and later-life AMR abundance in high-Bifidobacterium infants but a significant reduction in AMR abundance in low-Bifidobacterium infants. These results support the hypothesis that early Bifidobacterium dominance of the infant gut microbiome may help reduce colonization by taxa containing ARGs.IMPORTANCE Infants are vulnerable to an array of infectious diseases, and as the gut microbiome may serve as a reservoir of AMR for pathogens, reducing the levels of AMR in infants is important to infant health. This study demonstrates that high levels of Bifidobacterium are associated with reduced levels of AMR in early life and suggests that probiotic interventions to increase infant Bifidobacterium levels have the potential to reduce AMR in infants. However, this effect is not sustained at year 2 of age in Bangladeshi infants, underscoring the need for more detailed studies of the biogeography and timing of infant AMR acquisition

The Use of Neuroscience and Psychological Measurement in England's Court of Protection

The 2005 Mental Capacity Act of England and Wales provides a description in statute law of a test determining if a person lacks “mental capacity” to take a particular decision and describes how the “best interests” of such a person should be determined. The Act established a new Court of Protection (CoP) to hear cases related to the Act and to rule on disputes over mental capacity. The court gathers a range of evidence, including reports from clinicians and experts. Human rights organisations and others have raised concerns about the nature of assessments for incapacity, including the role of brain investigations and psychometric tests. Aim: Describe use and interpretation of structured measures of psychological and brain function in CoP cases, to facilitate standardisation and improvement of practices, both in the courtroom and in non-legal settings. Method: Quantitative review of case law using all CoP judgments published until 2019. The judgments (n = 408) were read to generate a subset referring to structured testing (n = 50). These were then examined in detail to extract the nature of the measurements, circumstances of their use and features of interpretation by the court. Results: The 408 judgments contained 146 references to structured measurement of psychological or brain function, spread over 50 cases. 120/146 (82.2%) referred to “impairment of mind or brain,” with this being part of assessment for incapacity in 58/146 (39.7%). Measurement referred on 25/146 (17.1%) occasions to “functional decision-making abilities.” Structured measures were used most commonly by psychiatrists and psychologists. Psychological measurements comprised 66.4% of measures. Neuroimaging and electrophysiology were presented for diagnostic purposes only. A small number of behavioural measures were used for people with disorders of consciousness. When assessing incapacity, IQ and the Mini-MentalState Examination were the commonest measures. A standardised measure of mental capacity itself was employed just once. Judges rarely integrated measurements in their capacity determinations. Conclusion: Structured testing of brain and psychological function is used in limited ways in the Court of Protection. Whilst there are challenges in creating measures of capacity, we highlight an opportunity for the neuroscience community to improve objectivity in assessment, inside and outside the courtroom

On Security and reliability using cooperative transmissions in sensor networks

Cooperative transmissions have received recent attention and research papers have demonstrated their benefits for wireless networks. Such benefits include improving the reliability of links through diversity and/or increasing the reach of a link compared to a single transmitter transmitting to a single receiver (single-input single-output or SISO). In one form of cooperative transmissions, multiple nodes can act as virtual antenna elements and provide diversity gain or range improvement using space-time coding. In a multi-hop ad hoc or sensor network, a source node can make use of its neighbors as relays with itself to reach an intermediate node with greater reliability or at a larger distance than otherwise possible. The intermediate node will use its neighbors in a similar manner and this process continues till the destination is reached. Thus, for the same reliability of a link as SISO, the number of hops between a source and destination may be reduced using cooperative transmissions as each hop spans a larger distance. However, the presence of ma-licious or compromised nodes in the network impacts the benefits obtained with cooperative transmissions. Using more relays can increase the reach of a link, but if one or more relays are malicious, the transmission may fail. However, the relationships between the number of relays, the number of hops, and success probabilities are not trivial to determine. In this paper, we analyze this problem to understand the conditions under which cooperative transmissions fare better or worse than SISO transmissions. We take into consideration additional parameters such as the path-loss exponent and provide a framework that allows us to evaluate the conditions when cooperative transmissions are better than SISO transmissions. This analysis provides insights that can be employed before resorting to simulations or experimentation. © Springer Science+Business Media, LLC 2012

Using mouse transgenic and human stem cell technologies to model genetic mutations associated with schizophrenia and autism

Funding M.J. is funded by a Wellcome Trust Clinical Postdoctoral Research Fellowship, the Sackler Foundation and the RS Macdonald Trust. Acknowledgements We are grateful to the Royal Society for their support of the costs of attending the meeting ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists' convened by Amy Milton and Emily A. Holmes.Peer reviewedPublisher PD

Dynamical Belyi maps

We study the dynamical properties of a large class of rational maps with exactly three ramification points. By constructing families of such maps, we obtain infinitely many conservative maps of degree $d$; this answers a question of Silverman. Rather precise results on the reduction of these maps yield strong information on the rational dynamics.Comment: 21 page

Age-related decreases in global metacognition are independent of local metacognition and task performance

Metacognition refers to a capacity to reflect on and control other cognitive processes, commonly quantified as the extent to which confidence tracks objective performance. There is conflicting evidence about how “local” metacognition (monitoring of individual judgments) and “global” metacognition (estimates of self-performance) change across the lifespan. Additionally, the degree to which metacognition generalises across cognitive domains may itself change with age due to increased experience with one's own abilities. Using a gamified suite of performance-controlled memory and visual perception tasks, we measured local and global metacognition in an age-stratified sample of 304 healthy volunteers (18–83 years; N = 50 in each of 6 age groups). We calculated both local and global metrics of metacognition and quantified how and whether domain-generality changes with age. First-order task performance was stable across the age range. People's global self-performance estimates and local metacognitive bias decreased with age, indicating overall lower confidence in performance. In contrast, local metacognitive efficiency was spared in older age and remained correlated across the two cognitive domains. A stability of local metacognition indicates distinct mechanisms contributing to local and global metacognition. Our study reveals how local and global metacognition change across the lifespan and provide a benchmark against which disease-related changes in metacognition can be compared

A Primary Care Nurse-Delivered Walking Intervention in Older Adults: PACE (Pedometer Accelerometer Consultation Evaluation)-Lift Cluster Randomised Controlled Trial.

Background: Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity (MVPA) in ≥10-minute bouts, as advised in World Health Organization guidelines. Previous interventions have reported step-count increases, but not change in objectively measured MVPA in older people. We assessed whether a primary care nurse-delivered complex intervention increased objectively measured step-counts and MVPA. Methods and Findings: A total of 988 60–75 year olds, able to increase walking and randomly selected from three UK family practices, were invited to participate in a parallel two-arm cluster randomised trial; randomisation was by household. Two-hundred-ninety-eight people from 250 households were randomised between 2011 and 2012; 150 individuals to the intervention group, 148 to the usual care control group. Intervention participants received four primary care nurse physical activity (PA) consultations over 3 months, incorporating behaviour change techniques, pedometer step-count and accelerometer PA intensity feedback, and an individual PA diary and plan. Assessors were not blinded to group status, but statistical analyses were conducted blind. The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months, with change at 12 months a secondary outcome. Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts, accelerometer counts, and counts/minute at 3 months and 12 months. Other outcomes were adverse events, anthropometric measures, mood, and pain. Qualitative evaluations of intervention participants and practice nurses assessed the intervention’s acceptability. At 3 months, eight participants had withdrawn or were lost to follow-up, 280 (94%) individuals provided primary outcome data. At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group: by 1,037 (95% CI 513–1,560) steps/day and 63 (95% CI 40–87) minutes/week, respectively. At 12 months corresponding differences were 609 (95% CI 104–1,115) steps/day and 40 (95% CI 17–63) minutes/week. Counts and counts/minute showed similar effects to steps and MVPA. Adverse events, anthropometry, mood, and pain were similar in the two groups. Participants and practice nurses found the intervention acceptable and enjoyable. Conclusions : The PACE-Lift trial increased both step-counts and objectively measured MVPA in ≥10-minute bouts in 60–75 year olds at 3 and 12 months, with no effect on adverse events. To our knowledge, this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting. Trial Registration: Controlled-Trials.com ISRCTN4212256

The relationship between galaxy and dark matter halo size from z ∼ 3 to the present

We explore empirical constraints on the statistical relationship between the radial size of galaxies and the radius of their host dark matter haloes from z similar to 0.1-3 using the Galaxy And Mass Assembly (GAMA) and Cosmic Assembly Near Infrared Deep Extragalactic Legacy Survey (CANDELS) surveys. We map dark matter halo mass to galaxy stellar mass using relationships from abundance matching, applied to the Bolshoi-Planck dissipationless N-body simulation. We define SRHR equivalent to r(e)/R-h as the ratio of galaxy radius to halo virial radius, and SRHR lambda equivalent to r(e)/(lambda R-h) as the ratio of galaxy radius to halo spin parameter times halo radius. At z similar to 0.1, we find an average value of SRHR similar or equal to 0.018 and SRHR. similar or equal to 0.5 with very little dependence on stellar mass. Stellar radius-halo radius (SRHR) and SRHR lambda have a weak dependence on cosmic time since z similar to 3. SRHR shows a mild decrease over cosmic time for low-mass galaxies, but increases slightly or does not evolve formoremassive galaxies. We find hints that at high redshift (z similar to 2-3), SRHR. is lower for more massive galaxies, while it shows no significant dependence on stellar mass at z less than or similar to 0.5. We find that for both the GAMA and CANDELS samples, at all redshifts from z similar to 0.1-3, the observed conditional size distribution in stellar mass bins is remarkably similar to the conditional distribution of lambda R-h. We discuss the physical interpretation and implications of these results