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"Noonan, J"
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When someone you know has depression : words to say and things to do
\"Following on the success of Managing Your Depression, Susan Noonan's new book is for family members and friends of people with depression or bipolar disorder. A certified peer specialist at McLean Hospital (a comprehensive psychiatric hospital affiliated with Harvard University), Susan draws on her experiences providing support and education for those living with or caring for a person who has a mood disorder. A family member who has a mood disorder affects the entire family. Further, family members and close friends are often the first to recognize the subtle changes and symptoms of depression--and they are also the people who provide daily support to their loved ones, often at great personal price. Caring for someone with a mood disorder differs from caring for someone with a physical medical disorder, in ways that complicate the caregiving role. A concise and practical guide to the daily management of depression and bipolar depression written for the caregiver, the book explains how to reinforce lessons the patient has been taught in therapy, how to role model resilience skills, and how caregivers can and must care for themselves. It describes effective communication strategies and advises how to find appropriate professional help. Its many tables and worksheets convey much needed information in an accessible way. References, Resources, and a Glossary complete the package. Overall the book helps readers navigate the depression or biopolar disorder of someone close to them, providing readers with words to say and things to do as they try to help someone change the course of a sometimes confounding and often disabling illness\"-- Provided by publisher.
Book
miR-449a targets HDAC-1 and induces growth arrest in prostate cancer
Histone deacetylases (HDACs) are frequently overexpressed in broad range of cancer types, where they alter cellular epigenetic programming to promote cell proliferation and survival. However, the mechanism by which HDACs become overexpressed in human cancers remains somewhat of a mystery. In this study, we investigated the expression and functional significance of miR-449a in prostate cancer cells. Using real-time PCR, we found that miR-449a is downregulated in prostate cancer tissues relative to patient-matched control tissue. Introduction of miR-449a into PC-3 prostate cancer cells resulted in cell-cycle arrest, apoptosis and a senescent-like phenotype.
In silico
analysis of 3′-UTR regions identified a number of genes involved in cell-cycle regulation as putative targets of miR-449a. Using a luciferase 3′-UTR reporter system, we established that
HDAC-1
(histone deacetylase 1), a gene that is frequently overexpressed in many types of cancer, is a direct target of miR-449a. Further, our data indicate that miR-449a regulates cell growth and viability in part by repressing the expression of HDAC-1 in prostate cancer cells. Our findings provide new insight into the function of miRNA in regulating HDAC expression in normal versus cancerous tissue.
Journal Article
MicroRNA-373 Induces Expression of Genes with Complementary Promoter Sequences
Recent studies have shown that microRNA (miRNA) regulates gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report new evidence in which miRNA may also function to induce gene expression. By scanning gene promoters in silico for sequences complementary to known miRNAs, we identified a putative miR-373 target site in the promoter of E-cadherin. Transfection of miR-373 and its precursor hairpin RNA (pre-miR-373) into PC-3 cells readily induced E-cadherin expression. Knockdown experiments confirmed that induction of E-cadherin by pre-miR-373 required the miRNA maturation protein Dicer. Further analysis revealed that cold-shock domain-containing protein C2 (CSDC2), which possesses a putative miR-373 target site within its promoter, was also readily induced in response to miR-373 and pre-miR-373. Furthermore, enrichment of RNA polymerase II was detected at both E-cadherin and CSDC2 promoters after miR-373 transfection. Mismatch mutations to miR-373 indicated that gene induction was specific to the miR-373 sequence. Transfection of promoter-specific dsRNAs revealed that the concurrent induction of E-cadherin and CSDC2 by miR-373 required the miRNA target sites in both promoters. In conclusion, we have identified a miRNA that targets promoter sequences and induces gene expression. These findings reveal a new mode by which miRNAs may regulate gene expression.
Journal Article
Efficacy of school-based interventions for improving muscular fitness outcomes in adolescent boys
Background: It has been reported that boys' and girls' physical activity (PA) levels decline throughout adolescence. Boys are at risk of physical inactivity during adolescence; however, in intervention research, they are an under-represented group relative to girls. It is suggested that the school environment may be central to developing interventions that support adolescents in meeting the current PA guidelines. The aim of this systematic review and meta-analysis was to investigate the efficacy of school-based physical activity interventions for improving muscular fitness (MF) in adolescent males. Methods: This systematic review and meta-analysis followed the preferred reporting systems for meta-analyses guidelines and was registered on PROSPERO (Registration number: CRD42018091023). Eligible studies were published in English within peer-reviewed articles. Searches were conducted in three databases, with an additional grey literature search in Google Scholar. Studies investigating MF outcomes were included. Results: There were 43 data sets identified across 11 studies, from seven countries. Overall methodological quality of the studies was moderate-to-strong. Interventions targeting MF evidenced a small-to-medium effect (g = 0.32, CI 0.17, 0.48, p ( 0.00). Subgroup analyses of MF delivery method resulted in small-to-medium effects: upper limb MF measures (g = 0.28, 95% CI - 0.02, 0.58, p = 0.07), lower limb MF measures (g = 0.28, 95% CI 0.09, 0.68, p = 0.03), combined MF activities (g = 0.24, 95% CI - 0.04 to 0.49, p = 0.05), plyometric activities (g = 0.39, 95% CI 0.09, 0.68, p = 0.01), body weight (g = 0.27, 95% CI - 0.10, 0.65, p = 0.15), and traditional MF methods (g = 0.43, 95% CI 0.09, 0.78, p = 0.01). Conclusions: School-based interventions which aimed to increase MF outcomes in adolescent boys demonstrated small-to-moderate effects. Traditional and plyometric methods of resistance training appear to be the most effective form of PA delivery in adolescent males. More quality research is required to assess the impact of MF delivered in the school environment to inform future intervention design. (Autor).
Journal Article
Write, draw, show, and tell: a child-centred dual methodology to explore perceptions of out-of-school physical activity
Background
Research to increase children’s physical activity and inform intervention design has, to date, largely underrepresented children’s voices. Further, research has been limited to singular qualitative methods that overlook children’s varied linguistic ability and interaction preference. The aim of this study was to use a novel combination of qualitative techniques to explore children’s current views, experiences and perceptions of out-of-school physical activity as well as offering formative opinion about future intervention design.
Methods
Write, draw, show and tell (WDST) groups were conducted with 35 children aged 10–11 years from 7 primary schools. Data were analysed through a deductive and inductive process, firstly using the Youth Physical Activity Promotion Model as a thematic framework, and then inductively to enable emergent themes to be further explored. Pen profiles were constructed representing key emergent themes.
Results
The WDST combination of qualitative techniques generated complimentary interconnected data which both confirmed and uncovered new insights into factors relevant to children’s out-of-school physical activity. Physical activity was most frequently associated with organised sports. Fun, enjoyment, competence, and physical activity provision were all important predictors of children’s out-of-school physical activity. Paradoxically, parents served as both significant enablers (i.e. encouragement) and barriers (i.e. restricting participation) to physical activity participation. Some of these key findings would have otherwise remained hidden when compared to more traditional singular methods based approaches.
Conclusions
Parents are in a unique position to promote health promoting behaviours serving as role models, physical activity gatekeepers and choice architects. Given the strong socialising effect parents have on children’s physical activity, family-based physical activity intervention may offer a promising alternative compared to traditional school-based approaches. Parents' qualitative input is important to supplement children’s voices and inform future family-based intervention design. The WDST method developed here is an inclusive, interactive and child-centred methodology which facilitates the exploration of a wide range of topics and enhances data credibility.
Journal Article
Non-coding RNAs turn up the heat: An emerging layer of novel regulators in the mammalian heat shock response
The field of non-coding RNA (ncRNA) has expanded over the last decade following the discoveries of several new classes of regulatory ncRNA. A growing amount of evidence now indicates that ncRNAs are involved even in the most fundamental of cellular processes. The heat shock response is no exception as ncRNAs are being identified as integral components of this process. Although this area of research is only in its infancy, this article focuses on several classes of regulatory ncRNA (i.e., miRNA, IncRNA, and circRNA), while summarizing their activities in mammalian heat shock. We also present an updated model integrating the traditional heat shock response with the activities of regulatory ncRNA. Our model expands on the mechanisms for efficient execution of the stress response, while offering a more comprehensive summary of the major regulators and responders in heat shock signaling. It is our hope that much of what is discussed herein may help researchers in integrating the fields of heat shock and ncRNA in mammals.
Journal Article
The carbon monoxide-rich interstellar comet 2I/Borisov
Interstellar comets offer direct samples of volatiles from distant protoplanetary disks. 2I/Borisov is the first notably active interstellar comet discovered in our Solar System
1
. Comets are condensed samples of the gas, ice and dust that were in a star’s protoplanetary disk during the formation of its planets, and inform our understanding on how chemical compositions and abundances vary with distance from the central star. Their orbital migration distributes volatiles
2
, organic material and prebiotic chemicals around their host system
3
. In our Solar System, hundreds of comets have been observed remotely, and a few have been studied up close by space missions
4
. However, knowledge of extrasolar comets has been limited to what could be gleaned from distant, unresolved observations of cometary regions around other stars, with only one detection of carbon monoxide
5
. Here we report that the coma of 2I/Borisov contains substantially more CO than H
2
O gas, with abundances of at least 173%, more than three times higher than previously measured for any comet in the inner (<2.5 au) Solar System
4
. Our ultraviolet Hubble Space Telescope observations of 2I/Borisov provide the first glimpse into the ice content and chemical composition of the protoplanetary disk of another star that is substantially different from our own.
Hubble Space Telescope data show that interstellar comet 2I/Borisov has an unusually high CO/H
2
O ratio—higher than any other comet that has been seen in the inner regions of our Solar System. This allows us to constrain the nature and location of the circumstellar region from which 2I/Borisov originated.
Journal Article
Movement ecology of vulnerable lowland tapirs between areas of varying human disturbance
Background
Animal movement is a key ecological process that is tightly coupled to local environmental conditions. While agriculture, urbanisation, and transportation infrastructure are critical to human socio-economic improvement, these have spurred substantial changes in animal movement across the globe with potential impacts on fitness and survival. Notably, however, human disturbance can have differential effects across species, and responses to human activities are thus largely taxa and context specific. As human disturbance is only expected to worsen over the next decade it is critical to better understand how species respond to human disturbance in order to develop effective, case-specific conservation strategies.
Methods
Here, we use an extensive telemetry dataset collected over 22 years to fill a critical knowledge gap in the movement ecology of lowland tapirs (
Tapirus terrestris
) across areas of varying human disturbance within three biomes in southern Brazil: the Pantanal, Cerrado, and Atlantic Forest.
Results
From these data we found that the mean home range size across all monitored tapirs was 8.31 km
2
(95% CI 6.53–10.42), with no evidence that home range sizes differed between sexes nor age groups. Interestingly, although the Atlantic Forest, Cerrado, and Pantanal vary substantially in habitat composition, levels of human disturbance, and tapir population densities, we found that lowland tapir movement behaviour and space use were consistent across all three biomes. Human disturbance also had no detectable effect on lowland tapir movement. Lowland tapirs living in the most altered habitats we monitored exhibited movement behaviour that was comparable to that of tapirs living in a near pristine environment.
Conclusions
Contrary to our expectations, although we observed individual variability in lowland tapir space use and movement, human impacts on the landscape also had no measurable effect on their movement. Lowland tapir movement behaviour thus appears to exhibit very little phenotypic plasticity in response to human disturbance. Crucially, the lack of any detectable response to anthropogenic disturbance suggests that human modified habitats risk being ecological traps for tapirs and this information should be factored into conservation actions and species management aimed towards protecting lowland tapir populations.
Journal Article
Potassium dependent structural changes in the selectivity filter of HERG potassium channels
The fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to the role they play in regulating cardiac electrical activity. Here, we exploit the K
+
sensitivity of HERG inactivation to determine structures of both a conductive and non-conductive selectivity filter structure of HERG. The conductive state has a canonical cylindrical shaped selectivity filter. The non-conductive state is characterized by flipping of the selectivity filter valine backbone carbonyls to point away from the central axis. The side chain of S620 on the pore helix plays a central role in this process, by coordinating distinct sets of interactions in the conductive, non-conductive, and transition states. Our model represents a distinct mechanism by which ion channels fine tune their activity and could explain the uniquely rapid inactivation kinetics of HERG.
HERG channel inactivation is critical for normal heart rhythm. Authors determine structures of open and non-conducting states of HERG and identify a key role for S620 on the pore helix in coordinating transitions between open and inactivated states.
Journal Article