79 research outputs found
A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.
In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix
Review of Person Re-identification Techniques
Person re-identification across different surveillance cameras with disjoint
fields of view has become one of the most interesting and challenging subjects
in the area of intelligent video surveillance. Although several methods have
been developed and proposed, certain limitations and unresolved issues remain.
In all of the existing re-identification approaches, feature vectors are
extracted from segmented still images or video frames. Different similarity or
dissimilarity measures have been applied to these vectors. Some methods have
used simple constant metrics, whereas others have utilised models to obtain
optimised metrics. Some have created models based on local colour or texture
information, and others have built models based on the gait of people. In
general, the main objective of all these approaches is to achieve a
higher-accuracy rate and lowercomputational costs. This study summarises
several developments in recent literature and discusses the various available
methods used in person re-identification. Specifically, their advantages and
disadvantages are mentioned and compared.Comment: Published 201
Mechanisms of Risk and Resilience in Military Families: Theoretical and Empirical Basis of a Family-Focused Resilience Enhancement Program
Recent studies have confirmed that repeated wartime deployment of a parent exacts a toll on military children and families and that the quality and functionality of familial relations is linked to force preservation and readiness. As a result, family-centered care has increasingly become a priority across the military health system. FOCUS (Families OverComing Under Stress), a family-centered, resilience-enhancing program developed by a team at UCLA and Harvard Schools of Medicine, is a primary initiative in this movement. In a large-scale implementation project initiated by the Bureau of Navy Medicine, FOCUS has been delivered to thousands of Navy, Marine, Navy Special Warfare, Army, and Air Force families since 2008. This article describes the theoretical and empirical foundation and rationale for FOCUS, which is rooted in a broad conception of family resilience. We review the literature on family resilience, noting that an important next step in building a clinically useful theory of family resilience is to move beyond developing broad βshopping listsβ of risk indicators by proposing specific mechanisms of risk and resilience. Based on the literature, we propose five primary risk mechanisms for military families and common negative βchain reactionβ pathways through which they undermine the resilience of families contending with wartime deployments and parental injury. In addition, we propose specific mechanisms that mobilize and enhance resilience in military families and that comprise central features of the FOCUS Program. We describe these resilience-enhancing mechanisms in detail, followed by a discussion of the ways in which evaluation data from the programβs first 2Β years of operation supports the proposed model and the specified mechanisms of action
Plasma and neutrophil fatty acid composition in advanced cancer patients and response to fish oil supplementation
Metabolic demand and altered supply of essential nutrients is poorly characterised in patients with advanced cancer. A possible imbalance or deficiency of essential fatty acids is suggested by reported beneficial effects of fish oil supplementation. To assess fatty acid status (composition of plasma and neutrophil phospholipids) in advanced cancer patients before and after 14 days of supplementation (12Β±1βgβdayβ1) with fish (eicosapentaenoic acid, and docosahexaenoic acid) or placebo (olive) oil. Blood was drawn from cancer patients experiencing weight loss of >5% body weight (n=23). Fatty acid composition of plasma phospholipids and the major phospholipid classes of isolated neutrophils were determined using gas liquid chromatography. At baseline, patients with advanced cancer exhibited low levels (<30% of normal values) of plasma phospholipids and constituent fatty acids and elevated 20β:β4 n-6 content in neutrophil phospholipids. High n-6/n-3 fatty acid ratios in neutrophil and plasma phospholipids were inversely related to body mass index. Fish oil supplementation raised eicosapentaenoic acid and docosahexaenoic acid content in plasma but not neutrophil phospholipids. 20β:β4 n-6 content was reduced in neutrophil PI following supplementation with fish oil. Change in body weight during the supplementation period related directly to increases in eicosapentaenoic acid in plasma. Advanced cancer patients have alterations in lipid metabolism potentially due to nutritional status and/or chemotherapy. Potential obstacles in fatty acid utilisation must be addressed in future trials aiming to improve outcomes using nutritional intervention with fish oils
Young off-axis volcanism along the ultraslow-spreading Southwest Indian Ridge
Author Posting. Β© The Authors, 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 3 (2010): 286-292, doi:10.1038/ngeo824.Mid-ocean ridge crustal accretion occurs continuously at all spreading rates
through a combination of magmatic and tectonic processes. Fast to slow spreading
ridges are largely built by adding magma to narrowly focused neovolcanic zones. In
contrast, ultraslow spreading ridge construction significantly relies on tectonic
accretion, which is characterized by thin volcanic crust, emplacement of mantle
peridotite directly to the seafloor, and unique seafloor fabrics with variable
segmentation patterns. While advances in remote imaging have enhanced our
observational understanding of crustal accretion at all spreading rates, temporal
information is required in order to quantitatively understand mid-ocean ridge
construction. However, temporal information does not exist for ultraslow spreading
environments. Here, we utilize U-series eruption ages to investigate crustal
accretion at an ultraslow spreading ridge for the first time. Unexpectedly young
eruption ages throughout the Southwest Indian ridge rift valley indicate that
neovolcanic activity is not confined to the spreading axis, and that magmatic crustal
accretion occurs over a wider zone than at faster spreading ridges. These
observations not only suggest that crustal accretion at ultraslow spreading ridges is
distinct from faster spreading ridges, but also that the magma transport
mechanisms may differ as a function of spreading rate.This work was supported by
the following NSF grants: NSF-OCE 0137325; NSF-OCE 060383800; and NSF-OCE
062705300
Altered Cerebellar-Cerebral Functional Connectivity in Geriatric Depression
Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (nβ=β11) and healthy controls (nβ=β18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus IIβvmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermisβposterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellumβvmPFC coupling may be related to cognitive function whereas cerebellumβPCC coupling may be related to emotion processing in geriatric depression
Functional Stability of Unliganded Envelope Glycoprotein Spikes among Isolates of Human Immunodeficiency Virus Type 1 (HIV-1)
The HIV-1 envelope glycoprotein (Env) spike is challenging to study at the molecular level, due in part to its genetic variability, structural heterogeneity and lability. However, the extent of lability in Env function, particularly for primary isolates across clades, has not been explored. Here, we probe stability of function for variant Envs of a range of isolates from chronic and acute infection, and from clades A, B and C, all on a constant virus backbone. Stability is elucidated in terms of the sensitivity of isolate infectivity to destabilizing conditions. A heat-gradient assay was used to determine T90 values, the temperature at which HIV-1 infectivity is decreased by 90% in 1 h, which ranged between βΌ40 to 49Β°C (nβ=β34). For select Envs (nβ=β10), the half-lives of infectivity decay at 37Β°C were also determined and these correlated significantly with the T90 (pβ=β0.029), though two βoutliersβ were identified. Specificity in functional Env stability was also evident. For example, Env variant HIV-1ADA was found to be labile to heat, 37Β°C decay, and guanidinium hydrochloride but not to urea or extremes of pH, when compared to its thermostable counterpart, HIV-1JR-CSF. Blue native PAGE analyses revealed that Env-dependent viral inactivation preceded complete dissociation of Env trimers. The viral membrane and membrane-proximal external region (MPER) of gp41 were also shown to be important for maintaining trimer stability at physiological temperature. Overall, our results indicate that primary HIV-1 Envs can have diverse sensitivities to functional inactivation in vitro, including at physiological temperature, and suggest that parameters of functional Env stability may be helpful in the study and optimization of native Env mimetics and vaccines
Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise
Corrected by: Erratum: Molecular Psychiatry (2016) 21, 1645β1645; doi:10.1038/mp.2016.57; published online 19 April 2016. Following publication of the above article, the authors noticed that the second authorβs name was presented incorrectly. The authorβs name should have appeared as M Fiatarone Singh. The publisher regrets the error.Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.Β±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.C Suo, M Fiatarone Singh, N Gates, W Wen, P Sachdev, H Brodaty, N Saigal, GC Wilson, J Meiklejohn, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Y Mavros, A Lampit, I Leung, and MJ Valenzuel
The effects of different sensory augmentation on weight-shifting balance exercises in Parkinsonβs disease and healthy elderly people: a proof-of-concept study
Differential roles of childhood adversities and stressful war experiences in the development of mental health symptoms in post-war adolescents in northern Uganda
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