Telomerase is perceived as an immortality enzyme that might provide longevity to cells and whole organisms. Importantly, it is generally inactive in most somatic cells of healthy, adult men. ...Consequently, its substrates, i.e. telomeres, get shorter in most human cells with time. Noteworthy, cell life limitation due to telomere attrition during cell divisions, may not be as bad as it looks since longer cell life means longer exposition to harmful factors. Consequently, telomere length (attrition rate) becomes a factor that is responsible for inducing the signaling that leads to the elimination of cells that lived long enough to acquire severe damage. It seems that telomere length that depends on many different factors (including telomerase activity but also genetic factors, a hormonal profile that reflects sex, etc.) might become a useful marker of aging and exposition to stress. Thus in the current paper, we review the factors that affect telomere length in human cells focusing on sex that all together with different environmental and hormonal regulations as well as parental aspect affect telomere attrition rate. We also raise some limitations in the assessment of telomere length that hinders a trustworthy meta-analysis that might lead to acknowledgment of the real value of this parameter.
We examined an association between ghrelin, including its major isoforms, interleukin-6 (IL-6), body mass index (BMI), and mean arterial pressure (MAP) in male overweight patients with essential ...hypertension. Twenty hypertensive male patients with newly diagnosed essential hypertension (EH) before starting drug treatment and 22 age-matched healthy controls were enrolled in the study. Fasting total plasma ghrelin (TGhr), acyl ghrelin (AGhr), des-acyl ghrelin (DGhr) and IL-6 were determined and correlations between studied parameters were calculated. We found significantly lower total plasma ghrelin and higher plasma IL-6 in hypertensives when compared with the control. In patients with hypertension the negative correlations were found: between TGhr and BMI, DGhr and BMI, TGhr and MAP, and between DGhr and MAP. IL-6 positively correlated with BMI and MAP in hypertensive subjects. No correlations between all forms of ghrelin and IL-6 were noted. The changes in plasma ghrelin and IL-6 contribute independently to the elevated blood pressure in essential hypertension. Negative correlation of DGhr and MAP may suggest its hemodynamic involvement in regulation of blood pressure.
Autism spectrum disorder (ASD) is a broad diagnostic category describing a group of neurodevelopmental disorders which includes the autistic disorder. Failure to develop normal social relationships ...is a hallmark of autism. An inability to understand and cope with the social environment can occur regardless of IQ. One of the hypotheses of the appearance of ASD symptoms is associated with the theory of mind (TOM). ASD patients do not have the ability to attribute the full range of mental states (goal states and epistemic states) to themselves and to others. Eye-tracking allows for observation of early signs of TOM in ASD individuals, even before they are 1 year old, without the need of developed motor and language skills. This provides a window for looking at the very basics of mindreading - detecting intentionality and eyes in our environment. Studies show that ASD children fail to recognize biological motion, while being highly sensitive to physical contingency within the random movement. Their perception of faces seems disorganized and undirected, while object recognition is intact. Evidence suggests that this orientation of attention following gaze cues is diminished in ASD patients. Available data also show deficits in emotion recognition, that cannot be accounted for by impairments in face processing or visual modality alone. Such observations provide an insight into disturbances of information processing and offer an explanation for poor social functioning of ASD patients. When combined with other methods, Eye-tracking has the potential to reveal differences in processing information on a neural circuitry level. Thus, it may help in understanding the complexity of TOM mechanisms, and their role in social functioning.
The aim of the study is to compare data on the examined population of informal caregivers of people suffering from dementia with previous studies, as well as to assess the correlation between (i) ...depression determined on the basis of the Center for Epidemiologic Studies Depression Scale and (ii) caregiver burden measured by means of the Zarit Caregiver Burden Scale and some chosen parameters, such as total time devoted to caregiving, time of caregiving in hours per week and level of dementia severity measured by Global Deterioration Scale.
41 informal caregivers of people suffering from dementia from different backgrounds were evaluated using the Zarit Caregiver Burden Scale and the Center for Epidemiologic Studies Depression Scale. Demographic data about the time devoted to caregiving and the number of hours spend on caregiving weekly were gathered. The type of dementia and its stage were registered using the Global Deterioration Scale (GDS). With the aid of the Statistica StatSoft program, mutual correlations between the parameters were measured. The study was conducted within the framework of AAL UnderstAID--a platform that supports and helps to understand and assist caregivers in the care of a relative with dementia. The international project is co-founded by the Joint Programme Ambient Assisted Living (Grant code: ESR-aal 2012 5 107).
No significant correlations between the level of depression severity evaluated in caregivers and the total time of taking care of a demented person or time of caregiving in hours per week were observed. Similarly, no significant correlation between depression severity level and dementia severity level measured on the GDS scale were noted. There was also no significant correlation between Zarit Caregiver Burden Scale scores and the above-mentioned parameters.
The level of depression among caregivers do not depend on socio-demographic factors.
Mass spectrometry (MS)-based targeted lipidomics enables the robust quantification of selected lipids under various biological conditions but comprehensive software tools to support such analyses are ...lacking. Here we present LipidCreator, a software that fully supports targeted lipidomics assay development. LipidCreator offers a comprehensive framework to compute MS/MS fragment masses for over 60 lipid classes. LipidCreator provides all functionalities needed to define fragments, manage stable isotope labeling, optimize collision energy and generate in silico spectral libraries. We validate LipidCreator assays computationally and analytically and prove that it is capable to generate large targeted experiments to analyze blood and to dissect lipid-signaling pathways such as in human platelets.
The mitochondrial proteome comprises ~1000 (yeast)-1500 (human) different proteins, which are distributed into four different subcompartments. The sublocalization of these proteins within the ...organelle in most cases remains poorly defined. Here we describe an integrated approach combining stable isotope labeling, various protein enrichment and extraction strategies and quantitative mass spectrometry to produce a quantitative map of submitochondrial protein distribution in S. cerevisiae. This quantitative landscape enables a proteome-wide classification of 986 proteins into soluble, peripheral, and integral mitochondrial membrane proteins, and the assignment of 818 proteins into the four subcompartments: outer membrane, inner membrane, intermembrane space, or matrix. We also identified 206 proteins that were not previously annotated as localized to mitochondria. Furthermore, the protease Prd1, misannotated as intermembrane space protein, could be re-assigned and characterized as a presequence peptide degrading enzyme in the matrix.Protein localization plays an important role in the regulation of cellular physiology. Here the authors use an integrated proteomics approach to localize proteins to the mitochondria and provide a detailed map of their specific localization within the organelle.
Glaucoma is a leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is considered to be a predominant risk factor for primary open angle glaucoma, the most prevalent ...form of glaucoma. Although the etiological mechanisms responsible for increased IOP are not completely clear, impairment in aqueous humor (AH) drainage through the conventional or trabecular pathway is recognized to be a primary cause in glaucoma patients. Importantly, lowering of IOP has been demonstrated to reduce progression of vision loss and is a mainstay of treatment for all types of glaucoma. Currently however, there are limited therapeutic options available for lowering IOP especially as it relates to enhancement of AH outflow through the trabecular pathway. Towards addressing this challenge, bench and bedside research conducted over the course of the last decade and a half has identified the significance of inhibiting Rho kinase for lowering IOP. Rho kinase is a downstream effector of Rho GTPase signaling that regulates actomyosin dynamics in numerous cell types. Studies from several laboratories have demonstrated that inhibition of Rho kinase lowers IOP via relaxation of the trabecular meshwork which enhances AH outflow. By contrast, activation of Rho GTPase/Rho kinase signaling in the trabecular outflow pathway increases IOP by altering the contractile, cell adhesive and permeability barrier characteristics of the trabecular meshwork and Schlemm's canal tissues, and by influencing extracellular matrix production and fibrotic activity. This article, written in honor of the late David Epstein, MD, summarizes findings from both basic and clinical studies that have been instrumental for recognition of the importance of the Rho/Rho kinase signaling pathway in regulation of AH outflow, and in the development of Rho kinase inhibitors as promising IOP- lowering agents for glaucoma treatment.
•Rho/Rho kinase signaling plays a crucial role in homeostasis of AH outflow and IOP.•Dysregulation of Rho/Rho kinase signaling impairs AH outflow and leads to increased IOP.•Inhibition of Rho/Rho kinase signaling results in an ocular hypotensive response.•Inhibition of Rho/Rho kinase has neuroprotective effects.•Rho kinase inhibition exhibits anti-fibrotic effects in TM and Tenon fibroblasts.
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