The roughness of cell membrane is a very interesting indicator of cell's health state. Atomic Force Microscopy allows us to investigate the roughness of cell membrane in great detail, but the ...obtained roughness value is scale-dependent, i.e. it strongly depends on measurement parameters, as scanning area and step size. The scale-dependence of the roughness value can be reduced by means of data filtration techniques, that are not standardized at nanometric scale, especially as far as biological data are concerned. In this work, a new method, based on the changes of values of some roughness parameter (root mean square roughness and skewness) as a function of filtration frequencies, has been implemented to optimize data filtering procedure in the calculation of cell membrane roughness. In this way, a root mean square roughness value independent of cell shape, membrane micro-irregularities and measurement parameters can be obtained. Moreover, different filtration frequencies selected with this method allow us to discriminate different surface regimes (nominal form, waviness and roughness) belonging to the raw cell profile, each one related to different features of the cell surface.
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► The AFM technique allows us to determine cell membrane roughness value with great detail. ► The filtered roughness values are independent on the scanning scale sizes. ► Filtered roughness parameters characterize the different-size surface features.
The worldwide spread of COVID-19 has upset the normality of Italian daily life, forcing population to social distancing and self-isolation. Since the containment precautions also concern ...sport-related activities, home workout remained the only possibility to play sports and stay active during the pandemic.
The present study aimed to examine changes in the physical activity levels during self-quarantine in Italy, and the impact of exercise on psychological health.
A total of 2974 Italian subjects has completed an online survey, but only 2524 subjects resulted eligible for this study. The questionnaire measured the total weekly physical activity energy expenditure before and during quarantine (i.e. the sum of walking, moderate-intensity physical activities, and vigorous-intensity physical activities) in Metabolic Equivalent Task minutes per week (MET–min/wk) using an adapted version of International Physical Activity Questionnaire and their psychological well-being using the Psychological General Well Being Index. Of the 2524 Italian subjects included in the study, 1426 were females (56.4%) and 1098 males (43.6%). Total physical activity significantly decreased between before and during COVID-19 pandemic (Mean: 2429 vs. 1577 MET–min/wk, ∗∗∗∗p < 0.0001), in all age groups and especially in men (Female, mean: 1994 vs. 1443 MET–min/wk, ∗∗∗∗p < 0.0001; Male, mean: 2998 vs. 1754 MET–min/wk, ∗∗∗∗p < 0.0001). Furthermore, a significant positive correlation was found between the variation of physical activity and mental well-being (r = 0.07541, ∗∗∗p = 0.0002), suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population.
Based on this scientific evidence, maintaining a regular exercise routine is a key strategy for physical and mental health during a forced rest period like the current coronavirus emergency.
Exercise; Epidemiology; Public health; Psychology; COVID-19; Pandemic; Quarantine; Physical activity; Home based exercise; IPAQ-SF; Psychological well-being; PGWBI.
In humans, the adaptive immune system uses the exchange of information between cells to detect and eliminate foreign or damaged cells; however, the removal of unwanted cells does not always require ...an adaptive immune system
. For example, cell selection in Drosophila uses a cell selection mechanism based on 'fitness fingerprints', which allow it to delay ageing
, prevent developmental malformations
and replace old tissues during regeneration
. At the molecular level, these fitness fingerprints consist of combinations of Flower membrane proteins
. Proteins that indicate reduced fitness are called Flower-Lose, because they are expressed in cells marked to be eliminated
. However, the presence of Flower-Lose isoforms at a cell's membrane does not always lead to elimination, because if neighbouring cells have similar levels of Lose proteins, the cell will not be killed
. Humans could benefit from the capability to recognize unfit cells, because accumulation of damaged but viable cells during development and ageing causes organ dysfunction and disease
. However, in Drosophila this mechanism is hijacked by premalignant cells to gain a competitive growth advantage
. This would be undesirable for humans because it might make tumours more aggressive
. It is unknown whether a similar mechanism of cell-fitness comparison is present in humans. Here we show that two human Flower isoforms (hFWE1 and hFWE3) behave as Flower-Lose proteins, whereas the other two isoforms (hFWE2 and hFWE4) behave as Flower-Win proteins. The latter give cells a competitive advantage over cells expressing Lose isoforms, but Lose-expressing cells are not eliminated if their neighbours express similar levels of Lose isoforms; these proteins therefore act as fitness fingerprints. Moreover, human cancer cells show increased Win isoform expression and proliferate in the presence of Lose-expressing stroma, which confers a competitive growth advantage on the cancer cells. Inhibition of the expression of Flower proteins reduces tumour growth and metastasis, and induces sensitivity to chemotherapy. Our results show that ancient mechanisms of cell recognition and selection are active in humans and affect oncogenic growth.
Intermittent fasting (IF) is an increasingly popular dietary approach used for weight loss and overall health. While there is an increasing body of evidence demonstrating beneficial effects of IF on ...blood lipids and other health outcomes in the overweight and obese, limited data are available about the effect of IF in athletes. Thus, the present study sought to investigate the effects of a modified IF protocol (i.e. time-restricted feeding) during resistance training in healthy resistance-trained males.
Thirty-four resistance-trained males were randomly assigned to time-restricted feeding (TRF) or normal diet group (ND). TRF subjects consumed 100 % of their energy needs in an 8-h period of time each day, with their caloric intake divided into three meals consumed at 1 p.m., 4 p.m., and 8 p.m. The remaining 16 h per 24-h period made up the fasting period. Subjects in the ND group consumed 100 % of their energy needs divided into three meals consumed at 8 a.m., 1 p.m., and 8 p.m. Groups were matched for kilocalories consumed and macronutrient distribution (TRF 2826 ± 412.3 kcal/day, carbohydrates 53.2 ± 1.4 %, fat 24.7 ± 3.1 %, protein 22.1 ± 2.6 %, ND 3007 ± 444.7 kcal/day, carbohydrates 54.7 ± 2.2 %, fat 23.9 ± 3.5 %, protein 21.4 ± 1.8). Subjects were tested before and after 8 weeks of the assigned diet and standardized resistance training program. Fat mass and fat-free mass were assessed by dual-energy x-ray absorptiometry and muscle area of the thigh and arm were measured using an anthropometric system. Total and free testosterone, insulin-like growth factor 1, blood glucose, insulin, adiponectin, leptin, triiodothyronine, thyroid stimulating hormone, interleukin-6, interleukin-1β, tumor necrosis factor α, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. Bench press and leg press maximal strength, resting energy expenditure, and respiratory ratio were also tested.
After 8 weeks, the 2 Way ANOVA (Time * Diet interaction) showed a decrease in fat mass in TRF compared to ND (p = 0.0448), while fat-free mass, muscle area of the arm and thigh, and maximal strength were maintained in both groups. Testosterone and insulin-like growth factor 1 decreased significantly in TRF, with no changes in ND (p = 0.0476; p = 0.0397). Adiponectin increased (p = 0.0000) in TRF while total leptin decreased (p = 0.0001), although not when adjusted for fat mass. Triiodothyronine decreased in TRF, but no significant changes were detected in thyroid-stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, or triglycerides. Resting energy expenditure was unchanged, but a significant decrease in respiratory ratio was observed in the TRF group.
Our results suggest that an intermittent fasting program in which all calories are consumed in an 8-h window each day, in conjunction with resistance training, could improve some health-related biomarkers, decrease fat mass, and maintain muscle mass in resistance-trained males.
In the context of a public health physical fitness (PF) examination in adolescence, a countermovement jump (CMJ) and a squat jump (SJ) are two vertical jump (VJ) tests widely used to evaluate lower ...limb muscle strength and power, respectively. The main criticism of both the CMJ and SJ test is the lack of test standardization. Therefore, the objectives of this review are: (a) to gather information about both jumps; (b) to investigate whether it is possible to identify common procedures referred to in the CMJ and SJ technical execution, and (c) to design standard operating procedures (SOPs) to promote CMJ and SJ standardization in an adolescent population aged 12-18 years.
The review partially adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Due to growing attention in monitoring physical health through field tests in recent years, articles were collected using the PubMed, Web of Science, and Scopus databases from January 2009 to July 2019. Original articles in which CMJ or SJ were used to assess the muscular strength in adolescents were eligible for further analysis. Articles written in English was imposed as a limit.
A total of 117 studies met the inclusion criteria. The description of the CMJ and SJ test procedures was different within the literature, with discrepancies in the jump technique, number of jumps, and measurement devices used.
A lack of method standardization for both the CMJ and the SJ test was identified. Based on the literature, SOPs for both VJs were proposed. These are useful in the context of public health PF examination in adolescents, as they facilitate an unbiased comparison of jump performance data between published studies.
Cell Competition in Carcinogenesis Madan, Esha; Palma, António M; Vudatha, Vignesh ...
Cancer research (Chicago, Ill.),
12/2022, Letnik:
82, Številka:
24
Journal Article
Recenzirano
Odprti dostop
The majority of human cancers evolve over time through the stepwise accumulation of somatic mutations followed by clonal selection akin to Darwinian evolution. However, the in-depth mechanisms that ...govern clonal dynamics and selection remain elusive, particularly during the earliest stages of tissue transformation. Cell competition (CC), often referred to as 'survival of the fittest' at the cellular level, results in the elimination of less fit cells by their more fit neighbors supporting optimal organism health and function. Alternatively, CC may allow an uncontrolled expansion of super-fit cancer cells to outcompete their less fit neighbors thereby fueling tumorigenesis. Recent research discussed herein highlights the various non-cell-autonomous principles, including interclonal competition and cancer microenvironment competition supporting the ability of a tumor to progress from the initial stages to tissue colonization. In addition, we extend current insights from CC-mediated clonal interactions and selection in normal tissues to better comprehend those factors that contribute to cancer development.
Development of multicellular organisms is orchestrated by persistent cell-cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals ...that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell-cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell-cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate
and
genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate
and
when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis.
HIF-transcribed p53 chaperones HIF-1α Madan, Esha; Parker, Taylor M; Pelham, Christopher J ...
Nucleic acids research,
11/2019, Letnik:
47, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Abstract
Chronic hypoxia is associated with a variety of physiological conditions such as rheumatoid arthritis, ischemia/reperfusion injury, stroke, diabetic vasculopathy, epilepsy and cancer. At the ...molecular level, hypoxia manifests its effects via activation of HIF-dependent transcription. On the other hand, an important transcription factor p53, which controls a myriad of biological functions, is rendered transcriptionally inactive under hypoxic conditions. p53 and HIF-1α are known to share a mysterious relationship and play an ambiguous role in the regulation of hypoxia-induced cellular changes. Here we demonstrate a novel pathway where HIF-1α transcriptionally upregulates both WT and MT p53 by binding to five response elements in p53 promoter. In hypoxic cells, this HIF-1α-induced p53 is transcriptionally inefficient but is abundantly available for protein-protein interactions. Further, both WT and MT p53 proteins bind and chaperone HIF-1α to stabilize its binding at its downstream DNA response elements. This p53-induced chaperoning of HIF-1α increases synthesis of HIF-regulated genes and thus the efficiency of hypoxia-induced molecular changes. This basic biology finding has important implications not only in the design of anti-cancer strategies but also for other physiological conditions where hypoxia results in disease manifestation.
Epidemiological clinical reports have shown an association between iodine excess with diabetes mellitus type 2 and higher blood glucose. However, the relationship between iodine, the pancreas, ...adipose tissue, and glucose transport is unclear. The goal of this study was to analyze the effect of iodine concentrations (in Lugol solution) on glucose transport, insulin secretion, and its cytotoxic effects in mature 3T3-L1 adipocytes and pancreatic beta-TC-6 cells.
Fibroblast 3T3-L1, mature adipocytes, and pancreatic beta-TC-6 cells were treated with 1 to 1000 µM of Lugol (molecular iodine dissolved in potassium iodide) for 30 min to 24 h for an MTT proliferation assay. Then, glucose uptake was measured with the fluorescent analog 2-NBDG, insulin receptor, Akt protein, p-Akt (ser-473), PPAR-gamma, and Glut4 by immunoblot; furthermore, insulin, alpha-amylase, oxidative stress, and caspase-3 activation were measured by colorimetric methods and the expression of markers of the apoptotic pathway at the RNAm level by real-time PCR.
Low concentrations of Lugol significantly induce insulin secretion and glucose uptake in pancreatic beta-TC-6 cells, and in adipose cells, iodine-induced glucose uptake depends on the serine-473 phosphorylation of Akt (p-Akt) and Glut4. Higher doses of Lugol lead to cell growth inhibition, oxidative stress, and cellular apoptosis dependent on PPAR-gamma, Bax mRNA expression, and caspase-3 activation in pancreatic beta-TC-6 cells.
Iodine could influence glucose metabolism in mature adipocytes and insulin secretion in pancreatic beta cells, but excessive levels may cause cytotoxic damage to pancreatic beta cells.
It is known in the literature that fundamental motor skill acquisition is strongly associated with the development of neuromotor, cognitive, social, and emotional aspects in childhood. Unfortunately, ...in Italy, the physical education teacher is not included in the school's core personnel, and it is very hard to find a specific physical education program (PEP) that could improve preschool children's motor and cognitive status. The aim of this study was to investigate whether the quotient of gross motor development (QGMD) and pre-literacy skills concerning visual analysis and spatial orientation abilities changed after 16 weeks of PEP (2 h/week) in preschool children. We conducted a school-based non-randomized pilot trial. It involved 119 preschool children, clustered in a control group CG,
= 29, body mass index (BMI): 16.90 ± 3.16 Kg/m
and an intervention group (IG,
= 90, BMI: 16.00 ± 1.75 kg/m
). Participants were assessed for literacy readiness, locomotor and object control skills before and after the experimental period. IG increased the locomotor, object-control skills and QGMD in response to PEP. As concerns the pre-literacy domain, no significant difference was found in visual analysis and spatial orientation skills between IG and CG groups. However, we detected improvements from baseline to post-test in IG children. In conclusion, this study contributes additional evidence suggesting how a PEP could affect not only motor skills, but also cognitive ones. Consistently with the growing research, interventions based on structured ludic-motor activities ensure health benefits for preschool children.
www.ClinicalTrials.gov, identifier NCT01274117.
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