Monitoring the effects of daily activities on the physiological responses of the body calls for wearable devices that can simultaneously track metabolic and haemodynamic parameters. Here we describe ...a non-invasive skin-worn device for the simultaneous monitoring of blood pressure and heart rate via ultrasonic transducers and of multiple biomarkers via electrochemical sensors. We optimized the integrated device so that it provides mechanical resiliency and flexibility while conforming to curved skin surfaces, and to ensure reliable sensing of glucose in interstitial fluid and of lactate, caffeine and alcohol in sweat, without crosstalk between the individual sensors. In human volunteers, the device captured physiological effects of food intake and exercise, in particular the production of glucose after food digestion, the consumption of glucose via glycolysis, and increases in blood pressure and heart rate compensating for oxygen depletion and lactate generation. Continuous and simultaneous acoustic and electrochemical sensing via integrated wearable devices should enrich the understanding of the body's response to daily activities, and could facilitate the early prediction of abnormal physiological changes.
The basidiomycete Ustilago maydis causes smut disease in maize, with large plant tumors being formed as the most prominent disease symptoms. During all steps of infection, U. maydis depends on a ...biotrophic interaction, which requires an efficient suppression of plant immunity. In a previous study, we identified the secreted effector protein Pit2, which is essential for maintenance of biotrophy and induction of tumors. Deletion mutants for pit2 successfully penetrate host cells but elicit various defense responses, which stops further fungal proliferation. We now show that Pit2 functions as an inhibitor of a set of apoplastic maize cysteine proteases, whose activity is directly linked with salicylic-acid-associated plant defenses. Consequently, protease inhibition by Pit2 is required for U. maydis virulence. Sequence comparisons with Pit2 orthologs from related smut fungi identified a conserved sequence motif. Mutation of this sequence caused loss of Pit2 function. Consequently, expression of the mutated protein in U. maydis could not restore virulence of the pit2 deletion mutant, indicating that the protease inhibition by Pit2 is essential for fungal virulence. Moreover, synthetic peptides of the conserved sequence motif showed full activity as protease inhibitor, which identifies this domain as a new, minimal protease inhibitor domain in plant-pathogenic fungi.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
L’électromyogramme de détection, complété par la stimulodétection, l’étude des ondes F et du réflexe H est l’examen neurophysiologique de référence afin de diagnostiquer les atteintes radiculaires et ...d’établir leur pronostic. Les potentiels évoqués somesthésiques, en explorant différents niveaux lésionnels jusqu’à l’entrée de l’influx dans la corne postérieure de la moelle et les projections corticales, vont compléter ces informations sur le plan fonctionnel. Leur intérêt diagnostique dans le cadre des atteintes radiculaires est plus discuté. Les potentiels évoqués dermatomaux, plus focaux, ainsi que les potentiels évoqués laser qui explorent les projections A delta ont un intérêt complémentaire, permettant une exploration métamérique plus précise, mais ne sont disponibles que dans peu de centres. Si le recours systématique aux potentiels évoqués somesthésiques dans les pathologies radiculaires compressives apparaît d’un intérêt limité, ils gardent toute leur indication en cas de séquelle douloureuse, avant de poser une indication de stimulation cordonale à visée antalgique et en examen de seconde ligne dans les pathologies inflammatoires, pour objectiver une atteinte radiculaire proximale. Nous proposons d’illustrer la place des potentiels évoqués dans ces différentes indications par plusieurs cas cliniques.
Toll-like receptors (TLRs) and macrophages play an important role in rheumatoid arthritis (RA). Currently, it is not clear whether inflammatory M1 or anti-inflammatory M2 predominate among the ...resident macrophages in the synovium. In the present study, we set out to investigate the impact of TLR stimulation on monocyte-derived M1 and M2 macrophage function and phenotype by mimicking the exposure to abundant TLR agonists as occurs in the context of RA. The response of macrophage subsets to TLR2 and TLR4 activation was evaluated on cluster of differentiation (CD) marker profile; cytokine secretion; gene expression; and NF-κB, interferon regulatory factors 3 and 7 (IRF3/7), and mitogen-activated protein kinase (MAPK) activation.
Human monocytes were isolated from peripheral blood of healthy individuals and patients with RA and differentiated into M1-like and M2-like macrophages by granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Cells were either (1) stimulated with TLR ligands Pam3 or lipopolysaccharide (LPS) or (2) classically activated via interferon (IFN)-γ/LPS. Cytokine production was measured by enzyme-linked immunosorbent assay, and gene expression was measured by qPCR. Cells were stained for CD markers and analyzed by fluorescence-activated cell sorting. NF-κB, IRF3/7, and MAPKs were detected by Western blotting.
Monocyte-derived macrophages of healthy donors (HD) or patients with RA displayed comparable subset-specific phenotypes upon exposure to TLR agonists. CD14 and CD163 marker expression on M2 macrophages did not change upon TLR2 and TLR4 engagement. By contrast, M2 gene markers HMOX1, FOLR2, and SLC40A1 were decreased. Importantly, M2 macrophages derived from HD or patients with RA showed both a decreased ratio of interleukin (IL)-10/IL-6 and IL-10/IL-8 upon stimulation with TLR2 ligand Pam3 compared with TLR4 ligand LPS. Gene expression of TLR2 was increased, whereas TLR4 expression was decreased, by TLR ligand stimulation. MAPKs p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase were activated more strongly in M2 than in M1 macrophages by Pam3 or LPS.
We show that the anti-inflammatory activity of M2 macrophages is reduced in the presence of abundant TLR2 ligands without significant changes in cell surface markers. Thus, the classical M1/M2 paradigm based on cellular markers does not apply to macrophage functions in inflammatory conditions such as RA.
Macrophages are conventionally classified as pro-inflammatory (M1) and anti-inflammatory (M2) functional types. There is evidence for a predominance of macrophages with an inflammatory phenotype (M1) ...in the rheumatoid arthritis (RA) synovium. MicroRNAs (miRs) play a pivotal role in regulating the inflammatory response in innate immune cells and are found at dysregulated levels in RA patients. Here we explored miRs that tune the inflammatory function of M2-macrophages.
Expression profiles of miR-221-3p and miR-155-5p were analyzed in clinical samples from RA, other inflammatory arthritis (OIA), osteoarthritis (OA), and healthy donors (HD) by qPCR.
generated macrophages were transfected with miR-mimics and inhibitors. Transcriptome profiling through RNA-sequencing was performed on M2-macrophages overexpressing miR-221-3p mimic with or without LPS treatment. Secretion of IL-6, IL-10, IL-12, IL-8, and CXCL13 was measured in M1- and M2-macrophages upon TLR2/TLR3/TLR4-stimulation using ELISA. Inflammatory pathways including NF-κB, IRF3, MAPKs, and JAK3/STAT3 were evaluated by immunoblotting. Direct target interaction of miR-221-3p and predicted target sites in 3'UTR of JAK3 were examined by luciferase reporter gene assay.
miR-221-3p in synovial tissue and fluid was increased in RA vs. OA or OIA. Endogenous expression levels of miR-221-3p and miR-155-5p were higher in M1- than M2-macrophages derived from RA patients or HD. TLR4-stimulation of M1- and M2-macrophages resulted in downregulation of miR-221-3p, but upregulation of miR-155-5p. M2-macrophages transfected with miR-221-3p mimics secreted less IL-10 and CXCL13 but more IL-6 and IL-8, exhibited downregulation of JAK3 protein and decreased pSTAT3 activation. JAK3 was identified as new direct target of miR-221-3p in macrophages. Co-transfection of miR-221-3p/miR-155-5p mimics in M2-macrophages increased M1-specific IL-12 secretion.
miR-221-3p acts as a regulator of TLR4-induced inflammatory M2-macrophage function by directly targeting JAK3. Dysregulated miR-221-3p expression, as seen in synovium of RA patients, leads to a diminished anti-inflammatory response and drives M2-macrophages to exhibit a M1-cytokine profile.
Immigration often results in changes in family dynamics, and within this process of dynamic relational adjustment youth can be conceptualised as contested sites of culture and associated ...intergenerational conflicts. This paper considers the experiences of migrant youth in Greater Western Sydney, New South Wales, Australia using conflict as a useful lens through which to view issues of migrant youth identity and their sense of social connectedness, belonging, and agency. The aim of this study was twofold: 1) to explore how migrant youth cope with acculturative stress and intergenerational conflicts, and 2) to better understand the systemic and family-related factors that facilitate positive settlement experiences for migrant youth.
A total of 14 focus group discussions, comprising 164 people, were carried out in Greater Western Sydney, New South Wales, Australia. These focus groups targeted newly arrived migrant parents and young adults (aged 18-24) of African, Burmese, Nepalese, Indian, Afghani, Bangladeshi and Iraqi backgrounds. Each focus group was 1.5 hours in duration and was conducted by a team of three people (an experienced facilitator, an accredited interpreter/bilingual worker, and a note taker). Data were collected using a standard interview schedule, and an accredited interpreter/bilingual worker asked the questions in the appropriate language and translated participant responses into English.
The findings highlight how youth in new migrant families become contested sites of culture as they try to balance integration into the new culture while maintaining their originating country's cultural values. Two themes and four subthemes emerged from the analysis: Intergenerational acculturation gap (loss of family capital and intergenerational conflicts); and factors that successfully protected positive family values while still allowing young people to integrate (the legal system that disarm authoritarian parenting practices and family rules; and parental use of children's increased knowledge of the new environment to navigate their new environment). Migrant families conceptualised family capital as the social solidarity, influence, and control governing obligations and expectations, intergenerational knowledge transmission and information flow, social norms, and cultural identity. The loss of family capital was characterised by children's refusal to associate with or meet family members, preferring to be alone in their rooms and private space. Migrant youth find themselves caught between and negotiating two cultures, with unwanted negative consequences at the family level in the form of intergenerational conflicts. The new found freedom among children and their rapid transition into the Australian society gives children an increased sense of agency, which in turn threatens parental authority, allowing children to exercise three forms of power: increased assertiveness due to legal protection of children against any corporal punishment; and English language fluency and greater understanding of the functioning of Australian social institutions.
Our findings suggest the need for an inter-generational approach to healthy family dynamics within migrant communities when dealing with youth negotiating the complexity and sensitivity of forging their cultural identity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Young people in Uganda face various sexual and reproductive health risks, especially those living in urban slums. The aim of this study was to examine factors associated with comprehensive categories ...of sexual and reproductive health, including sexual behaviours; sexual education and access to contraceptive services; family planning; prevention of STDs; sexual consent as a right; gender based violence; as well as HIV testing, counselling, disclosure and support.
The study was cross-sectional in design and was carried out in July 2014 in Makindye and Nakawa Divisions of Kampala City, Uganda. Using systematic random sampling, data were collected on 663 participants aged between 13 and 24 years in Kampala's urban slums.
Sixty two percent of participants reported having ever had sex and the mean age of sexual debut was 16 years (95%CI: 15.6, 16.4 years, range: 5-23 years). The odds of reporting ever having had sexual intercourse were higher among respondents living alone (OR: 2.75; 95%CI: 1.35, 5.61; p<0.01) than those living in a nuclear family. However, condom use was only 54%. The number of sexual partners in the last 12 months preceding the survey averaged 1.8 partners (95%CI: 1.7, 1.9; range 1-4) with 18.1% reporting an age gap of 10 years or older. More than three quarters (80.6%) of sexually active participants reported that their first sexual encounter was consensual, suggesting that most young people are choosing when they make their sexual debut. Low prevalence of willing first sexual intercourse was associated with younger age (OR = 0.48, 95%CI: 0.25, 0.90, p<0.05), having a disability (OR = 0.40, 95%CI: 0.16, 0.98, p<0.05), living with non-relatives (OR = 0.44, 95%CI: 0.16, 0.97, p<0.05), and being still at school (OR = 0.29, 95%CI: 0.12, 0.67, p<0.01). These results remained significant after adjusting for covariates, except for disability and the age of participants. The proportion of unwilling first sexual intercourse was significantly higher among women for persuasion (13.2% vs. 2.4%, p<0.001), being tricked (7.1% vs 2.9%, p<0.05) and being forced or raped (9.9% vs 4.4%, p<0.05) than men. A high level of sexual abuse emerged from the data with 34.3% affirming that it was alright for a boy to force a girl to have sex if he had feelings for her; 73.3% affirming that it was common for strangers and relatives to force young females to have sexual intercourse with them without consent; 26.3% indicating that it was sometimes justifiable for a boy to hit his girlfriend, as long as they loved each other.
This study has explored current sexual practice among young people in a specific part of urban Kampala. Young people's sexual and reproductive health remains a challenge in Uganda. To address these barriers, a comprehensive and harmonised sexual and reproductive health system that is youth friendly and takes into account local socio-cultural contexts is urgently needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
What is a good workday for a software developer? What is a typical workday? We seek to answer these two questions to learn how to make good days typical. Concretely, answering these questions will ...help to optimize development processes and select tools that increase job satisfaction and productivity. Our work adds to a large body of research on how software developers spend their time. We report the results from 5,971 responses of professional developers at Microsoft, who reflected about what made their workdays good and typical, and self-reported about how they spent their time on various activities at work. We developed conceptual frameworks to help define and characterize developer workdays from two new perspectives: good and typical. Our analysis confirms some findings in previous work, including the fact that developers actually spend little time on development and developers' aversion for meetings and interruptions. It also discovered new findings, such as that only 1.7 percent of survey responses mentioned emails as a reason for a bad workday, and that meetings and interruptions are only unproductive during development phases; during phases of planning, specification and release, they are common and constructive. One key finding is the importance of agency, developers' control over their workday and whether it goes as planned or is disrupted by external factors. We present actionable recommendations for researchers and managers to prioritize process and tool improvements that make good workdays typical. For instance, in light of our finding on the importance of agency, we recommend that, where possible, managers empower developers to choose their tools and tasks.
Abstract
Patients who died from COVID-19 often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. Although angiotensin-converting enzyme 2 (ACE2) is crucial for ...SARS-CoV-2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples from patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. Our systems biology approach offers a possible explanation for increased COVID-19 severity in patients with certain comorbidities.
A comprehensive transcriptome analysis of over 700 lung samples revealed that the expression of ACE2, which encodes the entry receptor of SARS-CoV-2, is increased in the lungs of patients with some of the comorbidities associated with severe COVID-19.
•A novel feature selection algorithm based on Bat Algorithm and Optimum-Path Forest.•A comparison against different transfer functions for agent’s positioning.•Several datasets have been employed to ...the experimental section.
Besides optimizing classifier predictive performance and addressing the curse of the dimensionality problem, feature selection techniques support a classification model as simple as possible. In this paper, we present a wrapper feature selection approach based on Bat Algorithm (BA) and Optimum-Path Forest (OPF), in which we model the problem of feature selection as an binary-based optimization technique, guided by BA using the OPF accuracy over a validating set as the fitness function to be maximized. Moreover, we present a methodology to better estimate the quality of the reduced feature set. Experiments conducted over six public datasets demonstrated that the proposed approach provides statistically significant more compact sets and, in some cases, it can indeed improve the classification effectiveness.
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