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The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer's disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.
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The study aimed to assess household and child dietary diversity in Southern Somalia by identifying determinants of adequate dietary diversity in three internally displaced person (IDP) camps in Baidoa, Dayniile and Dharkanley. A total of 1655 female main caregivers with 2370 children (6-59 months old) were included. Data on household dietary diversity score and child dietary diversity score indicators were collected from all households. The questionnaire was read face-to-face to the female main caregivers. Multivariate logistic regression analysis was performed to identify factors associated with adequate dietary diversity, which was defined as the consumption of at least four food groups within 24 h before the survey. The proportion of households achieving adequate HDDS was high in all locations 95.8%, 96.9% and 89.0% in Baidoa, Dharkanley and Dayniile, respectively, and the total adequate household dietary diversity score (AHDDS) was 95.6%. The proportion of adequate child dietary diversity score (ACDDS) was achieved in 63.5%, 8.5% and 38.3%. The main factors associated with AHDDS were larger household size, greater wealth, attendance of antenatal care (ANC) and joint decision-making between husband and wife, while factors associated with ACDDS included ANC attendance, age, the consumption of ready-to-use therapeutic food and deworming tablets. These findings can guide future programmes and policies aimed at improving maternal and child nutrition in IDP camps in Somalia. By tackling these diverse factors, a promising pathway emerges to enhance the nutritional welfare of both households and children in IDP camps.
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BACKGROUND: The Democratic Republic of Congo (DRC) has one of the highest numbers of un and under-vaccinated children as well as number of refugees and internally displaced persons (IDPs) in the world. This study aims to determine and compare the proportion and characteristics of zero-dose (ZD) and under-vaccinated (UV) children among refugees and IDPs in the DRC, as well as the reasons for incomplete vaccination schedules. METHODS: Data from a rolling vaccination coverage survey conducted from September 10, 2022, to July 03, 2023, among refugees and IDPs in 12 provinces of the DRC. ZD was defined as a child aged 12-23 months who had not received any dose of pentavalent vaccine DTP-Hib-Hep B (by card or recall) and UV as a child who had not received the third dose of pentavalent vaccine. The proportions of non and under-vaccination and the associated factors using a logistic regression model are presented for ZD and UV children. The reasons for non-vaccination of these children are described using the WHO-Immunization behavioral and social-drivers-conceptual framework and compared using Pearson's Chi2 test. RESULTS: Of 692 children aged 12 to 23 months included in the analysis, 9.3% (95% CI: 7.2-11.7%) were ZD and 40.9% (95% CI: 95%: 37.2-44.6%) UV. The Penta1/Penta3 drop-out rate was 34.9%. After adjustment, ZD children had a significant history of home or road birth. And UV children were significantly associated with mothers/caregivers being under 40, uneducated, farmers, ranchers, employed, rural residents, as well as with home or road births. Reasons linked to people's perceptions and feelings were cited much more often for ZD (50.0%) than for UV (38.3%). Those related to social reasons were cited much more often by ZD (40.6%) than by UV (35.7%). Reasons related to "programmatic and practical issues" were cited less for ZD (90.5%) than for UV (97.1%). CONCLUSIONS: ZD and UV children represent significant proportions in refugee and IDPs sites in the DRC. However, the proportion of ZD is less than for the entire country, while the proportion of UV is comparable, reflected in a very high drop-out rate. Similarly to studies in the general population in DRC, the reasons for ZD children were mainly linked to challenges in caregiver motivation to vaccinate, while for UV children, they were more often linked to pro-grammatic and practical problems of the health system.
The Democratic Republic of Congo (DRC) has one of the highest numbers of un and under-vaccinated children as well as number of refugees and internally displaced persons (IDPs) in the world. This study aims to determine and compare the proportion and characteristics of zero-dose (ZD) and under-vaccinated (UV) children among refugees and IDPs in the DRC, as well as the reasons for incomplete vaccination schedules. Data from a rolling vaccination coverage survey conducted from September 10, 2022, to July 03, 2023, among refugees and IDPs in 12 provinces of the DRC. ZD was defined as a child aged 1223 months who had not received any dose of pentavalent vaccine DTP-Hib-Hep B (by card or recall) and UV as a child who had not received the third dose of pentavalent vaccine. The proportions of non and under-vaccination, the associated factors and reasons for non-vaccination are presented for ZD and UV children. Of 692 children aged 12 to 23 months included in the analysis, 9.3% (95% CI: 7.211.7%) were ZD and 40.9% (95% CI: 95%: 37.244.6%) UV. The Penta1/Penta3 drop-out rate was 34.9%. After adjustment, ZD children had a significant history of home or road birth. And UV children were significantly associated with mothers/caregivers being under 40, uneducated, farmers, ranchers, employed, rural residents, as well as with home or road births. Reasons linked to people's perceptions and feelings were cited much more often for ZD (50.0%) than for UV (38.3%). Those related to social reasons were cited much more often by ZD (40.6%) than by UV (35.7%). Reasons related to "programmatic and practical issues" were cited less for ZD (90.5%) than for UV (97.1%). ZD and UV children represent significant proportions in refugee and IDPs sites in the DRC. However, the proportion of ZD is less than for the entire country, while the proportion of UV is comparable, reflected in a very high drop-out rate. Similarly to studies in the general population in DRC, the reasons for ZD children were mainly linked to challenges in caregiver motivation to vaccinate, while for UV children, they were more often linked to pro-grammatic and practical problems of the health system.
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Acknowledging that violent communal conflicts can lead to increased displacement and overcrowding in IDP camps, this study investigates the impact of such conflicts on internally displaced persons (IDPs) and their camps in Benue State, Nigeria, amid the COVID-19 pandemic. Employing a mixed-method approach, 386 IDPs and 20 stakeholders were purposively selected. Based on the research objectives, descriptive and inferential statistics were employed to analyze the research objectives. Employing logistics and multi-linear regressions, the data reveal that unregulated access to IDP camps resulted in overcrowding, straining resources like food and shelter. The study identifies economic losses and various challenges stemming from communal conflict and COVID-19, causing chaos, anxiety, and uncertainty in the IDP camps. These findings highlight the urgent need for ongoing humanitarian assistance to alleviate the precarious conditions faced by IDPs and their camps nationwide and recommend that the IDPs camps across the country need constant humanitarian aid to mitigate the various precarious conditions in the camps.
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PA28γ is a proteasomal interactor whose main and most known function is to stimulate the hydrolytic activity of the 20 S proteasome independently of ubiquitin and ATP. Unlike its two paralogues, PA28α and PA28ß, PA28γ is largely present in the nuclear compartment and plays pivotal functions in important pathways such as cellular division, apoptosis, neoplastic transformation, chromatin structure and organization, fertility, lipid metabolism, and DNA repair mechanisms. Although it is known that a substantial fraction of PA28γ is found in the cell in a free form (i.e. not associated with 20 S), almost all of the studies so far have focused on its ability to modulate proteasomal enzymatic activities. In this respect, the ability of PA28γ to strongly stimulate degradation of proteins, especially if intrinsically disordered and therefore devoid of three-dimensional tightly folded structure, appears to be the main molecular mechanism underlying its multiple biological effects. Initial studies, conducted more than 20 years ago, came to the conclusion that among the many biological functions of PA28γ, the immunological ones were rather limited and circumscribed. In this review, we focus on recent evidence showing that PA28γ fulfills significant functions in cell-mediated acquired immunity, with a particular role in attenuating MHC class I antigen presentation, especially in relation to neoplastic transformation and autoimmune diseases.
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The vitreous is a vital component of the eye, occupying a substantial portion of its volume and maintaining its structure. This study delves into the presence and significance of intrinsically disordered proteins (IDPs) within the vitreous, utilizing a dataset of 1240 vitreous proteins previously discovered in the vitreous proteome by Murthy et al.in five healthy subjects. The results indicate that 26.9 % of vitreous proteins are highly disordered, 68.8 % possess moderate disorder, and only 4.3 % are highly ordered. A complex interaction network among these proteins suggests their biological importance, and approximately 25 % may undergo liquid-liquid phase separation (LLPS). These findings offer new perspectives on the vitreous' molecular composition and behavior, potentially impacting our understanding of eye-related diseases, physiological changes such as vitreous syneresis. Further research is needed to translate these insights into clinical applications, although the intrinsic protein disorder and its association with LLPS appears to play a role in vitreous proteome function.
Subject(s)
Intrinsically Disordered Proteins , Proteome , Vitreous Body , Humans , Intrinsically Disordered Proteins/metabolism , Intrinsically Disordered Proteins/chemistry , Proteome/metabolism , Vitreous Body/metabolism , Eye Proteins/metabolismABSTRACT
Circadian clocks are composed of transcription-translation negative feedback loops that pace rhythms of gene expression to the diurnal cycle. In the filamentous fungus Neurospora crassa, the proteins Frequency (FRQ), the FRQ-interacting RNA helicase (FRH), and Casein-Kinase I (CK1) form the FFC complex that represses expression of genes activated by the white-collar complex (WCC). FRQ orchestrates key molecular interactions of the clock despite containing little predicted tertiary structure. Spin labeling and pulse-dipolar electron spin resonance spectroscopy provide domain-specific structural insights into the 989-residue intrinsically disordered FRQ and the FFC. FRQ contains a compact core that associates and organizes FRH and CK1 to coordinate their roles in WCC repression. FRQ phosphorylation increases conformational flexibility and alters oligomeric state, but the changes in structure and dynamics are non-uniform. Full-length FRQ undergoes liquid-liquid phase separation (LLPS) to sequester FRH and CK1 and influence CK1 enzymatic activity. Although FRQ phosphorylation favors LLPS, LLPS feeds back to reduce FRQ phosphorylation by CK1 at higher temperatures. Live imaging of Neurospora hyphae reveals FRQ foci characteristic of condensates near the nuclear periphery. Analogous clock repressor proteins in higher organisms share little position-specific sequence identity with FRQ; yet, they contain amino acid compositions that promote LLPS. Hence, condensate formation may be a conserved feature of eukaryotic clocks.
Natural oscillations known as circadian rhythms influence many processes in humans and other animals including sleep, eating, brain activity and body temperature. These rhythms allow us to anticipate and prepare for regular changes in our environment including day-night cycles and the temperature of our surroundings. Circadian clocks in animals, fungi and other 'eukaryotic' organisms rely on networks of components that repress their own production to generate oscillations in their levels in cells over the course of a 24-hour period. The components in animal and fungus circadian clocks are different but there are strong similarities in their properties and how the networks operate. As a result, a type of fungus known as Neurospora crassa is often used as a model to study how circadian rhythms work in animals. A central component in the N. crassa circadian clock is a protein known as Frequency (FRQ). It is a large protein that, unlike most proteins, lacks a well-defined, three-dimensional structure. Despite this, it is able to bind to and regulate other proteins to repress its own production. One of its protein partners known as CK1 attaches small tags known as phosphate groups to FRQ to set the length of the circadian rhythm. However, it remains unclear how FRQ interacts with its protein partners or what effect the phosphate groups have on its activity. To address this question, Tariq, Maurici et al. used biochemical approaches to study the structure of FRQ. The experiments revealed that it contains a compact core that is able to bind to CK1 and other protein partners. The way FRQ regulates its protein partners is unusual: it undergoes a chemical process known as liquid-liquid phase separation to sequester other circadian clock proteins and modulate their enzymatic activities. In this process, a solution containing molecules of FRQ separates into two distinct components (known as phases), one of which contains FRQ and its partners in a concentrated liquid-like mixture. Evidence for such mixtures has also been found in living fungal cells. Further experiments suggest that liquid-liquid phase separation of FRQ may allow the clock to compensate for changes in temperature to maintain a regular rhythm. The circadian clocks of animals and other organisms all have proteins that perform similar roles as FRQ and maintain sequence properties that promote liquid-liquid phase separation. Therefore, it is possible that liquid-liquid phase separation may be a common feature of circadian rhythms in nature.
Subject(s)
Circadian Clocks , Neurospora crassa , Circadian Clocks/genetics , Phosphorylation , Phase Separation , Fungal Proteins/metabolism , Neurospora crassa/genetics , Circadian Rhythm/geneticsABSTRACT
Aid relations in protracted displacement comprise a diversity of actors with different influence and involvement over time. Building on the case of Sri Lanka's northern Muslim's expulsion from the north of the country in 1990, this paper investigates the dynamic space of aid relations in their drawn-out internal displacement. The study draws on 38 key informant interviews and 10 focus-group discussions, conducted in Sri Lanka (Jaffna, Mannar, Puttalam, and Colombo) in 2022. The paper contributes new knowledge of the local dynamics of assistance in protracted displacement, by analysing the roles of a wide set of actors within this dynamic space of aid relations over time. The analysis incorporates angles and voices often overlooked in mainstream humanitarian studies, including internally displaced persons, hosts, and Middle Eastern aid funders. The study argues that a long-term perspective and a variety of voices provide foundations for more productive engagement with localisation in humanitarian action in protracted displacement crises.
Subject(s)
Focus Groups , Islam , Relief Work , Sri Lanka , Humans , Relief Work/organization & administration , Refugees/psychology , AltruismABSTRACT
Many proteins lack stable 3D structures. These intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered domains with intrinsically disordered protein regions (IDPRs) often carry out regulatory functions related to molecular recognition and signal transduction. IDPs/IDPRs constitute a substantial portion of the human proteome and are termed "the unfoldome". Herein, we probe the human breast cancer unfoldome and investigate relations between IDPs and key disease genes and pathways. We utilized bottom-up proteomics, MudPIT (Multidimensional Protein Identification Technology), to profile differentially expressed IDPs in human normal (MCF-10A) and breast cancer (BT-549) cell lines. Overall, we identified 2271 protein groups in the unfoldome of normal and cancer proteomes, with 148 IDPs found to be significantly differentially expressed in cancer cells. Further analysis produced annotations of 140 IDPs, which were then classified to GO (Gene Ontology) categories and pathways. In total, 65% (91 of 140) IDPs were related to various diseases, and 20% (28 of 140) mapped to cancer terms. A substantial portion of the differentially expressed IDPs contained disordered regions, confirmed by in silico characterization. Overall, our analyses suggest high levels of interactivity in the human cancer unfoldome and a prevalence of moderately and highly disordered proteins in the network.
Subject(s)
Breast Neoplasms , Intrinsically Disordered Proteins , Humans , Female , Protein Folding , Protein Conformation , Proteomics , Intrinsically Disordered Proteins/chemistry , Proteome/metabolism , Breast Neoplasms/geneticsABSTRACT
Intrinsically disordered proteins (IDPs) are characterized by their inability to adopt well-defined tertiary structures under physiological conditions. Nonetheless, they often play pivotal roles in the progression of various diseases, including cancer, neurodegenerative disorders, and cardiovascular ailments. Owing to their inherent dynamism, conventional drug design approaches based on structural considerations encounter substantial challenges when applied to IDPs. Consequently, the pursuit of therapeutic interventions directed towards IDPs presents a complex endeavor. While there are indeed existing methodologies for targeting IDPs, they are encumbered by noteworthy constrains. Hence, there exists an imminent imperative to investigate more efficacious and universally applicable strategies for modulating IDPs. Here, we present an overview of the latest advancements in the research pertaining to IDPs, along with the indirect regulation approach involving the modulation of IDP degradation through proteasome. By comprehending these advancements in research, novel insights can be generated to facilitate the development of new drugs targeted at addressing the accumulation of IDPs in diverse pathological conditions.
Subject(s)
Intrinsically Disordered Proteins , Neoplasms , Humans , Intrinsically Disordered Proteins/chemistry , Intrinsically Disordered Proteins/metabolism , Proteasome Endopeptidase Complex/metabolism , Drug Design , Neoplasms/metabolism , Protein ConformationABSTRACT
Global climate change has caused severe abiotic and biotic stresses, affecting plant growth and food security. The mechanical understanding of plant stress responses is critical for achieving sustainable agriculture. Intrinsically disordered proteins (IDPs) are a group of proteins without unique three-dimensional structures. The environmental sensitivity and structural flexibility of IDPs contribute to the growth and developmental plasticity for sessile plants to deal with environmental challenges. This article discusses the roles of various disordered proteins in plant stress tolerance and resistance, describes the current mechanistic insights into unstructured proteins such as the disorder-to-order transition for adopting secondary structures to interact with specific partners (i.e., cellular membranes, membrane proteins, metal ions, and DNA), and elucidates the roles of liquid-liquid phase separation driven by protein disorder in stress responses. By comparing IDP studies in animal systems, this article provides conceptual principles of plant protein disorder in stress adaptation, reveals the current research gaps, and advises on the future research direction. The highlighting of relevant unanswered questions in plant protein disorder research aims to encourage more studies on these emerging topics to understand the mechanisms of action behind their stress resistance phenotypes.
Subject(s)
Intrinsically Disordered Proteins , Animals , Plant Proteins , Membrane Proteins , Agriculture , Embryonic DevelopmentABSTRACT
BACKGROUND: Existing research demonstrates the association of shorter leukocyte telomere length with increased risk of age-related health outcomes including cardiovascular diseases. However, the direct causality of these relationships has not been definitively established. Cardiovascular aging at an organ level may be captured using image-derived phenotypes of cardiac anatomy and function. METHODS AND RESULTS: In the current study, we use 2-sample Mendelian randomization to assess the causal link between leukocyte telomere length and 54 cardiac magnetic resonance imaging measures representing structure and function across the 4 cardiac chambers. Genetically predicted shorter leukocyte telomere length was causally linked to smaller ventricular cavity sizes including left ventricular end-systolic volume, left ventricular end-diastolic volume, lower left ventricular mass, and pulmonary artery. The association with left ventricular mass (ß =0.217, Pfalse discovery rate=0.016) remained significant after multiple testing adjustment, whereas other associations were attenuated. CONCLUSIONS: Our findings support a causal role for shorter leukocyte telomere length and faster cardiac aging, with the most prominent relationship with left ventricular mass.
Subject(s)
Heart , Mendelian Randomization Analysis , Mendelian Randomization Analysis/methods , Leukocytes , Telomere/genetics , Genome-Wide Association StudyABSTRACT
High structural flexibility has been reported in the central region of BRCA1, which hinders the structural and functional evaluations of mutations identified in the domain. Additionally, the need to categorize variants of unknown significance (VUS) has increased due to the growth in the number of variants reported in clinical settings. Therefore, unraveling the disease-causing mechanism of VUS identified in different functional domains of BRCA1 is still challenging. The current study uses a multidisciplinary approach to assess the structural impact of BRCA1 Arg866Cys mutation discovered in the central domain of BRCA1. The structural alterations have been characterized using Circular-Dichroism spectroscopy, nano-DSF, and molecular-dynamics simulations. BRCA1 Arg866Cys mutant demonstrated more flexibility and lesser affinity to DNA than the wild-type protein. The BRCA1(759-1064) wild-type protein was shown to be a ßII-rich protein with an induced D-O transition in the presence of DNA and 2,2,2-Trifluoroethanol (TFE). The protein's alpha-helical composition did not significantly change in the presence of TFE, besides an increase in ß-turns and loops. Under Transmission Electron Microscopes (TEM), amyloid-like fibrils structure was detected for Arg866Cys mutant whereas the wild-type protein showed amorphous aggregates. An increased ThT fluorescence indicated ß-rich composition and aggregation-prone behaviour for BRCA1 wild-type protein, while the fluorescence intensity was significantly quenched in the Arg866Cys mutant. Furthermore, increased conformational flexibility in the Arg866Cys variant was observed by principal component analysis. This work aims to comprehend the inherently disordered region of BRCA1 as well as the impact of missense mutations on folding patterns and binding to DNA for functional aspects.
Subject(s)
BRCA1 Protein , Mutation, Missense , BRCA1 Protein/genetics , BRCA1 Protein/chemistry , BRCA1 Protein/metabolism , DNA , Molecular Dynamics Simulation , Mutation , Humans , FemaleABSTRACT
Preliminary studies have shown BRCA1 (170-1600) residues to be intrinsically disordered with unknown structural details. However, thousands of clinically reported variants have been identified in this central region of BRCA1. Therefore, we aimed to characterize h-BRCA1(260-553) to assess the structural basis for pathogenicity of two rare missense variants Ser282Leu, Gln356Arg identified from the Indian and Russian populations respectively. Small-angle X-ray scattering analysis revealed WT scores Rg -32 Å, Dmax -93 Å, and Rflex-51% which are partially disordered, whereas Ser282Leu variant displayed a higher degree of disorderedness and Gln356Arg was observed to be aggregated. WT protein also possesses an inherent propensity to undergo a disorder-to-order transition in the presence of cruciform DNA and 2,2,2-Trifluoroethanol (TFE). An increased alpha-helical pattern was observed with increasing concentration of TFE for the Gln356Arg mutant whereas Ser282Leu mutant showed significant differences only at the highest TFE concentration. Furthermore, higher thermal shift was observed for WT-DNA complex compared to the Gln356Arg and Ser282Leu protein-DNA complex. Moreover, mature amyloid-like fibrils were observed with 30 µM thioflavin T (ThT) at 37°C for Ser282Leu and Gln356Arg proteins while the WT protein exists in a protofibril state as observed by TEM. Gln356Arg formed higher-order aggregates with amyloidogenesis over time as monitored by ThT fluorescence. In addition, computational analyses confirmed larger conformational fluctuations for Ser282Leu and Gln356Arg mutants than for the WT. The global structural alterations caused by these variants provide a mechanistic approach for further classification of the variants of uncertain clinical significance in BRCA1 into amyloidogenic variants which may have a significant role in disease pathogenesis.
Subject(s)
Amyloid , Mutation, Missense , DNAABSTRACT
Regression analysis was carried out to examine the association between certain socio-demographic characteristics and substance use among internally displaced persons (IDPs). Using an adapted version of the Drug Use Disorder Identification Test (DUDIT) instrument, cross-sectional survey data were obtained from 520 IDPs living in three camps located in Maiduguri, Borno state of Nigeria. The data were analyzed using Statistical Package for Social Sciences software version 21.0. Specifically, this article provides data about the participants' demographic characteristics, the types of substances they use, reasons for using such substances, and the prevalence of substance use. This dataset can offer valuable multivariate information for future research agendas in similar, or closely related study populations. This cross-sectional dataset is also valuable for policymakers who are seeking ways to intervene in the substance use problem, as well as other associated social vices, affecting the vulnerable population of IDPs.
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Forcibly displaced populations are among the most vulnerable groups in disasters. They experience poorer health conditions compared with nondisplaced individuals. However, a clear picture is lacking regarding the overall health problems encountered by disaster-induced mid- to long-term displaced people. This study investigated these disorders prevalence and identified their correlates among long-settled displaced populations worldwide. The current scoping review follows the PRISMA-ScR guidelines; a systematic search was conducted on PubMed, Web of Science, and CINAHL and included original peer-reviewed studies, commentary, reviews, and grey literature published in English between January 1990 to June 2022. In the thematic and content analysis, the authors applied the narrative review approach to identify themes and sub-themes. Forty-eight documents were identified as fully relevant to this study. The largest number of published papers were from Asia, followed by the Middle East, the United States, and Europe. IDPs in developed countries were the most researched populations. Human-made disasters were addressed by 89% of the included studies. The four main thematic categories included were "physical health," "mental health," "inadequate facilities," and "lack of healthy behaviour." The worsening of noncommunicable diseases had the highest prevalence, followed by communicable diseases. Due to their condition, forcibly displaced migrants face a triple burden of communicable diseases and noncommunicable diseases such as mental health issues. Health-related research and policy need to consider the links among disasters, health problems, and forced migration as a determinant of health in the new era of climate change-driven displacements.
Subject(s)
Communicable Diseases , Disasters , Noncommunicable Diseases , Humans , Mental Health , Communicable Diseases/epidemiology , Middle EastABSTRACT
This paper discusses the properties of proteins and their relations in the interactomes of the selected subsets of SARS-CoV-2 proteome-the membrane protein, nonstructural proteins, and, finally, full proteome. Protein disorder according to several measures, liquid-liquid phase separation probabilities, and protein node degrees in the interaction networks were singled out as the features of interest. Additionally, viral interactomes were combined with the interactome of human lung tissue so as to examine if the new connections in the resulting viral-host interactome are linked to protein disorder. Correlation analysis shows that there is no clear relationship between raw features of interest, whereas there is a positive correlation between the protein disorder and its neighborhood mean disorder. There are also indications that highly connected viral hubs tend to be on average more ordered than proteins with a small number of connections. This is in contrast to previous similar studies conducted on eukaryotic interactomes and possibly raises new questions in research on viral interactomes.
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Introduction: The COVID-19 pandemic has exacerbated an already existing security crisis leading to massive population displacements that have been taking place since 2012. Purpose of research: This study aims to explore the representations of internally displaced persons (IDPs) about the existence of COVID-19 and their knowledge about its signs, symptoms, modes of transmission and prevention measures. Methods: The study was qualitative and exploratory. Individual and group interviews were used to collect data from 52 IDPs in six sites in Bamako and Segou. All interviews were recorded and transcribed. Thematic content analysis and N-Vivo software were used. Results: The majority of IDPs believed in the existence of COVID-19 and had good knowledge of the signs, symptoms, modes of transmission and prevention measures against the disease. However, this was not sufficient for the adoption of public health measures. Among those who believed in its existence, some thought that it was a disease of the white and rich. Finally, a group of participants believed in conspiracy theories and claimed that the government and humanitarian organizations were only trying to make money through these campaigns. Conclusion: To our knowledge, this is the first study in Mali to explore IDPs' beliefs and knowledge about COVID-19. These results could inform policies, strategies, and interventions to combat COVID-19 in IDP sites and in the general population.
Introduction: Le Mali fait face depuis 2012 à une crise sécuritaire qui a entraîné des déplacements massifs des populations à laquelle s'est greffée la pandémie de la COVID-19. But de l'étude: Cette étude vise à explorer les représentations des personnes « déplacées internes ¼ (PDIs), c'est-à-dire des personnes forcées de fuir leur lieu d'origine, sur l'existence de la COVID-19 ainsi que leurs connaissances sur ses signes, ses symptômes, les modes de transmission et les mesures de prévention. Méthodes: L'étude est qualitative et exploratoire. Des entretiens individuels et en groupes ont permis de collecter les données auprès de 52 PDIs de six sites de Bamako et Ségou. Tous les entretiens ont été enregistrés et transcrits. L'analyse de contenu thématique et le logiciel NVivo ont été utilisés. Résultats: Dans leur majorité, les PDIs croyaient en l'existence de la COVID-19 et avaient de bonnes connaissances sur les signes, les symptômes, les modes de transmission et les mesures de prévention contre la maladie. Toutefois, cela n'a pas été suffisant pour l'adoption des mesures de santé publique. Parmi ceux qui croient en son existence, certains pensent que c'est toutefois une maladie des blancs et des riches. Enfin, un groupe de participants croyait plutôt en des théories du complot selon lesquelles le gouvernement et les organisations humanitaires ne chercheraient qu'à gagner de l'argent à travers ces campagnes. Conclusions: Il s'agit à notre connaissance de la première étude au Mali explorant les représentations et les connaissances des PDIs sur la COVID-19. Ces résultats pourraient éclairer les politiques, stratégies et interventions de lutte contre la COVID-19 dans les sites PDI et dans la population générale.
Subject(s)
COVID-19 , Refugees , Humans , Mali/epidemiology , Pandemics , COVID-19/epidemiology , Qualitative ResearchABSTRACT
Circular Dichroism (CD) spectroscopy is a widely-used method for characterizing individual protein structures in solutions, membranes, films and macromolecular complexes, as well as for probing macromolecular interactions, conformational changes associated with binding substrates, and in different functionally-related environments. This paper describes a series of related computational and display tools that have been developed over many years to aid in those characterizations and functional interpretations. The new DichroPipeline described herein links a series of format-compatible data processing, analysis, and display tools to enable users to facilely produce the spectra, which can then be made available in the Protein Circular Dichroism Data Bank (https://pcddb.cryst.bbk.ac.uk/) resource, in which the CD spectral and associated metadata for each entry are linked to other structural and functional data bases including the Protein Data Bank (PDB), and the UniProt sequence data base, amongst others. These tools and resources thus provide the basis for a wide range of traceable structural characterizations of soluble, membrane and intrinsically-disordered proteins.