How intrinsically disordered proteins order plant gene silencing.

Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) possess low sequence complexity of amino acids and display non-globular tertiary structures. They can act as scaffolds, form regulatory hubs, or trigger biomolecular condensation to control diverse aspects of biology. Emerging evidence has recently implicated critical roles of IDPs and IDR-contained proteins in nuclear transcription and cytoplasmic post-transcriptional processes, among other molecular functions. We here summarize the concepts and organizing principles of IDPs. We then illustrate recent progress in understanding the roles of key IDPs in machineries that regulate transcriptional and post-transcriptional gene silencing (PTGS) in plants, aiming at highlighting new modes of action of IDPs in controlling biological processes.

The bacterial DNA sliding clamp, ß-clamp: structure, interactions, dynamics and drug discovery.

DNA replication is a tightly coordinated event carried out by a multiprotein replication complex. An essential factor in the bacterial replication complex is the ring-shaped DNA sliding clamp, ß-clamp, ensuring processive DNA replication and DNA repair through tethering of polymerases and DNA repair proteins to DNA. ß -clamp is a hub protein with multiple interaction partners all binding through a conserved clamp binding sequence motif. Due to its central role as a DNA scaffold protein, ß-clamp is an interesting target for antimicrobial drugs, yet little effort has been put into understanding the functional interactions of ß-clamp. In this review, we scrutinize the ß-clamp structure and dynamics, examine how its interactions with a plethora of binding partners are regulated through short linear binding motifs and discuss how contexts play into selection. We describe the dynamic process of clamp loading onto DNA and cover the recent advances in drug development targeting ß-clamp. Despite decades of research in ß-clamps and recent landmark structural insight, much remains undisclosed fostering an increased focus on this very central protein.

PQBP3/NOL7 is an intrinsically disordered protein.

PQBP3 is a protein binding to polyglutamine tract sequences that are expanded in a group of neurodegenerative diseases called polyglutamine diseases. The function of PQBP3 was revealed recently as an inhibitor protein of proteasome-dependent degradation of Lamin B1 that is shifted from nucleolus to peripheral region of nucleus to keep nuclear membrane stability. Here, we address whether PQBP3 is an intrinsically disordered protein (IDP) like other polyglutamine binding proteins including PQBP1, PQBP5 and VCP. Multiple bioinformatics analyses predict that N-terminal region of PQBP3 is unstructured. High-speed atomic force microscopy (HS-AFM) reveals that N-terminal region of PQBP3 is dynamically changed in the structure consistently with the predictions of the bioinformatics analyses. These data support that PQBP3 is also an IDP.

Prevalence of depression and associated factors among community hosted internally displaced people of Tigray; during war and siege.

BACKGROUND: Displacement is a psychologically stressful event. Since the war began, the people of Tigray were subjected to stressful events such as torture, rape, the killing of a family member, forced displacement, and even ethnic cleansing in their home countries. Especially displaced individuals are faced mental health problems. This study aimed to assess the prevalence of depression and associated factors among community internally displaced people due to the war on Tigray, in 2021. METHODS: The community-based cross-sectional study design was applied from August 06 to 30, 2021 in all Weredas of Tigray. A total of 1,990 cIDP were recruited through a two-stage sampling technique. A structured and standardized questionnaire was used to collect data. Both bivariate and multivariable logistic regression was applied to identify associated risk factors and AOR with 95% confidence interval was used to select statistically significant variables. RESULTS: The prevalence of depression among internally displaced people was 81.2% (95% CI: 79.4-83%), with more than 60% categorized as moderate and severe depression. The married and divorced marital status, being government employee, having family size > = 4, destruction of household fixed assets, looting of cereals, and having disabled family members due to the war were the significantly associated risk factors of depression. CONCLUSIONS: The prevalence of depression among community internally displaced people during the war on Tigray is very high compared to other studies conducted elsewhere. Almost 8 of 10 IDPs are developed depression and this is a very series health issue that needs immediate intervention by local, international organizations and communities around the world.

'Displaced in the name of Religion': Girl child abuse and community healthcare workers' response to women crying for help in IDP camps in North Central, Nigeria.

This study examines girl child abuse in an internally displaced people's camp in north-central Nigeria and the response of community health workers. The conflict in Benue State is caused by religious differences between the natives (Tiv people) and the invading Fulani herdsmen. During these conflicts, women and girls were displaced, and they were kept in internally displaced persons (IDPs) located in different parts of the state. Literature has been extensively written on internal displacement in Nigeria, but none has been able to elucidate the health needs of girls and the various abuses girls and women are suffering in IDP camps. In this study, literature was extended (1) to explore the environment of the girl child in IDP camps, (2) to identify reasons for the abuse of the girl child in IDP camps, (3) to investigate the impacts of the abuse on the girl child in IDP camps and (4) to investigate how healthcare workers could be used to alleviate the plight of girl children in IDP camps. This is a qualitative case study, with data obtained from relevant academic literature and personal observation. The data were analysed using content analysis. Findings reveal that the girl child is suffering from psychological, economic and health challenges due to the various forms of abuse they are going through. Following the devastation in Benue State, healthcare workers from the community relocated to neighbouring states. There is a need to recall those healthcare workers and provide them with the necessary materials to assist girls in IDP camps. Recommendations are discussed.

Deoxyxylulose 5-Phosphate Synthase Does Not Play a Major Role in Regulating the Methylerythritol 4-Phosphate Pathway in Poplar.

The plastidic 2-C-methylerythritol 4-phosphate (MEP) pathway supplies the precursors of a large variety of essential plant isoprenoids, but its regulation is still not well understood. Using metabolic control analysis (MCA), we examined the first enzyme of this pathway, 1-deoxyxylulose 5-phosphate synthase (DXS), in multiple grey poplar (Populus × canescens) lines modified in their DXS activity. Single leaves were dynamically labeled with 13CO2 in an illuminated, climate-controlled gas exchange cuvette coupled to a proton transfer reaction mass spectrometer, and the carbon flux through the MEP pathway was calculated. Carbon was rapidly assimilated into MEP pathway intermediates and labeled both the isoprene released and the IDP+DMADP pool by up to 90%. DXS activity was increased by 25% in lines overexpressing the DXS gene and reduced by 50% in RNA interference lines, while the carbon flux in the MEP pathway was 25-35% greater in overexpressing lines and unchanged in RNA interference lines. Isoprene emission was also not altered in these different genetic backgrounds. By correlating absolute flux to DXS activity under different conditions of light and temperature, the flux control coefficient was found to be low. Among isoprenoid end products, isoprene itself was unchanged in DXS transgenic lines, but the levels of the chlorophylls and most carotenoids measured were 20-30% less in RNA interference lines than in overexpression lines. Our data thus demonstrate that DXS in the isoprene-emitting grey poplar plays only a minor part in controlling flux through the MEP pathway.

Trends in the Management of Miscarriages with the Implementation of the Volunteer Obstetrician Scheme in Selected Primary Health Care Centres in Maiduguri, Northeastern Nigeria.

BACKGROUND: Post-abortion care (PAC) is a crucial component of emergency obstetric care, and many of the primary health care centres (PHC) in the internally displaced person (IDP) camps and host communities in Maiduguri lack it. Improved access to high-quality PACs is essential for meeting the reproductive health needs of the IDPs and reducing the maternal morbidity and mortality that can result from miscarriages. OBJECTIVE: To determine the trend in managing miscarriages in the IDP camps and host communities in Maiduguri and the impact of the volunteer obstetrician scheme (VOS) on PAC. METHODOLOGY: We conducted a longitudinal study in selected PHCs serving IDP camps and host communities in Maiduguri. The study spanned five (5) years, and we compared the management of miscarriages and PAC services one year before the VOS project, two years during the project and two years after the project. During the two-year VOS project, staff manning the PHCs had supportive supervision with hands-on training on PAC. Chi-square for trend and odd ratio with a 95% confidence interval was used as appropriate to compare the trend in PAC services provided during the study period. RESULTS: One thousand eight hundred and eight (1808) women presented with miscarriages, and 1562 (86.4%) required uterine evacuation. Medical evacuation with oral misoprostol was offered to 974 (62.4%), and manual vacuum aspiration (MVA) was used in 422 (27.0%) of the women who needed uterine evacuation. There was a statistically significant rise in the use of medical evacuation throughout the study period (52.2% before VOS, and 71.4% by the second year of VOS) with ꭓ2=41.64 and P<0.001. In comparison, the use of MVA fell from 38.6% in 2015 to 27.7% in 2019 (ꭓ2=34.74 and P<0.001). Similar rising trends were also observed in postabortion family planning acceptance (ꭓ2=22.27, P<0.001). CONCLUSION: The Volunteer Obstetrician Scheme project appears to have improved PAC services, especially medical evacuation and family planning uptake in the PHCs in IDP camps and host communities in Maiduguri, Borno State, Nigeria. We recommend task shifting of PAC services and periodic supportive supervision to ensure the quality of care.

CONTEXTE: Les soins après avortement (PAC) sont une composante cruciale des soins obstétricaux d'urgence, et de nombreux centres de soins de santé primaires (PHC) dans les camps de personnes déplacées internes (PDI) et les communautés d'accueil à Maiduguri en sont dépourvus. Un accès amélioré à des PAC de haute qualité est essentiel pour répondre aux besoins de santé reproductive des PDI et réduire la morbidité et la mortalité maternelles qui peuvent résulter des fausses couches. OBJECTIF: Déterminer la tendance dans la gestion des fausses couches dans les camps de PDI et les communautés d'accueil à Maiduguri et l'impact du Programme de bénévoles obstétriciens (VOS) sur la PAC. MÉTHODOLOGIE: Nous avons mené une étude longitudinale dans des PHC sélectionnés desservant des camps de PDI et des communautés d'accueil à Maiduguri. L'étude a duré cinq (5) ans, et nous avons comparé la gestion des fausses couches et les services de PAC un an avant le projet VOS, deux ans pendant le projet et deux ans après le projet. Pendant les deux ans du projet VOS, le personnel des PHC a bénéficié d'une supervision avec formation pratique sur la PAC. Le chi carré pour la tendance et le rapport de cotes avec un intervalle de confiance de 95% ont été utilisés, le cas échéant, pour comparer la tendance des services de PAC fournis pendant la période de l'étude. RÉSULTATS: Mille huit cent huit (1808) femmes ont présenté des fausses couches, et 1562 (86,4%) ont nécessité une évacuation utérine. Une évacuation médicale avec du misoprostol oral a été proposée à 974 (62,4%), et l'aspiration manuelle sous vide (AMV) a été utilisée chez 422 (27,0%) des femmes ayant besoin d'une évacuation utérine. On a observé une augmentation statistiquement significative de l'utilisation de l'évacuation médicale tout au long de la période de l'étude (52,2% avant le VOS et 71,4% la deuxième année du VOS) avec ꭓ2=41,64 et P<0,001. En revanche, l'utilisation de l'AMV est passée de 38,6% en 2015 à 27,7% en 2019 (ꭓ2=34,74 et P<0,001). Des tendances similaires à la hausse ont également été observées dans l'acceptation de la planification familiale après avortement (ꭓ2=22,27, P<0,001). CONCLUSION: Le projet de Programme de bénévoles obstétriciens semble avoir amélioré les services de PAC, en particulier l'évacuation médicale et l'acceptation de la planification familiale dans les PHC des camps de PDI et des communautés d'accueil à Maiduguri, dans l'État de Borno, au Nigéria. Nous recommandons de déléguer les services de PAC et une supervision de soutien périodique pour garantir la qualité des soins. MOTS-CLÉS: Communauté d'accueil, Camps de PDI, Aspiration manuelle sous vide, Évacuation médicale, Misoprostol, Soins après avortement.

Prevalence of Stunting and Its Associated Factors Among Children Residing in Internally Displaced Persons (IDP) Camps in Hargeisa, Somaliland: A Community-Based Cross-Sectional Study.

Background: Stunting, a consequence of prolonged malnutrition, remains a critical global health issue affecting 165 million children under the age of five, with 10.6 million associated deaths. Its stunting prevalence is particularly pronounced in developing nations, notably Sub-Saharan Africa. Chronic protein-energy malnutrition, identified as a major cause of morbidity and mortality in displaced settings, underscores the urgency of understanding its impact in such contexts. Objective: This study aimed to assess the prevalence and associated factors of stunting among children aged 12-59 months and residing in IDP camps in Hargeisa, Somaliland. Methods: A community-based cross-sectional study was conducted in Hargeisa from May 5 to July 30, 2022, utilizing systematic random sampling, online mobile surveys, and caregiver interviews with anthropometric measurements. The SPSS version 25 was utilized in handled data entry, processing and analysis. Multivariable logistic regression, with p < 0.05 significance, included variables from bivariate analysis (p < 0.2). Stunting assessment utilized WHO AnthroPlus software, categorizing HAZ scores < -2.0 SD. Results: The prevalence of stunting among children living in IDP camps was found to be 21.1% [95% CI: 17.0-24.91%]. Vaccination status (adjusted odds ratio [aOR] = 0.19, 95% CI: 0.09-0.38), deworming practice (aOR = 6.5, 95% CI: 2.91-14.52), place of delivery (aOR = 0.14, 95% CI: 0.07-0.30), measles experience in the last year (aOR = 0.12, 95% CI: 0.04-0.34), ANC visits (aOR = 0.33, 95% CI: 0.14-0.81), and maternal insufficient extra food intake (aOR = 2.15, 95% CI: 1.11-4.15) were significantly associated with stunting. Conclusion: The observed stunting prevalence in IDP camps (21.1%) was substantial, highlighting the need for targeted interventions. Future efforts should aim to reduce stunting from the current rate to an estimated 5-10%, emphasizing comprehensive measures such as deworming, maternal nutrition, postnatal care improvement, robust immunization, and promoting healthcare facility deliveries.

A federated authentication schema among multiple identity providers.

Single Sign-On (SSO) methods are the primary solution to authenticate users across multiple web systems. These mechanisms streamline the authentication procedure by avoiding duplicate developments of authentication modules for each application. Besides, these mechanisms also provide convenience to the end-user by keeping the user authenticated when switching between different contexts. To ensure this cross-application authentication, SSO relies on an Identity Provider (IdP), which is commonly set up and managed by each institution that needs to enforce SSO internally. However, the solution is not so straightforward when several institutions need to cooperate in a unique ecosystem. This could be tackled by centralizing the authentication mechanisms in one of the involved entities, a solution raising responsibilities that may be difficult for peers to accept. Moreover, this solution is not appropriate for dynamic groups, where peers may join or leave frequently. In this paper, we propose an architecture that uses a trusted third-party service to authenticate multiple entities, ensuring the isolation of the user's attributes between this service and the institutional SSO systems. This architecture was validated in the EHDEN Portal, which includes web tools and services of this European health project, to establish a Federated Authentication schema.

Cyclic-NDGA Effectively Inhibits Human γ-Synuclein Fibrillation, Forms Nontoxic Off-Pathway Species, and Disintegrates Preformed Mature Fibrils.

Parkinson's disease arises from protein misfolding, aggregation, and fibrillation and is characterized by LB (Lewy body) deposits, which contain the protein α-synuclein (α-syn) as their major component. Another synuclein, γ-synuclein (γ-syn), coexists with α-syn in Lewy bodies and is also implicated in various types of cancers, especially breast cancer. It is known to seed α-syn fibrillation after its oxidation at methionine residue, thereby contributing in synucleinopathy. Despite its involvement in synucleinopathy, the search for small molecule inhibitors and modulators of γ-syn fibrillation remains largely unexplored. This work reveals the modulatory properties of cyclic-nordihydroguaiaretic acid (cNDGA), a natural polyphenol, on the structural and aggregational properties of human γ-syn employing various biophysical and structural tools, namely, thioflavin T (ThT) fluorescence, Rayleigh light scattering, 8-anilinonaphthalene-1-sulfonic acid binding, far-UV circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR) spectroscopy, atomic force microscopy, ITC, molecular docking, and MTT-toxicity assay. cNDGA was observed to modulate the fibrillation of γ-syn to form off-pathway amorphous species that are nontoxic in nature at as low as 75 µM concentration. The modulation is dependent on oxidizing conditions, with cNDGA weakly interacting (Kd ∼10-5 M) with the residues at the N-terminal of γ-syn protein as investigated by isothermal titration calorimetry and molecular docking, respectively. Increasing cNDGA concentration results in an increased recovery of monomeric γ-syn as shown by sodium dodecyl sulfate and native-polyacrylamide gel electrophoresis. The retention of native structural properties of γ-syn in the presence of cNDGA was further confirmed by far-UV CD and FTIR. In addition, cNDGA is most effective in suppression of fibrillation when added at the beginning of the fibrillation kinetics and is also capable of disintegrating the preformed mature fibrils. These findings could, therefore, pave the ways for further exploring cNDGA as a potential therapeutic against γ-synucleinopathies.

The food and pharmaceutical additive benzoic acid induces amyloid fibrillation of an intrinsically disordered protein.

Benzoic acid (BA) is a microbe-inhibiting flavoring agent used extensively as an additive in foods, pharmaceuticals, and hygiene and cosmetic products. The level of BA in foodstuffs prescribed by world bodies and governmental agencies is assumed to be safe so as to prevent adverse health effects. The safety level of BA is however controversial, and whether different conditions of its use would be generally regarded as safe (GRAS) has been rarely determined. In the quest of how food additives affect the structure and conformation of proteins, this study evaluates the interaction of BA with an intrinsically disordered protein (IDP) at pH 4.2 that matches the pH conditions applicable for the commercial use of benzoate preservatives, and examines its structural transformation by NMR, fluorescence, and high-resolution microscopy. The interaction with BA transforms the protein to a denatured aggregated mesophase that undergoes reconfiguration to yield rigid amyloid fibrils. Significantly, fibrils are observed even with 0.1 mM BA while the recommended level of its use as a preservative is in the 0.4-8 mM range. The discussion refrains from safety comments with no projection of the BA level that could be GRAS.

Microscale Thermophoresis Analysis of Chromatin Interactions.

Architectural DNA-binding proteins are key to the organization and compaction of genomic DNA inside cells. The activity of architectural proteins is often subject to further modulation and regulation through the interaction with a diverse array of other protein factors. Detailed knowledge on the binding modes involved is crucial for our understanding of how these protein-protein and protein-DNA interactions shape the functional landscape of chromatin in all kingdoms of life: bacteria, archaea, and eukarya.Microscale thermophoresis (MST) is a biophysical technique for the study of biomolecular interactions. It has seen increasing application in recent years thanks to its solution-based nature, rapid application, modest sample demand, and the sensitivity of the thermophoresis effect to binding events.Here, we describe the use of MST in the study of chromatin interactions. The emphasis lies on the wide range of ways in which these experiments are set up and the diverse types of information they reveal. These aspects are illustrated with four very different systems: the sequence-dependent DNA compaction by architectural protein HMfB, the sequential binding of core histone complexes to histone chaperone APLF, the impact of the nucleosomal context on the recognition of histone modifications, and the binding of a viral peptide to the nucleosome. Special emphasis is given to the key steps in the design, execution, and analysis of MST experiments in the context of the provided examples.

The theory of the investment development path and agriculture in Eastern Europe.

The outdated investment development path results in Eastern Europe and the lack of focus on the agricultural sector necessitated this study. The generalised least squares estimator employed countries from 1993 to 2021 for agricultural sector data on 17 Eastern Europe. Eastern European agriculture is in the early phase of stage IV of the investment development path, consistent with the theory of the investment development path. Human capital enhanced net foreign direct investment. Agricultural trade openness, exchange rate, and inflation did not influence net foreign direct investment. Developed and transition countries in Eastern Europe were not distinguished regarding net foreign direct investment. Eastern European countries must increase agricultural growth relative to population growth. This would increase agricultural development. The increased income can be saved and channelled into domestic investments to spur additional growth. This would make capital available for export. The growth in human capital must be sustained to enhance technical know-how in agriculture that would accompany agricultural capital export. Agricultural sector managers of Eastern European countries must focus on enhancing the sector's supervisory and regulatory functions. The goal should be to reduce the costs of doing agricultural business through effective facilitation towards efficient agricultural markets.

From disorder comes function: Regulation of small GTPase function by intrinsically disordered lipidated membrane anchor.

The intrinsically disordered, lipid-modified membrane anchor of small GTPases is emerging as a critical modulator of function through its ability to sort lipids in a conformation-dependent manner. We reviewed recent computational and experimental studies that have begun to shed light on the sequence-ensemble-function relationship in this unique class of lipidated intrinsically disordered regions (LIDRs).

DR-BERT: A protein language model to annotate disordered regions.

Despite their lack of a rigid structure, intrinsically disordered regions (IDRs) in proteins play important roles in cellular functions, including mediating protein-protein interactions. Therefore, it is important to computationally annotate IDRs with high accuracy. In this study, we present Disordered Region prediction using Bidirectional Encoder Representations from Transformers (DR-BERT), a compact protein language model. Unlike most popular tools, DR-BERT is pretrained on unannotated proteins and trained to predict IDRs without relying on explicit evolutionary or biophysical data. Despite this, DR-BERT demonstrates significant improvement over existing methods on the Critical Assessment of protein Intrinsic Disorder (CAID) evaluation dataset and outperforms competitors on two out of four test cases in the CAID 2 dataset, while maintaining competitiveness in the others. This performance is due to the information learned during pretraining and DR-BERT's ability to use contextual information.

Intrinsically disordered Pseudomonas chaperone FapA slows down the fibrillation of major biofilm-forming functional amyloid FapC.

Functional bacterial amyloids play a crucial role in the formation of biofilms, which mediate chronic infections and contribute to antimicrobial resistance. This study focuses on the FapC amyloid fibrillar protein from Pseudomonas, a major contributor to biofilm formation. We investigate the initial steps of FapC amyloid formation and the impact of the chaperone-like protein FapA on this process. Using solution nuclear magnetic resonance (NMR), we recently showed that both FapC and FapA are intrinsically disordered proteins (IDPs). Here, the secondary structure propensities (SSPs) are compared to alphafold (DeepMind, protein structure prediction tool/algorithm: https://alphafold.ebi.ac.uk/) models. We further demonstrate that the FapA chaperone interacts with FapC and significantly slows down the formation of FapC fibrils. Our NMR titrations reveal ~ 18% of the resonances show FapA-induced chemical shift perturbations (CSPs), which has not been previously observed, the largest being for A82, N201, C237, C240, A241, and G245. These sites may suggest a specific interaction site and/or hotspots of fibrillation inhibition/control interface at the repeat-1 (R1)/loop-2 (L2) and L2/R3 transition areas and at the C-terminus of FapC. Remarkably, ~ 90% of FapA NMR signals exhibit substantial CSPs upon titration with FapC, the largest being for S63, A69, A80, and I92. A temperature-dependent effect of FapA was observed on FapC by thioflavin T (ThT) and NMR experiments. This study provides a detailed understanding of the interaction between the FapA and FapC, shedding light on the regulation and slowing down of amyloid formation, and has important implications for the development of therapeutic strategies targeting biofilms and associated infections.

Functional analysis of the methylerythritol phosphate pathway terminal enzymes IspG and IspH from Zymomonas mobilis.

Isoprenoids are a diverse family of compounds that are synthesized from two isomeric compounds, isopentenyl diphosphate and dimethylallyl diphosphate. In most bacteria, isoprenoids are produced from the essential methylerythritol phosphate (MEP) pathway. The terminal enzymes of the MEP pathway IspG and IspH are [4Fe-4S] cluster proteins, and in Zymomonas mobilis, the substrates of IspG and IspH accumulate in cells in response to O2, suggesting possible lability of their [4Fe-4S] clusters. Here, we show using complementation assays in Escherichia coli that even under anaerobic conditions, Z. mobilis IspG and IspH are not as functional as their E. coli counterparts, requiring higher levels of expression to rescue viability. A deficit of the sulfur utilization factor (SUF) Fe-S cluster biogenesis pathway did not explain the reduced function of Z. mobilis IspG and IspH since no improvement in viability was observed in E. coli expressing the Z. mobilis SUF pathway or having increased expression of the E. coli SUF pathway. Complementation of single and double mutants with various combinations of Z. mobilis and E. coli IspG and IspH indicated that optimal growth required the pairing of IspG and IspH from the same species. Furthermore, Z. mobilis IspH conferred an O2-sensitive growth defect to E. coli that could be partially rescued by co-expression of Z. mobilis IspG. In vitro analysis showed O2 sensitivity of the [4Fe-4S] cluster of both Z. mobilis IspG and IspH. Altogether, our data indicate an important role of the cognate protein IspG in Z. mobilis IspH function under both aerobic and anaerobic conditions. IMPORTANCE: Isoprenoids are one of the largest classes of natural products, exhibiting diversity in structure and function. They also include compounds that are essential for cellular life across the biological world. In bacteria, isoprenoids are derived from two precursors, isopentenyl diphosphate and dimethylallyl diphosphate, synthesized primarily by the methylerythritol phosphate pathway. The aerotolerant Z. mobilis has the potential for methylerythritol phosphate pathway engineering by diverting some of the glucose that is typically efficiently converted into ethanol to produce isoprenoid precursors to make bioproducts and biofuels. Our data revealed the surprising finding that Z. mobilis IspG and IspH need to be co-optimized to improve flux via the methyl erythritol phosphate pathway in part to evade the oxygen sensitivity of IspH.

14-3-3τ as a Modulator of Early α-Synuclein Multimerization and Amyloid Formation.

The aggregation of α-synuclein (αS) plays a key role in Parkinson's disease (PD) etiology. While the onset of PD is age-related, the cellular quality control system appears to regulate αS aggregation throughout most human life. Intriguingly, the protein 14-3-3τ has been demonstrated to delay αS aggregation and the onset of PD in various models. However, the molecular mechanisms behind this delay remain elusive. Our study confirms the delay in αS aggregation by 14-3-3τ, unveiling a concentration-dependent relation. Utilizing microscale thermophoresis (MST) and single-molecule burst analysis, we quantified the early αS multimers and concluded that these multimers exhibit properties that classify them as nanoscale condensates that form in a cooperative process, preceding the critical nucleus for fibril formation. Significantly, the αS multimer formation mechanism changes dramatically in the presence of scaffold protein 14-3-3τ. Our data modeling suggests that 14-3-3τ modulates the multimerization process, leading to the creation of mixed multimers or co-condensates, comprising both αS and 14-3-3τ. These mixed multimers form in a noncooperative process. They are smaller, more numerous, and distinctively not on the pathway to amyloid formation. Importantly, 14-3-3τ thus acts in the very early stage of αS multimerization, ensuring that αS does not aggregate but remains soluble and functional. This offers long-sought novel entries for the pharmacological modulation of PD.

Amino acid pattern reveals multi-functionality of ORF3 protein from HEV.

The smallest open reading frame (ORF) encoded protein ORF3 of hepatitis E virus (HEV), recently, has been demonstrated to perform multiple functions besides accessory roles. ORF3 could act as a target for vaccine against HEV infections. The IDR (intrinsically disordered region); IDP (ID protein)/IDPR (ID protein region), plays critical role in various regulatory functions of viruses. The dark proteome of HEV-ORF3 protein including its structure and function was systematically examined by computer predictors to explicate its role in viral pathogenesis and drug resistance beyond its functions as accessory viral protein. Amino acid distribution showed ORF3 enrichment with disorder-promoting residues (Ala, Pro, Ser, Gly) while deficiency in order-promoting residues (Asn, Ile, Phe, Tyr and Trp). Initial investigation revealed ORF3 as IDP (entirely disordered protein) or IDPR (proteins consisting of IDRs with structured globular domains). Structural examination revealed preponderance of disordered regions interpreting ORF3 as moderately/highly disordered protein. Further disorder predictors categorized ORF3 as highly disordered protein/IDP. Identified sites and associated-crucial molecular functions revealed ORF3 involvement in diverse biological processes, substantiating them as targets of regulation. As ORF3 functions are yet to completely explored, thus, data on its disorderness could help in elucidating its disorder related functions.

Prevalence and pattern of contraceptive uptake among adolescents in an internally displaced camp, North Central, Nigeria.

Internally displaced Persons are marginally sidelined in many areas of life, reproductive health issues inclusive. There is a need to know the prevalence and pattern of contraceptive use among this vulnerable group of people. This study determined the prevalence and pattern of contraceptive uptake among internally displaced adolescents in North-Central Camp, Abuja, Nigeria. A descriptive cross-sectional study, among 403 adolescents using semi-structured questionnaires. The mean age of the respondents was 19.53±6.4 years and 21.34±7.34 years at first birth. Awareness about FP was high, (483, 95.0%), however, only 169 (41.9%) ever used a family planning method, while 82 (20.3%) were current users, 72 (42.6%) of the 169 ever users admitted to have used pills, while 44 (53.7%) of the 82 current users were using condom only. One third, 160 (39.7%), were pregnant, while 78 (19.4%) of those pregnant were unintentional, therefore the unintended pregnancy rate was 19.4%. Bivariate analysis revealed that respondents' use of contraceptive was significantly related to religion (<0.001), ethnic group (<0.001), marital status (<0.001), family type (<0.001), and educational attainment (<0.001). While respondents' knowledge of contraceptive was significantly associated with age (P<0.00000001), educational level (P<0.002), and ethnic group (P<0.001). The prevalence of contraceptive use among respondents was 20.3%, while 41.9% ever used a method. Pill was the major Family planning method ever used, while condom was mostly used by the current users.