Mechanism Of Recruitment Research Articles

أثر استراتيجيات الموارد البشرية في الرئاسة العامة لشؤون المسجد الحرام في مدى تحقيقها رؤية المملكة 2030

The research aims at strategic planning for human resources. The results showed that the General Presidency applies strategies aimed at improving job performance, such as continuous training, leadership development, and modern technologies. It was found that there is a significant investment in digital transformation, which supports process automation and improves efficiency. It became clear that the Presidency faces challenges in areas such as job localization and achieving a balance between employee needs and the organization's goals. It also showed that training programs aimed at achieving the standards of Vision 2030 were enhanced, especially in the areas of leadership and visitor service. The study also aims to increase focus on motivation strategies to enhance job satisfaction and productivity. The Presidency seeks to improve recruitment and professional development mechanisms to ensure attracting the best competencies and localizing jobs. With the continuation of performance evaluation and linking results to indicators for measuring the goals of Vision 2030. It became clear that the Presidency plays a pivotal role in human resources strategies in enabling the General Presidency for the Affairs of the Grand Mosque to contribute to achieving the Kingdom's Vision 2030. However, it requires continuous review of these strategies to ensure adaptation to national and international variables and requirements.

“You don't need money to give alms”: The protective capacity of faith and spiritual kinship among domestic workers in Zanzibar

AbstractFew domestic workers on the semiautonomous Tanzanian archipelago of Zanzibar are registered union members, and most domestic workers neither receive nor demand their legal right to a formal contract. Relying on my yearlong engagement between 2017 and 2018 with a women's Islamic studies group and a life history interview with a domestic worker, this essay explores domestic workers' reliance on alternative protective mechanisms from unionization and formalization. The domestic workers I engaged with cultivated relationships with God, negotiated dignity, received affirmation of their spiritual equality, and developed spiritual kinship connections in faith‐based spaces. They also sought to ensure their physical and social well‐being through kin‐based connections and recruitment mechanisms. Kin‐based connections that were spiritual or that connected domestic workers to employers were more protective than kinship relations cultivated in the context of work. Furthermore, domestic workers transformed routine work tasks into opportunities to practice devotion, which reflects Swahili/Islamic understandings of personhood as going beyond the category of worker. Religious spaces and spiritual kinship offer protection to domestic workers through the forms of reciprocity they enable and are thus often a more viable framework than unionization and formalization for overcoming the compounding effects of economic crisis and social inequality on domestic workers' lives.

A structure-based mechanism for initiation of AP-3 coated vesicle formation

Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question. To understand the mechanism of AP-3 membrane recruitment and activation, we reconstituted human AP-3 and determined multiple structures in the soluble and membrane-bound states using electron cryo-microscopy. Similar to yeast AP-3, human AP-3 is in a constitutively open conformation. To reconstitute AP-3 activation by adenosine di-phosphate (ADP)-ribosylation factor 1 (Arf1), a small guanosine tri-phosphate (GTP)ase, we used lipid nanodiscs to build Arf1-AP-3 complexes on membranes and determined three structures showing the stepwise conformational changes required for formation of AP-3 coated vesicles. First, membrane recruitment is driven by one of two predicted Arf1 binding sites, which flexibly tethers AP-3 to the membrane. Second, cargo binding causes AP-3 to adopt a fixed position and rigidifies the complex, which stabilizes binding for a second Arf1 molecule. Finally, binding of the second Arf1 molecule provides the template for AP-3 dimerization, providing a glimpse into the first step of coat polymerization. We propose coat polymerization only occurs after cargo engagement, thereby linking cargo sorting with assembly of higher-order coat structures. Additionally, we provide evidence for two amphipathic helices in AP-3, suggesting that AP-3 contributes to membrane deformation during coat assembly. In total, these data provide evidence for the first stages of AP-3-mediated vesicle coat assembly.

Mechanisms of synergistic Mediator recruitment in RNA polymerase II transcription activation revealed by single-molecule fluorescence.

Transcription activators trigger transcript production by RNA Polymerase II (RNApII) via the Mediator coactivator complex. Here the dynamics of activator, Mediator, and RNApII binding at promoter DNA were analyzed using multi-wavelength single-molecule microscopy of fluorescently labeled proteins in budding yeast nuclear extract. Binding of Mediator and RNApII to the template required activator and an upstream activator sequence (UAS), but not a core promoter. While Mediator and RNApII sometimes bind as a pre-formed complex, more commonly Mediator binds first and subsequently recruits RNApII to form a preinitiation complex precursor (pre-PIC) tethered to activators on the UAS. Interestingly, Mediator occupancy has a highly non-linear response to activator concentration, and fluorescence intensity measurements show Mediator preferentially associates with templates having at least two activators bound. Statistical mechanical modeling suggests this "synergy" is not due to cooperative binding between activators, but instead occurs when multiple DNA-bound activator molecules simultaneously interact with a single Mediator.

Transcriptomic data reveals MYC as an upstream regulator in laying hen follicular recruitment

Understanding the mechanisms of follicular recruitment is essential for improving laying hen and broiler breeder productivity, as it directly influences egg production. Despite advancements in poultry breeding for enhanced egg production, the factors driving successful ovarian follicle maturation remain inadequately understood. This study investigates the genetic drivers mediating the transition of pre-recruitment follicles to the pre-ovulatory phase, a crucial stage before ovulation. Using RNA sequencing and bioinformatics approaches such as a differential gene expression analysis, we compared pre-recruitment follicles with the recently recruited F5 pre-ovulatory follicle to identify key genes and upstream regulators involved in this transition. Further validation through qRT-PCR confirmed these findings. Using Qiagen's Ingenuity Pathway Analysis we identified MYC proto-oncogene (C-Myc) as a pivotal upstream regulator, controlling genes essential for cell proliferation and differentiation. Additionally, TGFβ1 emerged as a key regulator, influencing pathways involving SMAD3, TNF, and TP53. The study highlights the intricate regulatory network involving MYC and other transcription factors such as CTNNB1, crucial for follicular development. These findings provide valuable insights into the molecular mechanisms governing follicular selection and maturation, which are essential for enhancing egg production efficiency. Future research should explore the roles of MYC, CTNNB1, and other driver genes in follicular development to further understand and improve reproductive efficiency in poultry.

Bilayer Scaffolds Synergize Immunomodulation and Rejuvenation via Layer-Specific Release of CK2.1 and the "Exercise Hormone" Lac-Phe for Enhanced Osteochondral Regeneration.

Repairing osteochondral defects necessitates the intricate reestablishment of the microenvironment. The cartilage layer consists of a porous gelatin methacryloyl hydrogel (PGelMA) covalently crosslinked with the chondroinductive peptide CK2.1 via a "linker" acrylate-PEG-N-hydroxysuccinimide (AC-PEG-NHS). This layer is optimized for remodeling the senescent microenvironment in the cartilage region, thereby establishing a regenerative microenvironment that supports chondrogenesis. For the bone layer, silk fibroin methacryloyl (SilMA) is coated onto a three dimensional (3D)-printed 45S5 bioactive glass scaffold (BG scaffold). The "exercise hormone" N-lactoyl-phenylalanine (Lac-Phe) is loaded onto the SilMA, endowing it with diversified functions to regulate the osteogenic microenvironment. Systematic analysis in vitro reveals that PGelMA-CK2.1 shifts the microenvironment from a pro-inflammatory into an anti-inflammatory condition, and alleviates cellular senescence, thus modifying the cartilage microenvironment to improve the recruitment, proliferation and chondral differentiation of bone marrow mesenchymal stem cells (BMSCs). The scaffold bone layer enhances microvascular endothelial cell proliferation, migration, and angiogenic activities, which, couple with increased BMSC recruitment and regulatory mechanisms directing BMSC differentiation, favor a shift in the "osteogenesis-adipogenesis" balance toward enhanced osteogenesis. In vivo, it is found that this biphasic biomimetic scaffold favors simultaneous dual tissue regeneration. This approach facilitates the development of bioactive regenerative scaffolds and holds great potential for clinical application.

Effects of molecular interaction and liver sinusoidal mechanical properties on leukocyte adhesions

It is interesting to find pathologically that leukocytes, especially neutrophils, tend to adhere in the liver sinusoids dominantly but not in the post-sinusoidal venules. While both views of receptor-ligand interactions and physical trapping are proposed for mediating leukocyte adhesion in liver sinusoids, integrated investigations for classifying their respective contributions are poorly presented. With a combination of Monte Carlo simulation and immersed boundary method (IBM), this study explored numerically the effects of molecular interaction kinetics and sinusoidal mechanical properties on leukocyte adhesion in liver sinusoid jointly. Results showed that, within the range of biological limitations, the lumen stenosis ratio, leukocyte stiffness, Disse space stiffness and endothelium permeability regulate the comprehensive adhesion process in a descending order of significance in the presence of receptor-ligand interactions. While leukocyte adhesions could be mutually promoted with proper combinations of leukocyte stiffness, lumen stenosis, and molecular interaction, the binding affinity is insensitive under the conditions with low leukocyte stiffness in normal lumen stenosis and high leukocyte stiffness in high lumen stenosis. This work deepened the understanding of recruitment mechanism of leukocyte in liver sinusoids.

Portfolio-Based User Recruitment Mechanism for Crowdsensing in Uncertain and Unpredictable Environments

Portfolio-Based User Recruitment Mechanism for Crowdsensing in Uncertain and Unpredictable Environments

Metabolic pathways fueling the suppressive activity of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSC) are considered an aberrant population of immature myeloid cells that have attracted considerable attention in recent years due to their potent immunosuppressive activity. These cells are typically absent or present in very low numbers in healthy individuals but become abundant under pathological conditions such as chronic infection, chronic inflammation and cancer. The immunosuppressive activity of MDSC helps to control excessive immune responses that might otherwise lead to tissue damage. This same immunosuppressive activity can be detrimental, particularly in cancer and chronic infection. In the cancer setting, tumors can secrete factors that promote the expansion and recruitment of MDSC, thereby creating a local environment that favors tumor progression by inhibiting the effective immune responses against cancer cells. This has made MDSC a target of interest in cancer therapy, with researchers exploring strategies to inhibit their function or reduce their numbers to improve the efficacy of cancer immunotherapies. In the context of chronic infections, MDSC can lead to persistent infections by suppressing protective immune responses thereby preventing the clearance of pathogens. Therefore, targeting MDSC may provide a novel approach to improve pathogen clearance during chronic infections. Ongoing research on MDSC aims to elucidate the exact processes behind their expansion, recruitment, activation and suppressive mechanisms. In this context, it is becoming increasingly clear that the metabolism of MDSC is closely linked to their immunosuppressive function. For example, MDSC exhibit high rates of glycolysis, which not only provides energy but also generates metabolites that facilitate their immunosuppressive activity. In addition, fatty acid metabolic pathways, such as fatty acid oxidation (FAO), have been implicated in the regulation of MDSC suppressive activity. Furthermore, amino acid metabolism, particularly arginine metabolism mediated by enzymes such as arginase-1, plays a critical role in MDSC-mediated immunosuppression. In this review, we discuss the metabolic signature of MDSC and highlight the therapeutic implications of targeting MDSC metabolism as a novel approach to modulate their immunosuppressive functions.

Sequencing CURLY LEAF-associated RNAs in Arabidopsis revealed prevalent intergenic RNAs from the nuclear mitochondrial sequence

Polycomb Group (PcG) proteins play key roles in development by repressing thousands of targets through histone modifications. However, how PcG is recruited to specific targets is poorly understood. In Arabidopsis, certain noncoding RNAs are necessary for recruiting the PcG protein CURLY LEAF (CLF) to its target sites. However, RNAs associated with CLF have not been analyzed on a genomic scale, thus it is unknown whether long noncoding RNA (lncRNA)-mediated PcG recruitment is a widespread mechanism. Here, we systematically searched for CLF-associated RNAs by RNA immunoprecipitation followed by deep sequencing. We identified 1299 genic and 138 intergenic regions that produced CLF-associated mRNAs and putative lncRNAs, respectively. The genes producing CLF-associated RNAs are depleted in PcG targets, carry active chromatin marks, and are highly expressed, suggesting that CLF may have a non-specific or promiscuous RNA-binding affinity, similar to animal PcG proteins. Notably, a significant portion of the CLF-associated lncRNAs is derived from the nuclear mitochondrial sequence, which is extensively marked by H3K27me3. These findings indicate that while CLF-RNA interactions are widespread, they may not always correlate with PcG target sites, highlighting the complexity of PcG recruitment mechanisms in Arabidopsis.

Chlamydia trachomatis Inc Ct226 is vital for FLI1 and LRRF1 recruitment to the chlamydial inclusion.

The obligate intracellular pathogen, Chlamydia trachomatis, establishes an intracellular niche within a host membrane-derived vacuole called the chlamydial inclusion. From within this inclusion, C. trachomatis orchestrates numerous host-pathogen interactions, in part, by utilizing a family of type III secreted effectors, termed inclusion membrane proteins (Incs). Incs are embedded within the inclusion membrane, and some function to recruit host proteins to the inclusion. Two such recruited host proteins are leucine rich repeat Flightless-1 interacting protein 1 (LRRF1/LRRFIP1) and its binding partner Flightless 1 (FLI1/FLII). Previously, LRRF1 has been shown to interact with Inc protein Ct226/CTL0478. This is the first study to examine interactions of FLI1 with candidate Incs or with LRRF1 during infection. We hypothesized that FLI1 recruitment to the inclusion would be dependent on LRRF1 localization. We demonstrated that FLI1 co-immunoprecipitated with Ct226 but only in the presence of LRRF1. Furthermore, FLI1 localized to the inclusion when LRRF1 was depleted via small interfering RNA, suggesting that FLI1 may have an alternative recruitment mechanism. We further developed a series of CRISPRi knockdown and complementation strains in C. trachomatis serovar L2 targeting ct226 and co-transcribed candidate Incs, ct225 and ct224. Simultaneous knockdown of ct226, ct225, and ct224 prevented localization of both FLI1 and LRRF1 to the inclusion, and only complementation of ct226 restored their localization. Thus, we demonstrated Ct226 is critical for FLI1 and LRRF1 localization to the inclusion. Our results also indicate an LRRF1-independent localization mechanism for FLI1, which likely influence their mechanism(s) of action during chlamydial infection.IMPORTANCEChlamydia trachomatis is a leading cause of both bacterial sexually transmitted infections and preventable infectious blindness worldwide. As an obligate intracellular pathogen, C. trachomatis has evolved multiple ways of manipulating the host to establish a successful infection. As such, it is important to understand host-chlamydial protein-protein interactions as these reveal strategies that C. trachomatis uses to shape its intracellular environment. This study looks in detail at interactions of two host proteins, FLI1 and LRRF1, during chlamydial infection. Importantly, the series of CRISPR inference knockdown and complement strains developed in this study suggest these proteins have both independent and overlapping mechanisms for localization, which ultimately will dictate how these proteins function during chlamydial infection.

Structural basis for synthase activation and cellulose modification in the E. coli Type II Bcs secretion system

Bacterial cellulosic polymers constitute a prevalent class of biofilm matrix exopolysaccharides that are synthesized by several types of bacterial cellulose secretion (Bcs) systems, which include conserved cyclic diguanylate (c-di-GMP)-dependent cellulose synthase modules together with diverse accessory subunits. In E. coli, the biogenesis of phosphoethanolamine (pEtN)-modified cellulose relies on the BcsRQABEFG macrocomplex, encompassing inner-membrane and cytosolic subunits, and an outer membrane porin, BcsC. Here, we use cryogenic electron microscopy to shed light on the molecular mechanisms of BcsA-dependent recruitment and stabilization of a trimeric BcsG pEtN-transferase for polymer modification, and a dimeric BcsF-dependent recruitment of an otherwise cytosolic BcsE2R2Q2 regulatory complex. We further demonstrate that BcsE, a secondary c-di-GMP sensor, can remain dinucleotide-bound and retain the essential-for-secretion BcsRQ partners onto the synthase even in the absence of direct c-di-GMP-synthase complexation, likely lowering the threshold for c-di-GMP-dependent synthase activation. Such activation-by-proxy mechanism could allow Bcs secretion system activity even in the absence of substantial intracellular c-di-GMP increase, and is reminiscent of other widespread synthase-dependent polysaccharide secretion systems where dinucleotide sensing and/or synthase stabilization are carried out by key co-polymerase subunits.

RECRUITMENT POLICY OF CIVIL SERVANT CANDIDATES OF THE MINISTRY OF EDUCATION, CULTURE, RESEARCH, AND TECHNOLOGY FOR DIASPORA APPLICANTS WITH INDONESIAN CITIZENSHIP

In this study, researchers used the Yuridis-Normative legal research and writing methodology by using 3 (three) approaches, including conceptual approaches, statutory approaches, and comparative approaches. This research discusses the opportunities for Diaspora with Indonesian citizenship in the recruitment of Civil Servant Candidates for the Ministry of Education, Culture, Research and Technology. The legal issues raised in this research are as Diaspora with Indonesian citizenship are part of Indonesian citizens who are constitutionally valid so that their rights and obligations apply absolutely based on the 1945 Constitution of the Republic of Indonesia. The issues discussed are the recruitment mechanism to accommodate the participation of Indonesian Diaspora who apply in the general formation and the continuation of studies for Diaspora who have passed the CPNS recruitment. Moreover, in this case, the Diaspora is not regulated in general formations, but special formations.

An Analysis of Women's Roles and Positions in geopolitical organizations

Driven by the global movement for gender equality, women's participation in various fields has gradually increased. This paper describes the evolution of women's roles and status in geopolitical organizations and their current status, and analyzes women's participation in geopolitical organizations, their proportion and positions in leadership, and their influence in policy making. Although the status of women in these organizations has improved, they still face many challenges such as gender stereotypes and inequality. Strategies for promoting the development of women's roles and status in geopolitical organizations include four aspects: formulating and implementing gender equality policies, promoting gender-balanced recruitment and promotion mechanisms, enhancing women's participation in decision-making processes, and establishing women's networks and support systems. These strategies are intended to further promote gender equality in geopolitical organizations and enhance organizational diversity and decision-making quality.

Kinetic mechanism and determinants of EF-P recruitment to translating ribosomes.

EF-P is a translation factor that facilitates the formation of peptide bonds between consecutive prolines. Using FRET between EF-P and ribosomal protein bL33, we studied dynamics and specificity of EF-P binding to the ribosome. Our findings reveal that EF-P rapidly scans for a free E site and can bind to any ribosome containing a P-site tRNA, regardless of the ribosome's functional state. The interaction with uL1 is essential for EF-P binding, while the β-Lys modification of EF-P doubles the association rate. Specific interactions with the D-loop of tRNAPro or tRNAfMet and via the β-Lys group with the tRNA in the peptidyl transferase center reduce the rate of EF-P dissociation from the ribosome, providing the specificity for complexes that need help in catalyzing peptide bond formation. The nature of the E-site codon has little effect on EF-P binding kinetics. Although EF-P dissociation is reduced upon recognizing its correct tRNA substrate, it remains sufficiently rapid compared to tRNA translocation and does not affect the translocation rate. These results highlight the importance of EF-P's scanning-engagement mechanism for dynamic substrate recognition during rapid translation.

Cryo-EM structure of the CBC-ALYREF complex

In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5′ end with a 7-methylguanosine (m7G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5′ end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the NCBP1 and NCBP2 subunits of the CBC. Comparing CBC-ALYREF with other cellular complexes containing CBC and/or ALYREF components provides insights into the coordinated events during mRNA transcription, splicing, and export.

Cryo-EM structure of the CBC-ALYREF complex.

In eukaryotes, RNAs transcribed by RNA Pol II are modified at the 5' end with a 7-methylguanosine (m7G) cap, which is recognized by the nuclear cap binding complex (CBC). The CBC plays multiple important roles in mRNA metabolism, including transcription, splicing, polyadenylation, and export. It promotes mRNA export through direct interaction with a key mRNA export factor, ALYREF, which in turn links the TRanscription and EXport (TREX) complex to the 5' end of mRNA. However, the molecular mechanism for CBC-mediated recruitment of the mRNA export machinery is not well understood. Here, we present the first structure of the CBC in complex with an mRNA export factor, ALYREF. The cryo-EM structure of CBC-ALYREF reveals that the RRM domain of ALYREF makes direct contact with both the NCBP1 and NCBP2 subunits of the CBC. Comparing CBC-ALYREF with other cellular complexes containing CBC and/or ALYREF components provides insights into the coordinated events during mRNA transcription, splicing, and export.

Vps4 substrate binding and coupled mechanisms of Vps4p substrate recruitment and release from autoinhibition.

The ESCRT pathway's AAA+ ATPase, Vps4p, remodels ESCRT-III complexes to drive membrane fission. Here, we use peptide binding assays to further the understanding of substrate specificity and the mechanism of autoinhibition. Our results reveal unexpected sequence preference to the substrate binding groove and an elegant mechanism of regulation that couples localization to substrate with release from autoinhibition.

The molecular mechanism for TERRA recruitment and annealing to telomeres.

Telomeric repeat containing RNA (TERRA) is a noncoding RNA that is transcribed from telomeres. Previous study showed that TERRA trans anneals by invading into the telomeric duplex to form an R-loop in mammalian cells. Here, we elucidate the molecular mechanism underlying TERRA recruitment and invasion into telomeres in the context of shelterin proteins, RAD51 and RNase H using single molecule (sm) assays. We demonstrate that TERRA trans annealing into telomeric DNA exhibits dynamic movement that is stabilized by TRF2. TERRA annealing to the telomeric duplex results in the formation of a stable triplex structure which differs from a conventional R-loop. We identified that the presence of a sub-telomeric DNA and a telomeric overhang in the form of a G-quadruplex significantly enhances TERRA annealing to telomeric duplex. We also demonstrate that RAD51-TERRA complex invades telomere duplex more efficiently than TERRA alone. Additionally, TRF2 increases TERRA affinity to telomeric duplex and protects it from RNase H digestion. In contrast, TRF1 represses TERRA annealing to telomeric duplex and fails to provide protection against RNase H digestion. Our findings provide an in-depth molecular mechanism underpinning TERRA recruitment and annealing to the telomere.

Vacuolar recruitment of retromer by a SNARE complex enables infection-related trafficking in rice blast.

The retromer complex is a conserved sorting machinery that maintains cellular protein homeostasis by transporting vesicles containing cargo proteins to defined destinations. It is known to sort proteins at the vacuole membranes for retrograde trafficking, preventing their degradation in the vacuole. However, the detailed mechanism of retromer recruitment to the vacuole membrane has not yet been elucidated. Here, we show that the vacuolar SNARE complex MoPep12-MoVti1-MoVam7-MoYkt6 regulates retromer-mediated vesicle trafficking by recruiting the retromer to the vacuole membrane, which promotes host invasion in Magnaporthe oryzae. Such recruitment is also essential for the retrieval of the autophagy regulator MoAtg8 and enables appressorium-mediated host penetration. Furthermore, the vacuolar SNARE subunits are involved in suppressing the host defense response by regulating the deployment of retromer-MoSnc1-mediated effector secretion. Altogether, our results provide insights into the mechanism of vacuolar SNAREs-dependent retromer recruitment which is necessary for pathogenicity-related membrane trafficking events in the rice blast fungus.