THE PAULINE CONCEPT OF DISCIPLESHIP AS A MODEL FOR ADDRESSING THE YOUTH DROPOUT IN THE TWENTY-FIRST CENTURY UNITED STATES OF AMERICA CHURCH.

The dropout rate of more than five million young adults from faith and church in the last decade, who were originally born and raised in Christian homes, has reached a critical point. The Christian community must rethink its discipleship methods in order to impact the youth of today. The researcher explored the root causes of the problem and identified that the current discipleship assumptions and strategies, rooted in modern mechanistic mass production paradigm do not work. Therefore, these assumptions and strategies must give way to a personally crafted one-on-one relational fatherly mentorship interconnected approach for the faith formation of the youth of the Church in the United States. Existing research findings from Barna, Pew, and Fuller Institute indicated a crucial need for a new ecosystem of spiritual and vocational apprenticeship. This system can support deeper relationships and more vibrant faith formation and discipleship, which must be intentionally pursued by church leaders of today. During the first century, the Apostle Paul, undoubtedly understood the concept of one-on-one relational mentorship. His discipleship efforts impacted significantly the lives of young adults like Timothy, Titus, Luke, and Onesimus, to name a few. Paul\u27s influence on these young men was so impactful that his departure from active ministry following his arrest in Jerusalem did not affect negatively the growth of the church. The researcher identified the great principles of the Pauline concept of discipleship, including love, relationship, fathering, and mentorship, and has employed these concepts to address the reasons youth gave for their disconnection from faith and church. These include, but are not limited to overprotective parents and leaders, shallow teachings, anti-science rhetoric, repressive bias, doubts, and exclusivity. Leaders of the twenty-first-century church in the United States of America must innovatively adopt and incorporate the basic principles of the Pauline model of discipleship to end or at least minimize the current youth dropout rate

Modulation of inflammatory process and tissue regeneration in calvaria mouse models

MicroRNAs (miRNAs) are short, non-coding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert innate immune response. In this study, we analyzed bacterial modulation of miRNAs in bone-marrow-derived macrophages (BMMs), in which activity was induced by infection with Porphyromonas gingivalis (Pg) through a microarray analysis. Several miRNA expressions levels were modulated 3 hours post infection (at a multiplicity of infection (MOI) of 25). A bioinformatics analysis was performed to further identify pathways related to the innate immune host-response pathways that are under the influence of the selected miRNAs. To assess the effects of the identified miRNAs on cytokines secretion (pro inflammatory TNF-α and anti-inflammatory IL-10), BMMs were transfected with selected miRNAs mimics or inhibitors. Transfection with mmu-miR-155 and mmu-miR- 2137 did not modify TNF-α secretion while their inhibitors increased it. Inhibitors of mmumiR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory IL-10. In Pginfected BMMs, mmu-miR-155-5p significantly decreased TNF-α secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a Pg-induced calvarial bone resorption mouse model, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatorycell infiltration, osteoclast activity and bone loss. Bioinformatics analysis demonstrated that pathways related to cytokines and chemokines related pathways but also osteoclast differentiation may be involved in the observed effects. The study highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmu-miR-2137 to control inflammation induced by Pg infection. To assess the regenerative process in the same animal model, we aimed to compare the effect of Bone Morphogenic Protien 2 (BMP2), Platelets Rich Plasma (PRP), Leukocyte-Platelets Rich Fibrin (L-PRF), and Polygucosamine (PGIcNAc) on bone formation in critical size bone defects in mice. One-hundred-thirty-eight mice were divided into 23 groups (n=6), negative control, different combinations of the PGIcNAc with or without of BMP2, Collagen Sponge (SurgiFoam), PRP, and L-PRF. The 5mm defect, then, was allowed to heal. After six weeks, samples were analyzed for bone formation utilizing radiographs, H&E staining, alkaline phosphatase staining. Our results show that BMP2 were able to produce 90-95% healing of critical size defects after six weeks histologically and radiographically. However, SurgiFoam, PRP and L-PRF with or without PGIcNAc were able to close 60% of the original defect. This study supports that BMP2 is more effective for bone regeneration than SurgiFoam, PRP, L-PRF and PGIcNAc

Characterization of Bismuth Titanate by Line Profile Analysis

Bismuth Titanate (BIT), Bi4Ti3O12, was synthesized using the solid-state reaction process from the oxide mixture of Bi2O3CO3 and TiO2. The characterization analysis of the prepared sample was done by X-ray diffraction technique. The X-ray diffraction data revealed an orthorhombic perovskite phase that was clearly explained. The Scherrer method, modified W-H analysis, and the SSP studies were conducted to figure out the crystallite size and micro strain in Bi4Ti3O12. Morphological studies included SEM and TEM analysis.  FTIR spectral investigation supports the M-O coordination of the synthesized Bi4Ti3O12 sample. The phase formation patterns of Bi4Ti3O12 determined by different methods are highly connected

HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.</div

Lem2 is essential for cardiac development by maintaining nuclear integrity

AIMS: Nuclear envelope integrity is essential for the compartmentalization of the nucleus and cytoplasm. Importantly, mutations in genes encoding nuclear envelope (NE) and associated proteins are the second highest cause of familial dilated cardiomyopathy. One such NE protein that causes cardiomyopathy in humans and affects mouse heart development is Lem2. However, its role in the heart remains poorly understood. METHODS AND RESULTS: We generated mice in which Lem2 was specifically ablated either in embryonic cardiomyocytes (Lem2 cKO) or in adult cardiomyocytes (Lem2 iCKO) and carried out detailed physiological, tissue, and cellular analyses. High-resolution episcopic microscopy was used for three-dimensional reconstructions and detailed morphological analyses. RNA-sequencing and immunofluorescence identified altered pathways and cellular phenotypes, and cardiomyocytes were isolated to interrogate nuclear integrity in more detail. In addition, echocardiography provided a physiological assessment of Lem2 iCKO adult mice. We found that Lem2 was essential for cardiac development, and hearts from Lem2 cKO mice were morphologically and transcriptionally underdeveloped. Lem2 cKO hearts displayed high levels of DNA damage, nuclear rupture, and apoptosis. Crucially, we found that these defects were driven by muscle contraction as they were ameliorated by inhibiting myosin contraction and L-type calcium channels. Conversely, reducing Lem2 levels to ∼45% in adult cardiomyocytes did not lead to overt cardiac dysfunction up to 18 months of age. CONCLUSIONS: Our data suggest that Lem2 is critical for integrity at the nascent NE in foetal hearts, and protects the nucleus from the mechanical forces of muscle contraction. In contrast, the adult heart is not detectably affected by partial Lem2 depletion, perhaps owing to a more established NE and increased adaptation to mechanical stress. Taken together, these data provide insights into mechanisms underlying cardiomyopathy in patients with mutations in Lem2 and cardio-laminopathies in general

A comprehensive resource for induced pluripotent stem cells from patients with primary tauopathies

Primary tauopathies are characterized neuropathologically by inclusions containing abnormal forms of the microtubule-associated protein tau (MAPT) and clinically by diverse neuropsychiatric, cognitive, and motor impairments. Autosomal dominant mutations in the MAPT gene cause heterogeneous forms of frontotemporal lobar degeneration with tauopathy (FTLD-Tau). Common and rare variants in the MAPT gene increase the risk for sporadic FTLD-Tau, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). We generated a collection of fibroblasts from 140 MAPT mutation/risk variant carriers, PSP, CBD, and cognitively normal controls; 31 induced pluripotent stem cell (iPSC) lines from MAPT mutation carriers, non-carrier family members, and autopsy-confirmed PSP patients; 33 genome engineered iPSCs that were corrected or mutagenized; and forebrain neural progenitor cells (NPCs). Here, we present a resource of fibroblasts, iPSCs, and NPCs with comprehensive clinical histories that can be accessed by the scientific community for disease modeling and development of novel therapeutics for tauopathies

Learning Cyber Defence Tactics from Scratch with Multi-Agent Reinforcement Learning

Recent advancements in deep learning techniques have opened new possibilities for designing solutions for autonomous cyber defence. Teams of intelligent agents in computer network defence roles may reveal promising avenues to safeguard cyber and kinetic assets. In a simulated game environment, agents are evaluated on their ability to jointly mitigate attacker activity in host-based defence scenarios. Defender systems are evaluated against heuristic attackers with the goals of compromising network confidentiality, integrity, and availability. Value-based Independent Learning and Centralized Training Decentralized Execution (CTDE) cooperative Multi-Agent Reinforcement Learning (MARL) methods are compared revealing that both approaches outperform a simple multi-agent heuristic defender. This work demonstrates the ability of cooperative MARL to learn effective cyber defence tactics against varied threats.Comment: Presented at 2nd International Workshop on Adaptive Cyber Defense, 2023 (arXiv:2308.09520

Respiratory distress of unknown etiology in a transplant recipient: think toxoplasmosis!

Disseminated toxoplasmosis is a life-threatening disease in immunocompromised individuals. Infection is contracted from handling contaminated soil, cat litter, or through the consumption of contaminated water or food. It is the third most common lethal foodborne infection in the United States. In transplant patients, most cases occur as a result of reactivation of a latent infection resulting from immunosuppression. We present a case of disseminated toxoplasmosis diagnosed at the time of autopsy. This case emphasizes the importance of maintaining a high index of clinical suspicion and active disease surveillance in this era of sophisticated diagnostic testing