Search Results (34)

Background: Insecticide resistance challenges the vector control efforts towards malaria elimination and proving the development of complementary tools. Targeting the genes that are involved in mosquito fertility and susceptibility to Plasmodium with small molecule inhibitors has been a promising alternative to curb the vector population and drive the transmission down. However, such an approach would require a comprehensive knowledge of the genetic diversity of the targeted genes to ensure the broad efficacy of new tools across the natural vector populations. Methods: Four fertility and parasite susceptibility genes were identified from a systematic review of the literature. The Single Nucleotide Polymorphisms (SNPs) found within the regions spanned by these four genes, genotyped across 2784 wild-caught Anopheles gambiae s.l. from 19 sub-Saharan African (SSA) countries, were extracted from the whole genome SNP data of the Ag1000G project (Ag3.0). The population genetic analysis on gene-specific data included the determination of the population structure, estimation of the differentiation level between the populations, evaluation of the linkage between the non-synonymous SNPs (nsSNPs), and a few statistical tests. Results: As potential targets for small molecule inhibitors to reduce malaria transmission, our set of four genes associated with Anopheles fertility and their susceptibility to Plasmodium comprises the mating-induced stimulator of oogenesis protein (MISO, AGAP002620), Vitellogenin (Vg, AGAP004203), Lipophorin (Lp, AGAP001826), and Haem-peroxidase 15 (HPX15, AGAP013327). The analyses performed on these potential targets of small inhibitor molecules revealed that the genes are conserved within SSA populations of An. gambiae s.l. The overall low Fst values and low clustering of principal component analysis between species indicated low genetic differentiation at all the genes (MISO, Vg, Lp and HPX15). The low nucleotide diversity (>0.10), negative Tajima’s D values, and heterozygosity analysis provided ecological insights into the purifying selection that acts to remove deleterious mutations, maintaining genetic diversity at low levels within the populations. None of MISO nsSNPs were identified in linkage disequilibrium, whereas a few weakly linked nsSNPs with ambiguous haplotyping were detected at other genes. Conclusions: This integrated finding on the genetic features of major malaria vectors’ biological factors across natural populations offer new insights for developing sustainable malaria control tools. These loci were reasonably conserved, allowing for the design of effective targeting with small molecule inhibitors towards controlling vector populations and lowering global malaria transmission. Full article

Drawing on patristic sources and modern Orthodox authors, this paper explores the paradoxes of the heart as the deepest and most hidden place of the human being. The heart can be both the highest and deepest point of an encounter with God, as well as the highest and deepest place of the secret self. The paper describes the difficulty of searching for the place of the heart in the context of the philosophies of interiority, subjectivity, and self and examines the spatial metaphors involving the centrality of the heart. The paper also considers the dynamics of purification, which places the heart at the crossroads between purifying the body and achieving the transparency of intellect through divine illumination. The heart is revealed as the coincidence of dispassion (apatheia) and the purest and most intense charity (agape), which means regaining the purity of desire (oriented to God). As a space of both hiddenness and revelation, the heart invites an apophatic anthropology. Full article

Epilepsy is a multifaceted neurological disorder characterized by recurrent seizures and associated with molecular and immune alterations in key brain regions. The GASH/Sal (Genetic Audiogenic Seizure Hamster, Salamanca), a genetic model for audiogenic epilepsy, provides a powerful tool to study seizure mechanisms and resistance in predisposed individuals. This study investigates the proteomic and immune responses triggered by audiogenic kindling in the inferior colliculus, comparing non-responder animals exhibiting reduced seizure severity following repeated stimulation versus GASH/Sal naïve hamsters. To assess auditory pathway functionality, Auditory Brainstem Responses (ABRs) were recorded, revealing reduced neuronal activity in the auditory nerve of non-responders, while central auditory processing remained unaffected. Cytokine profiling demonstrated increased levels of proinflammatory markers, including IL-1 alpha (Interleukin-1 alpha), IL-10 (Interleukin-10), and TGF-beta (Transforming Growth Factor beta), alongside decreased IGF-1 (Insulin-like Growth Factor 1) levels, highlighting systemic inflammation and its interplay with neuroprotection. Building on these findings, a proteomic analysis identified 159 differentially expressed proteins (DEPs). Additionally, bioinformatic approaches, including Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-expression Network Analysis (WGCNA), revealed disrupted pathways related to metabolic and inflammatory epileptic processes and a module potentially linked to a rise in the threshold of seizures, respectively. Differentially expressed genes, identified through bioinformatic and statistical analyses, were validated by RT-qPCR. This confirmed the upregulation of six genes (Gpc1—Glypican-1; Sdc3—Syndecan-3; Vgf—Nerve Growth Factor Inducible; Cpne5—Copine 5; Agap2—Arf-GAP with GTPase domain, ANK repeat, and PH domain-containing protein 2; and Dpp8—Dipeptidyl Peptidase 8) and the downregulation of two (Ralb—RAS-like proto-oncogene B—and S100b—S100 calcium-binding protein B), aligning with reduced seizure severity. This study may uncover key proteomic and immune mechanisms underlying seizure susceptibility, providing possible novel therapeutic targets for refractory epilepsy. Full article

Ongoing discussions on creation care and agapeic ethic have paid less attention to the interplay between love, creation, waste management challenges, and mission. This paper, therefore, discusses a missional perspective of agapeic ethic as a ground norm for eco-theology and motivation for eco-care (especially proper waste management). An attempt is made to discuss the concept and dimensions of love and the nexus between love, creation, and missional purpose. This paper adopts a non-participant observation of refuse collection as carried out by refuse collectors, the waste disposal practices of people, and the waste handling and disposal practices of selected churches. This research was conducted across Port Harcourt City, Obio Akpor, Ogba/Egbema/Ndoni, Oyibo, and Eleme municipal areas of Rivers State, Nigeria. The churches observed include Protestant Churches (Seventh-Day Adventist Church, Church of Nigeria that is Anglican Communion, and Church of Jesus Christ of Latter-Day Saints); the Roman Catholic Church; Pentecostal Churches (such as Salvation Ministries Worldwide, Redeemed Christian Church of God, and Deeper Life Bible Church); and African Indigenous Churches (namely, the Christ Apostolic Church, Cherubim and Seraphim, and Celestial Church of Christ). The information gathered was critically analysed and used in measuring stakeholders’ disposition to and understanding of the research focus. Ecological liberation hermeneutics was adopted as an interpretative framework, while the eco-justice principles of interconnectedness and purpose were engaged to foreground the underlying issues in this study. This paper argued that Christians’ involvement in proper waste management, keeping both private and public spaces clean, is a morally and divinely imposed duty and a practical testimonial of their love for God, their fellow human beings, and non-human others. This is a fulfilment of the mission where Christian love (agape) serves as an ethical principle of inflicting ‘no harm’ to humans or non-human others. Full article

Strain tolerance is a crucial factor affecting the thermal life of coatings, and a higher strain tolerance can effectively alleviate the thermal stresses on coatings during thermal shock. To improve the strain tolerance, the coating structure was optimized by introducing an intermediate transition layer in this study. The intermediate transition layer material was prepared using a 1:1 volume ratio mixture of 6–8 wt. % Yttria-stabilized zirconia (YSZ) and NiCrAlY powders in the experiments. The coating structure consisted of an Al₂O₃-GdAlO₃ (AGAP) anti-erosion layer, a YSZ layer, an intermediate transition layer, and a bonding layer from top to bottom. After thermal shock experiments at 1500 °C, the coatings with the addition of the intermediate transition layer exhibited different failure modes, with the crack location shifting from between the YSZ and the bonding layer to within the intermediate transition layer, compared to the coatings without the intermediate transition layer. Finite element simulation analysis showed that the intermediate transition layer effectively increased the strain tolerance of the coating and significantly reduced the thermal stress. Furthermore, incorporating an embedded micron agglomerated particle-based (EMAP) thermal barrier coating structure into the intermediate transition layer effectively alleviated thermal stresses and enhanced the coating’s thermal insulation performance. Full article

This research examines the subjective experiences of 10–11-year-old students participating in a social-emotional Education Program on Forgiveness and Agape Love (EPFAL) in Israel. The EPFAL is designed to help students acquire a social-emotional tool to help them deal with the wrongs, vulnerabilities, and injustices they will likely experience later in life. The EPFAL took place as part of a larger international research project evaluating the program’s effectiveness in enhancing students’ well-being and improving the class environment in Northern Ireland, Taiwan, and Israel. The present article presents findings from qualitative, semi-structured interviews of forty students and thirteen teachers who participated in the study in Israel and field notes of class observations conducted during data collection for the larger study. A thematic analysis of the findings suggests that students found the EPFAL interesting, enjoyable, and valuable. The participants experienced cognitive, emotional, and behavioral changes, including changes in the perception of forgiveness. They experienced a sense of empowerment and openness, reduced anger and empathy, and learned to talk about their feelings. This study demonstrates how emotional, behavioral, and cognitive transformations promoted by the EPFAL affect children’s relationships with friends and family and improve the classroom atmosphere. Full article

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues. By comparing genomic patterns, we identified a high level of variability across samples with distinctive genetic changes which allow for the definition of profiles of the early phase with respect to the late metastatic stages. Pathogenic and likely pathogenic variants were abundant in the primary tumor, whereas the metastatic samples exhibited a high level of copy-number variations (CNVs), highlighting a possible genomic instability in the late phases. The most known MPNST-related genes, such as TP53 and SUZ12, were identified in CNVs observed within the primary tumor. Pathway analysis of altered early genes in MPNST pointed to a potential role in cell motility, division and metabolism. Moreover, we employed survival analysis with the TCGA sarcoma genomic dataset on 262 affected patients, in order to corroborate the predictive significance of the identified early and metastatic MPNST driver genes. Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness. Full article

Notably, 56 worldwide experts gathered for the Antimicrobial Assessment on Global Aquaculture Production (AGAP) series of workshops to (1) evaluate the current state of knowledge on antimicrobial use and identify existing gaps; (2) formulate strategies to identify ecologically relevant impact indicators and establish thresholds for assessment; (3) identify pivotal socioeconomic factors and effective governance mechanisms essential for implementing monitoring practices in aquaculture and extending them across sectors and countries for aquaculture sustainability; (4) develop pathways to enhance our comprehension between antibiotic use in aquaculture and antimicrobial resistance; and (5) explore potential antibiotic monitoring tools that can be universally adapted and implemented across region and sectors. The main outcomes were a roadmap for establishing investigation priorities on the relevant topics regarding antibiotic use in aquaculture, socioeconomic drivers for using antibiotics and behaviors that need more robust and transparent regulatory frameworks to guide farmers, training on antimicrobial use, and access to veterinarians and extension services agents for education. Overall, the workshop evidenced the power of collaboration in addressing complex global challenges to achieve sustainable aquaculture. Despite diligent efforts, some constraints may have inadvertently narrowed the possibility of having more experts and left some pertinent topics unaddressed, but they are needed in the discussion. Full article

Long non-coding RNAs (lncRNAs) are well known for their oncogenic or anti-oncogenic roles in cancer development. AGAP2-AS1, a new lncRNA, has been extensively demonstrated as an oncogenic lncRNA in various cancers. Abundant experimental results have proved the aberrantly high level of AGAP2-AS1 in a great number of malignancies, such as glioma, colorectal, lung, ovarian, prostate, breast, cholangiocarcinoma, bladder, colon and pancreatic cancers. Importantly, the biological functions of AGAP2-AS1 have been extensively demonstrated. It could promote the proliferation, migration and invasion of cancer cells. Simultaneously, the clinical significances of AGAP2-AS1 were also illustrated. AGAP2-AS1 was exceptionally overexpressed in various cancer tissues. Clinical studies disclosed that the abnormal overexpression of AGAP2-AS1 was tightly connected with overall survival (OS), lymph nodes metastasis (LNM), clinical stage, tumor infiltration, high histological grade (HG), serous subtype and PFI times. However, to date, the biological actions and clinical significances of AGAP2-AS1 have not been systematically reviewed in human cancers. In the present review, the authors overviewed the biological actions, potential mechanisms and clinical features of AGAP2-AS1 according to the previous studies. In summary, AGAP2-AS1, as a vital oncogenic gene, is a promising biomarker and potential target for carcinoma prognosis and therapy. Full article

Love is a keystone in Franz Rosenzweig’s philosophy, which reaffirmed Judaism’s emphasis on vital, relational love. What “love” exactly means, however, is controversial. In the Christian context, love is often denoted by Agape—which implies (1) that “God is Love”, (2) that love is universal, impartial, and rather endorses the sinner; and (3) that humans should practice and emulate such love. The ultimate expression of Agape is the commandment to love one’s enemy, which is rooted in the Sermon on the Mount (Matthew 5:44). This essay considers Rosenzweig’s understanding of Agape, at the implicit level (since the coining by Anders Nygren of Christian love as “Agape” became widespread only after Rosenzweig’s death). This essay opens by contextualizing Rosenzweig within political theology, in particular vis-à-vis Schmitt. Secondly, it considers Rosenzweig’s approach to Agape in the sense of divine love, and in the sense of the love of enemy. Concerning divine love, Rosenzweig criticized theological Agapism (‘God is love’) which equates God with love, and hence makes love into a dogma or noun, rather than an action or verb, thus depriving divinity’s personal loving agency. Concerning the agapic love of enemy, Rosenzweig discredits its Christian version (for being imperialistic), and advocates its Jewish version of accepting divine judgement. His surprising advocacy of the love of enemies may result from Rosenzweig’s opposition to Gnosticism, which excludes the ‘good God’ from involvement in the physical world. The essay’s conclusion reflects on the role of Agape and its pragmatist versions in the post-secular world of the 21st century and conveys Rosenzweig’s pragmatist contribution in this regard, of recognizing the significance of worldliness and togetherness. Full article

Social isolation and loneliness greatly contribute to negative health consequences in older adults. Technological solutions can be an asset in promoting social connections and healthy behaviours. This paper presents an innovative structure for an Internet of Things (IoT) platform specifically tailored for older persons. The framework utilises a supervised learning algorithm to classify users into four identified profiles to facilitate the adoption and engagement of technology. The platform incorporates wearables, such as socks and smart bands, to track physical activity, and a messaging module to encourage social interaction. The platform processes the acquired data to quantify steps and deliver tailored interventions remotely to the older adults through the AGAPE Assistant, the mHealth solution of the platform. Furthermore, the AGAPE Assistant has a user interface design for older adults, with a focus on their specific needs. Additionally, improving digital literacy among older adults is crucial for maximizing the long-term compliance and benefits of such technological solutions. On the other hand, AGAPE Monitor is a web application used by formal caregivers to configure the tailored interventions. The platform’s usability was assessed using different usability scale questionnaires, which revealed a mild level of user satisfaction and acceptance. The proposed framework is currently being deployed on more than 112 older adults across three countries: Italy, Romania, and Portugal. The proposed framework provides a holistic solution to encourage active ageing by adopting technology, implementing hybrid interventions, and promoting social interactions. Full article

The aim of this paper is to establish a series of links between some of the main religious formulas that arise in Judaism and Christianism and the romantic and confluent love characteristic of modern societies. To carry it out, firstly, we analyze love in historical Judaism, reflecting on the Ahavah formula, the predominant formula in this religious context. Secondly, to study the Christian drift of love, we first analyze how the emergence of this new religious faith (Christianism) provokes a change in the Jewish way of understanding it (love). Subsequently, we analyze some of the three main formulas in which love materializes in Christianism: Agape, Caritas, and Amor Sui. Regarding modern love, we first carry out a contextualization focused on the processes of secularization and individualization, and their impact on it. Afterwards, we present the main features that define both romantic and confluent love, and finally, we analyze the Judeo-Christian characters inherited for such types of love. The methodology used focused on a literature review and theoretical reflection based on this review. The research carried out allows us to establish sociological continuities between Judeo-Christian religious love and modern secular love in the terms used throughout the paper. Full article

HBV infection is challenging to cure due to the persistence of viral covalently closed circular viral DNA (cccDNA). The dedicator of cytokinesis 11 (DOCK11) is recognized as a guanine nucleotide exchange factor (GEF) for CDC42 that has been reported to be required for HBV persistence. DOCK11 is expressed in both the cytoplasm and nucleus of human hepatocytes and is functionally associated with retrograde trafficking proteins Arf-GAP with GTPase domain, ankyrin repeat, and pleckstrin homology domain-containing protein 2 (AGAP2), and ADP-ribosylation factor 1 (ARF1), together with the HBV capsid, in the trans-Golgi network (TGN). This opens an alternative retrograde trafficking route for HBV from early endosomes (EEs) to the TGN and then to the endoplasmic reticulum (ER), thereby avoiding lysosomal degradation. DOCK11 also facilitates the association of cccDNA with H3K4me3 and RNA Pol II for activating cccDNA transcription. In addition, DOCK11 plays a crucial role in the host DNA repair system, being essential for cccDNA synthesis. This function can be inhibited by 10M-D42AN, a novel DOCK11-binding peptide, leading to the suppression of HBV replication both in vitro and in vivo. Treatment with a combination of 10M-D42AN and entecavir may represent a promising therapeutic strategy for patients with chronic hepatitis B (CHB). Consequently, DOCK11 may be seen as a potential candidate molecule in the development of molecularly targeted drugs against CHB. Full article

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients’ blood. Full article

Cannabinoids are receiving great attention as a novel approach in the treatment of cognitive and motor disabilities, which characterize neurological disorders. To date, over 100 phytocannabinoids have been extracted from Cannabis sativa, and some of them have shown neuroprotective properties and the capacity to influence synaptic transmission. In this study, we investigated the effects of a less-known phytocannabinoid, cannabinerol (CBNR), on neuronal physiology. Using the NSC-34 motor-neuron-like cell line and next-generation sequencing analysis, we discovered that CBNR influences synaptic genes associated with synapse organization and specialization, including genes related to the cytoskeleton and ion channels. Specifically, the calcium, sodium, and potassium channel subunits (Cacna1b, Cacna1c, Cacnb1, Grin1, Scn8a, Kcnc1, Kcnj9) were upregulated, along with genes related to NMDAR (Agap3, Syngap1) and calcium (Cabp1, Camkv) signaling. Moreover, cytoskeletal and cytoskeleton-associated genes (Actn2, Ina, Trio, Marcks, Bsn, Rtn4, Dgkz, Htt) were also regulated by CBNR. These findings highlight the important role played by CBNR in the regulation of synaptogenesis and synaptic transmission, suggesting the need for further studies to evaluate the neuroprotective role of CBNR in the treatment of synaptic dysfunctions that characterize motor disabilities in many neurological disorders. Full article