The region encompassing the Sahara and the Arabian Peninsula has seen dramatic changes in Holocene moisture availability. While the highlands of Yemen are sensitive to moisture dynamics, their history remains poorly known. This study provides new information on Holocene environmental change in the Yemeni highlands through analyses of the lithostratigraphy and ostracod stratigraphy of two localities. The diversity and abundance of ostracod populations serve as key environmental indicators, reflecting stability and change in aquatic habitats. Six time periods are identified, each representing distinct phases of environmental and climatic change. Undated gravelly fine sands, possibly of late-glacial or Early Holocene age, indicate dry conditions. Subsequent stages indicate a progression of moister conditions and warmer climates characterized by the formation of ponds and lakes and fluctuations in water availability. Shifts occurred between oligotrophic and eutrophic conditions, and between desiccation trends and wetter conditions. We found the taxonomic composition of ostracod populations in Yemen’s highlands to include species from mountainous regions of Africa and the broader Palaearctic. This research aligns with previously reported data and expands our understanding of past ecosystems and climatic conditions in highland Yemen.

Trichinellosis is a global zoonotic disease affecting humans and nearly all animal species. The intestinal (enteric) phase of trichinellosis is critical, as it determines the course and prognosis of the disease. The medications used in the management of trichinellosis demonstrate inadequate bioavailability, along with a significant level of resistance. Therefore, there is a need for the development of novel agents that enhance the bioavailability of administered medications. Nanobiotechnology has emerged as a significant strategy in treating parasitic diseases. This study examined the use of solid lipid nanoparticles (SLNs) to improve the efficacy of oral ivermectin (IVM) in treating the enteric phase of trichinellosis. Thirty-five Swiss albino mice were divided into seven equal groups as follows: negative control, positive control, albendazole, ivermectin, SLNs, ivermectin loaded on solid lipid nanoparticles (IVM-SLNs), and a combination of IVM-SLNs and albendazole. Mice were sacrificed on the seventh day post-infection. The drugs’ effects were assessed using parasitological, biochemical, histological, histochemical and immunohistochemical analyses. The co-administration of albendazole and IVM-SLNs resulted in a significant decrease in adult burden, inflammatory cell infiltration, and apoptosis. Furthermore, a significant reduction in Cyclooxygenase-2 (COX-2) expression was observed compared to the infected untreated control group, along with improved liver and kidney function indices. In conclusion, the potent trichinocidal effect of a single oral dose of IVM-SLNs against Trichinella adults makes them a promising alternative or adjunct to existing nematicidal agents.

In this opinion article, we discuss the application of critical realism as an alternative model to the biopsychosocial model in the understanding of psychiatric disorders. Critical realism presents a stratified view of reality and recognises mental disorders as emergent phenomena; that is, their full explanation cannot be reduced to explanations at any lower level of biological processes alone. It thus underscores the significance of the depth of ontology, the interaction between agency and structure, and the context dependency and complex nature of causality. Critical realism provides the conceptual and epistemological basis for a more subtle understanding of the aetiology of psychiatric conditions, which is polyfactorial and includes biological, psychological and social dimensions. Through the realisation of the conceptual and applicative shortcomings in the biopsychosocial model, critical realism promises to advance the understanding of mental disorders and enable a more holistic approach to the problem of people with mental disorders.

We introduce the exponentially preferential recursive tree and study some properties related to the degree profile of nodes in the tree. The definition of the tree involves a radix $a\gt 0$. In a tree of size $n$ (nodes), the nodes are labeled with the numbers $1,2, \ldots ,n$. The node labeled $i$ attracts the future entrant $n+1$ with probability proportional to $a^i$.

We dedicate an early section for algorithms to generate and visualize the trees in different regimes. We study the asymptotic distribution of the outdegree of node $i$, as $n\to \infty$, and find three regimes according to whether $0 \lt a \lt 1$ (subcritical regime), $a=1$ (critical regime), or $a\gt 1$ (supercritical regime). Within any regime, there are also phases depending on a delicate interplay between $i$ and $n$, ramifying the asymptotic distribution within the regime into “early,” “intermediate” and “late” phases. In certain phases of certain regimes, we find asymptotic Gaussian laws. In certain phases of some other regimes, small oscillations in the asymototic laws are detected by the Poisson approximation techniques.

Objectives/Goals: Germinal matrix hemorrhage (GMH) is a devastating disease of infancy that results in brain-related pathologies. Following rupture of vasculature in the brain, red blood cell (RBC) lysis, and hemoglobin breakdown results in heme/iron-related toxicities. We hypothesize that these cellular pathologies are mediated in part by the complement system. Methods/Study Population: Post-natal mice on day 4 (P4) were subjected to collagenase induced-GMH and treated with various complement inhibitors that function at different points in the complement pathway and differentially prevent the generation of specific complement activation products. The principle bioactive complement activation products are C3 opsonins (C3b, iC3b, and C3d), the proinflammatory anaphylatoxins (soluble C3a and C5a peptides), and the terminal cytolytic membrane attack complex (MAC). Experimental groups consisted of: Wild-type (WT) naïve mice, and WT GMH-mice treated with either PBS (vehicle), CR2-Crry (C3 inhibitor that blocks all activation products), anti-C5 mAb (blocks C5a and MAC), C5aRA (blocks C5a-C5a receptor interaction), or anti-C7 mAb (blocks MAC). Study endpoints were P7 or P14. Results/Anticipated Results: Following GMH, CR2-Crry treatment decreased MAC deposition on RBC and additionally decreased heme oxygenase-1 expression, heme deposition, and iron-induced inflammation measured at P7. In support of a specific role for the MAC, anti-C7 mAb treatment resulted in similar outcomes and was similarly protective. Anti-C7 mAb treatment also reduced hydrocephalus development at a later time point (P14). A similar result was obtained using C7 deficient mice and with anti-C5 mAb treatment. On the other hand, no protective effect was seen with C5aR blockade, and double knock out of C3aR/C5aR also did not provide protection, indicating no role for the anaphylatoxins C3a and C5a and their receptors expressed on leukocytes and endothelial cells in exacerbating deteriorating outcomes. Discussion/Significance of Impact: Our data indicate a key role for the MAC in RBC induced hemolysis after GMH which serves as a driver of inflammation and early GMH pathogenesis. We further show that we can effectively increase precision by targeting solely the MAC complex acutely. Future work will be undertaken to determine temporal roles of individual complement activation products.

Objectives/Goals: Tacrolimus (TAC) is an immunosuppressant used after hematopoietic stem cell transplant (HSCT). Recently, TAC was found to be metabolized to a novel, less active metabolite by common gut microbiota. Our objective is to determine a microbiome signature that influences oral TAC pharmacokinetic (PK) and to develop a clinical tool to select the TAC dose. Methods/Study Population: This is an observational IRB approved microbiome-pharmacogenomic study using banked biospecimens and clinical data, TAC dose, and PK information from the electronic health record. Adult HSCT patients with pre-transplant DNA and stool specimens were included in this analysis if they received TAC in the first 100 days post-HSCT. A global diversity array was used for DNA pharmacogenomic (PGx) genotyping, and metagenomic shotgun sequencing was used for stool microbiome analysis. Spearman correlation will be used to identify potential stool microbiota associated with TAC PK. TAC trough concentrations at steady state will be modeled using nonlinear mixed effects (NLME) modeling to identify potential genetic and microbiota covariates that influence TAC clearance. Results/Anticipated Results: We identified 53 eligible patients who had available DNA and 90 stool samples. The majority (n = 49, 92.5%) were of European ancestry. These patients had 920 (oral  =  622, IV infusion  =  298) TAC trough blood concentrations. We expect that patients who have high abundance of bacteria that metabolize or reduce the absorption of TAC will have lower blood concentrations and will require a higher IV to oral dose conversion ratio than those with lower abundance. Those patients will also require higher oral TAC daily doses. Low stool microbial diversity is expected to be associated with high oral TAC trough intra-patient variability in the first 100 days post-transplant. In the NLME model, PGx when combined with potential bacterial signature will better explain variability in TAC clearance. Discussion/Significance of Impact: Combining PGx and microbiome biomarkers will provide a better understanding of the factors influencing TAC PK and lead to models for individualized dosing. To our knowledge, this is the first study to investigate the combined influence of microbiome and PGx on drug PK. The study is limited to the availability of samples in the biobank.

Objectives/Goals: Congenital cytomegalovirus (cCMV) continues to be the primary infectious cause of fetal anomalies. The role of fetal natural killer (NK) cells in response to cCMV remains largely unexplored. This study seeks to investigate how fetal NK cells respond to human cytomegalovirus (HCMV) during gestation. Methods/Study Population: Umbilical cord blood and corresponding umbilical cord tissues were collected from fetuses that had no complications during gestation. These samples, provided by the Medical College of Wisconsin Tissue Bank, were processed within 24 hours after live birth. Single-cell suspensions were prepared from the samples, and fetal NK cells were isolated and exposed to HCMV antigen peptides VMAPRTLFL, VMAPRTLIL, VMAPQSLLL, and the human self-peptide ALALVRMLI. These peptides were presented on HLA-E*01:03 BV421-conjugated tetramers produced by the National Institutes of Health Tetramer Core Facility. Additionally, fetal NK cells were also prepared for single-cell RNA sequencing (scRNA-seq), and cells were filtered and clustered based on the number of uniquely expressed genes. Results/Anticipated Results: Through unbiased clustering, our scRNA-seq analysis identified five unique fetal NK cell subsets in umbilical cord blood and four in the corresponding umbilical cord tissue. Notably, fetal NK cells exposed to HCMV during gestation were primarily mature NK cell subsets, while those from unexposed fetuses were mostly immature subsets. Additionally, HCMV-exposed fetal NK cells exhibited a strong recall response to the HCMV antigen, with a notably higher frequency and elevated production of IFN-γ. Conversely, naïve fetal NK cells from fetuses unexposed to HCMV produced significantly lower levels of IFN-γ. Finally, we identified a distinct subset of fetal NK cells that emerge following exposure to the HCMV antigen. Discussion/Significance of Impact: In this study, we show that HCMV infection can influence the formation of specific NK cell subsets and re-exposure to the HCMV antigen can trigger a recall response. These insights could pave the way for the development of innovative NK cell-based immunotherapies aimed at preventing fetuses from developing symptomatic cCMV.

Bobtail squids of the family Sepiolidae, which includes the genus Euprymna, are closely related to, but distinct from the true squids (Teuthoidea). Despite their ecological importance, there have been few studies on the age and growth of bobtail squids using hard parts. This study is the first to use statolith increments to estimate the age of Euprymna hyllebergi collected from the southeastern Arabian Sea. Statoliths were extracted from 80 individuals (24 males, 56 females) of dorsal mantle length (DML) 8–50 mm and total weight 0.45–37 g and assessed for their age. Statolith size ranged from 328 to 836 μm. Assuming a daily deposition of increments, growth was rapid and adult sizes were attained in around 2 months. The age of the individuals varied between 25 days (DML = 8 mm) and 91 days (DML = 37 mm) for males; 33 days (DML = 10 mm) and 92 days (DML = 44 mm) for females. The daily growth rate ranged from 0.20 to 0.49 mm DML day−1 for males and 0.23–0.59 mm DML day−1 for females. The lifespan of E. hyllebergi is short, based on the statolith increment analysis.

Monkeypox virus (MPXV) is a contagious disease that has been endemic in central and west Africa since 1970, characterized by symptoms such as fever, headache, and skin rash. While there is no approved treatment for MPXV infections, vaccination has proven effective in limiting its transmission, and previous smallpox vaccinations may also provide protection against monkeypox. However, the dependence of monkeypox on animal hosts makes eradication more complicated than with smallpox. Research should focus on assessing the safety of the vaccines, their duration of immunity, and their efficacy against the prevalent strains of monkeypox. The virus’s accelerated rate of mutation poses additional challenges, as does the fact that it can be transmitted through animals, making eradication more complex than with smallpox. A comprehensive global immunization strategy is needed to address these complexities and draw on lessons learned from past eradication efforts.

Understanding the development and use of musical instruments in prehistory is often hampered by poor preservation of perishable materials and the relative rarity of durable examples. Here, the authors present a pair of third-millennium BC copper cymbals, excavated at Dahwa, Oman. Although they are the only well-contextualised examples from Arabia, the Dahwa cymbals are paralleled by contemporaneous examples from the Indus Valley and images in Mesopotamian iconography. Not only do the cymbals add to the body of evidence interpreted in terms of Indus migrants in Early Bronze Age Oman, they also suggest shared musical and potentially ritual practices around the Arabian Gulf at that time.

Analcime is an important nanomaterial in: heterogeneous catalysis, selective adsorption, stomatology, sensing, and nanoelectronics. Given its occurrence in limited regions worldwide, achieving low-cost, high-purity synthesis of this zeolite is crucial. The objective of the present study was to synthesize pure analcime from an abundant, naturally occurring clay-rich illite material without the use of an organic template. Various pretreatment methods – NaOH pre-fusion, sonication, and reflux – using 1.5 M NaOH were explored to enhance the material’s reactivity at nanoscale. The resulting samples were annealed hydrothermally at 150°C for 36 h. The effect of the Si/Al mass ratio, ranging from 2 to 4, was examined by incorporating a fumed silica by-product into the optimally pre-treated sample. Characterization using X-ray diffraction (XRD), X-ray fluorescence (XRF), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), Fourier-transform infrared spectroscopy (FT-IR), and Brunauer–Emmett–Teller (BET) surface area measurement confirmed that all pre-treatment routes converted illite (Si/Al≈2) effectively into analcime, demonstrating nanoscale control and synthesis precision. The analcime content achieved 77.8% through hydrothermal synthesis without pre-treatment, while it increased to 80.2%, 83.4%, and 91.7% with sonochemical, reflux, and NaOH pre-fusion pre-treatments, respectively. Notably, high-purity analcime with superior crystallinity was attained using the NaOH pre-fusion pre-treatment of a blend of clay and fumed silica with a Si/Al ratio of 3.71. The zeolite synthesized exhibited a surface area of 23.76 m2 g–1 and a significant cation exchange capacity of 510 meq 100 g–1. These results offer valuable insights into the synthesis of organic-template-free zeolites, emphasizing the importance of precise nanoscale methodology in enhancing clay-phase reactivity. Furthermore, this study distinguishes itself as one of the few in the literature to prepare pure analcime by innovatively combining low-cost precursor clay and fumed silica, contributing to the advancement of nanoscale material synthesis and its applications in technology.