The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis.

Pre-mRNA splicing is a precise regulated process and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs) and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remains largely unknown. Pre-mRNA processing factor 31 (PRPF31) is a constitutive spliceosomal component, which mutations are associated with autosomal dominant retinitis pigmentosa. PRPF31 was found to be mutated in several HMs, but the function of PRPF31 in normal hematopoiesis has not been explored. In our previous study, we generated a prpf31 knockout (KO) zebrafish line and reported that Prpf31 regulates the survival and differentiation of retinal progenitor cells by modulating the alternative splicing of genes involved in mitosis and DNA repair. In this study, by using the prpf31 KO zebrafish line, we discovered that prpf31 KO zebrafish exhibited severe defects in hematopoietic stem and progenitor cell (HSPC) expansion and its sequentially differentiated lineages. Immunofluorescence results showed that Prpf31-deficient HSPCs underwent malformed mitosis and M phase arrest during HSPC expansion. Transcriptome analysis and experimental validations revealed that Prpf31 deficiency extensively perturbed the alternative splicing of mitosis-related genes. Collectively, our findings elucidate a previously undescribed role for Prpf31 in HSPC expansion, through regulating the alternative splicing of mitosis-related genes.

The impact of natural resource consumption on carbon emissions: evidence of a symmetric and asymmetric effect from Sub-Saharan Africa.

Sub-Saharan African countries are among mineral-rich developing countries strategically competing to guarantee sustainable economic development through resource exploration. The possibility of increasing the level of carbon emission due to using low-cost fuels and high pollutants during mineral resource extraction activities leading to environmental degradation continues to draw the attention of researchers and policy makers. This research aims to analyze the response of carbon emissions in the African continent to symmetric and asymmetric shocks on resource consumption, economic growth, urbanization, and energy consumption. Following the Shin et al. (2014a) linear and nonlinear autoregressive distributed lag (ARDL) methodology in panel form, we construct symmetric and asymmetric panel ARDL-PMG model to evaluate both short- and long-run impacts of resource consumption on carbon dioxide emissions for a panel of 44 African countries over the period 2000-2019. The symmetric results show that the effect is not statistically significant despite natural resource consumption positively impacting carbon emission in the long and short runs. Energy consumption was found to affect environmental quality in the long and short runs adversely. Interestingly, economic growth was found to improve environmental quality in the long run significantly, and no significant impact was reported in the case of urbanization. However, the asymmetric results prove that a positive and negative shock to natural resource consumption contributes significantly to carbon emission, contrary to the insignificant impact established in the linear framework. The gradual growth in the manufacturing sector and an expansion in the transportation sector in Africa led to high demand and consumption of fossil fuels. This possibly accounts for the adverse effect of energy consumption on carbon emissions. Most African countries depend mainly on exploring natural resource endowment and agricultural activities to drive the growth of their economies. Due to the weak environmental regulatory frameworks in most African countries and public corruption, multinational companies (MNCs) in the extractive sector do not adhere to environmentally friendly activities. The majority of African countries are also battling illegal mining activities and illicit felling of trees, which may account for the positive relationship between natural resource rents and environmental quality reported. In terms of policy implications of the study, governments in Africa must preserve natural resources, use environmentally friendly and technologically advanced resource extraction methods, opt for green energy, and strictly apply environmental laws to promote environmental quality on the continent.

Incidence and Implications of Twin Gestational Surrogacy at Two Large U.S. Military Hospitals: A 10-Year Retrospective Cohort Study.

INTRODUCTION: Individuals seeking a gestational surrogate often turn to U.S. military dependents due to favorable insurance coverage. Surrogate pregnancies, including multiple gestations, may be at increased risk for adverse outcomes. The objectives of this study were to determine the incidence of surrogacy in a twin population conceived by assisted reproductive technology (ART), assess the impact on the military healthcare system, and determine if there is an increased rate of complications in twin surrogacy pregnancies. MATERIALS AND METHODS: We conducted a 10-year retrospective cohort study of ART-conceived twin gestations at two military hospitals. Charts were reviewed for demographic data, surrogacy status, and obstetric complications. Number of prenatal visits and formal sonograms were tabulated for surrogate pregnancies. Complication rates were compared between groups using Fisher's exact test. RESULTS: Over the 10-year period, 36 of the 249 pregnancies were identified as gestational surrogates, equating to a rate of 14.4%. Surrogate mothers were younger than non-surrogates (29.58 years vs. 33.11 years, P < .001). Care of surrogate pregnancies required a total of 306 prenatal visits and 98 formal ultrasounds. The incidence of gestational diabetes was higher among surrogates compared to other ART-conceived twin pregnancies at 27.8% vs. 12.2% (P < .05), while other complications did not significantly differ. CONCLUSIONS: Approximately one in seven ART-conceived twin gestations were surrogacy pregnancies, requiring significant clinical resources. The incidence of gestational diabetes was higher among surrogate gestations.

Optimizing Fetal Aneuploidy Screening in an Austere Military Clinical Environment: A Prenatal Cost Comparison.

INTRODUCTION: Austere clinical settings, including remote military installations, face unique challenges in screening pregnant women for aneuploidy. The objective of this study was to compare the direct and indirect prenatal costs of traditional 2-part serum-based screening to cell-free DNA (cfDNA) for detection of trisomies 18 and 21 for a military treatment facility with limited in-house perinatal resources. MATERIALS AND METHODS: We identified Naval Hospital Guantanamo Bay as a surrogate for an austere clinical environment. A prenatal cost of care analysis incorporating direct and indirect expenses was performed to compare the 2 aneuploidy screening strategies for a theoretical cohort of 100 patients for detection of trisomies 18 and 21. The baseline aneuploidy uptake rate was determined using a historical cohort. Test performance characteristics were obtained from the contracting laboratory. Aneuploidy rates and costs were calculated using previously published data. RESULTS: Assuming a baseline screen uptake rate of 87%, initial screening using the traditional approach would directly cost $8,285.01 versus $44,140.32 with cfDNA. Considering indirect costs such as travel, consultative services, evaluation and follow-up testing of an abnormal screen result, and lost productivity, the cost difference narrows to $14,458.25 over a 5- to 6-year period. Cost equivalence is achieved when cfDNA is priced at $341.17 per test. CONCLUSION: Cell-free DNA as an initial screening strategy offers enhanced detection rates for trisomies 18 and 21 but remains more costly than traditional screening when incorporating direct and indirect expenses. In a low volume setting with limited resources, the added cost may be justified given the implications of unrecognized aneuploidy.