Resolving haplotype variation and complex genetic architecture in the human immunoglobulin kappa chain locus in individuals of diverse ancestry.

Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of the IG loci has hindered use of standard high-throughput methods for characterizing genetic variation within these regions. To overcome these limitations, we use long-read sequencing to create haplotype-resolved IGK assemblies in an ancestrally diverse cohort (n = 36), representing the first comprehensive description of IGK haplotype variation. We identify extensive locus polymorphism, including novel single nucleotide variants (SNVs) and novel structural variants harboring functional IGKV genes. Among 47 functional IGKV genes, we identify 145 alleles, 67 of which were not previously curated. We report inter-population differences in allele frequencies for 10 IGKV genes, including alleles unique to specific populations within this dataset. We identify haplotypes carrying signatures of gene conversion that associate with SNV enrichment in the IGK distal region, and a haplotype with an inversion spanning the proximal and distal regions. These data provide a critical resource of curated genomic reference information from diverse ancestries, laying a foundation for advancing our understanding of population-level genetic variation in the IGK locus.

Vaccination induces broadly neutralizing antibody precursors to HIV gp41.

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates.

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

Proximity to Hospital-Based Obstetric Care in a Maternity Desert in the Deep South.

Objectives. To examine the accessibility of hospital facilities with maternity care services in 1 rural county in Alabama in preparation for the initiation of prenatal care services at a federally qualified health center. Methods. We analyzed driving distance (in miles) from maternal city of residence in Conecuh County, Alabama to hospital of delivery, using 2019-2021 vital statistics data and geographic information system (GIS) software. Results. A total of 370 births to mothers who have home addresses in Conecuh County were reported, and 368 of those were in hospital facilities. The majority of deliveries were less than 30 miles (median = 23 miles) from the maternal city of residence. Some women traveled more than 70 miles for obstetrical care. Conclusions. Pregnant patients in Conecuh County experience significant geographic barriers related to perinatal care access. Using GIS for this analysis is a promising approach to better understand the unique challenges of pregnant individuals in this rural population. Public health policy efforts need to be geographically tailored to address these disparities. (Am J Public Health. 2024;114(S4):S330-S333. https://doi.org/10.2105/AJPH.2024.307692).

Ticks of Alabama: the fauna and spatial distribution of medically important species across the state.

The last statewide survey of hard ticks in Alabama was in 1972. To address this deficit, we examined the distribution of the medically important species across the state, Ixodes scapularis (Say), Dermacentor variabilis (Say), Amblyomma americanum (L.), and A. maculatum (Koch), between April, 2018 and February, 2021. Collections primarily involved dragging (April to July) and examination of harvested deer (November to February). A total of 2,927 ticks was collected from 110 sites; three species, I. scapularis, A. americanum, and D. variabilis, represented 91.70% of all ticks collected. Amblyomma americanum and D. variabilis were the most common species encountered in drags; I. scapularis dominated deer collections. Dermacentor variabilis was never found on deer, whereas D. albipictus was only found on deer. Stepwise regression (AIC) of drag data was linked to several site variables. Results suggest a linear response along a south (low abundance) to north (high abundance) gradient, in addition to increased abundance at sites with lower temperatures and greater precipitation and canopy cover.

Exploration of sub-field microclimates and winter temperatures: Implications for precision agriculture.

The field of precision agriculture has brought the concept for "big data" to farming by bringing sensor technology into the field allowing growers to make more efficient management decisions. However much of the research and practice of precision agriculture has focused on soil-related issues while sub-field microclimates have been mostly unstudied despite their known importance to crop production. This study sought to explore the differences in temperature at a sub-field level during an entire season using weather microsensors recording data every minute from 11 Dec 2017 to 11 Apr 2018. Twenty-two cost-effective sensors were placed within a ~ .5 ha area satsuma orange (Citrus unshiu) grove along the Gulf Coast on Baldwin County, Alabama. The sensors were placed in aerated housings in a vertical column on the west face of eleven trees at a height of 1 and 2 m off the ground. We focus on several events where temperatures hovered near 0 °C or near - 7 °C, a temperature known to damage satsuma trees and find that temperatures can vary by as much as 1.5 to 2 °C at the same moment in the same grove. Extreme cold events were also found to be non-uniform within the grove, and the response was seen on a tree-by-tree basis where increased exposure to < - 7 °C temperatures led to increase defoliation (r2 = 0.92) and lower fruit count in the following year (r2 = 0.71). We discuss the implication of these differences in temperature and what it may mean for the future of precision agriculture.

Impacts of Pre-bloom Leaf Removal on Wine Grape Production and Quality Parameters: A Systematic Review and Meta-Analysis.

Wine grape (Vitis vinifera L.) is the most widely cultivated fruit crop in the world. However, the climactic characteristics in some growing regions are suboptimal for grape production, including short season length and excess precipitation. Grape growers can utilize an array of methods to mitigate these issues, including "early leaf removal," a management practice involving the removal of leaves from selected basal nodes along shoots around bloom. This meta-analysis reviews the extensive literature on this practice, with specific regards to application at "pre-bloom" (PB). One hundred seventy-five publications on the topic of "early leaf removal" were identified using key terms and subsequently narrowed via eight data curation steps. The comparison between treated (PB) and control plants in these studies revealed two important results. First, PB lowered bunch rot disease (-61%), partially through reducing the compactness of clusters. Second, PB promoted a significant increase in fruit total soluble solids (°Brix, +5.2%), which was related to the increase in the leaf-to-fruit ratio. Furthermore, cultivar and rootstock were found to have a large influence on the success of PB, while the contribution of climate was smaller. In conclusion, PB significantly lowers yield and bunch rot disease and increases °Brix, both of which improve grape and wine quality.

Demographic and spatial trends in diabetes-related virtual nursing examinations.

Diabetes currently affects nearly 30 million Americans, but the distribution of cases is not uniform across all demographics or every state. In the course of their education, nurses learn how to become important conduits for information on diabetes management during their eventual interactions with patients. Exploring the status and trends of diabetes-related knowledge in nursing students is one method to explore the idea that one's community affects how one sees disease. However, they are not yet experts, which places them in a period of transition. This study used data mined from the Shadow Health Digital Clinical Experience™ virtual patient exams conducted by nursing students between the years of 2012 and 2015 to find any potential demographic or spatial trends within simulation performance results from nursing students who examined a virtual patient with self-managed diabetes. Findings of the analysis indicated that age and experience affected the way in which an examination was conducted, where older and more experienced nursing students asked 8% fewer examination questions, yet showed 32% more empathy and offered 76% more educational statements than their younger counterparts. Spatial trends were less pronounced, although deeper analysis revealed that students in states closer to the national mean for population rate with diabetes perform better, show more empathy, and offer more educational statements during examinations compared to states well above or well below the national mean. This suggests that targeted information may be preferable to "one-size-fits-all" public health awareness and education programs for diabetes programs used uniformly across the country.

Effects of a warming trend on cool climate viticulture in Michigan, USA.

Historically, Michigan's climate had mainly three challenges for grape production: growing season temperatures were too low, the growing season was too short and there was too much rain near harvest. However, climate change in the past decades has led to a vastly different landscape that is evolving to meet the new climate. Recently, there has been a significant move from Vitis labrusca (North American) grape plantings to Vitis vinifera (wine grapes) as a consequence of Michigan's shifting climate. The goal of this study was to analyze the historical shift in climate and its potential future impact on the grape industry. We obtained data climate model projection data from two greenhouse gas (GHG) emission scenarios. First, a multi-linear regression model was built to predict future grape yields (t/ac) using data from the climate model projections. Second, trends in the severity of the three challenges (temperature, season length, precipitation timing) were analyzed. In both GHG scenarios grape yields are seen to improve, but to different extents. The improvement is likely a response to warmer season temperatures canceling out losses to early season frost. Model projections recommend that Michigan's future climate will be more accommodating for all varieties of grapes. This suggests that grape production will continue to grow, but the landscape will continue to evolve with more emphasis on varieties that are more climatically sensitive to cold temperatures. Climate change has greatly affected Michigan's viticultural landscape, and will continue to do so in the coming decades.