The management and prevention of food losses and waste in low- and middle-income countries: A mini-review in the Africa region.

This mini-review analyses food losses and waste (FLW) management in low- and middle-income countries (LMICs) and identifies potential strategies to improve FLW management efficiency on the African continent. To achieve this aim, a search of grey and published scientific literature-case studies, feasibility studies, theses, peer-reviewed journals, governments and technical reports was performed. Food waste (FW) per capita in sub-Saharan Africa (SSA) was determined to be between 6 and 11 kg capita-1 year-1. Factors militating against FLW management include a lack of infrastructure, waste reduction and mandatory waste management plans, financial support for food redistribution programmes, awareness and a lack of knowledge of FW management and effective approaches. Poor recovery systems, a lack of incentives in FW recycling programmes, a lack of a regulatory and policy framework and institutional weaknesses as well as a lack of sufficient and appropriate education programmes to improve FW source separation and collection rates are all significant challenges in the African region, with negative consequences for the environment and public health. Except for fuel conversion and food scraps for digestion to recover energy, there is a huge potential for composting and using FW as a digestate, which could eventually lead to a reduction in the amount of FW being landfilled or incinerated. The study explores potential interventions to reduce amount of FLW and form a basis for future research in this field and improving FW management efficiency in LMCs, especially on the continent of Africa. It also provides information that could assist researchers, policymakers and decision-makers reduce amount of FLW, aid in the utilization of FW for energy production, and reduce greenhouse gas emissions in the continent, as well as support the achievement of other sustainable development goals, such as 12.3, which is particularly important in the context of the African continent, which is dependent on food imports.

rJararacin, a recombinant disintegrin from Bothrops jararaca venom: Exploring its effects on hemostasis and thrombosis.

Integrins are a family of heterodimeric transmembrane receptors which link the extracellular matrix to the cell cytoskeleton. These receptors play a role in many cellular processes: adhesion, proliferation, migration, apoptosis, and platelet aggregation, thus modulating a wide range of scenarios in health and disease. Therefore, integrins have been the target of new antithrombotic drugs. Disintegrins from snake venoms are recognized by the ability to modulate the activity of integrins, such as integrin αIIbß3, a fundamental platelet glycoprotein, and αvß3 expressed on tumor cells. For this reason, disintegrins are unique and potential tools for examining integrin-matrix interaction and the development of novel antithrombotic agents. The present study aims to obtain the recombinant form of jararacin and evaluate the secondary structure and its effects on hemostasis and thrombosis. rJararacin was expressed in the Pichia pastoris (P. pastoris) expression system and purified the recombinant protein with a yield of 40 mg/L of culture. The molecular mass (7722 Da) and internal sequence were confirmed by mass spectrometry. Structure and folding analysis were obtained by Circular Dichroism and 1H Nuclear Magnetic Resonance spectra. Disintegrin structure reveals properly folded with the presence of ß-sheet structure. rJararacin significantly demonstrated inhibition of the adhesion of B16F10 cells and platelets to the fibronectin matrix under static conditions. rJararacin inhibited platelet aggregation induced by ADP (IC50 95 nM), collagen (IC50 57 nM), and thrombin (IC50 22 nM) in a dose-dependent manner. This disintegrin also inhibited 81% and 94% of the adhesion of platelets to fibrinogen and collagen under continuous flow, respectively. In addition, rjararacin efficaciously prevents platelet aggregation in vitro and ex vivo with rat platelets and thrombus occlusion at an effective dose (5 mg/kg). The data here provides evidence that rjararacin possesses the potential as an αIIbß3 antagonist, capable of preventing arterial thrombosis.

Cationic exchange SPE combined with triple quadrupole UHPLC-MS/MS for detection of GHRHs in urine samples.

The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). Considering the complexity of urine samples and the low concentrations at which these analytes should be detected, analyzing GHRHs is a challenging task. In most of the studies, GHRHs are analyzed using UHPLC-HRMS with an orbitrap. The present developed and validated method for some GHRHs (tesamorelin, CJC-1295, sermorelin (GRF 1-29), sermorelin (3-29)-NH2, somatorelin) is based on the triple quadrupole UHPLC/MS-MS method with solid phase extraction (SPE) with weak cation exchange and is able to detect concentrations as low as 0.2 ng/mL (LOD), a limit of quantification (LOQ) at 0.6 ng/mL, and linearity across the range of 0.1 ng/mL to 1.2 ng/mL. The present method developed by our doping control laboratory was validated according to WADA technical documents for selectivity, limit of detection (LOD), carryover, reliability of detection, stability and recovery. The results show that the method has adequate recoveries and sensitivity, hence, it can be employed for routine screening in anti-doping laboratories.

Thiols as a marker of inflammatory bowel disease activity: a systematic review.

BACKGROUND: Evidence indicates that inflammation in Inflammatory Bowel Disease (IBD) is associated with increased systemic levels of reactive oxygen species. Systemic oxidative stress has been associated with reduced levels of plasma thiols. Less invasive tests capable of reflecting and predicting IBD activity are increasingly sought after. We sought to systematically review the evidence inherent in serum thiol levels as a marker of Crohn's Disease and Ulcerative Colitis activity (PROSPERO: CRD42021255521). METHODS: The highest quality documents for systematic reviews standards were used as reference. Articles were searched on Medline via PubMed, VHL, LILACS, WOS, EMBASE, SCOPUS, COCHRANE, CINAHL, OVID, CTGOV, WHO/ICTRP, OPENGREY, BDTD and CAPES, between August, 03 and September, 03 on 2021. Descriptors were defined according to the Medical Subject Heading. Of the 11 articles selected for full reading, 8 were included in the review. It was not possible to perform a pooled analysis of the studies, as there were no combinable studies between subjects with active IBD and controls/inactive disease. RESULTS: Findings from the individual studies included in this review suggest an association between disease activity and systemic oxidation, as measured by serum thiol levels, however, there are limitations that preclude weighting the study results in a meta-analysis. CONCLUSIONS: We recommend conducting better-designed and controlled studies, that include individuals of both phenotypes and at different stages of IBD, involving a larger number of participants, using the standardization of the technique for measuring serum thiols, to confirm whether thiols can be a good parameter for monitoring the clinical course of these intestinal diseases and the degree of clinical applicability.

Revisiting the dependence of retention factor on the content of organic component in the mobile phase in reversed-phase HPLC.

In high-performance liquid chromatography, the dependence of retention factor k on volumetric fraction ϕ of organic phase is expressed by log k = F(ϕ) with F(ϕ) obtained by measuring log k at different ϕ values. From F(ϕ), a value kw is calculated by taking ϕ = 0. The equation log k = F(ϕ) is applied for predicting k, and kw is a descriptor of hydrophobic character of solutes and stationary phases. Calculated kw should not depend on the nature of organic component of mobile phase but extrapolation procedure leads to different kw for different organic components. The present study shows that the expression of F(ϕ) changes depending on the range of ϕ and the same function F(ϕ) cannot be used for the full range of ϕ from 0 to 1. Consequently, kw obtained by extrapolation of ϕ to zero is not correct because the expression of F(ϕ) was generated by fitting the data using ϕ with higher values. The present study shows the proper way to obtain the value of kw .

Association of GSTM1 Deletion With Progression of CKD in Children: Findings From the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: Loss of function of the product of the GSTM1 gene has been implicated in rapid progression of adult chronic kidney disease (CKD). Its role in pediatric CKD has not been previously described. STUDY DESIGN: Secondary analysis of a prospective observational cohort examining the association between deletions in GSTM1 and progression of CKD. SETTING & PARTICIPANTS: We used data and samples from the prospective Chronic Kidney Disease in Children (CKiD) cohort aged 1-16 years at enrollment with CKD. EXPOSURE: We defined the exposure as fewer than 2 GSTM1 alleles on real-time polymerase chain reaction amplification. OUTCOME: The primary outcome was a composite of 50% decrease in estimated glomerular filtration rate (eGFR) or start of kidney replacement therapy. Secondary outcomes included remission of proteinuria in children with glomerular disease and cardiovascular complications. ANALYTICAL APPROACH: The primary analysis was by Cox proportional hazards model. Analysis was adjusted for age, sex, race, ethnicity, body mass index category, diagnosis category, and eGFR. RESULTS: The analysis included 674 children. Their mean age at most recent visit was 11.9 years; 61% were male, and 20% were Black. There were 241 occurrences of the primary outcome at the time of analysis. After adjustment for baseline characteristics, the risk of progression of CKD for exposed children was 1.94 (95% CI, 1.27-2.97). The effect size was similar with either 1 or 2 deletions (autosomal dominant inheritance). The relationships between number of functional GSTM1 alleles and prespecified secondary outcomes were not statistically significant after adjustment. LIMITATIONS: Missing data, especially for secondary outcomes, and relatively small sample size compared to genetic studies in adults. CONCLUSIONS: GSTM1 deletion is associated with more rapid progression of pediatric CKD after adjustment in this large prospective cohort. No statistically significant associations were seen with secondary outcomes. If replicated, these findings may inform development of interventions for CKD in children.

Role of mesenchymal stromal cells derivatives in diabetic foot ulcers: a controlled randomized phase 1/2 clinical trial.

BACKGROUND: Diabetes-related foot complications have been identified as the most common isolated cause of morbidity among patients with diabetes and the leading cause of amputation. Therefore, new strategies to stimulate skin regeneration may provide a novel therapeutic approach to reduce non-healing ulcer disease. Recently, we demonstrated in proof-of-concept in humans that administration of allogeneic bone marrow mesenchymal stromal cellss derivatives (allo-hBM-MSCDs) is effective in a similar way to the use of allogeneic bone marrow mesenchymal stromal cellss (allo-hBM-MSCs) in grade 2 diabetic foot ulcers (DFUs). AIM: To assess the safety and efficacy profile of the allo-hBM-MSCDs relative to the conventional approach (PolyMen® dressing) in 1/2 clinical trial phases in patients with grade 1 and 2 DFUs. METHODS: In the present study, we used 2 doses of allo-hBM-MSCDs (1 mL) or 1 dose of allo-hBM-MSCs (1 × 106 cells) intradermally injected around wounds and assessed their safety and effectiveness, relative to the conventional approach (PolyMem dressing). Allo-hBM-MSCDs and allo-hBM-MSCs were produced in a certified Good Manufacturing Practice-type Laboratory. Patients with grade 1 and 2 DFUs were randomized to receive allo-hBM-MSCDs (n=12), allo-hBM-MSCs (n=6) or conventional treatment (PolyMem dressing) (n=10). The wound-healing process was macroscopically evaluated until the complete closure of the ulcers. RESULTS: No adverse events were reported. Patients with grade 1 and 2 DFUs treated with either allo-hBM-MSCDs or allo-hBM-MSCs, achieved greater percentages of wound closure, enhanced skin regeneration in shorter times and a greater ulcer-free survival relative to the patients who received conventional treatment. Finally, through proteomic analysis, we elucidated the proteins and growth factors that are secreted by allo-hBM-MSCs and relevant to the wound-healing process. In addition, by combining proteomics with Gene Ontology analysis, we comprehensively classified secreted proteins on both biological process and molecular function. CONCLUSIONS: In this phase 1/2 trial, our cumulative results suggest that 2 doses of allo-hBM-MSCDs combined with a wound dressing are a safe and effective treatment for grade 1 and 2 DFUs.

Ternary water-organic solvent mixtures used for insecticide SPE extraction and analysis with acetylcholinesterase biosensor.

Few biosensors are reported for usage in combination with the organic solvent due to their negative impact on the enzymes. The usage of ternary water-organic solvent mixtures in combination with acetylcholinesterase biosensors allows to increase the useable total content of organic solvents with minimum negative effects to a higher content in comparison with a single organic solvent in water. The combination of acetonitrile/ethanol/water has a smaller negative effect on both enzyme activity and inhibition by insecticides in comparison with acetonitrile/methanol/water mixtures. The insecticides were eluted from solid-phase extraction (SPE) columns with a binary mixture of organic solvents acetonitrile/ethanol in 1/3 ratio and subsequently analysed with an acetylcholinesterase biosensor and the optimum total content of organic solvents of 12%. The analytical method allows the analysis of complex samples with improved selectivity and at improved limits of detection for chlorpyrifos-oxon and carbofuran analysis in river waters and soil samples. The usage of mixtures of organic solvents in combination with enzymes is an interesting approach that allows working with a higher total content of organic solvents than each individual solvent.

Human papilloma virus in the etiopathogenesis of allergic nasal polyposis: A prospective study.

PURPOSE: To evaluate and compare the prevalence of high-risk HPV and low-risk HPV types in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and healthy controls. MATERIALS AND METHODS: A prospective cohort study was conducted in a tertiary care hospital on the patients of CRSwNP undergoing surgical management. All patients underwent preoperative endoscopic evaluation and radiological assessment using NCCT of the nose and paranasal sinuses. The severity of the disease was graded using the Lund-Mackay score on NCCT. All patients underwent endoscopic polypectomy and the sample of tissues was sent for HPV DNA detection using Hybrid Capture II® technique. The clinicopathological characteristics of HPV positive and negative patients were compared. RESULTS: Sixty cases and 20 controls were included in the study. All controls were negative for HPV DNA. 27 patients (45%) had the presence of HPV DNA, out of which 23 had only LR-HPV and 1 had only HR-HPV types. Three patients had both HR-HPV and LR-HPV subtypes. There was a significant difference between the cases and controls for the presence of HPV DNA (p < 0.001). However, the patients with HPV-positive DNA in the nasal specimen did not differ significantly from HPV-negative patients in age, gender, or severity of the disease. CONCLUSIONS: Human papillomaviruses may play a significant role in the etiopathogenesis of CRSwNP, however, do not impact the degree of sinus involvement.

Fetal-Not Maternal-APOL1 Genotype Associated with Risk for Preeclampsia in Those with African Ancestry.

Black Americans are at increased risk for preeclampsia. Genetic variants in apolipoprotein L1 (APOL1) account for much of the increased risk for kidney disease in blacks. APOL1 is expressed in human placenta and transgenic mice expressing APOL1 develop preeclampsia. We evaluated the role of APOL1 variants in human preeclampsia. We determined maternal and fetal APOL1 genotypes in black women with preeclampsia in two populations. At Einstein Montefiore Center (EMC) Affiliated Hospitals, we studied 121 pregnancies in black women with preeclampsia. At University of Tennessee Health Science Center (UTHSC), we studied 93 pregnancies in black women with preeclampsia and 793 pregnancies without preeclampsia. We measured serum markers of preeclampsia soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng). Fetal APOL1 high-risk (HR) genotype was associated with preeclampsia, with odds ratios at EMC and UTHSC of 1.84 (95% CI 1.11, 2.93) and 1.92 (95% CI 1.05, 3.49), respectively. Maternal APOL1 HR genotype was not associated with preeclampsia. Mothers with the fetal APOL1 HR genotype had more cerebral or visual disturbances (63% versus 37%, p = 0.04). In addition, fetal APOL1 HR genotype was associated with a higher sFLT-1/PlGF ratio at birth (p = 0.04). Fetal APOL1 high-risk genotype increases the risk for preeclampsia, likely by adversely affecting placental function. Further research is needed to assess whether APOL1 genetic testing can predict preeclampsia and improve pregnancy outcomes.

Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk.

RATIONALE & OBJECTIVES: Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. STUDY DESIGN: Nested case-control study. SETTING & PARTICIPANTS: 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. EXPOSURE: Maternal and fetal APOL1 risk alleles. OUTCOMES: Preeclampsia. ANALYTICAL APPROACH: Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. RESULTS: Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans. LIMITATIONS: Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. CONCLUSIONS: This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

Efficacy and cost-effectiveness of a Transdiagnostic group-based exercise intervention: study protocol for a pragmatic multi-site randomized controlled trial.

BACKGROUND: Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD). METHODS: This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and cost-effectiveness of the manualized, group-based six-months exercise intervention "ImPuls", among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be block-randomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be self-reported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and cost-utility ratios. DISCUSSION: Despite its promising therapeutic effects, exercise programs are currently not provided within the outpatient mental health care system in Germany. This trial will inform service providers and policy makers about the efficacy and cost-effectiveness of the group-based exercise intervention ImPuls within a naturalistic outpatient health care setting. Group-based exercise interventions might provide an option to close the treatment gap within outpatient mental health care settings. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Register (ID: DRKS00024152 , 05/02/2021).

Derivatization procedures and their analytical performances for HPLC determination in bioanalysis.

Derivatization, or chemical structure modification, is often used in bioanalysis performed by liquid chromatography technique in order to enhance detectability or to improve the chromatographic performance for the target analytes. The derivatization process is discussed according to the analytical procedure used to achieve the reaction between the reagent and the target compounds (containing hydroxyl, thiol, amino, carbonyl and carboxyl as the main functional groups involved in derivatization). Important procedures for derivatization used in bioanalysis are in situ or based on extraction processes (liquid-liquid, solid-phase and related techniques) applied to the biomatrix. In the review, chiral, isotope-labeling, hydrophobicity-tailored and post-column derivatizations are also included, based on representative publications in the literature during the last two decades. Examples of derivatization reagents and brief reaction conditions are included, together with some bioanalytical applications and performances (chromatographic conditions, detection limit, stability and sample biomatrix).

Rethinking sustainability: a review of Liberia's municipal solid waste management systems, status, and challenges.

The appalling state of Liberia's municipal solid waste management system (MSWM) is the motivation for this review and analysis. Solid waste management protocols and system dynamic modeling support policy development as it uses waste prevention to explain the complex waste management systems and suggests methods for effective management. However, creating an effective waste system goes beyond the formulation of policies and legislation; it involves financial and technological proficiency, skilled human capacity, technical, social, resource recycling, educational awareness programs, and active public participation. Because of urbanization, Liberia's municipal solid waste (MSW) problems have become heightened, thereby impacting the economic, social, and political fabric of society by overburdening infrastructure and social facilities. The impact of urbanization must be addressed because urbanization, amongst several factors, including unsustainable management of MSW, degrades the environment and presents risks to public health. The purpose of this review was to highlight the current waste management activities in Liberia and provide information to the readers about the challenges facing the waste management sector and the challenges impeding the development of a sustainable waste management system. In Liberia, waste management activities are getting worse daily due to shortage of a comprehensive waste management framework, the absence of guidelines regarding the responsibilities of waste generators, and the decision-makers' lack of intent to design and implement a sustainable and integrated management system. Recommendations for collaborative efforts are made by focusing on delivering a waste strategy which concentrates on waste minimization, recycling, resource recovery, and promoting sustainable waste management practices for communities, small businesses, corporations, and government institutions in Liberia and other developing countries.

Recurrent evolution of melanism in South American felids.

Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP) or the Melanocortin 1 receptor (MC1R) as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo), the kodkod (Leopardus guigna), and Geoffroy's cat (Leopardus geoffroyi). To assess population level variation in the regions surrounding the causative mutations we apply genomic resources from the domestic cat to carry out clone-based capture and targeted resequencing of 299 kb and 251 kb segments that contain ASIP and MC1R, respectively, from 54 individuals (13-21 per species), achieving enrichment of ~500-2500-fold and ~150x coverage. Our analysis points to unique evolutionary histories for each of the three species, with a strong selective sweep in the pampas cat, a distinctive but short melanism-specific haplotype in the Geoffroy's cat, and reduced nucleotide diversity for both ancestral and melanism-bearing chromosomes in the kodkod. These results reveal an important role for natural selection in a trait of longstanding interest to ecologists, geneticists, and the lay community, and provide a platform for comparative studies of morphological variation in other natural populations.

Sample preparation for large-scale bioanalytical studies based on liquid chromatographic techniques.

Quality of the analytical data obtained for large-scale and long term bioanalytical studies based on liquid chromatography depends on a number of experimental factors including the choice of sample preparation method. This review discusses this tedious part of bioanalytical studies, applied to large-scale samples and using liquid chromatography coupled with different detector types as core analytical technique. The main sample preparation methods included in this paper are protein precipitation, liquid-liquid extraction, solid-phase extraction, derivatization and their versions. They are discussed by analytical performances, fields of applications, advantages and disadvantages. The cited literature covers mainly the analytical achievements during the last decade, although several previous papers became more valuable in time and they are included in this review.

The Population Origins and Expansion of Feral Cats in Australia.

The historical literature suggests that in Australia, the domestic cat (Felis catus) had a European origin [~200 years before present (ybp)], but it is unclear if cats arrived from across the Asian land bridge contemporaneously with the dingo (4000 ybp), or perhaps immigrated ~40000 ybp in association with Aboriginal settlement from Asia. The origin of cats in Australia is important because the continent has a complex and ancient faunal assemblage that is dominated by endemic rodents and marsupials and lacks the large placental carnivores found on other large continents. Cats are now ubiquitous across the entire Australian continent and have been implicit in the range contraction or extinction of its small to medium sized (<3.5kg) mammals. We analyzed the population structure of 830 cats using 15 short tandem repeat (STR) genomic markers. Their origin appears to come exclusively from European founders. Feral cats in continental Australia exhibit high genetic diversity in comparison with the low diversity found in populations of feral cats living on islands. The genetic structure is consistent with a rapid westerly expansion from eastern Australia and a limited expansion in coastal Western Australia. Australian cats show modest if any population structure and a close genetic alignment with European feral cats as compared to cats from Asia, the Christmas and Cocos (Keeling) Islands (Indian Ocean), and European wildcats (F. silvestris silvestris).

Sequencing rare and common APOL1 coding variants to determine kidney disease risk.

A third of African Americans with sporadic focal segmental glomerulosclerosis (FSGS) or HIV-associated nephropathy (HIVAN) do not carry APOL1 renal risk genotypes. This raises the possibility that other APOL1 variants may contribute to kidney disease. To address this question, we sequenced all APOL1 exons in 1437 Americans of African and European descent, including 464 patients with biopsy-proven FSGS/HIVAN. Testing for association with 33 common and rare variants with FSGS/HIVAN revealed no association independent of strong recessive G1 and G2 effects. Seeking additional variants that might have been under selection by pathogens and could represent candidates for kidney disease risk, we also sequenced an additional 1112 individuals representing 53 global populations. Except for G1 and G2, none of the 7 common codon-altering variants showed evidence of selection or could restore lysis against trypanosomes causing human African trypanosomiasis. Thus, only APOL1 G1 and G2 confer renal risk, and other common and rare APOL1 missense variants, including the archaic G3 haplotype, do not contribute to sporadic FSGS and HIVAN in the US population. Hence, in most potential clinical or screening applications, our study suggests that sequencing APOL1 exons is unlikely to bring additional information compared to genotyping only APOL1 G1 and G2 risk alleles.

The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.4 × 10(-29); P (HLA-B-aa-site-116) = 6.5 × 10(-19); P (HLA-C-aa-site-156) = 6.8 × 10(-8) respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

Development of MHC-Linked Microsatellite Markers in the Domestic Cat and Their Use to Evaluate MHC Diversity in Domestic Cats, Cheetahs, and Gir Lions.

Diversity within the major histocompatibility complex (MHC) reflects the immunological fitness of a population. MHC-linked microsatellite markers provide a simple and an inexpensive method for studying MHC diversity in large-scale studies. We have developed 6 MHC-linked microsatellite markers in the domestic cat and used these, in conjunction with 5 neutral microsatellites, to assess MHC diversity in domestic mixed breed (n = 129) and purebred Burmese (n = 61) cat populations in Australia. The MHC of outbred Australian cats is polymorphic (average allelic richness = 8.52), whereas the Burmese population has significantly lower MHC diversity (average allelic richness = 6.81; P < 0.01). The MHC-linked microsatellites along with MHC cloning and sequencing demonstrated moderate MHC diversity in cheetahs (n = 13) and extremely low diversity in Gir lions (n = 13). Our MHC-linked microsatellite markers have potential future use in diversity and disease studies in other populations and breeds of cats as well as in wild felid species.