MBL2 variations and malaria susceptibility in Indian populations

Human Mannose-binding Lectin (MBL) encoded by the MBL2 gene is a pattern recognition protein and has been associated with many infectious diseases, including malaria. We sought to investigate the contribution of functional MBL2 gene variations to Plasmodium falciparum malaria in well-defined cases and in matched controls. We resequenced the 8.7 kb of the entire MBL2 gene in 434 individuals clinically classified with malaria from regions of India where malaria is endemic. The study cohort included 176 patients with severe malaria, 101 patients with mild malaria, and 157 ethnically matched asymptomatic individuals. In addition, 830 individuals from 32 socially, linguistically, and geographically diverse endogamous populations of India were investigated for the distribution of functional MBL2 variants. The MBL2 −221C (X) allelic variant is associated with increased risk of malaria (mild malaria odds ratio [OR] = 1.9, corrected P value [PCorr] = 0.0036; severe malaria OR = 1.6, PCorr = 0.02). The exon1 variants MBL2*B (severe malaria OR = 2.1, PCorr = 0.036; mild versus severe malaria OR = 2.5, PCorr = 0.039) and MBL2*C (mild versus severe malaria OR = 5.4, PCorr = 0.045) increased the odds of having malaria. The exon1 MBL2*D/*B/*C variant increased the risk for severe malaria (OR = 3.4, PCorr = 0.000045). The frequencies of low MBL haplotypes were significantly higher in severe malaria (14.2%) compared to mild malaria (7.9%) and asymptomatic (3.8%). The MBL2*LYPA haplotypes confer protection, whereas MBL2*LXPA increases the malaria risk. Our findings in Indian populations demonstrate that MBL2 functional variants are strongly associated with malaria and infection severity

Deep Rooting In-Situ Expansion of mtDNA Haplogroup R8 in South Asia

The phylogeny of the indigenous Indian-specific mitochondrial DNA (mtDNA) haplogroups have been determined and refined in previous reports. Similar to mtDNA superhaplogroups M and N, a profusion of reports are also available for superhaplogroup R. However, there is a dearth of information on South Asian subhaplogroups in particular, including R8. Therefore, we ought to access the genealogy and pre-historic expansion of haplogroup R8 which is considered one of the autochthonous lineages of South Asia.Upon screening the mtDNA of 5,836 individuals belonging to 104 distinct ethnic populations of the Indian subcontinent, we found 54 individuals with the HVS-I motif that defines the R8 haplogroup. Complete mtDNA sequencing of these 54 individuals revealed two deep-rooted subclades: R8a and R8b. Furthermore, these subclades split into several fine subclades. An isofrequency contour map detected the highest frequency of R8 in the state of Orissa. Spearman's rank correlation analysis suggests significant correlation of R8 occurrence with geography.The coalescent age of newly-characterized subclades of R8, R8a (15.4+/-7.2 Kya) and R8b (25.7+/-10.2 Kya) indicates that the initial maternal colonization of this haplogroup occurred during the middle and upper Paleolithic period, roughly around 40 to 45 Kya. These results signify that the southern part of Orissa currently inhabited by Munda speakers is likely the origin of these autochthonous maternal deep-rooted haplogroups. Our high-resolution study on the genesis of R8 haplogroup provides ample evidence of its deep-rooted ancestry among the Orissa (Austro-Asiatic) tribes

Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation

Our understanding of the genetics of skin pigmentation has been largely skewed towards populations of European ancestry, imparting less attention to South Asian populations, who behold huge pigmentation diversity. Here, we investigate skin pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic Plain of the Indian subcontinent. Our data confirm the association of rs1426654 with skin pigmentation among South Asians, consistent with previous studies, and also show association for rs2470102 single nucleotide polymorphism. Our haplotype analyses further help us delineate the haplotype distribution across social categories and skin color. Taken together, our findings suggest that the social structure defined by the caste system in India has a profound influence on the skin pigmentation patterns of the subcontinent. In particular, social category and associated single nucleotide polymorphisms explain about 32% and 6.4%, respectively, of the total phenotypic variance. Phylogeography of the associated single nucleotide polymorphisms studied across 52 diverse populations of the Indian subcontinent shows wide presence of the derived alleles, although their frequencies vary across populations. Our results show that both polymorphisms (rs1426654 and rs2470102) play an important role in the skin pigmentation diversity of South Asians

Dynamics and Bifurcation Analysis of an Eco-Epidemiological Model in a Crowley–Martin Functional Response with the Impact of Fear

This article describes a three-species food web model that was developed by considering the interaction between susceptible prey, infected prey, and predator species. It is assumed that susceptible prey species grow logistically in the absence of predators. It is assumed that predators consume susceptible and infected prey and that infected prey consumes susceptible prey. We consider the effect of fear on susceptible prey due to the predator species. Furthermore, the predator consumes its prey in the form of Holling-type and Crowley–Martin-type interactions. Also, infected prey consume susceptible prey in the form of a Holling-type interaction. The conditions of all biologically feasible equilibrium points were examined. The local stability of the systems around these equilibrium points was investigated. Furthermore, the occurrence of Hopf-bifurcation concerning fear ϱ in the system was investigated. Finally, we demonstrate some numerical simulation results to illustrate our main analytical findings

Generalizations and Extensions to Lifting Constructions for Coded Caching

Coded caching is a technique for achieving increased throughput in cached networks during peak hours. Placement delivery arrays (PDAs) capture both placement and delivery scheme requirements in coded caching in a single array. Lifting is a method of constructing PDAs, where entries in a small base PDA are replaced with constituent PDAs that satisfy a property called Blackburn-compatibility. We propose two new constructions for Blackburn-compatible PDAs including a novel method for lifting Blackburn-compatible PDAs to obtain new sets of Blackburn-compatible PDAs. Both of these constructions improve upon previous tradeoffs between rate, memory and subpacketization. We generalize lifting constructions by defining partial Blackburn-compatibility between two PDAs w.r.t. a third PDA. This is a wider notion of Blackburn-compatibility making the original definition a special case. We show that some popular coded caching schemes can be defined as lifting constructions in terms of this extended notion.Comment: Accepted to ISIT 2023, two figures, one tabl

An Eco-Epidemiological Model Involving Prey Refuge and Prey Harvesting with Beddington–DeAngelis, Crowley–Martin and Holling Type II Functional Responses

This paper represents a three-species food web model based on the connections between susceptible prey, infected prey, and predator species. It is considered that in the absence of predator species, prey species grow logistically. Predators consume susceptible and infected prey in the form of Crowley–Martin and Beddington–DeAngelis functional responses. Also, infected prey consumes susceptible prey in the form of Holling type II interactions. Here, prey refuge and harvesting in prey with disease in a prey population are taken into consideration. Positiveness, boundedness, and positive invariance are examined. All biologically feasible equilibrium points are investigated. The local stability of positive equilibria and their global stability are analyzed by the suitable Lyapunov functions. Finally, numerical solutions are analyzed according to our findings

Dynamical Analysis of a Fractional Order Prey–Predator Model in Crowley–Martin Functional Response with Prey Harvesting

In this paper, we investigate a fractional-order predator–prey model incorporating prey harvesting. In a non-delayed model, the Crowley–Martin functional response is studied. We first prove the existence, uniqueness, non-negativity and boundedness of the solutions for the proposed model. Furthermore, the existence of various equilibrium points is analyzed to examine the local asymptotically stable properties, and the suitable Lyapunov function is used to study the globally asymptotic stability. Finally, some numerical simulations are verified for the analytic results

Variations in ncRNA gene LOC284889 and MIF-794CATT repeats are associated with malaria susceptibility in Indian populations

Background: There are increasing evidences on the role of non-coding RNA (ncRNA) as key regulator of cellular homeostasis. LOC284889 is an uncharacterized ncRNA gene on reverse strand to MIF mapped to 22q11.23. MIF, a lymphokine, regulates innate immune response by up-regulating the expression of TLR4, suppressing the p53 activity and has been shown to be involved in malaria pathogenesis. Methods: In this study, the possible effect of MIF variations on malaria susceptibility was investigated by re-sequencing the complete MIF gene along with 1 kb each of 5′ and 3′ region in 425 individuals from malaria endemic regions of the Orissa and Chhattisgarh states of India. The subjects comprised of 160 cases of severe malaria, 101 of mild malaria and 164 ethnically matched asymptomatic controls. Data were statistically compared between cases and controls for their possible association with Plasmodium falciparum malarial outcome. Results: It is the first study, which shows that the allele A (rs34383331T > A) in ncRNA is significantly associated with increased risk to P. falciparum malaria [severe: OR = 2.08, p = 0.002 and mild: OR = 2.09, P = 0.005]. In addition, it has been observed that the higher MIF-794CATT repeats (>5) increases malaria risk (OR = 1.61, p = 0.01). Further, diplotype (MIF-794CATT and rs34383331T > A) 5 T confers protection to severe malaria (OR = 0.55, p = 0.002) while 6A (OR = 3.07, p = 0.001) increases malaria risk. Conclusions: These findings support the involvement of ncRNA in malarial pathogenesis and further emphasize the complex genetic regulation of malaria outcome. In addition, the study shows that the higher MIF-794CATT repeats (>5) is a risk factor for severe malaria. The study would help in identifying people who are at higher risk to malaria and adapt strategies for prevention and treatment