scholarly journals Sex-specific impact of inbreeding on pathogen load in the striped dolphin

2020 ◽  
Vol 287 (1922) ◽  
pp. 20200195
Author(s):  
Georgios A. Gkafas ◽  
Menno de Jong ◽  
Athanasios Exadactylos ◽  
Juan Antonio Raga ◽  
Francisco J. Aznar ◽  
...  

The impact of inbreeding on fitness has been widely studied and provides consequential inference about adaptive potential and the impact on survival for reduced and fragmented natural populations. Correlations between heterozygosity and fitness are common in the literature, but they rarely inform about the likely mechanisms. Here, we investigate a pathology with a clear impact on health in striped dolphin hosts (a nematode infection that compromises lung function). Dolphins varied with respect to their parasite burden of this highly pathogenic lung nematode ( Skrjabinalius guevarai ). Genetic diversity revealed by high-resolution restriction-associated DNA (43 018 RADseq single nucleotide polymorphisms) analyses showed a clear association between heterozygosity and pathogen load, but only for female dolphins, for which the more heterozygous individuals had lower Sk. guevarai burden. One locus identified by RADseq was a strong outlier in association with parasite load (heterozygous in all uninfected females, homozygous for 94% of infected females), found in an intron of the citron rho-interacting serine/threonine kinase locus (associated with milk production in mammals). Allelic variation at the Class II major histocompatability complex DQB locus was also assessed and found to be associated with both regional variation and with pathogen load. Both sex specificity and the identification of associating functional loci provide insight into the mechanisms by which more inbred individuals may be more susceptible to the infection of this parasite. This provides important insight towards our understanding of the impact of inbreeding in natural populations, relevant to both evolutionary and practical conservation considerations.

Parasitology ◽  
1995 ◽  
Vol 111 (S1) ◽  
pp. S135-S151 ◽  
Author(s):  
B. T. Grenfell ◽  
K. Wilson ◽  
V. S. Isham ◽  
H. E. G. Boyd ◽  
K. Dietz

SUMMARYThe characteristically aggregated frequency distribution of macroparasites in their hosts is a key feature of host–parasite population biology. We begin with a brief review of the theoretical literature concerning parasite aggregation. Though this work has illustrated much about both the sources and impact of parasite aggregation, there is still no definitive analysis of both these aspects. We then go on to illustrate the use of one approach to this problem – the construction of Moment Closure Equations (MCEs), which can be used to represent both the mean and second moments (variances and covariances) of the distribution of different parasite stages and phenomenological measures of host immunity. We apply these models to one of the best documented interactions involving free-living animal hosts – the interaction between trichostrongylid nematodes and ruminants. The analysis compares patterns of variability in experimental infections of Teladorsagia circumcincta in sheep with the equivalent wildlife situation – the epidemiology of T. circumcincta in a feral population of Soay sheep on St Kilda, Outer Hebrides. We focus on the relationship between mean parasite load and aggregation (inversely measured by the negative binomial parameter, k) for cohorts of hosts. The analysis and empirical data indicate that k tracks the increase and subsequent decline in the mean burden with host age. We discuss this result in terms of the degree of heterogeneity in the impact of host immunity or parasite-induced mortality required to shorten the tail of the parasite distribution (and therefore increase k) in older animals. The model is also used to analyse the relationship between estimated worm and egg counts (since only the latter are often available for wildlife hosts). Finally, we use these results to review directions for future work on the nature and impact of parasite aggregation.


2015 ◽  
Vol 26 (3-4) ◽  
pp. 116-123
Author(s):  
A. P. Korzh ◽  
T. V. Zahovalko

Recently, the number of published works devoted to the processes of synanthropization of fauna, is growing like an avalanche, which indicates the extreme urgency of this theme. In our view, the process of forming devices to coexist with human and the results of his life reflects the general tandency of the modern nature evolution. Urbanization is characteristic for such a specific group of animals like amphibians, the evidence of which are numerous literature data. Many researchers use this group to assess the bioindicative quality of the environment. For this aim a variety of indicators are used: from the cellular level of life of organization up to the species composition of the group in different territories. At the same time, the interpretation of the results is not always comparable for different areas and often have significantly different interpretations by experts. Urban environment, primarily due to the contamination is extremely aggressive to amphibians. As a consequence, the urban populations of amphibians may be a change in the demographic structure, affecting the reproductive ability of the population, the disappearance of the most sensitive species or individuals, resizing animals, the appearance of abnormalities in the development, etc. At the same time play an important amphibians in the ecosystems of cities, and some species in these conditions even feel relatively comfortable. Therefore, it is interesting to understand the mechanisms of self-sustaining populations of amphibians in urban environments. To assess the impact of natural and anthropogenic factors on the development of amphibian populations were used cognitive modeling using the program Vensim PLE. Cognitive map of the model for urban and suburban habitat conditions were the same. The differences concerned the strength of connections between individual factors (migration, fertility, pollution) and their orientation. In general, factors like pollution, parasites, predators had negative impact on the population, reducing its number. The birth rate, food and migration contributed to raising number of individuals. Some of the factors affected on the strength to of each other as well: the majority of the factors affected the structure of the population, had an influence on the fertility. Thanks to it the model reflects the additive effect of complex of factors on the subsequent status of the population. Proposed and analyzed four scenarios differing strength and duration of exposure. In the first scenario, a one-time contamination occurs and not subsequently repeated. The second and third scenario assumes half board contamination, 1 year (2 scenario) and two years (scenario 3). In the fourth scenario, the pollution affected the population of amphibians constantly. In accordance with the results of simulation, much weaker than the natural populations respond to pollution - have them as an intensive population growth and its disappearance at constant pollution is slow. Changes to other parameters of the model showed that this pollution is the decisive factor -only the constant action leads to a lethal outcome for the populations. All other components of the model have a corrective effect on the population dynamics, without changing its underlying trand. In urban areas due to the heavy impact of pollution maintaining the population is only possible thanks to the migration process – the constant replenishment of diminishing micropopulations of natural reserves. This confirms the assumption that the form of existence metapopulations lake frog in the city. In order to maintain the number of amphibians in urban areas at a high level it is necessary to maintain existing migration routes and the creation of new ones. Insular nature of the placement of suitable habitats in urban areas causes the metapopulation structure of the types of urbanists. Therefore, the process of urbanization is much easier for those species whicht are capable of migration in conditions of city. In the initial stages of settling the city micropopulationis formed by selective mortality of the most susceptible individuals to adverse effects. In future, maintaining the categories of individuals is provided mainly due to migration processes metapopulisation form of the species of existence is supported). It should be noted that the changes in the previous levels are always saved in future. In the case of reorganizations of individuals we of morphology can assume the existence of extremely adverse environmental conditions that threaten the extinction of the micropopulations. 


2021 ◽  
Vol 149 ◽  
Author(s):  
Jing Wang ◽  
Mian Wang ◽  
Zihao Li ◽  
Xinyin Wu ◽  
Xian Zhang ◽  
...  

Abstract The aim of this study was to explore the impact of polymorphism of PD-1 gene and its interaction with tea drinking on susceptibility to tuberculosis (TB). A total of 503 patients with TB and 494 controls were enrolled in this case–control study. Three single-nucleotide polymorphisms of PD-1 (rs7568402, rs2227982 and rs36084323) were genotyped and unconditional logistic regression analysis was used to identify the association between PD-1 polymorphism and TB, while marginal structural linear odds models were used to estimate the interactions. Genotypes GA (OR 1.434), AA (OR 1.891) and GA + AA (OR 1.493) at rs7568402 were more prevalent in the TB patients than in the controls (P < 0.05). The relative excess risk of interaction (RERI) between rs7568402 of PD-1 genes and tea drinking was −0.3856 (95% confidence interval −0.7920 to −0.0209, P < 0.05), which showed a negative interaction. However, the RERIs between tea drinking and both rs2227982 and rs36084323 of PD-1 genes were not statistically significant. Our data demonstrate that rs7568402 of PD-1 genes was associated with susceptibility to TB, and there was a significant negative interaction between rs7568402 and tea drinking. Therefore, preventive measures through promoting the consumption of tea should be emphasised in the high-risk populations.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 477-477
Author(s):  
Leah K Treffer ◽  
Edward S Rice ◽  
Anna M Fuller ◽  
Samuel Cutler ◽  
Jessica L Petersen

Abstract Domestic yak (Bos grunniens) are bovids native to the Asian Qinghai-Tibetan Plateau. Studies of Asian yak have revealed that introgression with domestic cattle has contributed to the evolution of the species. When imported to North America (NA), some hybridization with B. taurus did occur. The objective of this study was to use mitochondrial (mt) DNA sequence data to better understand the mtDNA origin of NA yak and their relationship to Asian yak and related species. The complete mtDNA sequence of 14 individuals (12 NA yak, 1 Tibetan yak, 1 Tibetan B. indicus) was generated and compared with sequences of similar species from GeneBank (B. indicus, B. grunniens (Chinese), B. taurus, B. gaurus, B. primigenius, B. frontalis, Bison bison, and Ovis aries). Individuals were aligned to the B. grunniens reference genome (ARS_UNL_BGru_maternal_1.0), which was also included in the analyses. The mtDNA genes were annotated using the ARS-UCD1.2 cattle sequence as a reference. Ten unique NA yak haplotypes were identified, which a haplotype network separated into two clusters. Variation among the NA haplotypes included 93 nonsynonymous single nucleotide polymorphisms. A maximum likelihood tree including all taxa was made using IQtree after the data were partitioned into twenty-two subgroups using PartitionFinder2. Notably, six NA yak haplotypes formed a clade with B. indicus; the other four haplotypes grouped with B. grunniens and fell as a sister clade to bison, gaur and gayal. These data demonstrate two mitochondrial origins of NA yak with genetic variation in protein coding genes. Although these data suggest yak introgression with B. indicus, it appears to date prior to importation into NA. In addition to contributing to our understanding of the species history, these results suggest the two major mtDNA haplotypes in NA yak may functionally differ. Characterization of the impact of these differences on cellular function is currently underway.


2021 ◽  
Vol 10 (5) ◽  
pp. 1148
Author(s):  
Makedonka Atanasovska Velkovska ◽  
Katja Goričar ◽  
Tanja Blagus ◽  
Vita Dolžan ◽  
Barbara Cvenkel

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.


Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 471
Author(s):  
Camino Gutiérrez-Corbo ◽  
Bárbara Domínguez-Asenjo ◽  
María Martínez-Valladares ◽  
Yolanda Pérez-Pertejo ◽  
Carlos García-Estrada ◽  
...  

Diseases caused by trypanosomatids (Sleeping sickness, Chagas disease, and leishmaniasis) are a serious public health concern in low-income endemic countries. These diseases are produced by single-celled parasites with a diploid genome (although aneuploidy is frequent) organized in pairs of non-condensable chromosomes. To explain the way they reproduce through the analysis of natural populations, the theory of strict clonal propagation of these microorganisms was taken as a rule at the beginning of the studies, since it partially justified their genomic stability. However, numerous experimental works provide evidence of sexual reproduction, thus explaining certain naturally occurring events that link the number of meiosis per mitosis and the frequency of mating. Recent techniques have demonstrated genetic exchange between individuals of the same species under laboratory conditions, as well as the expression of meiosis specific genes. The current debate focuses on the frequency of genomic recombination events and its impact on the natural parasite population structure. This paper reviews the results and techniques used to demonstrate the existence of sex in trypanosomatids, the inheritance of kinetoplast DNA (maxi- and minicircles), the impact of genetic exchange in these parasites, and how it can contribute to the phenotypic diversity of natural populations.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 516
Author(s):  
Katrien Van Bocxlaer ◽  
Kerri-Nicola McArthur ◽  
Andy Harris ◽  
Mo Alavijeh ◽  
Stéphanie Braillard ◽  
...  

In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form a thin film as the solvent evaporates. In contrast to conventional topical dosage forms, FFSs strongly adhere to the skin, favouring sustained drug delivery to the affected site, reducing the need for frequent applications, and enhancing patient compliance. This study reports the first investigation of the use of film-forming systems for the delivery of DNDI-0690, a nitroimidazole compound with potent activity against CL-causing Leishmania species. A total of seven polymers with or without plasticiser were evaluated for drying time, stickiness, film-flexibility, and cosmetic attributes; three FFSs yielded a positive evaluation for all test parameters. The impact of each of these FFSs on the permeation of the model skin permeant hydrocortisone (hydrocortisone, 1% (w/v) across the Strat-M membrane was evaluated, and the formulations resulting in the highest and lowest permeation flux (Klucel LF with triethyl citrate and Eudragit RS with dibutyl sebacate, respectively) were selected as the FFS vehicle for DNDI-0690. The release and skin distribution of the drug upon application to Leishmania-infected and uninfected BALB/c mouse skin were examined using Franz diffusion cells followed by an evaluation of the efficacy of both DNDI-0690 FFSs (1% (w/v)) in an experimental CL model. Whereas the Eudragit film resulted in a higher permeation of DNDI-0690, the Klucel film was able to deposit four times more drug into the skin, where the parasite resides. Of the FFSs formulations, only the Eudragit system resulted in a reduced parasite load, but not reduced lesion size, when compared to the vehicle only control. Whereas drug delivery into the skin was successfully modulated using different FFS systems, the FFS systems selected were not effective for the topical application of DNDI-0690. The convenience and aesthetic of FFS systems alongside their ability to modulate drug delivery to and into the skin merit further investigation using other promising antileishmanial drugs.


Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1169-1180 ◽  
Author(s):  
Daven C Presgraves ◽  
Emily Severance ◽  
Gerald S Willrinson

Meiotically driven sex chromosomes can quickly spread to fixation and cause population extinction unless balanced by selection or suppressed by genetic modifiers. We report results of genetic analyses that demonstrate that extreme female-biased sex ratios in two sister species of stalk-eyed flies, Cyrtodiopsis dalmanni and C. whitei, are due to a meiotic drive element on the X chromosome (Xd). Relatively high frequencies of Xd in C. dalmanni and C. whitei (13–17% and 29%, respectively) cause female-biased sex ratios in natural populations of both species. Sex ratio distortion is associated with spermatid degeneration in male carriers of Xd. Variation in sex ratios is caused by Y-linked and autosomal factors that decrease the intensity of meiotic drive. Y-linked polymorphism for resistance to drive exists in C. dalmanni in which a resistant Y chromosome reduces the intensity and reverses the direction of meiotic drive. When paired with Xd, modifying Y chromosomes (Ym) cause the transmission of predominantly Y-bearing sperm, and on average, production of 63% male progeny. The absence of sex ratio distortion in closely related monomorphic outgroup species suggests that this meiotic drive system may predate the origin of C. whitei and C. dalmanni. We discuss factors likely to be involved in the persistence of these sex-linked polymorphisms and consider the impact of Xd on the operational sex ratio and the intensity of sexual selection in these extremely sexually dimorphic flies.


Author(s):  
Paulo L. Pfitzinger ◽  
Laura Fangmann ◽  
Kun Wang ◽  
Elke Demir ◽  
Engin Gürlevik ◽  
...  

Abstract Background Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. Methods We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/−physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. Results We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. Conclusion For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.


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