Genetic Isolation Research Articles

A genetic perspective on the recent demographic history of Ireland and Britain.

While subtle yet discrete clusters of genetic identity across Ireland and Britain have been identified, their recent demographic history is unclear. Using genotype data from 6574 individuals with associated regional Irish or British ancestry, we identified genetic communities by applying Leiden community detection. Using haplotype segments segregated by length as proxy for time, we inferred regional Irish and British demographic histories. Using a subset of Irish participants, we provide genealogical context by estimating the enrichment/depletion of surnames within the Irish genetic communities. Through patterns of haplotype sharing, we find evidence of recent population bottlenecks in Orcadian, Manx and Welsh genetic communities. We observed temporal changes in genetic affinities within and between genetic communities in Ireland and Britain. Structure in Ireland is subtler compared to neighbouring British communities, with the Irish groups sharing relatively more short haplotype segments. In addition, we detected varying degrees of genetic isolation in peripheral Irish and British genetic communities across different time periods. Further, we observe a stable migration corridor between north-east Ireland and south-west Scotland while there is a recent migration barrier between south-east and west Ireland. Genealogical analysis of surnames in Ireland reflects history-Anglo-Norman surnames are enriched in the Wexford community while Scottish and Gallowglass surnames were enriched in the Ulster community. Using these new insights into the regional demographic history of Ireland and Britain across different time periods, we hope to understand the driving forces of rare allele frequencies and disease risk association within these populations.

Demographic and Genetic Impact of the 1742–1743 Plague Epidemic in Córdoba, Argentina: A Bioanthropological Perspective

Background: This study investigates the demographic, genetic, and socioeconomic impact of the 1742–1743 plague epidemic on Córdoba, a key region within the Viceroyalty of Peru. The research focuses on the epidemic’s influence along the Royal Road (Camino Real), the main route connecting Buenos Aires and Lima, addressing a historically overlooked period with a multidimensional approach. Methods: Historical records of deaths, baptisms, and marriages from the Córdoba Archbishopric Archive were analyzed using techniques from historical demography and bioanthropology. Variables such as endogamy, exogamy, average marital distance (AMD), and consanguinity coefficients were evaluated. Results: The findings reveal a significant increase in endogamy (75–82%) and a peak exogamy index of 375 during the 1740–1744 cohort. The AMD rose to 705 km during the epidemic, indicating a shift toward marriages involving individuals from more distant regions. The total consanguinity coefficient (Ft) reached 0.00056, with the non-random component (Fn) driving this increase, suggesting heightened genetic isolation. Conclusions: The 1742–1743 plague epidemic intensified genetic isolation and consanguinity, potentially increasing homozygosity and the prevalence of recessive conditions. These changes highlight the epidemic’s long-term impact on Córdoba’s genetic diversity and demographic patterns within the colonial context.

Evolution under intensive industrial breeding: skull size and shape comparison between historic and modern pig lineages.

Domestication and subsequent human-induced selection has enhanced profound changes in animal morphology. On modern domestic pigs, those transformations encompass not only overall increases in body size but also modifications in skull morphology. While skull morphological differences between modern domestic pigs and wild boar are relatively well-documented, less understood is the variation and underlying mechanisms associated with intensive breeding. In this study, we investigated the rate and direction of phenotypic change of skull morphology using a unique dataset that includes two lineages of German domestic pig that were subjected to similar intensive industrial selection pressures throughout the twentieth century, alongside contemporaneous populations of German wild boar. Size and shape variation of 135 specimens was quantified through geometric morphometrics, with 82 three-dimensional landmarks. We find expected differences in skull shape between wild and domestic pigs, but also convergence between the two domestic lineages through the century of directed breeding, despite population segregation. Our results suggest that cranial morphologies have rapidly responded to selection pressure that is independent of genetic isolation. This also suggests that pig morphotypes quickly reflect human agency and impact upon domestic animal phenotypes, revealing a pathway to investigate early human breeding activity in ancient and historical contexts.

P-593. Does Dolutegravir increase hypercholesterolemia and/or hypertriglyceridemia?

Abstract Background Antiretroviral therapy improved prognosis of people living with HIV (PLWA). WHO recommends Dolutegravir as the preferred treatment option for HIV in all populations considering its high genetic barrier and rare adverse effects compared to other treatments. In Morocco, the transition to Dolutegravir has begun in 2020 with the regimen: tenofovir desproxil fumarate/lamivudine/dolutegravir TDF/3TC/DTG (TLD). Some studies shown increased cholesterol and triglycerides levels on TLD regimens. The purpose of this study is to compare the effect of TLD on cholesterol and triglyceride levels compared to other antiretroviral therapy (ART) regimens. Methods We conducted an observational comparative study at the Infectious diseases department Mohammed VI university hospital Marrakesh, MOROCCO. We included all PLWA admitted between 1st January 2021 and 31 December 2022 put on any ART and having a lipidic dosage. We excluded all patients with previous hypercholesterolemia and/or hypertriglyceridemia. We compared the occurrence of hypercholesterolemia and/or hypertriglyceridemia in PLHIV on TLD with those on other ART. For the statistical analysis a pearson chi-square test was used with the R software. Results We included 173 PLWA; the median age was 33 years. 66.5% were male. The viral load was available in 152 people and was < 1000 copies/mL in 98%. The CD4 count was available in 161 persons and was >200 cells/mm3 in 69.6%. There were 120 persons on TLD arm (69.36%) and 53 on other ART arm (30.64%). On the TLD arm 15 people (12.5%) and 16 (13%) have developped an hypercholesterolemia and/or hypertriglyceridemia respectively versus 10 (18.86%) and 12 (22.64%) have developped an hypercholesterolemia and/or hypertriglyceridemia respectively on the others ART arm, but the difference was statistically non-significant (X2= 0.74; p=0.38) for hypercholesterolemia and (X2= 1.47; p=0.22) for hypertriglyceridemia. Conclusion This study shows that there is no strong evidence of any association between the TLD regimen and the hypercholesterolemia and/or hypertriglyceridemia. The TLD regimen is more safe on the lipidic metabolism compared with other ART. Further large studies are needed to prove this benefit. Disclosures All Authors: No reported disclosures

High speciation in the cryptic Pristimantis celator clade (Anura: Strabomantidae) of the Mira river basin, Ecuador-Colombia.

Over the past decade, research in the montane forests of the Mira River basin, spanning Ecuador and Colombia, has identified it as crucial for the adaptive radiation of flora and fauna, shaped by its complex geological and climatic history. This study focuses on the phylogenetic and systematic revision of a frog clade initially labeled as Pristimantis verecundus, revealing significant cryptic diversity. Through detailed analyses of type material and expanded molecular sampling, we found that the original description actually included specimens representing two additional species, which are described herein. In this work, we discovered and formally described four new species within montane forests at elevations from 1,600 to 2,300 meters. Genetic distances of 3.34% to 14% and clear morphological differences underscore the clade's hidden diversity. We propose renaming the group Pristimantis celator clade within Pristimantis myersi species group and subgenus Trachyphrynus, aligning with phylogenetic evidence and resolving taxonomic ambiguities using the oldest available name, Pristimantis celator (Lynch, 1976). This reclassification includes 14 species, seven formally described, and seven as candidates, distributed across northwestern Ecuador and southwestern Colombia, particularly in Mira and Esmeraldas River basins. The study highlights the Andean orogeny's role in species diversification within Pristimantis celator clade, with geographic barriers like Cerro Golondrinas influencing genetic isolation. Genetic divergences exceeding 3.34% indicate evolutionary isolation across these landscapes. Our findings provide insights into montane ecosystem speciation, emphasizing vicariance, niche adaptation, and altitudinal gradients in shaping biodiversity. A polytomy among three well-supported clades within Pristimantis myersi species group is noted due to incomplete genetic data, yet distinctiveness and evolutionary relationships are affirmed. Cryptic diversity within Pristimantis celator clade links to unique orogenic and climatic conditions, highlighting conservation needs. Lastly, we provide a redescription of Pristimantis verecundus and species identification key to aid future research and conservation in this biogeographically influential region.

Genome Wide Identification of Structure Variations in Five Italian Turkey Populations

Structural variants (SVs) are one of the main sources of genetic variants and have a significant impact on phenotype evolution, disease susceptibility, and environmental adaptations. We used 73 whole genome sequencing (12x) to apply a mapping approach to identify SVs in five turkey populations. A notable degree of genetic isolation was observed between the Basilicata and Apulian populations, as indicated by principal component analysis and admixture results. A total of 11,733 SVs were detected, including 6712 deletions, 2671 duplications, 1430 inversions, and 920 translocations. The Variant Effect Predictor (VEP) analysis predicted various consequences of filtered SVs as follows: intron variants (35.8%), intergenic variants (9.6%), coding sequence variants (8.3%), downstream gene variants (7.5%), and transcript ablations (7.3%). Our functional annotation of genes overlapping with SVs was mainly enriched in recognized pathways governing positive regulation of nucleoplasm, protein binding, mitochondrion, negative regulation of cell population proliferation, identical protein binding, and calcium signaling. We produced a comprehensive SV catalog utilizing unique whole-genome turkey data. This SV catalog not only increases our understanding of genetic diversity in turkeys but also enhances our knowledge of the role of SVs in their phenotypic traits.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry1,2. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter1,2. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry. These two nearby sites show little biological relatedness, despite sharing a distinctive late-Avar culture3,4. We reconstructed six-generation pedigrees at both sites including up to 450 closely related individuals, allowing per-generation demographic profiling of the communities. Despite different ancestry, these pedigrees together with large networks of distant relatedness show absence of consanguinity, patrilineal pattern with female exogamy, multiple reproductive partnerships (for example, levirate) and direct correlation of biological connectivity with archaeological markers of social status. The generation-long genetic barrier was maintained by systematically choosing partners with similar ancestry from other sites in the Avar realm. Leobersdorf had more biological connections with the Avar heartlands than with Mödling, which is instead linked to another site from the Vienna Basin with European-like ancestry. Mobility between sites was mostly due to female exogamy pointing to different marriage networks as the main driver of the maintenance of the genetic barrier.

The genetic demographic history of the last hunter-gatherer population of the Himalayas

Nepal, largely covered by the Himalayan mountains, hosts indigenous populations with distinct linguistic, cultural, and genetic characteristics. Among these populations, the Raute, Nepal’s last nomadic hunter-gatherers, offer a unique insight into the genetic and demographic history of Himalayan foragers. Despite strong cultural connections to other regional foragers, the genetic history of this population remains understudied. This study presents newly genotyped genome-wide SNP data of the Raute to explore their genetic isolation, their origins and potential as an older foraging lineage, and their genetic connections to other regional foragers. Our results show that high levels of inbreeding in the Raute indicate recent genetic isolation. Effective population size estimates suggest a dramatic population decline around 50 generations ago. Strong genetic similarity to Nepalese populations of various subsistence styles highlights a dynamic history of genetic interactions prior to isolation, with particular closeness to historical foragers like the Kusunda and Tharu, but excludes an ancient foraging lineage origin. The study underscores the complexity of human population dynamics in the Himalayas, suggesting a history of extensive interaction between foragers and farmers, followed by isolation and demographic decline among the Raute.

An orally available P1'-5-fluorinated Mpro inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (Mpro) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2XBB1.5 and SARS-CoV-2EG.5.1 than two Mpro inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2XBB1.5 replication without ritonavir in B6.Cg-Tg(K18-hACE2)2-Prlmn/J-transgenic mice, comparably as did ritonavir-boosted nirmatrelvir. When the ancestral SARS-CoV-2 was propagated with nirmatrelvir in vitro, a highly nirmatrelvir-resistant E166V-carrying variant (SARS-CoV-2E166V-P14) readily emerged by passage 14; however, when propagated with TKB272, no variants emerged by passage 25. SARS-CoV-2E166V showed some cross-resistance to TKB272 but was substantially sensitive to the compound. X-ray structural analyses and mass-spectrometric data showed that the E166V substitution disrupts the critical dimerization-initiating Ser1'-E166 interactions, thereby limiting nirmatrelvir's Mpro inhibition but that TKB272 nevertheless forms a tight binding with Mpro's catalytic active sight even in the presence of the E166V substitution. TKB272 shows no apparent genotoxicity as tested in the micro-Ames test. Highly potent TKB272 may serve as a COVID-19 therapeutic, overcome resistance to existing Mpro inhibitors.

Evolutionary Genomics of Two Co-occurring Congeneric Fore Reef Coral Species on Guam (Mariana Islands).

Population structure provides essential information for developing meaningful conservation plans. This is especially important in remote places, such as oceanic islands, where limited population sizes and genetic isolation can make populations more susceptible and self-dependent. In this study, we assess and compare the relatedness, population genetics and molecular ecology of two sympatric Acropora species, A. surculosa sensu Randall & Myers (1983) and A. cf. verweyi Veron & Wallace, 1984 around Guam, using genome-wide sequence data (ddRAD). We further contrast our findings with the results of a recent study on back reef A. cf. pulchra (Brook, 1891) to assess the impact of habitat, colony morphology, and phylogenetic relatedness on these basic population genetic characteristics and generate testable hypotheses for future studies. Both target species were found to have small effective population sizes, low levels of genetic diversity, and minimal population structure around Guam. Nonetheless, A. cf. verweyi had significantly higher levels of genetic diversity, some population structure as well as more clones, close relatives and putative loci under selection. Comparisons with A. cf. pulchra indicate a potentially significant impact by habitat on population structure and genetic diversity while colony morphology seems to significantly impact clonality. This study revealed significant differences in the basic population genetic makeup of two sympatric Acropora species on Guam. Our results suggest that colony morphology and habitat/ecology may have a significant impact on the population genetic makeup in reef corals, which could offer valuable insights for future management decisions in the absence of genetic data.

Sexual selection matters in genetic rescue, but productivity benefits fade over time: a multi-generation experiment to inform conservation.

Globally, many species are threatened by population decline because of anthropogenic changes leading to population fragmentation, genetic isolation and inbreeding depression. Genetic rescue, the controlled introduction of genetic variation, is a method used to relieve such effects in small populations. However, without understanding how the characteristics of rescuers impact rescue attempts interventions run the risk of being sub-optimal, or even counterproductive. We use the red flour beetle (Tribolium castaneum) to test the impact of rescuer sex, and sexual selection background, on population productivity. We record the impact of genetic rescue on population productivity in 24 and 36 replicated populations for ten generations following intervention. We find little or no impact of rescuer sex on the efficacy of rescue but show that a background of elevated sexual selection makes individuals more effective rescuers. In both experiments, rescue effects diminish 6-10 generations after the rescue. Our results confirm that the efficacy of genetic rescue can be influenced by characteristics of the rescuers and that the level of sexual selection in the rescuing population is an important factor. We show that any increase in fitness associated with rescue may last for a limited number of generations, suggesting implications for conservation policy and practice.

Fine-Scale Genetic Structure of Small Fish Populations in Islands: The Case of Brook Charr Salvelinus fontinalis (Mitchill, 1814) in Saint-Pierre and Miquelon (France).

Island ecosystems, particularly vulnerable to environmental challenges, host many endangered native species. Diadromous fish, in particular, are threatened throughout their marine and freshwater habitats. The conservation of these species requires an in-depth understanding of their genetic diversity and structure, to better understand their adaptive potential. We investigated fine-scale population diversity and structure in native brook charr (Salvelinus fontinalis) by genotyping 10 microsatellite loci in 244 individuals at three spatial scales in Saint-Pierre and Miquelon, France. We found limited genetic variability across the archipelago, with particularly low genetic diversity in one island, Langlade. A significant difference in allelic richness was also detected among the three islands, indicating a difference in genetic composition across the archipelago, probably induced by historical stocking actions on both Saint-Pierre and Miquelon. Finally, a strong genetic structure was detected across the archipelago among hydrosystems (overall F ST = 0.19) and even within several of them. The presence of predominant interisland gene flow combined with complete genetic isolation from certain hydrosystems suggests that this contemporary genetic structure is the result of both natural demographic processes during the species postglacial colonization and recent restocking actions. The complex genetic structure of such isolated brook charr subpopulations highlights the importance of considering fine-scale genetic structure in conservation management.

Agriculturally developed areas reduce genetic connectivity for a keystone Neotropical ungulate

AbstractModified landscapes can restrict the movement of organisms, leading to isolation and reduced population viability, particularly for species with extensive home ranges and long‐distance travel, such as white‐lipped peccaries (WLPs, Tayassu pecari). Previous studies have indicated that forested areas favor WLP herd movements, but the impact of the non‐forested areas on their genetic connectivity is unknown. In this study, we used land use and land cover maps and population genetic data to investigate the impact of non‐forested matrices on WLP's genetic connectivity in the Pantanal floodplain and surrounding Cerrado plateau of central‐west Brazil. We compared isolation‐by‐distance (IBD), isolation‐by‐barrier, and isolation‐by‐resistance models and tested 39 hypotheses within a modeling framework. Finally, we identified the optimal areas for ecological corridors based on the most effective landscape model. Barrier and landscape resistance were more strongly correlated with genetic relatedness than the IBD model. The model that received the most robust support considered only forest as habitat. All other classes formed a matrix that impeded gene flow, including agriculture, grassland, savannah, and paved and unpaved roads. WLP herds living in landscapes with reduced forest cover are more vulnerable to the effects of genetic isolation. To maintain gene flow, conservation programs should prioritize strategies that strengthen connections between habitats, including facilitating wildlife road‐crossing structures and creating/restoring ecological corridors to link isolated habitat fragments.Abstract in Portuguese is available with online material.

International Human Adaptability Studies in Skolt Sami Societies in the 1960s

ABSTRACT This article investigates the work of a group of scientists who spent their summers in Sami villages in Northern Finland researching a then-emerging topic: human adaptability. Although their research began as a Finnish endeavour, based on the assumption that the people they examined – the Skolt Sami, Säʹmmlaž in their own language – constituted a primitive genetic isolate, it was incorporated into the International Biological Program’s Human Adaptability section (IBP – HA). As the program’s only common Nordic human adaptability project it attained a prominent place in Nordic adaptability studies. By aligning with this large and ambitious program Nordic researchers gained access to a growing scientific environment that programmatically claimed to have left behind old racial thinking, while at the same time classified research subjects according to pre-war definitions of racial types. Old concepts used in former studies of race were similarly maintained. The project made intrusive claims on the populations under investigation ranging from taking blood to collecting information about mentalities and private lives. Defining indigenous peoples as primitive and isolated influenced every stage of the research conducted on the Sami, and that image was also transmitted to the wider society.

Changes in NNRTI use have not altered the ecology of NNRTI resistance over the last 10 years in people with HIV experiencing virological failure on antiretroviral drugs.

We aimed to determine how non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance profiles have changed over the last decade in people living with HIV (PLWHIV) experiencing virological failure on all antiretroviral treatments, including different NNRTIs. We analysed the use of the different NNRTIs in PLWHIV treated with antiretroviral drugs at an academic centre and the HIV NNRTI resistance profiles observed in cases of virological failure over the last 10 years (2014-23). We used the latest ANRS-MIE algorithm (v33; https://hivfrenchresistance.org/) to analyse the resistance mutation profiles of the HIV reverse transcriptase sequences. During this period, the frequency of NNRTI use remained high, fluctuating slightly between 43.5% (n = 1782/4094) and 39.9% (n = 1758/4421). The use of efavirenz (10.8%-1.5%), nevirapine (7.0%-1.2%), and etravirine (11.0%-1.1%) decreased, whereas the use of rilpivirine (14.7%-26.3%) and doravirine (available from 2018, rising to 9.7% in 2023) increased. These trends were statistically significant for etravirine (P = 0.033) and rilpivirine (P < 0.001). Resistance rates for efavirenz, nevirapine and rilpivirine remained above 15% (efavirenz: 17.3%-16.6%, nevirapine: 16.9%-15.4% and rilpivirine: 17.6%-16.1%). This reflects significant cross-resistance between these three NNRTIs. By contrast, resistance rates were lower for etravirine (7.8%-6.0%) and doravirine (4.9%-4.6%), probably due to differences in their resistance profiles and higher genetic barriers to resistance. The NNRTI class of antiretroviral drugs remains widely used. Changes in the usage of drugs from this class have not altered the ecology of NNRTI resistance in antiretroviral drug-treated PLWHIV with virological failure during the studied period.

The influence of post-glacial migration and hybridization on the gene pool of marginal Quercus pubescens populations in Central Europe.

In Central Europe, the drought-tolerant downy oak (Quercus pubescens) is at the northern edge of its natural distribution range, often growing in small and spatially isolated populations. Here, we elucidate how the population genetic structure of Central European Q. pubescens was shaped by geographic barriers, genetic drift and introgression with the closely related sessile oak (Q. petraea). 27 Q. pubescens populations from the northern margin of Q. pubescens' natural distribution range were sampled. Based on 16 nuclear microsatellite markers (nSSRs), Bayesian clustering and distance-based analyses were performed to determine the intraspecific genetic structure and to identify genetic barriers. To identify drivers of introgression with Q. petraea, generalised linear models were applied to link levels of introgression with environmental conditions. To track post-glacial migration routes, the spatial distribution of haplotypes based on 8 chloroplast microsatellite markers (cpSSRs) was investigated. Based on nSSRs, the study populations of Q. pubescens were divided into a western and an eastern genetic cluster. Within these clusters, more pronounced genetic substructure was observed in the west, probably due to a rugged topography and limited gene flow. Introgression from Q. petraea was more prevalent at wetter and north-exposed sites and in the west. The identified cpSSR haplotypes followed known migration pathways. Our results suggest two late-glacial refugia in or near the southwestern Alps and the southeastern Alps as potential sources for post-glacial migration. Although some genetic exchange is evident in Northern Italy, south of the Alps, the two clusters remain distinct at a large scale. Landscape features and introgression with Q. petraea shaped the genetic substructure at a smaller scale. Our study provides a comprehensive overview of the genetic structure of Q. pubescens in Central Europe, relevant for conservation.

Unraveling the potential structure of a Parnassius butterfly in Japan: Insights into the expansion history.

The Japanese Archipelago consists of a series of isolated yet interconnected islands off the Eurasian continent. The linear topography of the archipelago presents a unique biogeographic context for the dispersal of organisms from the continent. In this study, mitochondrial DNA (mtDNA) and single-nucleotide polymorphism (SNP) variation were employed to elucidate the dispersal history of the Japanese clouded butterfly (Parnassius glacialis) across the Japanese Archipelago, including the northern island (Hokkaido), the main island (Honshu), and Shikoku Island. Network analysis of 1192 bp of mtDNA (cytochrome oxidase I and II) regions revealed 49 haplotypes and three distinct haplotype groups, which correspond geographically to Eastern Japan, Western Japan, and Chugoku-Shikoku. The Chugoku-Shikoku group is the most ancient lineage. Divergence time estimates using whole-genome sequencing of mtDNA suggest that the Japanese lineage diverged from the continental P. glacialis approximately 3.08 million years ago (Ma). Subsequently, the Eastern Japan and Western Japan lineages diverged from the Chugoku-Shikoku lineage around 1.06 Ma, with subsequent divergence of the Eastern and Western Japan lineages at approximately 0.62 Ma. P. glacialis is estimated to have expanded its distribution via a land bridge that once connected China and the Japanese Archipelago. Population structure analysis based on 3067 SNP genotypes revealed five distinct genetic structures within the Japanese Archipelago, indicating geographical differentiation. Through mtDNA and SNP variation analyses, four primary genetic barriers were identified: between Hokkaido and Honshu, between Eastern and Central Japan, within the Kansai region, and in the Chugoku region. The first three barriers correspond to notable geographical features, the Blakiston Line, a line parallel to the Itoigawa-Shizuoka Tectonic Line, and a boundary crossing Lake Biwa. These findings suggest that Japanese P. glacialis diverged from the continental P. glacialis and expanded its range across the Japanese Archipelago via western routes, leading to its current distribution.

Structural aspects of HIV-1 integrase inhibitors: SAR studies and synthetic strategies.

Acquired immunodeficiency syndrome (AIDS) poses a significant threat to life. Antiretroviral therapy is employed to diminish the replication of the human immunodeficiency virus (HIV), extending life expectancy and improving the quality of patients' lives. These HIV-1 integrase inhibitors form robust covalent interactions with Mg2+ ions, contributing to their tight binding, thereby inhibiting the integration of viral DNA into the CD4 cell DNA. The second-generation INSTIs, the most recently approved, exhibit a higher genetic barrier compared to first-generation drugs. Hence, there is a need to develop novel and safe compounds as inhibitors of HIV-1 integrase. This article presents an overview of the current landscape of anti-HIV-1 integrase inhibitors, emphasizing the structure-activity relationship (SAR) of small molecules. The molecules discussed include monocyclic rings consisting of triazoles moiety, and pyrimidine analog along with bicyclic rings with nitrogen-containing moieties. Researchers are exploring anti-HIV-1 integrase inhibitors from natural sources like marine environments, plant extracts, and microbial products, emphasizing the importance of diverse bioactive compounds in combating the virus, which have also been included in the manuscript. The current manuscript will be helpful to the scientific community engaged in the manipulation of small molecules as anti-HIV integrase inhibitors for designing newer leads.

Genetic Variation in the Atlantic Bobtail Squid-Vibrio Symbiosis From the Galician Rías.

Symbiotic marine bacteria that are transmitted through the environment are susceptible to abiotic factors (salinity, temperature, physical barriers) that can influence their ability to colonize their specific hosts. Given that many symbioses are driven by host specificity, environmentally transmitted symbionts are more susceptible to extrinsic factors depending on conditions over space and time. In order to determine whether the population structure of environmentally transmitted symbionts reflects host specificity or biogeography, we analysed the genetic structure of Sepiola atlantica (Cephalopoda: Sepiolidae) and their Vibrio symbionts (V. fischeri and V. logei) in four Galician Rías (Spain). This geographical location is characterized by a jagged coastline with a deep-sea entrance into the land, ideal for testing whether such population barriers exist due to genetic isolation. We used haplotype estimates combined with nested clade analysis to determine the genetic relatedness for both S. atlantica and Vibrio bacteria. Analyses of molecular variance (AMOVA) were used to estimate variation within and between populations for both host and symbiont genetic data. Our analyses reveal a low percentage of variation among and between host populations, suggesting that these populations are panmictic. In contrast, Vibrio symbiont populations show certain degree of genetic structure, demonstrating that the hydrology of the rías is driving bacterial distribution (and not host specificity). Thus, for environmentally transmitted symbioses such as the sepiolid squid-Vibrio association, abiotic factors can be a major selective force for determining population structure for one of the partners.

Development of Broad‐Spectrum β‐Cyclodextrins‐Based Nanomaterials Against Influenza Viruses

ABSTRACTIn recent decades, epidemics and pandemics have multiplied throughout the world, with viruses generally being the primary responsible agents. Among these, influenza viruses play a key role, as they potentially cause severe respiratory distress, representing a major threat to public health. Our study aims to develop new broad‐spectrum antivirals against influenza to improve the response to viral disease outbreaks. We engineered macromolecules (named CD‐SA) consisting of a β‐cyclodextrin scaffold modified with hydrophobic linkers in the primary face, onto which unitary sialic acid epitopes are covalently grafted to mimic influenza virus−host receptors. We assessed the antiviral efficacy, mechanism of action, and the genetic barrier to resistance of this compound against influenza in vitro, ex vivo, and in vivo. We demonstrated that CD‐SA, with a unitary SA, without extensive polysaccharides or specific connectivity, acts as a potent virucidal antiviral against several human influenza A and B viruses. Additionally, CD‐SA displayed antiviral activity against SARS‐CoV‐2, a virus that also relies on sialic acid for attachment. We then assessed the genetic barrier to resistance for CD‐SA. While resistance emerged after six passages with CD‐SA alone, the virus remained sensitive through eight passages when co‐treated with interferon‐λ1 (IFN λ1). Finally, we completed the characterization of the antiviral activity by conducting both ex vivo and in vivo studies, demonstrating a potent antiviral effect in human airway epithelia and in a mouse model of infection, higher than that of Oseltamivir, a currently approved anti‐influenza antiviral. The findings presented in this study support the potential therapeutic utility of a novel β‐cyclodextrin‐based nanomaterial for the treatment of influenza infections and potentially other sialic acid‐dependent viruses.