A high-density linkage map reveals broad- and fine-scale sex differences in recombination in the hihi (stitchbird; Notiomystis cincta).

Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy.

Genomic Tools in Biological Invasions: Current State and Future Frontiers.

Human activities are accelerating rates of biological invasions and climate-driven range expansions globally, yet we understand little of how genomic processes facilitate the invasion process. Although most of the literature has focused on underlying phenotypic correlates of invasiveness, advances in genomic technologies are showing a strong link between genomic variation and invasion success. Here, we consider the ability of genomic tools and technologies to (i) inform mechanistic understanding of biological invasions and (ii) solve real-world issues in predicting and managing biological invasions. For both, we examine the current state of the field and discuss how genomics can be leveraged in the future. In addition, we make recommendations pertinent to broader research issues, such as data sovereignty, metadata standards, collaboration, and science communication best practices that will require concerted efforts from the global invasion genomics community.

Two centuries of biodiversity discovery and loss in Singapore.

There is an urgent need for reliable data on the impacts of deforestation on tropical biodiversity. The city-state of Singapore has one of the most detailed biodiversity records in the tropics, dating back to the turn of the 19th century. In 1819, Singapore was almost entirely covered in primary forest, but this has since been largely cleared. We compiled more than 200 y of records for 10 major taxonomic groups in Singapore (>50,000 individual records; >3,000 species), and we estimated extinction rates using recently developed and novel statistical models that account for "dark extinctions," i.e., extinctions of undiscovered species. The estimated overall extinction rate was 37% (95% CI [31 to 42%]). Extrapolating our Singapore observations to a future business-as-usual deforestation scenario for Southeast Asia suggests that 18% (95% CI [16 to 22%]) of species will be lost regionally by 2100. Our extinction estimates for Singapore and Southeast Asia are a factor of two lower than previous estimates that also attempted to account for dark extinctions. However, we caution that particular groups such as large mammals, forest-dependent birds, orchids, and butterflies are disproportionately vulnerable.

Dense residential areas promote gene flow in dengue vector mosquito Aedes albopictus.

Aedes albopictus is a successful disease vector due to its ability to survive in a wide range of habitats. Despite its ubiquity and impact on public health, little is known about its differential gene flow capabilities across different city habitats. We obtained a comprehensive dataset of >27,000 genome-wide DNA markers across 105 wild-caught Ae. albopictus individuals from Singapore, a dengue-endemic tropical city with heterogeneous landscapes from densely populated urban areas to forests. Despite Singapore's challenging small-scale heterogeneity, our landscape-genomic approach indicated that dense urban areas are characterized by higher Aedes gene flow rates than managed parks and forests. We documented the incidence of Wolbachia infections of Ae. albopictus involving two strains (wAlbA and wAlbB). Our results dispel the misconception that substantial dispersal of Ae. albopictus is limited to urban greenery, with wide implications for vector management and critical insights into urban planning strategies to combat dengue transmission.

Megafaunal extinctions, not climate change, may explain Holocene genetic diversity declines in Numenius shorebirds.

Understanding the relative contributions of historical and anthropogenic factors to declines in genetic diversity is important for informing conservation action. Using genome-wide DNA of fresh and historic specimens, including that of two species widely thought to be extinct, we investigated fluctuations in genetic diversity and present the first complete phylogenomic tree for all nine species of the threatened shorebird genus Numenius, known as whimbrels and curlews. Most species faced sharp declines in effective population size, a proxy for genetic diversity, soon after the Last Glacial Maximum (around 20,000 years ago). These declines occurred prior to the Anthropocene and in spite of an increase in the breeding area predicted by environmental niche modeling, suggesting that they were not caused by climatic or recent anthropogenic factors. Crucially, these genetic diversity declines coincide with mass extinctions of mammalian megafauna in the Northern Hemisphere. Among other factors, the demise of ecosystem-engineering megafauna which maintained open habitats may have been detrimental for grassland and tundra-breeding Numenius shorebirds. Our work suggests that the impact of historical factors such as megafaunal extinction may have had wider repercussions on present-day population dynamics of open habitat biota than previously appreciated.

About 20,000 years ago, the Earth was a much colder world roamed by giant mastodons, gigantic elks, woolly mammoths and sabre-tooth tigers. Yet these imposing creatures were living on borrowed time: by the start of the Holocene, around 10,000 years later, many animals over 45kg had vanished across the Northern Hemisphere, closing the book on what is known as the Quaternary extinction event. As large grazers disappeared, the landscape likely changed too. Where open tundra and grasslands may have once dominated, woodlands and shrubs probably took over, creating ripple effects for surviving species. These extinction events took place in a changing world, with glaciers starting to retreat about 20,000 years ago and human populations colonizing an increasing share of this planet's land area. In fact, since the end of this last glacial maximum, ecosystems have been reshaped by a succession and a combination of climatic, historical and human-driven forces. This makes it difficult for scientists to disentangle the relative contribution of these factors on the lives of animals. Tan et al. decided to explore this question by reconstructing how effective population sizes changed over the past 20,000 years for nine species of curlews and whimbrels. These shorebirds, which together comprise the genus Numenius, breed slowly and nest in open environments such as moorlands or tundra. Many are currently under threat. Fluctuations in the numbers of breeding individuals affect the genetic diversity of a species, and these events leave tell-tale genetic signatures that can be uncovered through DNA analyses. Tan et al. had enough fresh and museum samples to infer these changes for five Numenius species, revealing that genetic diversity brutally dropped soon after the last glacial period ended. At the time, humans were yet to make significant changes on their environment and a warming world should have supported population growth. Tan et al. suggest that, instead, this sharp decline is linked to the late Quaternary extinctions of large mammals: with the demise of grazing animals which could keep woodlands at bay, the shorebirds lost their open nesting grounds. This event has left its mark in the genome of existing species, with these birds still exhibiting a low level of genetic diversity that may put them at further risk for extinction.

Spatial and temporal resource partitioning in a mixed-species colony of avian echolocators.

Resource partitioning may facilitate the coexistence of sympatric species with similar ecological requirements. Here, we study a colony of unusual echolocating birds called swiftlets, which nest underground on an island off the coast of Singapore. The colony comprises two congeneric swiftlet species, black-nest swiftlets (Aerodramus maximus) and edible-nest swiftlets (A. fuciphagus), nesting at high densities and in close proximity. Bioacoustic recordings and monitoring of nesting biology at the site across multiple seasons revealed significant differences in echolocation calls as well as survival rates between the species, with the larger black-nest swiftlet nesting at locations with the highest fledging rates. We also observe an additional off-season breeding peak by the smaller species, the edible-nest swiftlet. Unexpectedly, off-season egg-hatching rates were significantly higher compared with the rates during the shared breeding season (mean difference = 14%). Our study on the breeding biology of these echolocating cave-dwelling birds provides an example of spatial and temporal strategies that animals employ to partition resources within a confined habitat.

Metagenomic insights into the influence of mobile genetic elements on ARGs along typical wastewater treatment system on pig farms in China.

The wastewater treatment processes (WTP) on pig farms are heavily contaminated by antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) play an important role in shaping ARG profiles. Here we first employed metagenomic sequencing to follow the diversities and shifts of ARG associated mobile genetic elements (AAMGEs) including insertion sequences (ISs) and plasmids along the WTP for three pig farms in southeast China. The IS average relative abundance rose from the initial pig feces source to the wastewater storage lagoon (WSL) but decreased in the influent and rose in the effluent of the anaerobic digestor (AD). In contrast, plasmids were eliminated rapidly along this process. These results indicated that the AD reduced plasmid copies while IS abundance increased. We found a great diversity ISs, including IS91, ISNCY, IS630 and IS701, were large contributors to the transfer of multi-drug resistance. In addition, the tetracycline resistance genes co-occurred with a greater diversity of ISs than other ARG classes and this likely contributed to the high abundance of tetracycline resistance genes we found. The transfer of ARGs mediated by MGEs along the WTP of pig farms was a key contributor for the ARGs persistence in the environment of pig farms. Collectively, our findings demonstrated different fates for ISs and plasmids along the WTP for pig farms and suggested that AAMGE monitoring served as an important role in controlling ARGs in pig waste.

Extinction rate of discovered and undiscovered plants in Singapore.

Extinction is a key issue in the assessment of global biodiversity. However, many extinction rate measures do not account for species that went extinct before they could be discovered. The highly developed island city-state of Singapore has one of the best-documented tropical floras in the world. This allowed us to estimate the total rate of floristic extinctions in Singapore since 1822 after accounting for sampling effort and crypto extinctions by collating herbaria records. Our database comprised 34,224 specimens from 2076 native species, of which 464 species (22%) were considered nationally extinct. We assumed that undiscovered species had the same annual per-species extinction rates as discovered species and that no undiscovered species remained extant. With classical and Bayesian algorithms, we estimated that 304 (95% confidence interval, 213-414) and 412 (95% credible interval, 313-534) additional species went extinct before they could be discovered, respectively; corresponding total extinction rate estimates were 32% and 35% (range 30-38%). We detected violations of our 2 assumptions that could cause our extinction estimates, particularly the absolute numbers, to be biased downward. Thus, our estimates should be treated as lower bounds. Our results illustrate the possible magnitudes of plant extirpations that can be expected in the tropics as development continues.

Tasa de Extinción de Plantas Descubiertas y No Descubiertas en Singapur Resumen La extinción es un tema importante para la valoración de la biodiversidad global. Sin embargo, muchas medidas de la tasa de extinción no consideran a las especies que se extinguieron antes de que pudieran ser descubiertas. Singapur, la ciudad-estado isleña altamente desarrollada, tiene una de las floras mejor documentadas del mundo. Esto nos permitió estimar la tasa total de las extinciones florísticas en Singapur desde 1822 después de considerar el esfuerzo de muestreo y las criptoextinciones cuando recopilamos los registros de herbarios. Nuestra base de datos incluyó 34,224 especímenes de unas 2,076 especies nativas, de las cuales 464 especies (22%) estaban consideradas como extintas a nivel nacional. Asumimos que las especies no descubiertas tuvieron la misma tasa anual de extinción por especie que las especies descubiertas y que ninguna especie no descubierta permanecía en existencia. Con algoritmos clásicos y bayesianos, respectivamente, estimamos que 304 (95% IC 213-414) y 412 (95% IC 313-534) especies adicionales se extinguieron antes de que fueran descubiertas; las estimaciones correspondientes de la tasa de extinción total fueron 32% y 35% (rango de 30-38%). Detectamos violaciones en nuestras dos suposiciones que podrían causar que nuestras estimaciones de extinción, particularmente los números absolutos, tuvieran un sesgo hacia abajo. Por lo tanto, nuestras estimaciones deberían ser tratadas como límites inferiores. Nuestros resultados ilustran las magnitudes posibles de las extirpaciones de plantas que pueden esperarse en los trópicos conforme el desarrollo continúa.

Population genomics of two congeneric Palaearctic shorebirds reveals differential impacts of Quaternary climate oscillations across habitats types.

Intracontinental biotic divisions across the vast Palaearctic region are not well-characterized. Past research has revealed patterns ranging from a lack of population structure to deep divergences along varied lines of separation. Here we compared biogeographic patterns of two Palaearctic shorebirds with different habitat preferences, Whimbrel (Numenius phaeopus) and Eurasian curlew (N. arquata). Using genome-wide markers from populations across the Palaearctic, we applied a multitude of population genomic and phylogenomic approaches to elucidate population structure. Most importantly, we tested for isolation by distance and visualized barriers and corridors to gene flow. We found shallow Palaearctic population structure in subpolar bog and tundra-breeding whimbrels, consistent with other species breeding at a similarly high latitude, indicating connectivity across the tundra belt, both presently and during southward shifts in periods of global cooling. In contrast, the temperate grassland-breeding Eurasian curlew emerged in three distinct clades corresponding to glacial refugia. Barriers to gene flow coincided with areas of topographic relief in the central Palaearctic for whimbrels and further east for Eurasian curlews. Our findings highlight the interplay of historic and ecological factors in influencing present-day population structure of Palaearctic biota.

Asiatic acid ameliorates pulmonary fibrosis induced by bleomycin (BLM) via suppressing pro-fibrotic and inflammatory signaling pathways.

Idiopathic pulmonary fibrosis is known as a life-threatening disease with high mortality and limited therapeutic strategies. In addition, the molecular mechanism by which pulmonary fibrosis developed is not fully understood. Asiatic acid (AA) is a triterpenoid, isolated from Centella asiatica, exhibiting efficient anti-inflammatory and anti-oxidative activities. In our study, we attempted to explore the effect of Asiatic acid on bleomycin (BLM)-induced pulmonary fibrosis in mice. The findings indicated that pre-treatment with Asiatic acid inhibited BLM-induced lung injury and fibrosis progression in mice. Further, Asiatic acid down-regulates inflammatory cells infiltration in bronchoalveolar lavage fluid (BALF) and pro-inflammatory cytokines expression in lung tissue specimens induced by BLM. Also, Asiatic acid apparently suppressed transforming growth factor-beta 1 (TGF-ß1) expression in tissues of lung, accompanied with Collagen I, Collagen III, α-SMA and matrix metalloproteinase (TIMP)-1 decreasing, as well as Smads and ERK1/2 inactivation. Of note, Asiatic acid reduces NOD-like receptor, pyrin domain containing-3 (NLRP3) inflammasome. The findings indicated that Asiatic acid might be an effective candidate for pulmonary fibrosis and inflammation treatment.

Arsenic trioxide and all-trans-retinoic acid selectively exert synergistic cytotoxicity against FLT3-ITD AML cells via co-inhibition of FLT3 signaling pathways.

FLT3-ITD mutations occur in approximately 30% of acute myeloid leukemia (AML) and are associated with a poor outcome. Currently available FLT3 inhibitors have in vitro but limited clinical activity in FLT3-ITD AML. Reports have shown that an arsenic trioxide (ATO)/all-trans-retinoic acid (ATRA) combination improves prognosis in acute promyelocytic leukemia, especially with FLT3-ITD, and ATO or ATRA alone enhances apoptosis in FLT3-ITD AML cells treated with FLT3 inhibitors, providing a rationale to investigate the role of ATO/ATRA in FLT3-ITD AML. Here, we demonstrate that an ATO/ATRA combination selectively exerts synergistic cytotoxicity against FLT3-ITD AML cell lines (MV4;11/MOLM-13). The signaling pathways affected by ATO/ATRA include FLT3/STAT5/MYC, FLT3/STAT5/E2F1, FLT3/ERK/ATF5 and FLT3/AKT/ATF5.ATF5 may function as an oncogene in FLT3-ITD AML. Our findings provide experimental evidence that supports further exploration of ATO/ATRA in FLT3-ITD AML in vivo and warrants a clinical evaluation of regimens comprising an ATO/ATRA combination.

[Serotonin transporter gene polymorphisms in irritable bowel syndrome and their impact on tegaserod treatment].

OBJECTIVE: To investigate the serotonin reuptake transporter (SERT) genetic polymorphisms in the 5-hydroxytryptamine (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 among Chinese people, and their relationship to the pathogenesis of irritable bowel syndrome (IBS); and to investigate the impact of SERT genotypes on the efficacy of 5-HT(4) receptor agonist tegaserod in constipation predominant type (C-IBS) patients. METHODS: PCR was used to detect the genetic polymorphisms in 87 patients with IBS confirmed with Rome II criteria and 96 healthy subjects, then 41 C-IBS patients received tegaserod 6 mg twice daily for 4 weeks. Each patient recorded his or her symptoms in a diary. Efficacy was assessed by patient's experience of overall symptoms and severity of constipation before and after the treatment. RESULTS: The 5-HTTLPR genotypes frequencies were: S/S 52.9%, S/L 31.0%, L/L 16.1% in IBS patients; and S/S 57.3%, S/L 35.4%, L/L 7.3% in control. VNTRs genotypes were STin2.10/10: 2.3%, STin2.12/10: 17.2%, STin2.12/12: 80.5% in IBS patients; and STin2.10/10: 2.1%, STin2.12/10: 11.4%, STin2.12/12: 86.5% in control. There was no significant difference in the two genotypes frequencies between IBS and control groups (P > 0.05). However, the allele frequency of the L/L genotype was significantly higher in the C-IBS group than in control (25.0% vs 7.3%, P < 0.05). The clinical responder rates of tegaserod in S/S (85.0%) and S/L (70.0%) genotypes differed significantly from that (36.4%) in L/L genotype (P < 0.05). The scores of Subject's Global Assessment of relief after treatment were: S/S 1.35 +/- 0.81, S/L 1.70 +/- 0.95 vs L/L 2.27 +/- 0.45 (P < 0.05). All other variables for assessment of efficacy including stool frequency, stool consistency and sensation of bowel complete evacuation in L/L genotype were also significantly poorer than those in S/S and S/L (P < 0.05). CONCLUSIONS: 5-HTTLPR and VNTRs genetic polymorphisms existed in Chinese people. In general, the genotypes were not involved in the pathogenesis of IBS. However people with L/L genotype were vulnerable for development of C-IBS. The 5-HTTLPR genetic polymorphisms influenced the efficacy of tegaserod treatment in C-IBS patients with L/L being poorer than S/S and S/L genotypes.