The Amphibian Genomics Consortium: advancing genomic and genetic resources for amphibian research and conservation.

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomics resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomics resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, antipredator strategies, and resilience and adaptive responses. They also serve as critical models for understanding widespread genomic characteristics, including evolutionary genome expansions and contractions given they have the largest range in genome sizes of any animal taxon and multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The advent of long-read sequencing technologies, along with computational techniques that enhance scaffolding capabilities and streamline computational workload is now enabling the ability to overcome some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC) in early 2023. This burgeoning community already has more than 282 members from 41 countries (6 in Africa, 131 in the Americas, 27 in Asia, 29 in Australasia, and 89 in Europe). The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and outline how the AGC can enable amphibian genomics research to "leap" to the next level.

Multinational evaluation of genetic diversity indicators for the Kunming-Montreal Global Biodiversity Framework.

Under the recently adopted Kunming-Montreal Global Biodiversity Framework, 196 Parties committed to reporting the status of genetic diversity for all species. To facilitate reporting, three genetic diversity indicators were developed, two of which focus on processes contributing to genetic diversity conservation: maintaining genetically distinct populations and ensuring populations are large enough to maintain genetic diversity. The major advantage of these indicators is that they can be estimated with or without DNA-based data. However, demonstrating their feasibility requires addressing the methodological challenges of using data gathered from diverse sources, across diverse taxonomic groups, and for countries of varying socio-economic status and biodiversity levels. Here, we assess the genetic indicators for 919 taxa, representing 5271 populations across nine countries, including megadiverse countries and developing economies. Eighty-three percent of the taxa assessed had data available to calculate at least one indicator. Our results show that although the majority of species maintain most populations, 58% of species have populations too small to maintain genetic diversity. Moreover, genetic indicator values suggest that IUCN Red List status and other initiatives fail to assess genetic status, highlighting the critical importance of genetic indicators.

Genetic diversity goals and targets have improved, but remain insufficient for clear implementation of the post-2020 global biodiversity framework.

Genetic diversity among and within populations of all species is necessary for people and nature to survive and thrive in a changing world. Over the past three years, commitments for conserving genetic diversity have become more ambitious and specific under the Convention on Biological Diversity's (CBD) draft post-2020 global biodiversity framework (GBF). This Perspective article comments on how goals and targets of the GBF have evolved, the improvements that are still needed, lessons learned from this process, and connections between goals and targets and the actions and reporting that will be needed to maintain, protect, manage and monitor genetic diversity. It is possible and necessary that the GBF strives to maintain genetic diversity within and among populations of all species, to restore genetic connectivity, and to develop national genetic conservation strategies, and to report on these using proposed, feasible indicators.

Current Perspectives on Circulating Tumor DNA, Precision Medicine, and Personalized Clinical Management of Cancer.

Circulating tumor DNA (ctDNA) has recently emerged as a minimally invasive "liquid biopsy" tool in precision medicine. ctDNA-genomic DNA fragments that are released into the bloodstream after the active secretion of microvesicles or tumor cell lysis reflects tumor evolution and the genomic alterations present in primary and/or metastatic tumors. Notably, ctDNA analysis might allow the stratification of patients, the monitoring of the therapeutic response, and the establishment of an opportunity for early intervention independent of detection by imaging modalities or clinical symptoms. As oncology moves towards precision medicine, the information in ctDNA provides a means for the individual management of the patient based on their tumor's genetic profile. This review presents current evidence on the potential role for ctDNA in helping to guide individualized clinical treatment decisions for patients with melanoma, castration-resistant prostate cancer, breast cancer, metastatic colorectal cancer, and non-small cell lung cancer.

Horizon scanning for South African biodiversity: A need for social engagement as well as science.

A horizon scan was conducted to identify emerging and intensifying issues for biodiversity conservation in South Africa over the next 5-10 years. South African biodiversity experts submitted 63 issues of which ten were identified as priorities using the Delphi method. These priority issues were then plotted along axes of social agreement and scientific certainty, to ascertain whether issues might be "simple" (amenable to solutions from science alone), "complicated" (socially agreed upon but technically complicated), "complex" (scientifically challenging and significant levels of social disagreement) or "chaotic" (high social disagreement and highly scientifically challenging). Only three of the issues were likely to be resolved by improved science alone, while the remainder require engagement with social, economic and political factors. Fortunately, none of the issues were considered chaotic. Nevertheless, strategic communication, education and engagement with the populace and policy makers were considered vital for addressing emerging issues.

Role of histone acetylation in gastric cancer: implications of dietetic compounds and clinical perspectives.

Histone modifications regulate the structural status of chromatin and thereby influence the transcriptional status of genes. These processes are controlled by the recruitment of different enzymes to a specific genomic site. Furthermore, obtaining an understanding of these mechanisms could help delineate alternative treatment and preventive strategies for cancer. For example, in gastric cancer, cholecalciferol, curcumin, resveratrol, quercetin, garcinol and sodium butyrate are natural regulators of acetylation and deacetylation enzyme activity that exert chemopreventive and anticancer effects. Here, we review the recent findings on histone acetylation in gastric cancer and discuss the effects of nutrients and bioactive compounds on histone acetylation and their potential role in the prevention and treatment of this type of cancer.

Sexual dimorphism in bite performance drives morphological variation in chameleons.

Phenotypic performance in different environments is central to understanding the evolutionary and ecological processes that drive adaptive divergence and, ultimately, speciation. Because habitat structure can affect an animal's foraging behaviour, anti-predator defences, and communication behaviour, it can influence both natural and sexual selection pressures. These selective pressures, in turn, act upon morphological traits to maximize an animal's performance. For performance traits involved in both social and ecological activities, such as bite force, natural and sexual selection often interact in complex ways, providing an opportunity to understand the adaptive significance of morphological variation with respect to habitat. Dwarf chameleons within the Bradypodion melanocephalum-Bradypodion thamnobates species complex have multiple phenotypic forms, each with a specific head morphology that could reflect its use of either open- or closed-canopy habitats. To determine whether these morphological differences represent adaptations to their habitats, we tested for differences in both absolute and relative bite performance. Only absolute differences were found between forms, with the closed-canopy forms biting harder than their open-canopy counterparts. In contrast, sexual dimorphism was found for both absolute and relative bite force, but the relative differences were limited to the closed-canopy forms. These results indicate that both natural and sexual selection are acting within both habitat types, but to varying degrees. Sexual selection seems to be the predominant force within the closed-canopy habitats, which are more protected from aerial predators, enabling chameleons to invest more in ornamentation for communication. In contrast, natural selection is likely to be the predominant force in the open-canopy habitats, inhibiting the development of conspicuous secondary sexual characteristics and, ultimately, enforcing their overall diminutive body size and constraining performance.

Slow but tenacious: an analysis of running and gripping performance in chameleons.

Chameleons are highly specialized and mostly arboreal lizards characterized by a suite of derived characters. The grasping feet and tail are thought to be related to the arboreal lifestyle of chameleons, yet specializations for grasping are thought to exhibit a trade-off with running ability. Indeed, previous studies have demonstrated a trade-off between running and clinging performance, with faster species being poorer clingers. Here we investigate the presence of trade-offs by measuring running and grasping performance in four species of chameleon belonging to two different clades (Chamaeleo and Bradypodion). Within each clade we selected a largely terrestrial species and a more arboreal species to test whether morphology and performance are related to habitat use. Our results show that habitat drives the evolution of morphology and performance but that some of these effects are specific to each clade. Terrestrial species in both clades show poorer grasping performance than more arboreal species and have smaller hands. Moreover, hand size best predicts gripping performance, suggesting that habitat use drives the evolution of hand morphology through its effects on performance. Arboreal species also had longer tails and better tail gripping performance. No differences in sprint speed were observed between the two Chamaeleo species. Within Bradypodion, differences in sprint speed were significant after correcting for body size, yet the arboreal species were both better sprinters and had greater clinging strength. These results suggest that previously documented trade-offs may have been caused by differences between clades (i.e. a phylogenetic effect) rather than by design conflicts between running and gripping per se.

A molecular phylogeny of the African plated lizards, genus Gerrhosaurus Wiegmann, 1828 (Squamata: Gerrhosauridae), with the description of two new genera.

We constructed a molecular phylogeny of the African plated lizard family Gerrhosauridae using two mitochondrial markers (ND2, 732 bp; 16S, 576 bp) and one nuclear marker (PRLR, 538 bp). This analysis showed that the subfamily Gerrhosaurinae consists of five major clades which we interpret as representing five genera. The genera Tetradactylus and Cordylosaurus were each recovered as monophyletic, but Gerrhosaurus as currently conceived is paraphyletic, consisting of three distinct genus-level assemblages. The two clades consisting of Gerrhosaurus major Duméril, 1851 and Gerrhosaurus validus Smith, 1849 are both described here as new genera, namely Broadleysaurus Bates & Tolley gen. nov. and Matobosaurus Bates & Tolley gen. nov., respectively. Two subspecies of 'Gerrhosaurus major' that were historically separated on the basis of differences in colour pattern are not reciprocally monophyletic, so Gerrhosaurus bottegoi Del Prato, 1895 is relegated to the synonomy of Broadleysaurus major (Duméril, 1851) comb. nov., which is rendered monotypic. Gerrhosaurus validus maltzahni De Grys, 1938 is genetically and morphologically well differentiated from G. v. validus and the two taxa also occur in allopatry. We therefore re-instate the former as Matobosaurus maltzahni (De Grys, 1938) comb. nov., rendering Matobosaurus validus (Smith, 1849) comb. nov. a monotypic species. Our analysis also showed that Gerrhosaurus sensu stricto comprises two major subclades, one consisting of Gerrhosaurus typicus (Smith, 1837) + Gerrhosaurus skoogi Andersson, 1916, and the other containing the remaining species. In this latter subclade we show that west-Central African Gerrhosaurus nigrolineatus Hallowell, 1857 is most closely related to Gerrhosaurus auritus Boettger, 1887 rather than to G. nigrolineatus from East and Southern Africa. The west-Central African clade of G. nigrolineatus differs from the East and Southern African clade by a p-distance of 13.0% (ND2) and 6.9% (16S), and can be differentiated morphologically. We accordingly apply the name Gerrhosaurus intermedius Lönnberg, 1907 comb. nov. to populations from Kenya, Uganda, Rwanda, Tanzania, Malawi, Mozambique, Zimbabwe and South Africa previously identified under the name G. nigrolineatus. Our analysis also confirms that Gerrhosaurus bulsi Laurent, 1954 is a distinct species and sister taxon to a clade containing G. nigrolineatus, G. auritus and G. intermedius. The latter four taxa form a closely-related 'G. nigrolineatus species complex' with a widespread distribution in Africa. Most closely related to this complex of species is Gerrhosaurus flavigularis Wiegmann, 1828 which has an extensive range in East and Southern Africa, and displays genetic substructure which requires further investigation. The status of Gerrhosaurus multilineatus Bocage, 1866, and Angolan populations referred to G. nigrolineatus, remains problematic.

LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation.

More than 98% of the human genome is comprised of non-protein coding sequences. Interestingly, a considerable fraction of these sequences is transcribed into non-protein coding RNA transcripts. These transcripts range in size from very small RNAs such as the miRNAs (20-25 base pairs) to transcripts that can range up to 100 kb or more. Some longer non-coding RNAs (lncRNAs) have been found to play important regulatory roles within cells. In this report, we demonstrate that LSINCT5 is a 2.6 Kb polyadenylated, long stress-induced non-coding transcript that is on the negative strand, localized in the nucleus and potentially transcribed by RNA polymerase III. LSINCT5 is overexpressed in breast and ovarian cancer cell lines and tumor tissues, relative to their normal counterpart. In addition, knocking down the expression of LSINCT5 in cancer-derived cell lines causes a decrease in cellular proliferation. Finally, we identified 95 genes with more than 2-fold changes when knocking down LSINCT5 expression by using the Affymetrix U133 Plus 2 array. We chose a subset of these genes to validate using qPCR and found that ten of these genes were indeed significantly affected by the LSINCT5 knockdown. Interestingly, two genes that were significantly downregulated were the lncRNA NEAT-1 and a protein coding gene PSPC1. We have therefore characterized a novel lncRNA that is overexpressed in breast and ovarian cancers, enhances cellular proliferation and may play a significant role in multiple processes.

Identification of long stress-induced non-coding transcripts that have altered expression in cancer.

It has recently become clear that the transcriptional output of the human genome is far more abundant than previously anticipated, with the vast majority of transcripts not coding for protein. Utilizing whole-genome tiling arrays, we analyzed the transcription across the entire genome in both normal human bronchial epithelial cells (NHBE) and NHBE cells exposed to the tobacco carcinogen NNK. Our efforts focused on the characterization of non-coding transcripts that were greater than 300 nucleotides in length and whose expression was increased in response to NNK. We identified 12 Long Stress-Induced Non-coding Transcripts that we term LSINCTs. Northern blot analysis revealed that these transcripts were larger than predicted from the tiling array data. Quantitative real-time RT-PCR performed across a panel of normal cell lines indicates that these transcripts are more abundantly expressed in rapidly growing tissues or in tissues that are more prone to cellular stress. These transcripts that have increased expression after exposure to NNK also had increased expression in a number of lung cancer cell lines and also in many breast cancer cell lines. Collectively, our results identified a new class of long stress responsive non-coding transcripts, LSINCTs, which have increased expression in response to DNA damage induced by NNK. LSINCTs interestingly also have increased expression in a number of cancer-derived cell lines, indicating that the expression is increased in both, correlating cellular stress and cancer.

Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity.

The Akt kinase is a serine/threonine protein kinase that has been implicated in mediating a variety of biological responses. Studies show that high Akt activity in breast carcinoma is associated with a poor pathophenotype, as well as hormone and chemotherapy resistance. Additionally, high Akt activity is associated with other features of poor prognosis. Thus, a chemotherapeutic agent directed specifically toward tumors with high Akt activity could prove extremely potent in treating those breast tumors with the most aggressive phenotypes. Several studies have demonstrated that rapamycin, which inhibits mammalian target of rapamycin (mTOR), a downstream target of Akt, sensitizes certain resistant cancer cells to chemotherapeutic agents. This study evaluated the efficacy of mTOR inhibition in the treatment of tamoxifen-resistant breast carcinoma characterized by high Akt activity. We found that MCF-7 breast cancer cell lines expressing a constitutively active Akt are able to proliferate under reduced estrogen conditions and are resistant to the growth inhibitory effects of tamoxifen, both in vitro as well as in vivo in xenograft models. Cotreatment with the mTOR inhibitor rapamycin in vitro, or the ester of rapamycin, CCI-779 (Wyeth) in vivo, inhibited mTOR activity and restored sensitivity to tamoxifen, suggesting that Akt-induced tamoxifen resistance is mediated in part by signaling through the mTOR pathway. Although the mechanism underlying the synergism remains to be understood, the results were associated with rapamycin's ability to block transcriptional activity mediated by estrogen receptor alpha, as assessed by reporter gene assays with estrogen-responsive element luciferase. These data corroborate prior findings indicating that Akt activation induces resistance to tamoxifen in breast cancer cells. Importantly, these data indicate a novel mechanism for tamoxifen resistance and suggest that blockage of the phosphatidylinositol 3'-kinase/Akt signaling pathway by mTOR inhibition effectively restores the susceptibility of these cells to tamoxifen. These data may have implication for future clinical studies of mTOR inhibition in breast carcinoma.