Transcriptomic and genomic structural variation analyses on grape cultivars reveal new insights into the genotype-dependent responses to water stress

Grapevine (Vitis vinifera L.) is importantly cultivated worldwide for table grape and wine production. Its cultivation requires irrigation supply, especially in arid and semiarid areas. Water deficiency can affect berry and wine quality mostly depending on the extent of plant perceived stress, which is a cultivar-specific trait. We tested the physiological and molecular responses to water deficiency of two table grape cultivars, Italia and Autumn royal, and we highlighted their different adaptation. Microarray analyses revealed that Autumn royal reacts involving only 29 genes, related to plant stress response and ABA/hormone signal transduction, to modulate the response to water deficit. Instead, cultivar Italia orchestrates a very broad response (we found 1037 differentially expressed genes) that modifies the cell wall organization, carbohydrate metabolism, response to reactive oxygen species, hormones and osmotic stress. For the first time, we integrated transcriptomic data with cultivar-specific genomics and found that ABA-perception and –signalling are key factors mediating the varietal-specific behaviour of the early response to drought. We were thus able to isolate candidate genes for the genotype-dependent response to drought. These insights will allow the identification of reliable plant stress indicators and the definition of sustainable cultivar-specific protocols for water management

Genomic and personalized medicine approaches for substance use disorders (SUDs) looking at genome-wide association studies

Drug addiction, or substance use disorder (SUD), is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behaviour persist despite serious negative consequences. Drug abuse represents a problem that deserves great attention from a social point of view, and focuses on the importance of genetic studies to help in understanding the genetic basis of addiction and its medical treatment. Despite the complexity of drug addiction disorders, and the high number of environmental variables playing a role in the onset, recurrence, and duration of the symptoms, several studies have highlighted the non-negligible role of genetics, as demonstrated by heritability and genome-wide association studies. A correlation between the relative risk of addiction to specific substances and heritability has been recently observed, suggesting that neurobiological mechanisms may be, at least in part, inherited. All these observations point towards a scenario where the core neurobiological factors of addiction, involving the reward system, impulsivity, compulsivity, stress, and anxiety response, are transmitted, and therefore, genes and mutations underlying their variation might be detected. In the last few years, the development of new and more efficient sequencing technologies has paved the way for large-scale studies in searching for genetic and epigenetic factors affecting drug addiction disorders and their treatments. These studies have been crucial to pinpoint single nucleotide polymorphisms (SNPs) in genes that affect the reaction to medical treatments. This is critically important to identify pharmacogenomic approaches for substance use disorder, such as OPRM1 SNPs and methadone required doses for maintenance treatment (MMT). Nevertheless, despite the promising results obtained by genome-wide association and pharmacogenomic studies, specific studies related to population genetics diversity are lacking, undermining the overall applicability of the preliminary findings, and thus potentially affecting the portability and the accuracy of the genetic studies. In this review, focusing on cannabis, cocaine and heroin use, we report the state-of-the-art genomics and pharmacogenomics of SUDs, and the possible future perspectives related to medical treatment response in people that ask for assistance in solving drug-related problems

Inter-varietal structural variation in grapevine genomes

Grapevine (Vitis vinifera L.) is one of the world's most important crop plants, which is of large economic value for fruit and wine production. There is much interest in identifying genomic variations and their functional effects on inter-varietal, phenotypic differences. Using an approach developed for the analysis of human and mammalian genomes, which combines high-throughput sequencing, array comparative genomic hybridization, fluorescent in�situ hybridization and quantitative PCR, we created an inter-varietal atlas of structural variations and single nucleotide variants (SNVs) for the grapevine genome analyzing four economically and genetically relevant table grapevine varieties. We found 4.8 million SNVs and detected 8% of the grapevine genome to be affected by genomic variations. We identified more than 700 copy number variation (CNV) regions and more than 2000 genes subjected to CNV as potential candidates for phenotypic differences between varieties. � 2016 The Authors The Plant Journal � 2016 John Wiley & Sons Lt

A High-Quality Bonobo Genome Refines The Analysis Of Hominid Evolution

The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation(1,2). Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps are closed, including the resolution of about half of the segmental duplications and almost all of the full-length mobile elements. We compare the bonobo genome to those of other great apes(1,3-5) and identify more than 5,569 fixed structural variants that specifically distinguish the bonobo and chimpanzee lineages. We focus on genes that have been lost, changed in structure or expanded in the last few million years of bonobo evolution. We produce a high-resolution map of incomplete lineage sorting and estimate that around 5.1% of the human genome is genetically closer to chimpanzee or bonobo and that more than 36.5% of the genome shows incomplete lineage sorting if we consider a deeper phylogeny including gorilla and orangutan. We also show that 26% of the segments of incomplete lineage sorting between human and chimpanzee or human and bonobo are non-randomly distributed and that genes within these clustered segments show significant excess of amino acid replacement compared to the rest of the genome

A high-quality bonobo genome refines the analysis of hominid evolution

The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation1,2. Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps are closed, including the resolution of about half of the segmental duplications and almost all of the full-length mobile elements. We compare the bonobo genome to those of other great apes1,3,4,5 and identify more than 5,569 fixed structural variants that specifically distinguish the bonobo and chimpanzee lineages. We focus on genes that have been lost, changed in structure or expanded in the last few million years of bonobo evolution. We produce a high-resolution map of incomplete lineage sorting and estimate that around 5.1% of the human genome is genetically closer to chimpanzee or bonobo and that more than 36.5% of the genome shows incomplete lineage sorting if we consider a deeper phylogeny including gorilla and orangutan. We also show that 26% of the segments of incomplete lineage sorting between human and chimpanzee or human and bonobo are non-randomly distributed and that genes within these clustered segments show significant excess of amino acid replacement compared to the rest of the genome

Alu insertion polymorphisms shared by Papio baboons and Theropithecus gelada reveal an intertwined common ancestry

© 2019 The Author(s). Background: Baboons (genus Papio) and geladas (Theropithecus gelada) are now generally recognized as close phylogenetic relatives, though morphologically quite distinct and generally classified in separate genera. Primate specific Alu retrotransposons are well-established genomic markers for the study of phylogenetic and population genetic relationships. We previously reported a computational reconstruction of Papio phylogeny using large-scale whole genome sequence (WGS) analysis of Alu insertion polymorphisms. Recently, high coverage WGS was generated for Theropithecus gelada. The objective of this study was to apply the high-Throughput poly-Detect method to computationally determine the number of Alu insertion polymorphisms shared by T. gelada and Papio, and vice versa, by each individual Papio species and T. gelada. Secondly, we performed locus-specific polymerase chain reaction (PCR) assays on a diverse DNA panel to complement the computational data. Results: We identified 27,700 Alu insertions from T. gelada WGS that were also present among six Papio species, with nearly half (12,956) remaining unfixed among 12 Papio individuals. Similarly, each of the six Papio species had species-indicative Alu insertions that were also present in T. gelada. In general, P. kindae shared more insertion polymorphisms with T. gelada than did any of the other five Papio species. PCR-based genotype data provided additional support for the computational findings. Conclusions: Our discovery that several thousand Alu insertion polymorphisms are shared by T. gelada and Papio baboons suggests a much more permeable reproductive barrier between the two genera then previously suspected. Their intertwined evolution likely involves a long history of admixture, gene flow and incomplete lineage sorting

Levels of different subtypes of tumour-infiltrating lymphocytes correlate with each other, with matched circulating lymphocytes, and with survival in breast cancer

Purpose: Breast cancer tumour-infiltrating lymphocytes associate with clinico-pathological factors, including survival, although the literature includes many conflicting findings. Our aim was to assess these associations for key lymphocyte subtypes and in different tumour compartments, to determine whether these provide differential correlations and could, therefore, explain published inconsistencies. Uniquely, we also examine whether infiltrating levels merely reflect systemic lymphocyte levels or whether local factors are predominant in recruitment. Methods: Immunohistochemistry was used to detect tumour-infiltrating CD20+ (B), CD4+ (helper T), CD8+ (cytotoxic T) and FoxP3+ (regulatory T) cells in breast cancers from 62 patients, with quantification in tumour stroma, tumour cell nests, and tumour margins. Levels were analysed with respect to clinico-pathological characteristics and matched circulating levels (determined by flow-cytometry). Results: CD4+ lymphocytes were the most prevalent subtype in tumour stroma and at tumour edge and CD8+ lymphocytes were most prevalent in tumour nests; FoxP3+ lymphocytes were rarest in all compartments. High grade or hormone receptor negative tumours generally had significantly increased lymphocytes, especially in tumour stroma. Only intra-tumoural levels of CD8+ lymphocytes correlated significantly with matched circulating levels (p < 0.03), suggesting that recruitment is mainly unrelated to systemic activity. High levels of stromal CD4+ and CD20+ cells associated with improved survival in hormone receptor negative cases (p < 0.04), while tumour nest CD8+ and FoxP3+ cells associated with poor survival in hormone receptor positives (p < 0.005). Conclusions: Lymphocyte subtype and location define differential impacts on tumour biology, therefore, roles of tumour-infiltrating lymphocytes will only be unravelled through thorough analyses that take this into account

Scaffolds for cartilage regeneration: to use or not to use?

Joint cartilage has been a significant focus on the field of tissue engineering and regenerative medicine (TERM) since its inception in the 1980s. Represented by only one cell type, cartilage has been a simple tissue that is thought to be straightforward to deal with. After three decades, engineering cartilage has proven to be anything but easy. With the demographic shift in the distribution of world population towards ageing, it is expected that there is a growing need for more effective options for joint restoration and repair. Despite the increasing understanding of the factors governing cartilage development, there is still a lot to do to bridge the gap from bench to bedside. Dedicated methods to regenerate reliable articular cartilage that would be equivalent to the original tissue are still lacking. The use of cells, scaffolds and signalling factors has always been central to the TERM. However, without denying the importance of cells and signalling factors, the question posed in this chapter is whether the answer would come from the methods to use or not to use scaffold for cartilage TERM. This paper presents some efforts in TERM area and proposes a solution that will transpire from the ongoing attempts to understand certain aspects of cartilage development, degeneration and regeneration. While an ideal formulation for cartilage regeneration has yet to be resolved, it is felt that scaffold is still needed for cartilage TERM for years to come

Rhatany-based preparation in vulvovaginitis and vaginosis

Aim of this study was the clinical testing of a vaginal tablet containing lactic acid, L. acidophilus and Krameria triandra standardized dry extract in subjects (165) affected by infective vaginal disorders caused by Candida spp., Gardnerella or Trichomonas. Results and conclusion. The product administered for 10 days (1 tablet per night) treats effectively vaginal symptoms (itch, burning, leucorrhoea), making negative 100% of the vaginal swabs in case of Gardnerella or Trichomonas infection and from 66% to 100% in case of Candida spp. infection (results evaluated 7 days after last tablet administration). Tolerability was good with only 12 cases reporting burning sensation for the first 2-3 days of application. No adverse events or drop outs have been observed