Appearance Of Phenotype Research Articles

Diversity of flax morphological characters in VIR genetic collection as a result of crop domestication

Background. Almost all described flax (Linum usitatissimum L.) biodiversity is presented in VIR genetic collection(GC).
 Materials and methods. 316 lines from GC belonging to 5 subspecies (indo-abyssinicum, hindustanicum, eurasiaticum, mediterraneum, transitorium) were characterized by morphological traits (MT), for some of them Mendels genetic control was evaluated.
 Results. MT groups, genotypes typical for each of subspecies are revealed, but appearance of other phenotypes cannot be excluded, because subspecies can differ only in frequency of their occurrence. The genetic analysis was carried out. It expanded the list of MT genes. It was shown that many lines have similar mutations of MT regardless of their origin. Many MT genes are promising or already use in breeding for example YSED1 and ysed (yellow seed), pf-ad (pink flower, yellow seeds), dlb3 (pale blue flower), sfbs1 (white deformed flower). Soon lines carrier s1 gene (anthocyanin biosynthesis inhibitor), will be used because mucilage from seeds s1s1 has special polysaccharide compound and with wf1 (white flower) gene which is linked with early flowering. The linkage between the genes controlling dark blue flower (sfc6, sfc10) and yellow seeds (ysed2) was found, which must be taken into account while breeding for yellow seed.
 Conclusion. The old landraces of GC can serve as source for any direction of breeding.

Phenotypic appearance the yield character of five genotypes of cayenne pepper at Sukamantri, Ciamis

The purpose of this experiment is to evaluate the phenotypic appearance the yield character of five genotypes of cayenne pepper at Sukamantri, Ciamis region. The experiment used a randomized block design, with five replications. The experiment material consists of five genotypes of cayenne pepper, namely Unpad Ratuni, CR8873, Dewata, Taruna, and Rabani. The experiment was conducted at Sukamantri, Ciamis with altitude of 983 m above sea level (asl.) from August 2017 to February 2018. Data observed included fruit length, fruit diameter, fruit weight per fruit, fruit weight per plant, fruit weight per plot, and fruit weight per hectare. The experiment results show that there are differences in phenotypic characters among the five genotypes tested. Genotypes of the Gods, CR8873, and Ratuni Unpad show the highest potential yield (10.961 ton/ha, 0.345, and 10.232), with fruit weight of fruit per 1.382 gram, 0.911 grams, and 1.311 grams.Keywords: cayenne pepper, phenotypic character, yield

The effects of a human food additive, titanium dioxide nanoparticles E171, on Drosophila melanogaster - a 20 generation dietary exposure experiment

In this study, fruit flies (Drosophila melanogaster) were exposed to an estimated daily human E171 consumption concentration for 20 generations. Exposure to E171 resulted in: a change in normal developmental and reproductive dynamics, reduced fecundity after repetitive breeding, increased genotoxicity, the appearance of aberrant phenotypes and morphologic changes to the adult fat body. Marks of adaptive evolution and directional selection were also exhibited. The larval stages were at a higher risk of sustaining damage from E171 as they had a slower elimination rate of TiO2 compared to the adults. This is particularly worrisome, since among the human population, children tend to consume higher daily concentrations of E171 than do adults. The genotoxic effect of E171 was statistically higher in each subsequent generation compared to the previous one. Aberrant phenotypes were likely caused by developmental defects induced by E171, and were not mutations, since the phenotypic features were not transferred to any progeny even after 5 generations of consecutive crossbreeding. Therefore, exposure to E171 during the early developmental period carries a higher risk of toxicity. The fact that the daily human consumption concentration of E171 interferes with and influences fruit fly physiological, ontogenetic, genotoxic, and adaptive processes certainly raises safety concerns.

Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes.

SummaryInduced pluripotent stem cell (iPSC)-derived dopamine neurons provide an opportunity to model Parkinson’s disease (PD), but neuronal cultures are confounded by asynchronous and heterogeneous appearance of disease phenotypes in vitro. Using high-resolution, single-cell transcriptomic analyses of iPSC-derived dopamine neurons carrying the GBA-N370S PD risk variant, we identified a progressive axis of gene expression variation leading to endoplasmic reticulum stress. Pseudotime analysis of genes differentially expressed (DE) along this axis identified the transcriptional repressor histone deacetylase 4 (HDAC4) as an upstream regulator of disease progression. HDAC4 was mislocalized to the nucleus in PD iPSC-derived dopamine neurons and repressed genes early in the disease axis, leading to late deficits in protein homeostasis. Treatment of iPSC-derived dopamine neurons with HDAC4-modulating compounds upregulated genes early in the DE axis and corrected PD-related cellular phenotypes. Our study demonstrates how single-cell transcriptomics can exploit cellular heterogeneity to reveal disease mechanisms and identify therapeutic targets.

535P - Association of immune-related pneumonitis with the phenotypic appearance of concurrent ILD in patients treated with anti-PD-1 antibody

535P - Association of immune-related pneumonitis with the phenotypic appearance of concurrent ILD in patients treated with anti-PD-1 antibody

307 - Hyperactivation of Nrf2 increases stress tolerance at the cost of aging acceleration due to metabolic deregulation

Metazoans respond to harmful challenges by mounting anti-stress responses. This adaptation along with the evolvement of metabolic networks, were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors and restore tissue homeodynamics. We have found that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila flies activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in larvae lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics; the appearance of diabetic phenotypes and reduced longevity. Genetic or dietary suppression of Insulin/IGF-like signaling (IIS) alleviated these effects and extended flies’ lifespan. Our observations indicate that prolonged stress signaling by otherwise cytoprotective short-lived stress sensors re-allocates resources from growth and longevity to somatic preservation and stress tolerance. They also suggest a role for potential dietary-restriction-like therapeutic interventions in various diseases of chronic stress including progeroid genome instability syndromes and/or neurodegeneration. Finally, as our in vivo insights indicate that long-term mild Nrf2 activation exerts benign effects we screen marine natural products (derived from the mesophotic zone) libraries for the discovery of (among others) novel bioactive Nrf2-activating small molecules.

Transcriptome Analysis of Cardiac Hypertrophic Growth in MYBPC3-Null Mice Suggests Early Responders in Hypertrophic Remodeling

Rationale: With a prevalence of 1 in 200 individuals, hypertrophic cardiomyopathy (HCM) is thought to be the most common genetic cardiac disease, with potential outcomes that include severe hypertrophy, heart failure, and sudden cardiac death (SCD). Though much research has furthered our understanding of how HCM-causing mutations in genes such as cardiac myosin-binding protein C (MYBPC3) impair contractile function, it remains unclear how such dysfunction leads to hypertrophy and/or arrhythmias, which comprise the HCM phenotype. Identification of early response mediators could provide rational therapeutic targets to reduce disease severity. Our goal was to differentiate physiologic and pathophysiologic hypertrophic growth responses and identify early genetic mediators in the development of cardiomegaly in the cardiac myosin-binding protein C-null (cMyBP-C-/-) mouse model of HCM.Methods and Results: We performed microarray analysis on left ventricles of wild-type (WT) and cMyBPC-/- mice (n = 7 each) at postnatal day (PND) 1 and PND 9, before and after the appearance of an overt HCM phenotype. Applying the criteria of ≥2-fold change, we identified genes whose change was exclusive to pathophysiologic growth (n = 61), physiologic growth (n = 30), and genes whose expression changed ≥2-fold in both WT and cMyBP-C-/- hearts (n = 130). Furthermore, we identified genes that were dysregulated in PND1 cMyBP-C-/- hearts prior to hypertrophy, including genes in mechanosensing pathways and potassium channels linked to arrhythmias. One gene of interest, Xirp2, and its protein product, are regulated during growth but also show early, robust prehypertrophic upregulation in cMyBP-C-/- hearts. Additionally, the transcription factor Zbtb16 also shows prehypertrophic upregulation at both gene and protein levels.Conclusion: Our transcriptome analysis generated a comprehensive data set comparing physiologic vs. hypertrophic growth in mice lacking cMyBP-C. It highlights the importance of extracellular matrix pathways in hypertrophic growth and early dysregulation of potassium channels. Prehypertrophic upregulation of Xirp2 in cMyBP-C-/- hearts supports a growing body of evidence suggesting Xirp2 has the capacity to elicit both hypertrophy and arrhythmias in HCM. Dysregulation of Xirp2, as well as Zbtb16, along with other genes associated with mechanosensing regions of the cardiomyocyte implicate stress-sensing in these regions as a potentially important early response in HCM.

Both pre-frailty and frailty increase healthcare utilization and adverse health outcomes in patients with type 2 diabetes mellitus

BackgroundDiabetes mellitus (DM) correlates with accelerated aging and earlier appearance of geriatric phenotypes, including frailty. However, whether pre-frailty or frailty predicts greater healthcare utilization in diabetes patients is unclear.MethodsFrom the Longitudinal Cohort of Diabetes Patients in Taiwan (n = 840,000) between 2004 and 2010, we identified 560,795 patients with incident type 2 DM, categorized into patients without frailty, or with 1, 2 (pre-frail) and ≥ 3 frailty components, based on FRAIL scale (Fatigue, Resistance, Ambulation, Illness, and body weight Loss). We examined their long-term mortality, cardiovascular risk, all-cause hospitalization, and intensive care unit (ICU) admission.ResultsAmong all participants (56.4 ± 13.8 year-old, 46.1% female, and 84.8% community-dwelling), 77.8% (n = 436,521), 19.2% (n = 107,757), 2.7% (n = 15,101), and 0.3% (n = 1416) patients did not have or had 1, 2 (pre-frail), and ≥ 3 frailty components (frail), respectively, with Fatigue and Illness being the most common components. After 3.14 years of follow-up, 7.8% patients died, whereas 36.6% and 9.1% experienced hospitalization and ICU stay, respectively. Cox proportional hazard modeling discovered that patients with 1, 2 (pre-frail), and ≥ 3 frailty components (frail) had an increased risk of mortality (for 1, 2, and ≥ 3 components, hazard ratio [HR] 1.05, 1.13, and 1.25; 95% confidence interval [CI] 1.02–1.07, 1.08–1.17, and 1.15–1.36, respectively), cardiovascular events (HR 1.05, 1.15, and 1.13; 95% CI 1.02–1.07, 1.1–1.2, and 1.01–1.25, respectively), hospitalization (HR 1.06, 1.16, and 1.25; 95% CI 1.05–1.07, 1.14–1.19, and 1.18–1.33, respectively), and ICU admission (HR 1.05, 1.13, and 1.17; 95% CI 1.03–1.07, 1.08–1.14, and 1.06–1.28, respectively) compared to non-frail ones. Approximately 6–7% risk elevation in mortality and healthcare utilization was noted for every frailty component increase.ConclusionPre-frailty and frailty increased the risk of mortality and cardiovascular events, and entailed greater healthcare utilization in patients with type 2 DM.

Experimental evidence of the role of heterochrony in evolution of the Mesoamerican cichlids pigment patterns.

The Mesoamerican cichlids display a spectacular diversity of pigment patterns, which serve a variety of functions and serve as a strong selective trait for this lineage. The development and variation of coloration in the Mesoamerican cichlids have been detailed by several groups. In particular, Říčan, Musilová, Muška, and Novák () and Říčan, Piálek, Dragová, and Novák () determined homology of pattern and revealed four alternative types of coloration and their ontogeny. In this work, this group posed an "ontogenetic timing hypothesis" proposing heterochronic shifts underlying major transitions in the evolution of the Mesoamerican cichlids. Here, we experimentally test this hypothesis by experimentally altering timing of pigment pattern formation in the convict cichlid Amatitlania nigrofasciata, a member of the Mesoamerican cichlids, via manipulations of thyroid hormone (TH) function. The response of different pigment cell lineages to TH-perturbations revealed that the transition from larval to juvenile coloration in the convict cichlid is under the control of TH-signaling. Importantly, hormonally induced changes in the timing of pigment cell lineages' development resulted in shifts of coloration ontogeny type observed between lineages and led to the appearance of phenotypes mimicking those in phylogenetically close and distant species. Thus, our findings support the hypothesis that simple changes in ontogenetic timing underlies species specific patterns in pigmentation and provide new perspectives for studying the role of endocrine signaling in the evolution of cichlids.

Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life.

Resveratrol (RSV) and nicotinamide riboside (NR) are food compounds with anti-obesity actions in adult rodents. Here, the long-term effects of RSV and NR mild supplementation throughout lactation on adiposity-related parameters and the appearance of the beige phenotype in white adipose tissue (WAT) in adulthood are assessed. Newborn mice received orally RSV or NR from day 2 to 20 of life. Control littermates received the vehicle. All animals are weaned onto a chow diet on day 21. On day 90, half the animals of each group are assigned to a high-fat diet (HFD) for 10 weeks, while the other remained on a normal-fat diet. Energy-balance-related parameters, blood parameters, and gene expression and immunohistochemical analysis of WAT are assessed. Treated male mice show an improved response to the HFD, such as delayed body weight gain, a blunted increase in the plasma leptin/adiponectin ratio, and a decreased lipolytic response, together with signs of white-to-brown fat remodeling in inguinal WAT. These effects are absent in female mice. RSV and NR supplementations in early postnatal life affect WAT's thermogenic/oxidative transcriptional phenotype and metabolic responses in adulthood, with upregulatory and beneficial effects evidenced in male animals.

Mitochondrial genomes organization in alloplasmic lines of sunflower (Helianthus annuus L.) with various types of cytoplasmic male sterility.

BackgroundCytoplasmic male sterility (CMS) is a common phenotype in higher plants, that is often associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce hybrid seeds in a variety of valuable crop species. Investigation of the CMS phenomenon promotes understanding of fundamental issues of nuclear-cytoplasmic interactions in the ontogeny of higher plants. In the present study, we analyzed the structural changes in mitochondrial genomes of three alloplasmic lines of sunflower (Helianthus annuus L.). The investigation was focused on CMS line PET2, as there are very few reports about its mtDNA organization.MethodsThe NGS sequencing, de novo assembly, and annotation of sunflower mitochondrial genomes were performed. The comparative analysis of mtDNA of HA89 fertile line and two HA89 CMS lines (PET1, PET2) occurred.ResultsThe mtDNA of the HA89 fertile line was almost identical to the HA412 line (NC_023337). The comparative analysis of HA89 fertile and CMS (PET1) analog mitochondrial genomes revealed 11,852 bp inversion, 4,732 bp insertion, 451 bp deletion and 18 variant sites. In the mtDNA of HA89 (PET2) CMS line we determined 27.5 kb and 106.5 kb translocations, 711 bp and 3,780 bp deletions, as well as, 5,050 bp and 15,885 bp insertions. There are also 83 polymorphic sites in the PET2 mitochondrial genome, as compared with the fertile line.DiscussionThe observed mitochondrial reorganizations in PET1 resulted in only one new open reading frame formation (orfH522), and PET2 mtDNA rearrangements led to the elimination of orf777, duplication of atp6 gene and appearance of four new ORFs with transcription activity specific for the HA89 (PET2) CMS line—orf645, orf2565, orf228 and orf285. Orf228 and orf285 are the atp9 chimeric ORFs, containing transmembrane domains and possibly may impact on mitochondrial membrane potential. So orf228 and orf285 may be the cause for the appearance of the PET2 CMS phenotype, while the contribution of other mtDNA reorganizations in CMS formation is negligible.

Abstract 293: Heterogeneous nucleocytoplasmic regulation of an incompletely penetrant ErbB2 onco-phenotype

Abstract Perturbation of cancer cells often leads to heterogeneous outcomes, in that most cells exhibit a dominant phenotype, but the rest appear resistant or hypersensitive to the perturbation. If the penetrance of such a phenotype is heritably incomplete, then it becomes extremely difficult to decipher the upstream molecular events that heterogenize the population and cause response variability. By combining quantitative measurements with dynamical models, systems approaches should be useful if provided with a core network of important biomolecules. The daunting hurdle lies in identifying phenotype-relevant regulatory heterogeneities that define the network for penetrance at the single-cell level. Here, we exploit a new approach, called stochastic frequency matching (SFM), which elaborates the molecular networks upstream of incompletely penetrant phenotypes. SFM identifies and parameterizes single-cell heterogeneities—which emerge after a uniform perturbation but before the appearance of a variable phenotype—to hone in on regulatory states corresponding to future penetrance. For a multi-acinar onco-phenotype incompletely triggered by ErbB receptor tyrosine kinase signaling in 3D cultured breast epithelia, we implemented SFM using microarrays to uncover a network of critical nucleocytoplasmic regulators, including the inner-ring nucleoporin NUP37 and the exportin CSE1L. Gain- and loss-of-function perturbations of NUP37 and CSE1L alter the frequency of ErbB2-triggered multiacinus formation, supporting that SFM can identify mechanisms of incompletely penetrant phenotypes. In addition, population-level transcriptomics revealed other ErbB2-induced changes in nucleocytoplasmic shuttling proteins: KPNA2, RANBP1, and XPO1. The net result of these alterations on shuttling is complicated, and the specific cargo relocalized by ErbB2 signaling is not known. We hypothesize that ErbB signaling heterogeneously reconfigures the nucleocytoplasmic shuttling state of cells to determine incomplete penetrance of the onco-phenotype. Using proximity labeling, we seek to identify novel ErbB2-induced NUP37 and CSE1L interactors that may serve as effectors for the multiacinar phenotype. Systems models of the nucleocytoplasmic shuttling network will evaluate the impact of observed abundance changes and identify characteristics of cargo predicted to be most sensitive to network reconfiguration. The importance of key effectors will ultimately be tested in vivo with murine cells engineered for spontaneous Erbb2 amplification and in patient samples with HER2 amplification. Citation Format: Lixin Wang, Kevin A. Janes. Heterogeneous nucleocytoplasmic regulation of an incompletely penetrant ErbB2 onco-phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 293.

DNA Damage Signatures in Peripheral Blood Cells as Biomarkers in Prodromal Huntington's Disease

Background: Blood biomarkers, that may improve the management of the pre−manifest phase of Huntington's disease (PRE−HD), are actively searched. We investigated telomere length (TL) and DNA damage signatures (DDS) as potential predictive biomarkers in peripheral blood mononuclear cells (PBMC) of PRE−HD and HD patients. Methods: We analysed the DNA isolated from fresh PBMC of 58 HD and 23 PRE−HD subjects with similar CAG expansion in the huntingtin (HTT) gene (44·20±2·85, 43·55±2·70; mean±SD) and 44 healthy controls (HC). We measured the TL by qPCR and double−strand DNA breaks by flow cytometric analysis of phosphorylated γ−H2AX (pγ−H2AX). Findings: PBMC from PRE−HD and HD groups showed shorter telomeres (p<0·0001) and significant increase of DDS compared to the controls (p<0·0001). Four individuals with pre−HD were monitored at several time points: the pγ−H2AX signal increased overtime; in three of them pγ−H2AX levels decreased with the appearance of clinical signs, although remained higher compared to HC. In PRE−HD subjects, the baseline levels of pγ−H2AX correlated robustly with the progression of the HD phenotype measured after three years. Interpretation: PBMC from PRE−HD subjects show progressive DDS in the absence of clinical signs. The basal levels of DNA damage are predictive factors of disease progression over time. The availability of an easily accessible and detectable biomarker in PRE−HD, negligible in HC, and potentially reversible, provides a novel tool to identify patient−specific drugs that prevent or slow down the appearance of HD phenotype in carriers. Funding Statement: LIRH Foundation received funding from the Cure Huntington’s Disease Initiative Foundation for collecting patient data and samples in the REGISTRY and ENROLL-HD platforms and from the Italian Government (funds from “5x1000” of taxes). The Italian Ministry of Health supports the research on Huntington’s disease to IRCCS Casa Sollievo della Sofferenza (CSS, funds from Ricerca Corrente [RC1601MD13] and from Ricerca Finalizzata [RF2016-02364123] to FS and SM). GR received funding from the University of Rome La Sapienza (Ricerca di Ateneo RM116154EC242C10). GR and SR received funding from the Cure Huntington’s Disease Initiative Foundation for collecting patient data and samples in the REGISTRY and ENROLLHD platforms. Declaration of Interests: All the authors declare no competing interests. Ethics Approval Statement: All human studies were carried in compliance with the Declaration of Helsinki, approved by local ethics committees and all participants have given written informed consent.

Abstract IA06: Driver mutations and cell-of-origin as critical factors determining the phenotypic characteristics of thoracic tumor subtypes

Abstract IA06: Driver mutations and cell-of-origin as critical factors determining the phenotypic characteristics of thoracic tumor subtypes

Stability Results Of New Rice Pulses (Oryza sativa L.) F4 and F5

The challenge for plant breeders can not be separated from the interaction effects between genotypes and the environment, where the tested strains show different results at each test site. Therefore, to know a strain or genotype that has a level of stability it is necessary to do the testing phase. The currently developed strains are RG1, RG2, RG3, and RG4. Currently the strains have entered the third generation. Furthermore, the four rice strains will be planted in the fourth generation and continued by the fifth generation. This research was conducted at Field Polytechnic of Lampung State of Lampung, Bandar Lampung on September 2015 - January 2016 planting F4 and January - May 2016 planting F5. The objective of this research is to obtain new strain of rice that is able to maintain the stability of the results by looking at the phenotypic appearance character and the potential yield that is planted on F4 and F5. The design used in this study is the design of split plot with main plot treatment using two generations (F) that is F4 and F5. While in sub plots using 4 new rice strains (G) are RG1, RG2, RG3, and RG4. Data were analyzed by LSD Test at 5% level. Stability analysis using Francis and Kenneberg (1978) models, by looking at the mean squares (Si2) and the Coefficient of Varians (CVi). From the result of observation of stability result of four rice strains in two different planting generations it can be concluded that the strains that exhibit phenotypic character and stable yield potential on F4 and F5 are RG1 and RG2. The strings showing potential unstable results on F4 and F5 are RG3 and RG4.

Three-dimensional coculture of primary hepatocytes and stellate cells in silk scaffold improves hepatic morphology and functionality in vitro.

A vigorous in vitro model of liver that could recapitulate hepatic phenotype and functionality in vivo would exclusively improve the efficiency of bioartificial liver, drug discovery, or even transplantation therapy. Owing to the indispensable role of three-dimensional (3D) microenvironment in supporting viability and function of hepatocytes in vitro, much effort recently has been focused on improving reproducibility and standardization of primary hepatocyte cultures with a paradigm shift to 3D culture system, In the present study, an improved 3D coculture system of hepatocytes was established in which rat primary hepatocytes were cocultured with hepatic stellate cells in silk porous scaffolds. Silk scaffolds with incorporated extracellular matrix provided a suitable microenvironment for maintaining the viability, morphology and gene expression of the primary hepatocyte in vitro. The presence of stromal cells promoted primary hepatocyte to generate cellular aggregates with well-organized 3D architecture after 3 days of coculture in vitro. These aggregates exhibited proper morphology similar to liver tissue in vivo. Consistent with their phenotypic appearance, well-maintained functionality of hepatocytes was also observed in the cocultures, where albumin secretion/expression, urea synthesis as well as messenger ribonucleic acid expression of multiple cytochrome Ps (CYPs) enzymes increased significantly compared to either the 3D monocultures or monolayer cultures. Additionally, this 3D multicellular coculture model displayed an improved metabolic activity of CYPs enzymes to the probe drugs treatment. Thus, this culture system would not only contribute to the construction of micro-organoid tissue of liver but also potentially provide a robust tool for drug metabolism evaluation in vitro. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2171-2180, 2018.

Synapsin I and Synapsin II regulate neurogenesis in the dentate gyrus of adult mice.

Adult neurogenesis is emerging as an important player in brain functions and homeostasis, while impaired or altered adult neurogenesis has been associated with a number of neuropsychiatric diseases, such as depression and epilepsy. Here we investigated the possibility that synapsins (Syns) I and II, beyond their known functions in developing and mature neurons, also play a role in adult neurogenesis. We performed a systematic evaluation of the distinct stages of neurogenesis in the hippocampal dentate gyrus of Syn I and Syn II knockout (KO) mice, before (2-months-old) and after (6-months-old) the appearance of the epileptic phenotype. We found that Syns I and II play an important role in the regulation of adult neurogenesis. In juvenile mice, Syn II deletion was associated with a specific decrease in the proliferation of neuronal progenitors, whereas Syn I deletion impaired the survival of newborn neurons. These defects were reverted after the appearance of the epileptic phenotype, with Syn I KO and Syn II KO mice exhibiting significant increases in survival and proliferation, respectively. Interestingly, long-term potentiation dependent on newborn neurons was present in both juvenile Syn mutants while, at later ages, it was only preserved in Syn II KO mice that also displayed an increased expression of brain-derived neurotrophic factor. This study suggests that Syns I and II play a role in adult neurogenesis and the defects in neurogenesis associated with Syn deletion may contribute to the alterations of cognitive functions observed in Syn-deficient mice.

The roles of histone methyl‐transferase kmt2d in vasculogenesis

INTRODUCTIONCongenital heart defects (CHD) arise from abnormal development of the heart and major blood vessels. An estimated 40,000 infants are affected by CHD each year in the United States. Despite its high incidence, our understanding of the complex genetic anomalies leading these defects is limited. Recent studies linked mutations in the ubiquitous histone methyl‐transferase KMT2D with congenital heart defects and Kabuki Syndrome, a condition with a spectrum of CHD and other congenital disorders. While KMT2D has well‐described roles in myocardium development during cardiogenesis, it is unknown whether KMT2D has regulatory functions during vasculogenesis, which could contribute to the spectrum of heart and other defects in Kabuki Syndrome. KMTD2 has recently been shown to interact with Notch signaling in Drosophila. While Notch pathway has well‐established roles in vasculogenesis and angiogenesis, its regulation by KMT2D during cardiovascular development has not been explored. Zebrafish provide a strong model for the analysis of vasculogenesis defects, since it can survive early development in absence of blood circulation.OBJECTIVEThe primary objective of this study is to describe the roles of Kmt2d and its regulatory link with Notch signaling during zebrafish vasculogenesis.METHODSUsing the CRISPR/Cas9 technology, we generated Zebrafish kmt2d null mutants that recapitulate the phenotypic features of human Kabuki Syndrome. In order to study endocardial/endothelial development, the stable mutant kmt2dzy59 was crossed with the transgenic line tg(kdrl:GFP). kmt2dzy59;tg(kdrl:GFP) cardiovascular phenotype was characterized with super resolution confocal microscopy and fluorescent‐activated cell sorting (FACS).Kmt2d and Notch pathway interaction was assessed by G0 knockdown analysis in the Notch reporter line tg(TP1:EGFP). Results were confirmed and expanded by RNAseq of single embryos from genetic crosses at 24hpf. Single embryo transcriptome analysis allows us to capture transcriptomes in clutches of embryos before the appearance of phenotypes, and to post‐facto genotype sibling embryos by transcriptome analysis with Kallisto and SNP mapping.RESULTSIn this study we generated Zebrafish kmt2d null mutants that recapitulate the phenotypic features of Kabuki Syndrome. We characterized for the first time a cardiovascular developmental defect in kmt2dzy59 embryos, including hypoplastic ventricle, aortic arch disruption, and altered cell cycle profiles. kmt2d CRISPR/Cas9 injection in a Notch reporter line showed expanded Notch signaling in endocardial/endothelial cells. RNAseq analysis of kmt2dzy59 embryos showed a substantial upregulation of Notch signaling components.CONCLUSIONOur results demonstrate that Kmt2d regulates zebrafish vasculogenesis. We also provide evidence of regulatory interactions between Kmt2d and Notch signaling which modify endothelial/endocardial cell behavior.Support or Funding InformationThis work in HJY laboratory was supported by NHLBI CvDC U01HL0981This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The phenotypic appearance of Japanese persimmon (Diospyros kaki L.f.) in Karo District, North Sumatra, Indonesia

Hanafiah DS, Sanggita S, Lubis K. 2018. The phenotypic appearance of Japanese persimmon (Diospyros kaki L.f.) in Karo District, North Sumatra, Indonesia. Biodiversitas 19: 559-564. The farmers in Karo District began to be less interested in cultivating kesemek or Japanese persimmon (Diospyros kaki L.f.). Due to the price of this commodity has dropped in the market, the farmers cut down the tree and cultivate more favorable horticultural crops, such as vegetable and citrus cultivation. It is necessary to conduct a study to obtained sufficient information to determine the necessary steps in order to preserve Japanese persimmon plants in Karo District. One first steps was to get information of accession characteristic of Japanese persimmon in Karo District. This research aimed to identify relationships of morphological characteristics among individuals of Japanese persimmon plants. The research was conducted from May until July 2017 at Berastagi, Merdeka, Kabanjahe, and Dolat Rayat sub-districts of Karo District, North Sumatra, Indonesia. The survey method using Japanese persimmon descriptor of Diospyros kaki L.f. by the International Union for the Protection of New Varieties (UPOV) with the purposive method for location determination and technique sampling. Thirty-six accessions of Japanese persimmon plants were studied. Based on clustering method of the morphological characteristic, 4 clusters are formed. This difference was canopy form, leaf shape and fruit morphological. Accession 34 from Dolat Rayat Distict has different fruit characters with other accessions.

A Unique Preparation and Delivery Method for Acitretin for Neonatal Harlequin Ichthyosis

Harlequin ichthyosis is a rare form of congenital ichthyosis with a distinct phenotypic appearance. We describe a case of a newborn baby with harlequin ichthyosis who was treated with an oral formulation of acitretin. The treatment resulted in a satisfactory improvement in the skin condition of the patient. The tolerance to the drug was good with no side effects in the patient. The aim of this case report is to highlight an extemporaneous preparation of acitretin from the commonly available capsule form, which is effective for use in neonates with harlequin ichthyosis. It also highlights the risk of exposure to health care providers to acitretin.