Amagat entre rostolls: registres fotogràfics i variació fenotípica de Leopardus pajeros Leopardus pajeros és un fèlid petit amb un rang de distribució restringit a l'Argentina i la zona austral de ...Xile. Hi ha molt poca literatura específica sobre aquest mamífer i la seva història natural continua sent un enigma. L'article recull quatre registres de Leopardus pajeros a la Patagònia i inclou fotografies i descripcions detallades a partir de les quals es fa una proposta d'espectre fenotípic que s'estén del color gris clar al gris terrós i al rovellat rogenc.
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the ...clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of alterations that sensitize to drugs, while machine learning demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.
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•We integrate heterogeneous molecular data of 11,289 tumors and 1,001 cell lines•We measure the response of 1,001 cancer cell lines to 265 anti-cancer drugs•We uncover numerous oncogenic aberrations that sensitize to an anti-cancer drug•Our study forms a resource to identify therapeutic options for cancer sub-populations
A look at the pharmacogenomic landscape of 1,001 human cancer cell lines points to new treatment applications for hundreds of known anti-cancer drugs.
Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1. This expansion encodes a mutant protein whose abnormal function is traditionally ...associated with HD pathogenesis; however, recent evidence has also linked HD pathogenesis to RNA stable hairpins formed by the mutant HTT expansion. Here, we have shown that a locked nucleic acid-modified antisense oligonucleotide complementary to the CAG repeat (LNA-CTG) preferentially binds to mutant HTT without affecting HTT mRNA or protein levels. LNA-CTGs produced rapid and sustained improvement of motor deficits in an R6/2 mouse HD model that was paralleled by persistent binding of LNA-CTG to the expanded HTT exon 1 transgene. Motor improvement was accompanied by a pronounced recovery in the levels of several striatal neuronal markers severely impaired in R6/2 mice. Furthermore, in R6/2 mice, LNA-CTG blocked several pathogenic mechanisms caused by expanded CAG RNA, including small RNA toxicity and decreased Rn45s expression levels. These results suggest that LNA-CTGs promote neuroprotection by blocking the detrimental activity of CAG repeats within HTT mRNA. The present data emphasize the relevance of expanded CAG RNA to HD pathogenesis, indicate that inhibition of HTT expression is not required to reverse motor deficits, and further suggest a therapeutic potential for LNA-CTG in polyglutamine disorders.
This work was supported by the Spanish government through the Plan Nacional de I+D+I and cofunded by grants from the Instituto de Salud Carlos III (ISCIII) – Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER) (project PI11/02036, to EM, and PI13/01250, to EPN); the Spanish Ministerio de Economía y Competitividad (MINECO) (SAF2008-00357 and SAF2013-49108-R, to XE, and SAF2014-60551-R: iRPaD, to EM); and the Generalitat de Catalunya, Departament Economia i Coneixement, Secretaria Universitats i Recerca (AGAUR 2014 SGR-1138, to XE).
Penyakit busuk bulir padi oleh bakteri Burkholderia glumae perlu diwaspadai termasuk di Jawa Barat sebagai salah satu sentra produksi padi nasional. Penelitian ini bertujuan untuk menentukan ...insidensi penyakit, identitas dan keragaman bakteri B. glumae pada beberapa varietas padi di Provinsi Jawa Barat. Pengamatan insidensi penyakit dan pengambilan sampel dilakukan di 9 kabupaten. Bakteri diisolasi dari bulir padi yang bergejala busuk bulir kemudian dilakukan uji biokimia dan fisiologi yang meliputi uji Gram serta uji pertumbuhan pada pH 4.8, dan NaCl 2%. Variasi fenotipik diamati dari warna koloni pada medium S-PG, produksi toksofalvin, respons hipersensitivitas pada daun tembakau, dan uji patogenisitas pada tanaman padi. Primer spesifik JLBgF/JLBgR dan primer universal 16S rRNA, yaitu 27F/1492R digunakan untuk menentukan identitas bakteri secara molekuler. Insidensi penyakit di lapangan berkisar antara 0–73.3%, tertinggi di Kecamatan Dawuan (Karawang) pada var. Mekongga. Berdasarkan uji biokimia dan fisiologi diperoleh 29 isolat terkonfirmasi sebagai B. glumae. Hasil pengamatan fenotipik menunjukkan 10 isolat tergolong koloni tipe A, 19 isolat tipe B; 25 isolat menghasilkan toksoflavin; 29 isolat menimbulkan respons hipersensitivitas pada daun tembakau dan gejala hawar pada tanaman padi. Identifikasi menggunakan primer spesifik dan universal membuktikan 29 isolat adalah B. glumae. Analisis keragaman genotip menunjukkan bahwa isolat KRCH-2 (Karawang) dan INCH-6 (Indramayu) memiliki hubungan kekerabatan yang dekat dengan B. glumae asal Cina dan Amerika
MOTIVATION: Psychiatric disorders have a great impact on morbidity and mortality. Genotype-phenotype resources for psychiatric diseases are key to enable the translation of research findings to a ...better care of patients. PsyGeNET is a knowledge resource on psychiatric diseases and their genes, developed by text mining and curated by domain experts. RESULTS: We present psygenet2r, an R package that contains a variety of functions for leveraging PsyGeNET database and facilitating its analysis and interpretation. The package offers different types of queries to the database along with variety of analysis and visualization tools, including the study of the anatomical structures in which the genes are expressed and gaining insight of gene's molecular function. Psygenet2r is especially suited for network medicine analysis of psychiatric disorders. AVAILABILITY AND IMPLEMENTATION: The package is implemented in R and is available under MIT license from Bioconductor (http://bioconductor.org/packages/release/bioc/html/psygenet2r.html).
This work was supported by ISCIII-FEDER PI13/00082, CP10/00524, CPII16/00026, MICINN MTM2015-68140-R, IMI-JU under grants agreements no. 115191 (Open PHACTS), no. 115372 (EMIF), no. 115735 (iPiE), resources of which are composed of financial contribution from the EU-FP7 FP7/2007–2013 and EFPIA companies in kind contribution, and the EU H2020 Programme 2014–2020 under grant agreements no. 634143 (MedBioinformatics) and no. 676559 (Elixir-Excelerate). The Research Programme on Biomedical Informatics (GRIB) is a member of ELIXIR-ES and the Spanish National Bioinformatics Institute (INB), PRB2-ISCIII and is supported by grant PT13/0001/0023, of the PE I + D+i 2013-2016, funded by ISCIII and FEDER. A.G.S. acknowledges financial support from the Spanish Ministry of Economy and Competitiveness, through the ‘María de Maeztu’ Programme for Units of Excellence in R&D MDM-2014-0370.
Bacteria and Archaea display a variety of phenotypic traits and can adapt to diverse ecological niches. However, systematic annotation of prokaryotic phenotypes is lacking. We have therefore ...developed ProTraits, a resource containing ∼545 000 novel phenotype inferences, spanning 424 traits assigned to 3046 bacterial and archaeal species. These annotations were assigned by a computational pipeline that associates microbes with phenotypes by text-mining the scientific literature and the broader World Wide Web, while also being able to define novel concepts from unstructured text. Moreover, the ProTraits pipeline assigns phenotypes by drawing extensively on comparative genomics, capturing patterns in gene repertoires, codon usage biases, proteome composition and co-occurrence in metagenomes. Notably, we find that gene synteny is highly predictive of many phenotypes, and highlight examples of gene neighborhoods associated with spore-forming ability. A global analysis of trait interrelatedness outlined clusters in the microbial phenotype network, suggesting common genetic underpinnings. Our extended set of phenotype annotations allows detection of 57 088 high confidence gene-trait links, which recover many known associations involving sporulation, flagella, catalase activity, aerobicity, photosynthesis and other traits. Over 99% of the commonly occurring gene families are involved in genetic interactions conditional on at least one phenotype, suggesting that epistasis has a major role in shaping microbial gene content.
Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular ...heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.
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•Evolutionary dynamics during neoadjuvant chemotherapy in breast cancer•Computational model to predict evolutionary trajectories and topologic patterns•Intratumor heterogeneity measures predict response to treatment•Changes in intratumor genetic and phenotypic diversity due to breast cancer therapy
Michor, Polyak, and colleagues investigated changes in intratumor cellular diversity during neoadjuvant chemotherapy in breast cancer. They found that lower pretreatment genetic diversity is associated with better response to treatment, pre- and posttreatment diversity is the same in patients who failed to achieve pathologic complete response, and the frequency of phenotypically distinct cell populations changes significantly due to differences in proliferation rates. These results highlight the need for combined analysis of genotypes and phenotypes in order to understand how tumors evolve.
Tujuan penelitian ini adalah untuk mengidentifikasi karakteristik sapi Madura betina tipe taccek berbagai umur. Penelitian dilakukan di wilayah sumber bibit sapi Madura yang berada di Kecamatan ...Pasean dan Kecamatan Batumarmar, Kabupaten Pamekasan, Provinsi Jawa Timur. Penelitian dimulai tanggal 1 Desember sampai 30 Desember 2019. Materi yang digunakan dalam penelitian adalah sapi Madura betina tipe taccek berbagai umur berdasarkan PI (Permanent incicivi) sebanyak 110 ekor dengan rincian PI0 22 ekor, PI2 10 ekor, PI4 25 ekor, PI6 19 ekor dan PI8 34 ekor. Metode penelitian yang digunakan adalah survei di lapangan dengan pengambilan datasecara purposive sampling. Data statistik vitaldihitung nilai rataan dan standar deviasinya, selanjutnya dianalisis dengan menggunakan ANOVA satu arah (one way anova) dan dilanjutkan Uji Beda Nyata Terkecil (BNT) untuk membedakan 2 rataan. Data fenotip dianalisis secara deskriptif dan diamati proporsi fenotipnya. Hasil penelitian disimpulkan bahwa seiring bertambahnya umur sapi taccek maka panjang kepala, lebar kepala, bobot badan, panjang badan dan lingkar dada ukuranya bertambah. Ukuran tinggi gumba dan tinggi pinggul juga bertambah mulai PI0, PI2, PI4, sampaiPI6,namun mengalami penurunan pada PI8. Sapi taccek memiliki ciri fenotip yang spesifik yaitu bentuk mata sipit dengan garis lingkar mata hitam, bentuk telinga kecil, tanduk melengkung ke atas, berpunuk, mempunyai gelambir dan rambut ekor berwarna hitam.
Od fenotipa do biološkog liječenja teške astme Kljaić Bukvić, Blaženka; Ivković Jureković, Irena; Navratil, Marta ...
Paediatria Croatica,
06/2022, Letnik:
66, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
Teška astma je složena i heterogena bolest koja kliničara stavlja pred težak zadatak razlikovanja bolesnika prema rizičnim manife- stacijama bolesti (fenotipovi) i specifičnim patofiziološkim ...mehanizmima u podlozi bolesti (endotipovi), a sve u cilju odabira što učinkovitijeg liječenja prilagođenog potrebama pojedinog bolesnika. Dosadašnja istraživanja i pokušaji fenotipiziranja bolesnika s astmom, pa tako i teškom astmom, kod djece nisu dovela do jedno- značnog zaključka, osim već otprije poznatih činjenica da najveći dio djece ima atopiju s višestrukim preosjetljivostima (nerijetko kombinacija nutritivnih i aeroalergena, uloga plijesni), reverzibilnu bronhoopstrukciju i rane znakove remodelacije bronha. Samo mali broj djece ima trajnu bronhoopstrukciju (FEV1< 80%). Endotipovi teške astme ne razlikuju se od onih opisanih u astmi općenito: tip 2 (visoki Th2; eozinofili u serumu i sputumu, visoki IgE, FeNO; ključni citokini IL-4, IL-5, IL-13) i ne-tip 2 (niski Th2, neutrofilna, pau- cigranulocitna ili miješana upala; ključni citokini IL-8, IL-17, IL-22). Tip 2 je češći endotip kod djece i za njega postoji dostupna i odo- brena biološka terapija (anti-IgE i anti-IL-5). Ne-tip 2 je rjeđi endotip, obilježen općenito ograničenim terapijskim opcijama, među kojima se razmatra primjena azitromicina. Teška astma, iako kod djece rijetko zastupljena, predstavlja rizični fenotip koji ozbiljno narušava kvalitetu života. Pažljivo praćenje bolesnika i određivanje temeljnog endotipa omogućuje izbor i primjenu ciljanog i personaliziranog liječenja.
Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model human disease in relevant cell types, but it is unclear whether they could successfully model age‐related diseases ...such as Parkinson's disease (PD). Here, we generated iPSC lines from seven patients with idiopathic PD (ID‐PD), four patients with familial PD associated to the G2019S mutation in the Leucine‐Rich Repeat Kinase 2 (LRRK2) gene (LRRK2‐PD) and four age‐ and sex‐matched healthy individuals (Ctrl). Over long‐time culture, dopaminergic neurons (DAn) differentiated from either ID‐PD‐ or LRRK2‐PD‐iPSC showed morphological alterations, including reduced numbers of neurites and neurite arborization, as well as accumulation of autophagic vacuoles, which were not evident in DAn differentiated from Ctrl‐iPSC. Further induction of autophagy and/or inhibition of lysosomal proteolysis greatly exacerbated the DAn morphological alterations, indicating autophagic compromise in DAn from ID‐PD‐ and LRRK2‐PD‐iPSC, which we demonstrate occurs at the level of autophagosome clearance. Our study provides an iPSC‐based in vitro model that captures the patients' genetic complexity and allows investigation of the pathogenesis of both sporadic and familial PD cases in a disease‐relevant cell type.
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