Genetics of Wilms' tumor: A blend of aberrant development and genomic imprinting

Wilms' tumor or nephroblastoma (WT), one of the most common childhood solid tumors (1:10,000, 8% of childhood tumors), is probably the one that best deserves the designation of embryonal tumor. Wilms' tumors are composed of three major elements in variable proportions: compact areas of blastemal cells, tubular structures of various sizes and fibrous or mixoid stroma containing elongated stellate-shaped large round cells. These components are reminiscent of normal human nephrogenesis, known to be initiated by the ingrowth of the ureteral bud into the metanephrogenic mesenchyma which then condenses and forms the different portions of the nephron. These tumors thus show a remarkable mimicry of the normal nephrogenic processes, although in an extravagant mode leading to incompletely differentiated structures with as many dead ends as a labyrinth [1]. These structures are accompanied, in a minority of cases, by heterologous ectopic tissues of mesodermal origin including bone, cartilage and skeletal muscle [2]

Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions

PELAKSANAAN KERJA SAMA PROGRAM ASURANSI TAKAFUL PEMBIAYAAN (BANCASSURANCE) ANTARA PT. ASURANSI TAKAFUL KELUARGA DENGAN PT. BANK SYARI’AH MANDIRI CABANG PEKANBARU DITINJAU MENURUT PERSPEKTIF EKONOMI ISLAM

Penelitian ini berjudul “ PELAKSANAAN KERJASAMA PROGRAM ASURANSI TAKAFUL PEMBIAYAAN ANTARA PT. ASURANSI TAKAFUL KELUARGA DENGAN PT. BANK SYARIAH MANDIRI CABANG PEKANBARU MENEURUT PERSPEKTIF EKONOMI ISLAM”. Penelitian ini dilatar belakangi oleh Pandangan Penulis akan perlunya mempersiapkan diri dalam menghadapi resiko, karena hidup manusia selalu dihadapkan kepada ketidakpastian atau kemungkinan yang akan terjadi kedepannya.Saat sekarang ini banyak jenis asuransi yang ditawarkan oleh perusahaan asuransi, salah satunya Program Asuransi Takaful Pembiayaan yaitu asuransi jiwa kumpulan,. Tujuan dari program ini adalah untuk Memberikan Manfaat Takaful kepada pemegang polis atau ahli waris Peserta, bila Peserta meninggal dunia dalam masa perjanjian asuransi. Ada beberapa alasan lembaga keuangan atau pihak bank menyediakan asuransi jiwa terhadap nasabahnya salah satunya untuk meminimalisir resiko yang terjadi jika dalam masa kontrak pembiayaan nasabah sakit atau kecelakaan yang menyebabkan nasabah meningal dunia, dan untuk mengurangi resiko kredit macet. Salah satu syarat yang harus diperhatikan pihak bank terhadap calon peserta pembiayaan adalah ketentuan seleksi resiko, dengan kriteria nasabah Free cover, non medical, dan medicalyang mana merupakan ketentuan pemeriksaan kesehatan produk asuransi takaful pembiayaan atau batasan penutupan asuransi takaful keluarga sebelum pembiayaan tercover, namun dilapangan persyaratan ini kurang diperhatikan. Berangkat dari hal tersebut diatas, maka yang akan menjadi pokok permasalahan adalah Bagaimana Pelaksanaan Kerjasama Program Asuransi Takaful Pembiayaan (Bancassurance) antara PT. Asuransi Takaful Keluarga dengan PT. Bank Syariah Mandiri Cabang Pekanbaru, apa factor-faktor yang menyebabkan terjadinya kendala-kendala di lapangan dalam pelaksanaa kerjasama ini, bagaimana tinjauan ekonomi islam terhadap Program Asuransi Takaful Pembiayaan (Bancassurance) Penelitian ini bersifat penelitian lapangan yaitu di PT. Asuransi Takaful Keluarga JL. JL. Tuanku Tambusai Komplek Perkantoran Mella No. 6 A. dan PT. Bank Syariah Mandiri (BSM) Cabang Pekanbaru di JL. Jendral Sudirman Nomor 169 Pekanbaru dan 5 Kacapem diantaranya adalah Kacapem Panam, Kacapem Nangka, Kacapem Tembilahan, Kacapem Ujung Batu, dan Kacapem Kerinci. Yang menjadi populasi dari penelitian ini adalah Pimpinan Karyawan/I yang berjumlah 4 orang, dan Nasabah atau Pihak Bank Syariah Mandiri Cabang Pekanbaru Dan 5 Kacapem , diambil 15 orang marketing. Sampel diambil dengan tekhnik Total Sampling. Penulis mendapatkan data di lapangan dengan menggunakan tekhnik observasi, angket, wawancara, dan studi dokumen, yang kemudian penulis analisa dengan menggunakan deskriptif kualitatif dengan metode deduktif,induktif dan deskriptif. Dari penelitian ini dihasilakan suatu kesimpulan tentang Pelaksanaan Kerjasama Program Asuransi Takaful Pembiayaan, kendala-kendala, dan tinjauan ekonomi islam terhadap pelaksanaan kerjasama ini. Dalam pelaksanaan kerjasama ini, menggunakan aqad Wakalah bil Ujroh dan tabarru’. Dan dalam pelaksanaandi lapangan belum sepenuhnya mematuhi pejanjian di awal aqad yakni ketentuan seleksi resiko terhadap calon peserta pembiayaan, khusunya untuk ketentuan nasabah Medical melakukan pemeriksaan kesehatan sesuai dengan ketentuan batasan seleksi resiko pihak asuransi, namun terkadang di lapanganpihak bankmelakukan pencairan pembiayaan terlebih dahulu sebelum mendapatkan kepastian asuransi, sehingga menyebabkan pihak asuransi kesulitan untuk menentukan tercover atau tidaknya nasabah, pengajuan asuransi nasabah ditolak, begitu juga menyebabkan proses pengcoveran lambat, dan sering terjadinya ketelambatan konfirmasi data-data yang kurang dari pihak asuransi. Sedangkan dalam kerjasama ini masih ditemukan kendala-kendala dilapangan diantaranya adalah jumlah SDM yang sangat terbatas,sehingga sosialisasi kurang dilakukan, Sistem jaringan internet yang lambat menyebabkan lambatnya proses pengcoveran, kurangnya pengawasan dan kurangnya pengetahuan karyawan tentang program ini dikarenakan banyaknya karyawan baru , dan sering di roling. Dan tinjauan Ekonomi Islam terhadap pelaksanaan kerjasama, dalam ekonomi islam melakukan kerjasama yang menghasilkan keuntungan antara kedua belah pihak yang bekerjasama dibolehkan dengan prinsip tolong menolong yang saling membutuhskan, saling memerlukan, dan saling menguntungkan. Jadi kerjasama yang dilakukan oleh PT. Asuransi Takaful Keluarga dengan PT. Bank Syariah Mandiri Cabang Pekanbaru dibolehkan dalam islam mengingat kedua lembaga ini sama-sama lembaga syariah, namun dalam pelaksanaannya masih ada ketentuan yang masih kurang diperhatikan salah satunya adalah ketentuan batasan seleksi resiko (Underwriting) untuk calon peserta pembiayaan, khusunya nasabah Medical

HUBUNGAN KEMANDIRIAN BELAJAR SISWA DENGAN PENGUASAAN SISWA PADA MATA PELAJARAN EKONOMI DI SEKOLAH MENENGAH ATAS NEGERI 9 PEKANBARU

Penelitian ini bertujuan untuk mengetahui hubungan kemandirian Belajar siswa Dengan Penguasaan Siswa Pada Mata Pelajaran Ekonomi di Sekolah Menengah Atas Negeri 9 Pekanbaru. Subjek dalam penelitian ini adalah siswa kelas X s/d XII di SMA Negeri 9 Pekanbaru, sedangkan objeknya adalah hubungan kemandirian Belajar siswa dengan penguasaan Siswa Pada Mata Pelajaran Ekonomi di Sekolah Menengah Atas Negeri 9 Pekanbaru. Populasinya adalah siswa kelas X, XI, dan XII yang berjumlah 340 orang dan penulis mengambil sampel dengan rumus Slovin sehingga diperoleh sampel sebanyak 77 orang siswa. Pengumpulan data diambil melalui angket dan dokumentasi. Data yang terkumpul, sesuai dengan jenis penelitian ini yaitu penelitian dua variabel, variabel pertama (X) dan Variabel kedua (Y) bersifat ordinal dan interval. maka penulis menggunakan rumus product moment dengan bantuan perangkat komputer program SPSS for windows Versi 17.0. Penelitian yang penulis lakukan ini menghasilkan kesimpulan akhir bahwa kemandirian belajar dikategorikan “baik” dengan persentase 81.81%, dan penguasaan siswa terkategori “baik” dengan persentase 66.2%. Sedangkan hubungan kemandirian Belajar siswa dengan penguasaan Siswa Pada Mata Pelajaran Ekonomi di Sekolah Menengah Atas Negeri 9 Pekanbaru, dengan Konstribusi kemandirian belajar dengan penguasaan siswa adalah 0.628x100% = 62,80% dan selebihnya dipengaruhi oleh variabel lain. Pada taraf signifikan 5% maupun 1% yaitu 0.2500.325, ini berarti Ha diterima, Ho ditolak. Kata Kunci: Kemandirian Belajar Siswa, Penguasaan Sisw

CTG Trinucleotide Repeat “Big Jumps”: Large Expansions, Small Mice

Trinucleotide repeat expansions are the genetic cause of numerous human diseases, including fragile X mental retardation, Huntington disease, and myotonic dystrophy type 1. Disease severity and age of onset are critically linked to expansion size. Previous mouse models of repeat instability have not recreated large intergenerational expansions (“big jumps”), observed when the repeat is transmitted from one generation to the next, and have never attained the very large tract lengths possible in humans. Here, we describe dramatic intergenerational CTG•CAG repeat expansions of several hundred repeats in a transgenic mouse model of myotonic dystrophy type 1, resulting in increasingly severe phenotypic and molecular abnormalities. Homozygous mice carrying over 700 trinucleotide repeats on both alleles display severely reduced body size and splicing abnormalities, notably in the central nervous system. Our findings demonstrate that large intergenerational trinucleotide repeat expansions can be recreated in mice, and endorse the use of transgenic mouse models to refine our understanding of triplet repeat expansion and the resulting pathogenesis

Comparison of voluntary food intake and palatability of commercial weight loss diets in healthy dogs and cats

Background Obesity in dogs and cats is usually managed by dietary energy restriction using a purpose-formulated weight loss diet, but signs of hunger and begging commonly occur causing poor owner compliance. Altering diet characteristics so as to reduce voluntary food intake (VFI) can improve the likelihood of success, although this should not be at the expense of palatability. The aim of the current study was to compare the VFI and palatibility of novel commercially available canine and feline weight loss diets. Methods The relative performance of two canine (C1 and C2) and two feline (F1 and F2) diets was assessed in groups of healthy adult dogs and cats, respectively. Diets varied in energy, protein, fibre, and fat content. To assess canine VFI, 12 (study 1) and 10 (study 2) dogs were offered food in 4 meals, for 15 min on each occasion, with hourly intervals between the meals. For feline VFI, 12 cats were offered food ad libitum for a period of 18 h per day over 5 consecutive days. The palatability studies used separate panels of 37 dogs and 30 cats, with the two diets being served, side-by-side, in identical bowls. Results In dogs, VFI was significantly less for diet C1 than diet C2 when assessed on energy intake (study 1, 42% less, P = 0.032; study 2, 28% less, P = 0.019), but there was no difference in gram weight intake (study 1: P = 0.964; study 2: P = 0.255). In cats, VFI was 17% less for diet F1 than diet F2 when assessed by energy intake (P < 0.001), but there was again no difference in gram weight (P = 0.207). There was no difference in palatability between the two canine diets (P = 0.490), whilst the panel of cats diet preferred F1 to F2 (P < 0.001). Conclusion Foods with different characteristics can decrease VFI without affecting palatability in both dogs and cats. The effects seen could be due to decreased energy content, decreased fat content, increased fibre content, different fibre source, and increased protein content. Further studies are now needed to determine whether similar findings occur in obese dogs and cats on controlled weight loss programmes

Fibulin-2: genetic mapping and exclusion as a candidate gene in Marfan syndrome type 2.

International audienceFibulin-2 (FBLN2) is a new extracellular matrix protein that has been considered a candidate gene for Marfan syndrome type 2 (locus MFS2) based on chromosomal colocation at 3p24.2-p25 and disease phenotype. In the absence of polymorphic markers reported for FBLN2, direct sequencing of the gene was performed and two intragenic polymorphisms were identified. Linkage was excluded between FBLN2 and the MFS2 gene. Furthermore, two-point lod scores were generated between these markers and anonymous markers arrayed on the genetic map of 3p and closely linked to MFS2. These analyses placed FBLN2 at marker D3S1585

The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis

Background: The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype. Methods: PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored. Results: Gene expression data were consistent with the downregulation of the PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose lanifibranor demonstrated significant protection from lung fibrosis after bleomycin and from right ventricular hypertrophy following induction of pulmonary hypertension by SU5416, despite no significant change in right ventricular systolic pressure. Conclusions: In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg lanifibranor reduces the development of lung fibrosis and right ventricular hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity may contribute to the exaggerated fibroproliferative response to tissue injury in this transgenic model of scleroderma and its pulmonary complications

Molecular Spectrum of Autosomal Dominant Hypercholesterolemia in France

Autosomal Dominant Hypercholesterolemia (ADH), characterized by isolated elevation of plasmatic LDL cholesterol and premature cardiovascular complications, is associated with mutations in 3 major genes: LDLR (LDL receptor), APOB (apolipoprotein B) and PCSK9 (proprotein convertase subtilisin-kexin type 9). Through the French ADH Research Network, we collected molecular data from 1358 French probands from eleven different regions in France. Mutations in the LDLR gene were identified in 1003 subjects representing 391 unique events with 46.0% missense, 14.6% frameshift, 13.6% splice, and 11.3% nonsense mutations, 9.7% major rearrangements, 3.8% small in frame deletions/insertions, and 1.0% UTR mutations. Interestingly, 175 are novel mutational events and represent 45% of the unique events we identified, highlighting a specificity of the LDLR mutation spectrum in France. Furthermore, mutations in the APOB gene were identified in 89 probands and in the PCSK9 gene in 10 probands. Comparison of available clinical and biochemical data showed a gradient of severity for ADH-causing mutations: FH=PCSK9>FDB>‘Others’ genes. The respective contribution of each known gene to ADH in this French cohort is: LDLR 73.9%, APOB 6.6%, PCSK9 0.7%. Finally, in 19.0% of the probands, no mutation was found, thus underscoring the existence of ADH mutations located in still unknown genes. © 2010 Wiley-Liss, Inc