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51.
Edmond Wonkam-Tingang Isabelle Schrauwen Kevin K Esoh Thashi Bharadwaj Liz M Nouel-Saied Anushree Acharya Abdul Nasir Suzanne M Leal Ambroise Wonkam 《Experimental biology and medicine (Maywood, N.J.)》2021,246(13):1524
Approximately half of congenital hearing impairment cases are inherited, with non-syndromic hearing impairment (NSHI) being the most frequent clinical entity of genetic hearing impairment cases. A family from Cameroon with NSHI was investigated by performing exome sequencing using DNA samples obtained from three family members, followed by direct Sanger sequencing in additional family members and controls participants. We identified an autosomal dominantly inherited novel missense variant [NM_001174116.2:c.918G>T; p.(Q306H)] in DMXL2 gene (MIM:612186) that co-segregates with mild to profound non-syndromic sensorineural hearing impairment . The p.(Q306H) variant which substitutes a highly conserved glutamine residue is predicted deleterious by various bioinformatics tools and is absent from several genome databases. This variant was also neither found in 121 apparently healthy controls without a family history of hearing impairment , nor 112 sporadic NSHI cases from Cameroon. There is one previous report of a large Han Chinese NSHI family that segregates a missense variant in DMXL2. The present study provides additional evidence that DMXL2 is involved in hearing impairment etiology, and we suggest DMXL2 should be considered in diagnostic hearing impairment panels. 相似文献
52.
Prof. Dr. Andreas Bürkert Sulaiman Al Khanjari Nadiya A. Al‐Saady Edmond De Langhe Dirk Hölscher Jens Gebauer Stephan Behrendt Stefan Happe Katja Brinkmann Eva Schlecht 《当今生物学》2010,40(5):334-341
Until recently little was known about the crop diversity in the Sultanate of Oman, situated at the NE tip of the Arabian Peninsula. Interdisciplinary research in the often millenia‐old oases provide evidence for their role as reservoirs for plant genetic resources of ancient varieties of wheat and banana. Two newly discovered banana clones show a highly efficient biochemical defense mechanisms against some of the most devastating pests and diseases of banana. If these mechanisms can be properly understood and exploited in breeding programs, may have major impact on the commercial production of edible banana. 相似文献
53.
Elizabeth C. White Jean-Thoussaint Dikangadissi Edmond Dimoto William B. Karesh Michael D. Kock Nathacha Ona Abiaga Ruth Starkey Tharcisse Ukizintambara Lee J. T. White Katharine A. Abernethy 《International journal of primatology》2010,31(4):627-645
The predicted relationship between home-range size and group mass in primates developed by Clutton-Brock and Harvey (1977) has proved extremely robust in describing the use of space by most primate species. However, mandrills (Mandrillus sphinx) are now known to have an extreme group mass in the wild, far larger than that of the species used originally to generate
that relationship, and so it was unknown whether this relationship would be robust for this species. We investigated the home-range
size and use of a wild horde of ca. 700 mandrills in Lopé National Park, Gabon, using radiotelemetry. The total area the horde used over a 6-yr period [100%
minimum convex polygon (MCP)] was 182 km2, including 89 km2 of suitable forest habitat. Mandrills used gallery forests and isolated forest fragments with high botanical diversity far
more intensively that the continuous forest and completely avoided savanna and marsh. Peeled polygons and fixed kernel contours
revealed multiple centres of use, with the horde spending more than half its time in <10% of the total documented range, typical
of a frugivore using a patchy environment. Home-range size and internal structure varied considerably between years, but total
home range fitted the predicted relationship between group mass and home range size, despite being an outlier to the dataset.
We discuss the conservation implications of the species’ space requirements, in light of current pressures on land use in
their range. 相似文献
54.
Sundl I Guardiola M Khoschsorur G Solà R Vallvé JC Godàs G Masana L Maritschnegg M Meinitzer A Cardinault N Roob JM Rock E Winklhofer-Roob BM Ribalta J 《Journal of lipid research》2007,48(11):2506-2513
The aim of this study was to investigate the effects of the apolipoprotein A5 (APOA5) 1131T>C gene variant on vitamin E status and lipid profile. The gene variant was determined in 297 healthy nonsmoking men aged 20-75 years and recruited in the VITAGE Project. Effects of the genotype on vitamin E in plasma, LDL, and buccal mucosa cells (BMC) as well as on cholesterol and triglyceride (TG) concentrations in plasma and apolipoprotein A-I (apoA-I), apoB, apoE, apoC-III, and plasma fatty acids were determined. Plasma malondialdehyde concentrations as a marker of in vivo lipid peroxidation were determined. C allele carriers showed significantly higher TG, VLDL, and LDL in plasma, higher cholesterol in VLDL and intermediate density lipoprotein, and higher plasma fatty acids. Plasma alpha-tocopherol (but not gamma-tocopherol, LDL alpha- and gamma-tocopherol, or BMC total vitamin E) was increased significantly in C allele carriers compared with homozygote T allele carriers (P = 0.02), but not after adjustment for cholesterol or TG. Plasma malondialdehyde concentrations did not differ between genotypes. In conclusion, higher plasma lipids in the TC+CC genotype are efficiently protected against lipid peroxidation by higher alpha-tocopherol concentrations. Lipid-standardized vitamin E should be used to reliably assess vitamin E status in genetic association studies. 相似文献
55.
siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy 总被引:9,自引:0,他引:9
Autophagy is a vital response to nutrient starvation. Here, we screened a kinase-specific siRNA library using an autophagy assay in human embryonic kidney 293 cells that measures lipidation of the marker protein GFP-LC3 following amino acid starvation. This screen identified ULK1 in addition to other novel candidates that could be confirmed with multiple siRNAs. Knockdown of ULK1, but not the related kinase ULK2, inhibited the autophagic response. Also, ULK1 knockdown inhibited rapamycin-induced autophagy consistent with a role downstream of mTOR. Overexpression of ULK1 inhibited autophagy and this inhibition was independent of its kinase activity. Deletion of the PDZ domain-binding Val-Tyr-Ala motif at the ULK1 C terminus generated a more potent dominant-negative protein. Further deletions revealed that the minimal ULK1 dominant-negative region could be mapped to residues 1-351. Full-length ULK1 localized to cytoplasmic structures, some of which were GFP-LC3-positive, and this localization required the conserved C-terminal domain. In contrast, ULK1-(1-351) was diffuse in the cytoplasm. These experiments reveal at least two domains in ULK1 which likely function via unique sets of effectors to regulate autophagy. 相似文献
56.
Barbieri CM Srinivasan AR Rzuczek SG Rice JE LaVoie EJ Pilch DS 《Nucleic acids research》2007,35(10):3272-3286
Oxazole-containing macrocycles represent a promising class of anticancer agents that target G-quadruplex DNA. We report the results of spectroscopic studies aimed at defining the mode, energetics and specificity with which a hexaoxazole-containing macrocycle (HXDV) binds to the intramolecular quadruplex formed by the human telomeric DNA model oligonucleotide d(T2AG3)4 in the presence of potassium ions. HXDV binds solely to the quadruplex nucleic acid form, but not to the duplex or triplex form. HXDV binds d(T2AG3)4 with a stoichiometry of two drug molecules per quadruplex, with these binding reactions being coupled to the destacking of adenine residues from the terminal G-tetrads. HXDV binding to d(T2AG3)4 does not alter the length of the quadruplex. These collective observations are indicative of a nonintercalative 'terminal capping' mode of interaction in which one HXDV molecule binds to each end of the quadruplex. The binding of HXDV to d(T2AG3)4 is entropy driven, with this entropic driving force reflecting contributions from favorable drug-induced alterations in the configurational entropy of the host quadruplex as well as in net hydration. The 'terminal capping' mode of binding revealed by our studies may prove to be a general feature of the interactions between oxazole-containing macrocyclic ligands (including telomestatin) and intramolecular DNA quadruplexes. 相似文献
57.
LTP inhibits LTD in the hippocampus via regulation of GSK3beta 总被引:2,自引:0,他引:2
Peineau S Taghibiglou C Bradley C Wong TP Liu L Lu J Lo E Wu D Saule E Bouschet T Matthews P Isaac JT Bortolotto ZA Wang YT Collingridge GL 《Neuron》2007,53(5):703-717
Glycogen synthase kinase-3 (GSK3) has been implicated in major neurological disorders, but its role in normal neuronal function is largely unknown. Here we show that GSK3beta mediates an interaction between two major forms of synaptic plasticity in the brain, N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and NMDA receptor-dependent long-term depression (LTD). In rat hippocampal slices, GSK3beta inhibitors block the induction of LTD. Furthermore, the activity of GSK3beta is enhanced during LTD via activation of PP1. Conversely, following the induction of LTP, there is inhibition of GSK3beta activity. This regulation of GSK3beta during LTP involves activation of NMDA receptors and the PI3K-Akt pathway and disrupts the ability of synapses to undergo LTD for up to 1 hr. We conclude that the regulation of GSK3beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information. 相似文献
58.
Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study 下载免费PDF全文
Yiyi Ma Caren E. Smith Chao‐Qiang Lai Marguerite R. Irvin Laurence D. Parnell Yu‐Chi Lee Lucia Pham Stella Aslibekyan Steven A. Claas Michael Y. Tsai Ingrid B. Borecki Edmond K. Kabagambe Silvia Berciano José M. Ordovás Devin M. Absher Donna K. Arnett 《Aging cell》2015,14(1):49-59
Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87 years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (> 50%) and were located in the promoter region, Group 2 exhibited hypomethylation (< 50%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (> 50%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r = −0.66, P = 0.004). APOE methylation was significantly associated with age (minimum P = 2.06E-08) and plasma total cholesterol (minimum P = 3.53E-03). Finally, APOE methylation patterns differed across APOE ε variants (minimum P = 3.51E-05) and the promoter variant rs405509 (minimum P = 0.01), which further showed a significant interaction with age (P = 0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies. 相似文献
59.
Edmond Puca Arben Pilaca Pellumb Pipero Silva Bino Majlinda Kote Elton Rogozi Entela Puca Dhimiter Kraja 《Virologica Sinica》2011,(4)
Hemorrhagic fever with renal syndrome (HFRS) is a disease caused by viruses of the family Bunyaviridae,genus Hantavirus.HFRS from Dobrava virus (DOBV) is a seldom reported disease in Albania.Clinically HFRS is manifested as mild,moderate,or severe.Therefore,the number of cases of Hantavirus' infection may be underestimated,and should be included in the differential diagnosis of many acute infections,hematologic diseases,acute abdominal diseases and renal diseases complicated by acute renal failure.We report... 相似文献
60.
The ITS1-5.8S-ITS2 sequence region in the Musaceae: structure, diversity and use in molecular phylogeny 总被引:1,自引:0,他引:1
Genes coding for 45S ribosomal RNA are organized in tandem arrays of up to several thousand copies and contain 18S, 5.8S and 26S rRNA units separated by internal transcribed spacers ITS1 and ITS2. While the rRNA units are evolutionary conserved, ITS show high level of interspecific divergence and have been used frequently in genetic diversity and phylogenetic studies. In this work we report on the structure and diversity of the ITS region in 87 representatives of the family Musaceae. We provide the first detailed information on ITS sequence diversity in the genus Musa and describe the presence of more than one type of ITS sequence within individual species. Both Sanger sequencing of amplified ITS regions and whole genome 454 sequencing lead to similar phylogenetic inferences. We show that it is necessary to identify putative pseudogenic ITS sequences, which may have negative effect on phylogenetic reconstruction at lower taxonomic levels. Phylogenetic reconstruction based on ITS sequence showed that the genus Musa is divided into two distinct clades--Callimusa and Australimusa and Eumusa and Rhodochlamys. Most of the intraspecific banana hybrids analyzed contain conserved parental ITS sequences, indicating incomplete concerted evolution of rDNA loci. Independent evolution of parental rDNA in hybrids enables determination of genomic constitution of hybrids using ITS. The observation of only one type of ITS sequence in some of the presumed interspecific hybrid clones warrants further study to confirm their hybrid origin and to unravel processes leading to evolution of their genomes. 相似文献