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131.
Chartier-Harlin MC Dachsel JC Vilariño-Güell C Lincoln SJ Leprêtre F Hulihan MM Kachergus J Milnerwood AJ Tapia L Song MS Le Rhun E Mutez E Larvor L Duflot A Vanbesien-Mailliot C Kreisler A Ross OA Nishioka K Soto-Ortolaza AI Cobb SA Melrose HL Behrouz B Keeling BH Bacon JA Hentati E Williams L Yanagiya A Sonenberg N Lockhart PJ Zubair AC Uitti RJ Aasly JO Krygowska-Wajs A Opala G Wszolek ZK Frigerio R Maraganore DM Gosal D Lynch T Hutchinson M Bentivoglio AR Valente EM Nichols WC Pankratz N 《American journal of human genetics》2011,(3):140-406
Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease. 相似文献
132.
de Alba CF Solórzano C Paytubi S Madrid C Juarez A García J Pons M 《FEBS letters》2011,585(12):1765-1770
Proteins of the Hha/YmoA family co-regulate with H-NS the expression of horizontally acquired genes in Enterobacteria. Systematic mutations of conserved acidic residues in Hha have allowed the identification of D48 as an essential residue for H-NS binding and the involvement of E25. Mutations of these residues resulted in deregulation of sensitive genes in vivo. D48 is only partially solvent accessible, yet it defines the functional binding interface between Hha and H-NS confirming that Hha has to undergo a conformational change to bind H-NS. Exposed acidic residues, such as E25, may electrostatically facilitate and direct the approach of Hha to the positively charged region of H-NS enabling the formation of the final complex when D48 becomes accessible by a conformational change of Hha. 相似文献
133.
134.
Fleishman SJ Whitehead TA Strauch EM Corn JE Qin S Zhou HX Mitchell JC Demerdash ON Takeda-Shitaka M Terashi G Moal IH Li X Bates PA Zacharias M Park H Ko JS Lee H Seok C Bourquard T Bernauer J Poupon A Azé J Soner S Ovali SK Ozbek P Tal NB Haliloglu T Hwang H Vreven T Pierce BG Weng Z Pérez-Cano L Pons C Fernández-Recio J Jiang F Yang F Gong X Cao L Xu X Liu B Wang P Li C Wang C Robert CH Guharoy M Liu S Huang Y Li L Guo D Chen Y Xiao Y London N Itzhaki Z Schueler-Furman O Inbar Y Potapov V 《Journal of molecular biology》2011,414(2):289-302
The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations. A total of 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the nonpolar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were, on average, structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a nonbinder. 相似文献
135.
Anna M. Romaní Carles M. Borrego Verónica Díaz‐Villanueva Anna Freixa Frederic Gich Irene Ylla 《Environmental microbiology》2014,16(8):2550-2567
Biofilms are dynamic players in biogeochemical cycling in running waters and are subjected to environmental stressors like those provoked by climate change. We investigated whether a 2°C increase in flowing water would affect prokaryotic community composition and heterotrophic metabolic activities of biofilms grown under light or dark conditions. Neither light nor temperature treatments were relevant for selecting a specific bacterial community at initial phases (7‐day‐old biofilms), but both variables affected the composition and function of mature biofilms (28‐day‐old). In dark‐grown biofilms, changes in the prokaryotic community composition due to warming were mainly related to rotifer grazing, but no significant changes were observed in functional fingerprints. In light‐grown biofilms, warming also affected protozoan densities, but its effect on prokaryotic density and composition was less evident. In contrast, heterotrophic metabolic activities in light‐grown biofilms under warming showed a decrease in the functional diversity towards a specialized use of several carbohydrates. Results suggest that prokaryotes are functionally redundant in dark biofilms but functionally plastic in light biofilms. The more complex and self‐serving light‐grown biofilm determines a more buffered response to temperature than dark‐grown biofilms. Despite the moderate increase in temperature of only 2°C, warming conditions drive significant changes in freshwater biofilms, which responded by finely tuning a complex network of interactions among microbial populations within the biofilm matrix. 相似文献
136.
Oscar Ramirez I?igo Olalde Jonas Berglund Belen Lorente-Galdos Jessica Hernandez-Rodriguez Javier Quilez Matthew T Webster Robert K Wayne Carles Lalueza-Fox Carles Vilà Tomas Marques-Bonet 《BMC genomics》2014,15(1)
Background
Although a variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood. Further, very limited knowledge exists on structural variation in the gray wolf, the ancestor of the dog, or other closely related wild canids. Documenting CNVs variation in wild canids is essential to identify ancestral states and variation that may have appeared after domestication.Results
In this work, we genotyped 1,611 dog CNVs in 23 wolf-like canids (4 purebred dogs, one dingo, 15 gray wolves, one red wolf, one coyote and one golden jackal) to identify CNVs that may have arisen after domestication. We have found an increase in GC-rich regions close to the breakpoints and around 1 kb away from them suggesting that some common motifs might be associated with the formation of CNVs. Among the CNV regions that showed the largest differentiation between dogs and wild canids we found 12 genes, nine of which are related to two known functions associated with dog domestication; growth (PDE4D, CRTC3 and NEB) and neurological function (PDE4D, EML5, ZNF500, SLC6A11, ELAVL2, RGS7 and CTSB).Conclusions
Our results provide insight into the evolution of structural variation in canines, where recombination is not regulated by PRDM9 due to the inactivation of this gene. We also identified genes within the most differentiated CNV regions between dogs and wolves, which could reflect selection during the domestication process.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-465) contains supplementary material, which is available to authorized users. 相似文献137.
Guillermo Horga Emilio Fernández-Egea Anna Mané Mireia Font Kelly C. Schatz Carles Falcon Francisco Lome?a Miguel Bernardo Eduard Parellada 《PloS one》2014,9(1)
Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia. 相似文献
138.
Daniel Gómez-Sánchez I?igo Olalde Federica Pierini Laura Matas-Lalueza Elena Gigli Martina Lari Sergi Civit Marina Lozano Josep Maria Vergès David Caramelli Oscar Ramírez Carles Lalueza-Fox 《PloS one》2014,9(8)
Previous mitochondrial DNA analyses on ancient European remains have suggested that the current distribution of haplogroup H was modeled by the expansion of the Bell Beaker culture (ca 4,500–4,050 years BP) out of Iberia during the Chalcolithic period. However, little is known on the genetic composition of contemporaneous Iberian populations that do not carry the archaeological tool kit defining this culture. Here we have retrieved mitochondrial DNA (mtDNA) sequences from 19 individuals from a Chalcolithic sample from El Mirador cave in Spain, dated to 4,760–4,200 years BP and we have analyzed the haplogroup composition in the context of modern and ancient populations. Regarding extant African, Asian and European populations, El Mirador shows affinities with Near Eastern groups. In different analyses with other ancient samples, El Mirador clusters with Middle and Late Neolithic populations from Germany, belonging to the Rössen, the Salzmünde and the Baalberge archaeological cultures but not with contemporaneous Bell Beakers. Our analyses support the existence of a common genetic signal between Western and Central Europe during the Middle and Late Neolithic and points to a heterogeneous genetic landscape among Chalcolithic groups. 相似文献
139.
Carles Gaig Dolores Vilas Jon Infante María Sierra Inés García-Gorostiaga Mariateresa Buongiorno Mario Ezquerra Maria José Martí Francesc Valldeoriola Miquel Aguilar Matilde Calopa Jorge Hernandez-Vara Eduardo Tolosa 《PloS one》2014,9(10)
Background
Idiopathic Parkinson’s disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.Objective
To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients.Methods
The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated.Results
University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p<0.01). The frequency of sleep and neuropsychiatric disturbances and of dysautonomic symptoms in LRRK2-G2019S-PD was not significantly different from that in IPD. Hyposmia, depression, constipation and excessive daytime sleepiness, were reported to occur before the onset of classical motor symptoms in more than 40% of LRRK2-PD patients in whom these symptoms were present at the time of examination.Conclusion
Neuropsychiatric, dysautonomic and sleep disturbances occur as frequently in patients with LRRK2-G2019S-PD as in IPD but smell loss was less frequent in LRRK2-PD. Like in IPD, disturbances such as hyposmia, depression, constipation and excessive daytime sleepiness may antedate the onset of classical motor symptoms in LRRK2-G2019S-PD. 相似文献140.
Oswaldo Lorenzo-Betancor Kotaro Ogaki Alexandra Soto-Ortolaza Catherine Labbé Carles Vilari?o-Güell Alex Rajput Ali H. Rajput Pau Pastor Sara Ortega Elena Lorenzo Audrey J. Strongosky Jay A. van Gerpen Ryan J. Uitti Zbigniew K. Wszolek Owen A. Ross 《PloS one》2014,9(11)