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31.
32.
Alexandra F. S. Breitenkamp Jan Matthes Robert Daniel Nass Judith Sinzig Gerd Lehmkuhl Peter Nürnberg Stefan Herzig 《PloS one》2014,9(4)
Autism Spectrum Disorders (ASD) are complex neurodevelopmental diseases clinically defined by dysfunction of social interaction. Dysregulation of cellular calcium homeostasis might be involved in ASD pathogenesis, and genes coding for the L-type calcium channel subunits CaV1.2 (CACNA1C) and CaVβ2 (CACNB2) were recently identified as risk loci for psychiatric diseases. Here, we present three rare missense mutations of CACNB2 (G167S, S197F, and F240L) found in ASD-affected families, two of them described here for the first time (G167S and F240L). All these mutations affect highly conserved regions while being absent in a sample of ethnically matched controls. We suggest the mutations to be of physiological relevance since they modulate whole-cell Ba2+ currents through calcium channels when expressed in a recombinant system (HEK-293 cells). Two mutations displayed significantly decelerated time-dependent inactivation as well as increased sensitivity of voltage-dependent inactivation. In contrast, the third mutation (F240L) showed significantly accelerated time-dependent inactivation. By altering the kinetic parameters, the mutations are reminiscent of the CACNA1C mutation causing Timothy Syndrome, a Mendelian disease presenting with ASD. In conclusion, the results of our first-time biophysical characterization of these three rare CACNB2 missense mutations identified in ASD patients support the hypothesis that calcium channel dysfunction may contribute to autism. 相似文献
33.
Characteristics of spinal cord-evoked responses in man 总被引:1,自引:0,他引:1
M R Dimitrijevic L D Lehmkuhl E M Sedgwick A M Sherwood W B McKay 《Applied neurophysiology》1980,43(3-5):118-127
The averaged electrical potentials evoked by the stimulation of the peripheral nerves were recorded with surface electrodes over the lumbosacral, lower thoracic and cervical spine and with epidurally placed electrodes in the cervical area. The waveforms of the lumbosacral and cervical spinal cord potentials show similar complexity reflecting peripheral and central generators. The larger negative wave with at least two components is followed by a slower positive deflection. Evoked potentials recorded over the cervical segments of the spinal cord with epidural electrodes are of much higher amplitude and more complex waveform than those recorded with surface electrodes. 相似文献
34.
RC Pritchett AM Al-Nawaiseh KK Pritchett V Nethery PA Bishop JM Green 《Biology of sport / Institute of Sport》2015,32(3):249-254
Sweat production is crucial for thermoregulation. However, sweating can be problematic for individuals with spinal cord injuries (SCI), as they display a blunting of sudomotor and vasomotor responses below the level of the injury. Sweat gland density and eccrine gland metabolism in SCI are not well understood. Consequently, this study examined sweat lactate (S-LA) (reflective of sweat gland metabolism), active sweat gland density (SGD), and sweat output per gland (S/G) in 7 SCI athletes and 8 able-bodied (AB) controls matched for arm ergometry VO2peak. A sweat collection device was positioned on the upper scapular and medial calf of each subject just prior to the beginning of the trial, with iodine sweat gland density patches positioned on the upper scapular and medial calf. Participants were tested on a ramp protocol (7 min per stage, 20 W increase per stage) in a common exercise environment (21±1°C, 45-65% relative humidity). An independent t-test revealed lower (p<0.05) SGD (upper scapular) for SCI (22.3 ±14.8 glands · cm−2) vs. AB. (41.0 ± 8.1 glands · cm−2). However, there was no significant difference for S/G between groups. S-LA was significantly greater (p<0.05) during the second exercise stage for SCI (11.5±10.9 mmol · l−1) vs. AB (26.8±11.07 mmol · l−1). These findings suggest that SCI athletes had less active sweat glands compared to the AB group, but the sweat response was similar (SLA, S/G) between AB and SCI athletes. The results suggest similar interglandular metabolic activity irrespective of overall sweat rate. 相似文献
35.
Natália H Mendes Fernando AF Melo Adolfo CB Santos José RC Pandolfi Elisabete A Almeida Rosilene F Cardoso Henri Berghs Suzana David Faber K Johansen Lívia G Espanha Sergio RA Leite Clarice QF Leite 《BMC research notes》2011,4(1):269
Background
Tuberculosis is a major health problem in São Paulo, Brazil, which is the most populous and one of the most cosmopolitan cities in South America. To characterize the genetic diversity of Mycobacterium tuberculosis in the population of this city, the genotyping techniques of spoligotyping and MIRU were applied to 93 isolates collected in two consecutive years from 93 different tuberculosis patients residing in São Paulo city and attending the Clemente Ferreira Institute (the reference clinic for the treatment of tuberculosis).Findings
Spoligotyping generated 53 different spoligotype patterns. Fifty-one isolates (54.8%) were grouped into 13 spoligotyping clusters. Seventy- two strains (77.4%) showed spoligotypes described in the international databases (SpolDB4, SITVIT), and 21 (22.6%) showed unidentified patterns. The most frequent spoligotype families were Latin American Mediterranean (LAM) (26 isolates), followed by the T family (24 isolates) and Haarlem (H) (11 isolates), which together accounted for 65.4% of all the isolates. These three families represent the major genotypes found in Africa, Central America, South America and Europe. Six Spoligo-International-types (designated SITs by the database) comprised 51.8% (37/72) of all the identified spoligotypes (SIT53, SIT50, SIT42, SIT60, SIT17 and SIT1). Other SITs found in this study indicated the great genetic diversity of M. tuberculosis, reflecting the remarkable ethnic diversity of São Paulo city inhabitants. The MIRU technique was more discriminatory and did not identify any genetic clusters with 100% similarity among the 93 isolates. The allelic analysis showed that MIRU loci 26, 40, 23 and 10 were the most discriminatory. When MIRU and spoligotyping techniques were combined, all isolates grouped in the 13 spoligotyping clusters were separated.Conclusions
Our data indicated the genomic stability of over 50% of spoligotypes identified in São Paulo and the great genetic diversity of M. tuberculosis isolates in the remaining SITs, reflecting the large ethnic mix of the São Paulo city inhabitants. The results also indicated that in this city, M. tuberculosis isolates acquired drug resistance independently of genotype and that resistance was more dependent on the selective pressure of treatment failure and the environmental circumstances of patients.36.
Dhritiman Das Subham Banerjee John Lehmkuhl Jagdish Krishnaswamy Robert John 《Journal of Plant Ecology》2022,15(1):155
印度特莱东部林地-草地系统中非生物和空间变量对木本和草本物种丰度的影响
目前尚不清楚哪些环境因素决定了热带稀树草原特别是在潮湿地带的林地和草地镶嵌处的林地和草地的物种多度。基于此,本研究探究了非生物和空间变量对印度东北部的台拉河生态系统木本和草本物种分布的影响,评估了气候和非气候因素在整个景观中保持可变的树草比和空间连通性和分散性的相对重要性。在519 km2的受保护的特莱栖息地中随机建立了134个30 m × 30 m的抽样样方,并调查了每个样方的木本和草本植物的物种多度和气候,以及非气候环境因素。基于不同的地点空间连通性模型,通过构建变量检验气候和非气候环境因素对物种多度的影响。使用冗余分析和方差分解定量解析环境变量和空间结构对林地和草地物种多度的相对重要性。研究结果表明,降雨、火灾、水分胁迫、地形和土壤养分在内的环境变量对物种多度和林草比有显著的影响。空间结构显著,最佳空间模型为反距离加权模型(inverse distance-weighted model), 而且显示最大的空间扩散距离可以达到23.5 km,表明扩散限制较弱。约21%的物种多度变化能够被环境和空间因素解释。这些结果揭示了植物群落动态的决定因素,即环境因子的时空变化可能驱动物种分布和多度的随机性,并对植被镶嵌产生主导影响。 相似文献
37.
H?Bukulmez AL?Matthews CM?Sullivan C?Chen MJ?Kraay RC?Elston RW?Moskowitz VM?Goldberg ML?WarmanEmail author 《Arthritis research & therapy》2005,8(1):R25
In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA),
we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family
histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses
to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis
of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing
total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We
compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings
of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the
siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age
and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to
identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with
hip OA than in those with knee OA. 相似文献
38.
Pradeep K. Mathur Harish Kumar John F. Lehmkuhl Anshuman Tripathi Vishwas B. Sawarkar Rupak De 《Biodiversity and Conservation》2011,20(1):1-17
There is a realization that managed forests and other natural areas in the landscape matrix can and must make significant
contributions to biodiversity conservation. Often, however, there are no consistent baseline vegetation or wildlife data for
assessing the status of biodiversity elements across protected and managed areas for conservation planning, nor is there a
rapid and efficient means to acquire those data. We used a unified vegetation classification and simple animal sampling design
to describe the patterns of abundance of selected mammals as indicator, or characteristic, species in different vegetation
types and protected areas vs. managed forest units in the Terai Conservation Area (TCA) in northern Uttar Pradesh state, India.
We quantified the relative abundance of 15 mammals of conservation concern from dung counts in vegetation sampling plots within
122 sample patches in 13 vegetation types and 4 management units. Assemblages of species differed both among vegetation types
and among management units. Species assemblages in the two protected areas differed strongly from those in two managed forests.
Grasslands in protected areas were the most species diverse among vegetation types and had several indicator species. Protected
forests were dominated by chital (Axis axis) and nilgai (Boselaphus
tragocamelus) in a second species group. A third species group in open grasslands and savannas in managed forests was characterized by
cattle (Bos
taurus) and Indian hare (Lepus
nigricollis). Protected areas clearly are the core conservation area of the TCA for their relatively high habitat value and species diversity,
and their protected status minimizes human disturbance. Impacts of human use are high in managed forests, indicating their
compromised value for biodiversity conservation. Our simple assessment methodology gives managers a simple way to assess the
status of important mammals across landscape conservation units. 相似文献
39.
40.
Jung B Englberger W Fröhlich R Schepmann D Lehmkuhl K Wünsch B 《Bioorganic & medicinal chemistry》2008,16(6):2870-2885
Directed by molecular modeling studies the pharmacophoric benzhydryl moiety of the delta opioid receptor agonist SNC80 was separated and the two phenyl residues were attached to different positions of the conformationally constrained 6,8-diazabicyclo[3.2.2]nonane framework in order to find novel delta agonists. The crucial reaction step in the chiral pool synthesis was the establishment of the three carbon bridge by a Dieckmann analogous cyclization of the allyl and propyl derivatives 6 and 7 to yield the mixed methyl silyl acetals 8 and 9, respectively. Stereoselective Grignard reaction, dehydration, and introduction of the pharmacophoric (N,N-diethylcarbamoylbenzyl) residue led to the designed delta receptor agonists 3, ent-3, and 20 with a double bond in the bicyclic framework. Hydrogenation of the allyl derivative 14 was performed with ammonium formate and Pd/C to yield the saturated ligands 24a and 24b. Removal of the allyl substituent with RhCl(3), hydrogenation of the ring system, and re-attachment of the allyl moiety provided the allyl derivatives 4a and 4b. In receptor binding studies with the radioligand [(3)H]-deltorphine II only ent-3 showed considerable delta receptor affinity (K(i)=740 nM). Since ent-3 also interacts with mu receptors (K(i)=250 nM) it belongs to the very interesting compound class of mixed delta/mu ligands. 相似文献