Investigation on Mitochondrial tRNA<Superscript>Leu/Lys</Superscript>, NDI and ATPase 6/8 in Iranian Multiple Sclerosis Patients

As with chromosomal DNA, the mitochondrial DNA (mtDNA) can contain mutations that are highly pathogenic .In fact, many diseases of the central nervous system are known to be caused by mutations in mtDNA. Dysfunction of the mitochondrial Respiratory Chain (RC) has been shown in patients with neurological disease including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Multiple sclerosis (MS). MS is a demyelinating disease of central nervous system characterized by morphological hallmarks of inflammation, demyelination and axonal loss. Considering this importance, we decided to investigate several highly mutative parts of mtDNA for point mutations as MT-LTI (tRNA^{Leucine1(UUA/G)}), MT-NDI (NADH Dehydrogenase subunit 1), MT-COII (Cytochrome c oxidase subunit II), MT-TK (tRNA^Lysine), MT-ATP8 (ATP synthase subunit F0 8) and MT-ATP6 (ATP synthase subunit F0 6) in 20 Iranian MS patients and 80 age-matched control subjects by PCR and automated DNA sequencing to evaluate any probable point mutations. Our results revealed that 15 (75%) out of 20 MS patients had point mutations. Some of point mutations were newly found in this study. This study suggested that point mutation occurred in mtDNA might be involved in pathogenesis of MS.     

Estimating the prevalence and strength of non-independent predator effects

Understanding whether multiple predator species have independent effects on shared prey is critical for understanding community dynamics. We describe the prevalence and strength of non-independence between predators by quantifying the prey’s risk of predation and the degree to which it deviates from the risk predicted from a null model of independent predator effects. Specifically, we document how frequently non-independent effects occur among ten different multiple predator combinations with mayfly larvae as prey. These predator combinations vary both predator density and predator species richness. Overall, the predator effects were non-independent and translated to an average of 27% fewer prey being consumed compared to independent predator effects. Non-independence of this magnitude is likely to have population level consequences for the prey and influence the distribution or prey preference of predators. Closer inspection shows that much of the risk reduction in this system is weak, to the point of being indistinguishable from independent predator effects, while few effects are strong. This pattern of many weak interactions and few strong ones parallels the pattern of interaction strengths documented previously in intertidal communities. Consequently, understanding strong interactors in multiple predator systems may help us understand the importance of a species.     

Alterations in the activity of phospholipases A2 in postmortem white matter from patients with multiple sclerosis

Activities toward arachidonyl-labelled phospholipase A₂ substrates were assayed in fractions of white matter and cerebral cortex from control subjects and in fractions of demyelinated plaque, normal-appearing white matter and cerebral cortex from subjects who died with multiple sclerosis. Membranous activity at pH 8.6 in the presence of Ca²⁺, characteristic of 14 kDa secretory phospholipase A₂, in either multiple sclerosis white matter or cortex did not differ from controls, whereas membranous activity at pH 4.5 in the absence of added Ca²⁺, characteristic of lysosomal enzymes was increased over controls in both plaque and normal-appearing white matter but not cerebral cortex. Activity in the cytosol fraction, at pH 8.6 in the presence of Ca²⁺ and glycerol characteristic of the cytosolic 85 kDa enzyme was decreased by greater than 50% in both white matter and cortex samples from multiple sclerosis subjects. Immuno-precipitation and-blotting confirmed that the deficient activity was largely attributable to the 85 kDa enzyme although the enzyme protein was not similarly reduced.Special issue dedicated to Dr. Leon S. Wolfe.     

序贯血液净化对严重创伤合并MODS患者炎性因子以及血流动力学的影响

目的:探讨序贯血液净化(SBP)对严重创伤合并多器官功能障碍综合征(MODS)患者血清炎性因子及血流动力学的影响。方法:选取2015年7月-2017年5月第三军医大学新桥医院收治的严重创伤合并MODS患者48例,根据患者的治疗方式分为对照组21例以及观察组27例,其中对照组接受常规内科治疗,观察组在对照组的基础上进行SBP治疗,在治疗前后对两组患者的肝肾功能、血清炎性因子水平、血流动力学指标进行检测,并对比两组患者ICU住院时间、病死率、机械通气时间。结果:治疗后两组患者的总胆红素(TBIL)、直接胆红素(DBIL)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、血尿素氮(BUN)、肌酐(Cr)水平均较治疗前降低,且治疗后观察组患者各指标低于对照组(P0.05);治疗后两组患者血清C反应蛋白(CRP)、白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平均较治疗前显著降低,且治疗后观察组患者各炎性因子水平显著低于对照组(P0.05);治疗后两组患者的心率(HR)、中心静脉压(CVP)较治疗前降低,平均动脉压(MAP)、心脏指数(CI)较治疗前升高,且治疗后观察组患者的HR、CVP显著低于对照组,MAP、CI显著高于对照组(P0.05);观察组患者的ICU住院时间、机械通气时间均较对照组缩短,病死率较对照组明显降低(P0.05)。结论:SBP应用于严重创伤合并MODS患者的治疗可以有效减轻患者的炎性反应,并可以显著改善患者血流动力学以及预后。     

Impact of long‐term chromosomal shuffling on the multispecies coalescent analysis of two anthropoid primate lineages

Multispecies coalescent (MSC) theory assumes that gene trees inferred from individual loci are independent trials of the MSC process. As genes might be physically close in syntenic associations spanning along chromosome regions, these assumptions might be flawed in evolutionary lineages with substantial karyotypic shuffling. Neotropical primates (NP) represent an ideal case for assessing the performance of MSC methods in such scenarios because chromosome diploid number varies significantly in this lineage. To this end, we investigated the effect of sequence length on the theoretical expectations of MSC model, as well as the results of coalescent‐based tree inference methods. This was carried out by comparing NP with hominids, a lineage in which chromosome macrostructure has been stable for at least 15 million years. We found that departure from the MSC model in Neotropical primates decreased with smaller sequence fragments, where sites sharing the same evolutionary history were more frequently found than in longer fragments. This scenario probably resulted from extensive karyotypic rearrangement occurring during the radiation of NP, contrary to the comparatively stable chromosome evolution in hominids.     

Phylogenetic analysis and evolutionary studies of plant carotenoid cleavage dioxygenase gene

The oxidative breakdown of carotenoid evidences the formation of apocarotenoids through carotenoid cleavage dioxygenases (CCDs). Numerous CCDs and apocarotenoids have been identified and characterized in plants. Using available sequence data, a study was performed to investigate the phylogenetic relationship among CCD genes and to statistically estimate the sequence conservation and functional divergence. In total, 77 genes were identified from 39 species belonging to 21 families. Our result of phylogenetic analysis indicated the existence of well-conserved subfamilies. Moreover, comparative genomic analysis showed that the gene structures of the CCDs were highly conserved across some different lineage species. Through functional divergence analysis, a substantial divergence was found between CCD subfamilies. In addition, examination of the site-specific profile revealed the critical amino acid residues accounting for functional divergence. This study mainly focused on the evolution of CCD genes and their functional divergence which may deliver an initial step for further experimental verifications.     

The Effect of Cauda Equina Constriction on Nitric Oxide Synthase Activity

Nitric oxide synthase (NOS) activity was studied in the gray and white matter regions of the spinal cord 2 and 5 days after multiple cauda equina constrictions of the central processes of L7-Co5 dorsal root ganglia neurons. The results show considerable differences in enzyme activity in the thoracic, upper lumbar, lower lumbar, and sacral segments. Increased NOS activity was observed at 2 days after multiple cauda equina constrictions in the dorsal, lateral, and ventral columns of the lower lumbar segments and in the ventral column of the upper lumbar segments. The values returned to control levels within 5 postconstriction days. In the lateral columns of thoracic segments taken 2 and 5 days after surgery, NOS activity was enhanced by 54% and 55% and in the upper lumbar segments by 130% and 163%, respectively. Multiple cauda equina constrictions performed surgically for 2 and 5 days caused a significant increase in NOS activity predominantly in the gray matter regions of thoracic segments. A quite different response was found 5 days postconstriction in the upper lumbar segments, where the enzyme activity was significantly decreased in the dorsal horn, intermediate zone, and ventral horn. No such extreme differences could be seen in the lower lumbar segments, where NOS activity was significantly enhanced only in the ventral horn. The data correspond with a higher number of NOS immunoreactive somata, quantitatively evaluated in the ventral horn of the lower lumbar segments at 5 days after multiple cauda equina constrictions. While the great region-dependent heterogeneity in NOS activity seen 2 and 5 days after multiple cauda equina constrictions is quite apparent and suggestive of an active role played by nitric oxide in neuroprotective or neurotoxic processes occurring in the gray and white matter of the spinal cord, the extent of damage or the degree of neuroprotection caused by nitric oxide in compartmentalized gray and white matter in this experimental paradigm would be possible only using longer postconstriction periods.     

A model for pathogen population structure with cross-protection depending on the extent of overlap in antigenic variant repertoires

The persistence of discrete antigenic types among pathogens with multiple immunogenic loci can be explained by the action of immune-mediated competition. It has previously been shown that pathogen populations will self-organize into non-overlapping subsets of antigenic variants if cross-protection between pathogen types sharing any variants is high. Here, we examine the critical question of whether such strain structure will emerge if the degree of immune-mediated competition is dependent on the number of variants shared between pathogen types, rather than in an all-or-nothing manner. Our analysis uncovers a progression from no strain structure through to discrete stable strain structure through intermediate partially structured states. This suggests that the number of loci or epitope regions required to detect linkage disequilibrium (as a manifestation of stable discrete strain structure) in pathogen populations correlates inversely with the strength of immune selection.     

Positioning accuracy of a single-isocenter multiple targets SRS treatment: A comparison between Varian TrueBeam CBCT and Brainlab ExacTrac

PurposeThis study compared the positioning accuracy between cone-beam CT (CBCT) and ExacTrac (ETX) for a single-isocenter multiple target stereotactic radiosurgery (SRS) on two TrueBeam STx systems.MethodsA single-isocenter treatment plan was simulated on an anthropomorphic head phantom with six spherical steel ball bearings (BBs). One of the BBs was chosen to be the isocenter. The five off-isocenter targets were located at various distances from the isocenter. MV portal images were generated to evaluate the deviations between the expected and the real center of the targets after CBCT and ETX positioning, respectively.ResultsThe evaluation of the positioning accuracy for the isocenter target showed that CBCT and ETX positioning provided comparable, sub-millimetric results. Deviations in positioning accuracy were also calculated for all other targets, also showing comparable results for CBCT and ETX. Moreover, our study showed that the deviation between CBCT and ETX positioning were in better agreement for TBSTx1 and deviated slightly higher on TBSTx2 (maximum: 1.23 mm at S/I direction), due to a less perfect alignment between the CBCT coordinate system and the ETX coordinate system on TBSTx2 compared to TBSTx1. This study also showed a correlation between the target positioning accuracy and the distance to the isocenter.ConclusionThe positioning accuracy of ETX and CBCT for targets located at isocenter and off-isocenter locations was compared on two treatment machines and found comparable. Our study highlights the importance of a proper calibration procedure, to ensure correct alignment between the CBCT, ETX and machine coordinate systems.