Revisit on the evolutionary relationship between alternative splicing and gene duplication

Gene duplications and alternative splicing (AS) isoforms are two widespread types of genetic variations that can facilitate diversification of protein function. A number of studies claimed that after gene duplication, two AS isoforms with differential functions can be 'fixed', respectively, in each of the duplicate copies. This simple 'functional-sharing' hypothesis was recently challenged by Roux and Robinson-Rechavi (2011). Instead, they proposed a more sophisticated hypothesis, invoking that less alternative splicing genes tend to be duplicated more frequently, and single-copy genes are younger than duplicate genes, or the 'duplicability-age' hypothesis for short. In this letter, we show that all these genome-wide analyses of AS isoforms actually did not provide clear-cut evidence to nullify the basic idea of functional-sharing hypothesis. After updating our understanding of genome-wide alternative splicing, duplicability and CNV (copy number variation), we argue that the foundation of the duplicability-age hypothesis remains to be justified carefully. Finally, we suggest that a better approach to resolving this controversy is the correspondence analysis of indels (insertions and deletions) between duplicate genes to the genomic exon-intron structure, which can be used to experimentally test the effect of functional-sharing hypothesis.     

Segmental Kinematic Coupling of the Human Spinal Column during Locomotion

As one of the most important daily motor activities, human locomotion has been investigated intensively in recent decades. The locomotor functions and mechanics of human lower limbs have become relatively well understood. However, so far our understanding of the motions and functional contributions of the human spine during locomotion is still very poor and simultaneous in-vivo limb and spinal column motion data are scarce. The objective of this study is to investigate the delicate in-vivo kinematic coupling between different functional regions of the human spinal column during locomotion as a stepping stone to explore the locomotor function of the human spine complex. A novel infrared reflective marker cluster system was constrncted using stereophotogrammetry techniques to record the 3D in-vivo geometric shape of the spinal column and the segmental position and orientation of each functional spinal region simultaneously. Gait measurements of normal walking were conducted. The preliminary results show that the spinal column shape changes periodically in the frontal plane during locomotion. The segmental motions of different spinal functional regions appear to be strongly coupled, indicating some synergistic strategy may be employed by the human spinal column to facilitate locomotion. In contrast to traditional medical imaging-based methods, the proposed technique can be used to investigate the dynamic characteristics of the spinal column, hence providing more insight into the functional biomechanics of the human spine.     

Genomic regions associated with microdeletion/microduplication syndromes exhibit extreme diversity of structural variation

Segmental duplications (SDs) are a class of long, repetitive DNA elements whose paralogs share a high level of sequence similarity with each other. SDs mediate chromosomal rearrangements that lead to structural variation in the general population as well as genomic disorders associated with multiple congenital anomalies, including the 7q11.23 (Williams–Beuren Syndrome, WBS), 15q13.3, and 16p12.2 microdeletion syndromes. Population-level characterization of SDs has generally been lacking because most techniques used for analyzing these complex regions are both labor and cost intensive. In this study, we have used a high-throughput technique to genotype complex structural variation with a single molecule, long-range optical mapping approach. We characterized SDs and identified novel structural variants (SVs) at 7q11.23, 15q13.3, and 16p12.2 using optical mapping data from 154 phenotypically normal individuals from 26 populations comprising five super-populations. We detected several novel SVs for each locus, some of which had significantly different prevalence between populations. Additionally, we localized the microdeletion breakpoints to specific paralogous duplicons located within complex SDs in two patients with WBS, one patient with 15q13.3, and one patient with 16p12.2 microdeletion syndromes. The population-level data presented here highlights the extreme diversity of large and complex SVs within SD-containing regions. The approach we outline will greatly facilitate the investigation of the role of inter-SD structural variation as a driver of chromosomal rearrangements and genomic disorders.     

Quantitative assessment of the accuracy for three interpolation techniques in kinematic analysis of human movement

Marker obstruction during human movement analyses requires interpolation to reconstruct missing kinematic data. This investigation quantifies errors associated with three interpolation techniques and varying interpolated durations. Right ulnar styloid kinematics from 13 participants performing manual wheelchair ramp ascent were reconstructed using linear, cubic spline and local coordinate system (LCS) interpolation from 11–90% of one propulsive cycle. Elbow angles (flexion/extension and pronation/supination) were calculated using real and reconstructed kinematics. Reconstructed kinematics produced maximum elbow flexion/extension errors of 37.1 (linear), 23.4 (spline) and 9.3 (LCS) degrees. Reconstruction errors are unavoidable [minimum errors of 6.7 mm (LCS); 0.29 mm (spline); 0.42 mm (linear)], emphasising careful motion capture system setup must be performed to minimise data interpolation. For the observed movement, LCS-based interpolation (average error of 14.3 mm; correlation of 0.976 for elbow flexion/extension) was most suitable for reconstructing durations longer than 200 ms. Spline interpolation was superior for shorter durations.     

Multi-drug resistance-1 gene polymorphisms in nephrotic syndrome: Impact on susceptibility and response to steroids

Background

Role of multidrug resistance-1 (MDR-1) gene polymorphisms has not been clarified in nephrotic syndrome (NS). Additionally, researchers studied several genetic polymorphisms to explain their influence on different patients' responses to steroid; however the data were inconsistent. Therefore, we aimed to investigate the association of MDR-1 gene polymorphisms [C1236T, G2677T/A, C3435T] and haplotypes with susceptibility to childhood nephrotic syndrome, and whether they influence steroid response.

Methods

We detected MDR-1 gene polymorphisms using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 138 NS patients and 140 age and sex matched healthy children.

Results

The frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele, MDR1 C3435T TT genotype, and T allele genotype frequencies were significantly increased in NS group. While no significant differences were observed in distributions of C1236T genotypes or allele between NS patients and healthy children. Moreover, steroid non-responder NS patients had significantly higher frequencies of MDR1 G2677T/A GT, GA, and TT + AA genotypes than steroid responsive NS patients. We observed also that NS patients with age less than 6 years old had increased frequencies of MDR1 G2677T/A GT, GA, TT + AA genotypes or T allele MDR1 C3435T CT, TT genotypes and T allele. Interestingly the frequency of the TGC haplotype of MDR1 was lower in the initial steroid responders than in non-responders NS patients. On the contrary, there were no any association between the MDR1 haplotypes with NS susceptibility and they did not influence renal pathological findings.

Conclusion

Our data suggested that MDR1 C3435T or G2677T/A gene polymorphisms are risk factors of increased susceptibility, earlier onset of NS, and steroid resistance.     

Varied development of trunk segmentation in three related Upper Devonian phacopine trilobites

In many arthropods, the development of the trunk region is a complex part of post-embryonic development. Consideration of fossil ontogeny provides an additional source of data and a broader evolutionary perspective on the evolution of arthropod body patterning. Here, I examine the development of the thoraco-pygidial exoskeleton of three related phacopine trilobites from the Upper Devonian according to the integrated ontogenetic scheme proposed by Hughes et al. Pygidial shields assigned to three ontogenetic series gave us the opportunity to further explore the evolutionary pattern of the trilobite segmentation. The analysis showed a different mode of development in two of three species and thus reveals variability between the related taxa. Comparison of the boundaries of different aspects of ontogenesis ratifies the diversity of the segmentation process among trilobites and even among related phacopine species. Results include (i) in a synarthromeric trunk condition recorded to date, there has consistently been a preceding ‘equilibrium’ phase for the late meraspid pygidium and (ii) two developmental modes, i.e. both hypoprotomeric development and synarthromeric development, occur contemporaneously in closely related taxa. Such developments suggest that aspects of segmental development such as segment accretion and segment articulation were able to vary in a labile manner.     

The PDZ-GEF Gef26 regulates synapse development and function via FasII and Rap1 at the Drosophila neuromuscular junction

Guanine nucleotide exchange factors (GEFs) are essential for small G proteins to activate their downstream signaling pathways, which are involved in morphogenesis, cell adhesion, and migration. Mutants of Gef26, a PDZ-GEF (PDZ domain-containing guanine nucleotide exchange factor) in Drosophila, exhibit strong defects in wings, eyes, and the reproductive and nervous systems. However, the precise roles of Gef26 in development remain unclear. In the present study, we analyzed the role of Gef26 in synaptic development and function. We identified significant decreases in bouton number and branch length at larval neuromuscular junctions (NMJs) in Gef26 mutants, and these defects were fully rescued by restoring Gef26 expression, indicating that Gef26 plays an important role in NMJ morphogenesis. In addition to the observed defects in NMJ morphology, electrophysiological analyses revealed functional defects at NMJs, and locomotor deficiency appeared in Gef26 mutant larvae. Furthermore, Gef26 regulated NMJ morphogenesis by regulating the level of synaptic Fasciclin II (FasII), a well-studied cell adhesion molecule that functions in NMJ development and remodeling. Finally, our data demonstrate that Gef26-specific small G protein Rap1 worked downstream of Gef26 to regulate the level of FasII at NMJs, possibly through a βPS integrin-mediated signaling pathway. Taken together, our findings define a novel role of Gef26 in regulating NMJ development and function.     

Birth of 'human-specific' genes during primate evolution

Humans and other Anthropoids share very similar chromosome structure and genomic sequence as seen in the 98.5% homology at the DNA level between us and Great Apes. However, anatomical and behavioral traits distinguish Homo sapiens from his closest relatives. I review here several recent studies that address the issue by using different approaches: large-scale sequence comparison (first release) between human and chimpanzee, characterization of recent segmental duplications in the human genome and analysis of exemplary gene families. As a major breakthrough in the field, the heretical concept of human-specific genes has recently received some supporting data. In addition, specific chromosomal regions have been mapped that display all the features of gene nurseries and could have played a major role in gene innovation and speciation during primate evolution. A model is proposed that integrates all known molecular mechanisms that can create new genes in the human lineage.     

经伤椎单节段固定与跨伤椎短节段固定治疗胸腰椎骨折的临床疗效比较研究

目的:研究经伤椎单节段固定和跨伤椎短节段固定对于胸腰椎骨折进行治疗的临床疗效。方法:从2011年6月至2014年6月,选择我院100例胸腰椎骨折患者作为研究对象。以数字法随机分为观察组50例以及对照组50例。观察组患者行经伤椎单节段固定,对照组患者行跨伤椎短节段固定,对比观察两组的临床效果。结果:观察组患者术中出血量及手术时间均明显低于对照组,差异均具有统计学意义(P0.05)。对两组患者手术前后的影像学检测结果进行比较,手术前后两组的压缩率以及Cobb角比较均无显著差异(P0.05),对所有患者进行末次随访时发现,观察组的压缩率明显高于对照组,Cobb角明显低于对照组,差异均具有统计学意义(P0.05)。治疗前两组在社会功能,情感职能以及躯体疼痛评分比较上均无统计学差异(P0.05),治疗后两组以上评分较治疗前均明显升高,并且观察组显著高于对照组,差异均具有统计学意义(P0.05)。结论:使用经伤椎单节段固定较跨伤椎短节段固定方式能更好地恢复患者Cobb角度,对于预防手术之后矫正度的丢失性具有明显优势,且其有利于术后患者生活质量的提高,值得临床推荐使用。