Association of <Emphasis Type="Italic">CILP</Emphasis>, <Emphasis Type="Italic">COL9A2</Emphasis> and <Emphasis Type="Italic">MMP3</Emphasis> Gene Polymorphisms with Lumbar Disc Degeneration in an Indian Population

Lumbar disc degeneration (LDD) is a multifactorial disorder caused by genetic and environmental factors. Polymorphisms in several structural and inflammatory genes like collagens, aggrecan, matrix metalloproteinases are associated with the risk of disc degeneration. In this study, we analyzed the role of a few important single nucleotide polymorphisms in cartilage intermediate layer protein (CILP), collagen 9A2 (COL9A2) and matrix metalloproteinase 3 (MMP3) genes in LDD from an Indian population. Two hundred patients with LDD and 200 healthy controls were recruited for the study. Genotyping was performed by allelic discrimination assay. The rs2073711 polymorphism (CILP gene - GG genotype) was associated with reduced risk of LDD in the Indian population (OR?=?0.43, p?=?0.016). The rs591058 polymorphism (MMP3 gene - TT genotype) is found to be associated with lower risk among women (OR?=?0.34, p?=?0.041). No significant association was found between COL9A2 polymorphism rs7533552 and the risk of LDD. We conclude that the CILP gene polymorphism (rs2073711) is associated with a lower risk of LDD, the MMP3 (rs591058) gene polymorphism is associated with LDD among women, and the TT genotype confers a lower risk of LDD.     

Mutation analysis of the Ras pathway genes<Emphasis Type="Italic"> NRAS</Emphasis>,<Emphasis Type="Italic"> HRAS</Emphasis>,<Emphasis Type="Italic"> KRAS</Emphasis> and<Emphasis Type="Italic"> BRAF</Emphasis> in glioblastomas

Aberrant activation of Ras signaling is a common finding in human glioblastomas. To determine the contribution of Ras gene mutations to this aberration, we screened 94 glioblastomas for mutations in the three Ras family genes NRAS, KRAS and HRAS. All tumors were additionally analyzed for mutations in BRAF, which encodes a Ras-regulated serine/threonine kinase with oncogenic properties. Mutation analysis of the entire coding regions of NRAS and KRAS, as well as the known mutation hot-spot sites in HRAS, identified somatic point mutations in two glioblastomas, both affecting codon 12 of NRAS (c.35G>A, p.G12D). Three additional tumors carried BRAF mutations altering the known hot-spot codon 599 (c.1796T>A, p.V599E). None of these five glioblastomas showed amplification of the EGFR or PDGFRA genes, while three of the tumors, including two with NRAS and one with BRAF mutation, demonstrated PTEN missense mutations or loss of PTEN mRNA expression. Taken together, our data suggest activating mutations in NRAS or BRAF as a molecular alteration that contributes to aberrant Ras signaling in a small fraction of glioblastomas.     

The complete mitochondrial genome of Chinese <Emphasis Type="Italic">Sarcocheilichthys kiangsiensis</Emphasis> (Cypriniformes: Cyprinidae: <Emphasis Type="Italic">Sarcocheilichthys</Emphasis>)

Sarcocheilichthys kiangsiensis: is a threatened (IUCN: Least Concern) and native fish in China. This study deals with the complete mitochondrial genome of Sarcocheilichthys kiangsiensis by using next-generation sequencing. The full length of the circular genome is 16,672 bp. It consists of 37 typical animal mitochondrial genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes and 2 ribosomal RNA (rRNA) genes and a control region. The overall nucleotide composition is: 29.7% A, 25.7% T, 27.4% C, and 17.2% G, with a total A?+?T content of 55.4%.     

Twenty-three microsatellite loci for <Emphasis Type="Italic">Styrax confusus</Emphasis> and <Emphasis Type="Italic">Styrax japonicus</Emphasis> (Styracaceae)

Twelve microsatellite loci were isolated from an enriched genomic library of the rock scallop (Spondylus calcifer). One locus was monomorphic. Overall polymorphic loci, the mean numbers of alleles per locus at one locality was 9.6 (range 3–16), and the average observed and expected heterozygosities were 0.650 and 0.707, respectively. Three loci deviated from Hardy–Weinberg equilibrium, and from these, one locus had and excess of heterozygotes and the other two loci showed deficits of heterozygotes likely due to the presence of null alleles. No evidence of linkage disequilibrium was found among loci. These loci are the first microsatellites ever reported for the monotypic family Spondylidae, and will be useful to validate the predictions of oceanographic larval transport models and connectivity between patchy reefs within fishing areas and marine reserves in the northern Gulf of California, Mexico.     

Association study of <Emphasis Type="Italic">interleukin 2</Emphasis> (<Emphasis Type="Italic">IL2</Emphasis>) and <Emphasis Type="Italic">IL4</Emphasis> with schizophrenia in a Japanese population

Interleukin 2 (IL-2) and IL-4 are pleiotropic cytokines regulating Th1/Th2 balance and have a regulatory activity in brain function. Thus these cytokines have been implicated in the pathophysiology of schizophrenia. The latest studies provided controversial results regarding the genetic associations of these cytokines. The functional polymorphisms, IL2-330T/G and IL4-590C/T, were associated with schizophrenia in a German population, although contradictory findings were also reported in a Korean population. To ascertain whether IL2 and IL4 contribute to vulnerability to schizophrenia, we conducted a moderate-scale case-control (536 patients and 510 controls) association study for seven polymorphisms in Japanese subjects. There were no significant associations of these genes with schizophrenia using either single marker or haplotype analyses. The present study suggests that IL2 and IL4 do not contribute to vulnerability to schizophrenia in the Japanese population.     

<Emphasis Type="Italic">c</Emphasis><Emphasis Type="Italic">-MYC</Emphasis> amplification and expression in astrocytic tumors

Point mutations and genomic multiplications in the α-synuclein (αSYN) gene cause autosomal-dominant Parkinson’s disease. Moreover, αSYN fibrils are the major component of Lewy bodies, the neuropathological hallmarks of Parkinson’s disease and dementia with Lewy bodies as well as of glial cytoplasmic inclusions in multiple system atrophy. These diseases are collectively referred to as α-synucleinopathies. Cellular mechanisms regulating αSYN fibril formation and toxicity are intensely studied in vitro, and in cell culture and diverse animal models. Specific neuropathology was achieved in transgenic mouse models using several promoters to express human wild-type and mutant αSYN in brain regions affected by the various α-synucleinopathies. Somatodendritic accumulation of the transgenic αSYN with neuritic distortions was a common finding. The nigrostriatal dopaminergic projections were surprisingly resistant to α-synucleinopathy in transgenic mice, although they tended to be more vulnerable to neurotoxins. In a few mouse models, αSYN aggregated in an age-dependent manner into genuine fibrillar amyloid. Brain region selective αSYN neuropathology correlated with specific behavioral impairments, such as locomotor dysfunction and cognitive decline. Thus, the αSYN fibrillization process is tightly linked to neuropathology. The role and thus therapeutic potential of post-translational modifications (ubiquitinylation, oxidation, phosphorylation, truncation) and modifier genes on αSYN neuropathology can now be assessed in valid transgenic mouse models of α-synucleinopathies.     

Sequence analysis of <Emphasis Type="Italic">Drd2</Emphasis>, <Emphasis Type="Italic">Drd4</Emphasis>, and <Emphasis Type="Italic">Dat1</Emphasis> in SHR and WKY rat strains

Background  

The Spontaneously Hypertensive Rat (SHR) shows a number of behaviours that closely parallel those seen in children with attention-deficit hyperactivity disorder. These include motor hyperactivity, excessive responses under a fixed-interval/extinction schedule, difficulty in acquiring operant tasks and increased sensitivity to immediate behavioural reinforcement. As in children with ADHD, the behavioural and cognitive deficits in the SHR are responsive to stimulants, including d-amphetamine and d,l-methylphenidate. The non-hyperactive Wistar Kyoto (WKY) rat strain is often used as a control in behavioural studies of the SHR, and WKY itself has been suggested to be a useful animal model of depression. Numerous studies have shown that dopaminergic neurotransmission is altered between the two strains. Human genetic studies have found associations between several dopaminergic genes and both ADHD and depression.     

Climbing Fiber Development Is Impaired in Postnatal <Emphasis Type="Italic">Car8</Emphasis><Superscript><Emphasis Type="Italic">wdl</Emphasis></Superscript> Mice

The cerebellum is critical for an array of motor functions. During postnatal development, the Purkinje cells (PCs) guide afferent topography to establish the final circuit. Perturbing PC morphogenesis or activity during development can result in climbing fiber (CF) multi-innervation or mis-patterning. Structural defects during circuit formation typically have long-term effects on behavior as they contribute to the phenotype of movement disorders such as cerebellar ataxia. The Car8 ^wdl mouse is one model in which early circuit destruction influences movement. However, although the loss of Car8 leads to the mis-wiring of afferent maps and abnormal PC firing, adult PC morphology is largely intact and there is no neurodegeneration. Here, we sought to uncover how defects in afferent connectivity arise in Car8 ^wdl mutants to resolve how functional deficits persist in motor diseases with subtle neuropathology. To address this problem, we analyzed CF development during the first 3 weeks of life. By immunolabeling CF terminals with VGLUT2, we found evidence of premature CF synapse elimination and delayed translocation from PC somata at postnatal day (P) 10 in Car8 ^wdl mice. Surprisingly, by P15, the wiring normalized, suggesting that CAR8 regulates the early but not the late stages of CF development. The data support the hypothesis of a defined sequence of events for cerebellar circuits to establish function.     

The complete chloroplast genome sequence of <Emphasis Type="Italic">Lilium fargesii</Emphasis> (<Emphasis Type="Italic">Lilium</Emphasis>, Liliaceae)

Lilium fargesii Franchet is an endangered species endemic to China. In this study, the complete chloroplast genome has been generated from the Next Generation Sequencing. The whole genome is 153,235 bp in length, and includes one large single copy region of 82,217 bp, one small single copy region of 17,038 bp and a pair of inverted repeat region of 26,990 bp. It contains 132 genes, comprising 86 protein-coding genes (78 PCG species), 38 transfer RNA (30 tRNA species) and eight ribosomal RNA genes (four rRNA species). In the maximum likelihood tree, all species of Lilium were clustered into two monophyletic groups with 100 % bootstrap value.     

Mitochondrial genome of the sand goby <Emphasis Type="Italic">Acentrogobius caninus</Emphasis> (<Emphasis Type="Italic">Acentrogobius</Emphasis>, Gobiidae)

In this study, we first determined and described the complete mitochondrial genome of Acentrogobius caninus, a member of the Family Gobiidae. The complete mitogenome sequence is 16,616 bp in length containing 13 protein-coding genes, two rRNA genes, 22 tRNA genes, a putative control region (CR), and a light-strand replication origin (OL). Phylogenetic analysis suggests that A. caninus boasts a close relationship with other two species of the genus Acentrogobius. Our results are expected to provide useful molecular information for species identification and further phylogenetic studies of the Gobiiformes family.     

<Emphasis Type="Italic">Clostridium septicum</Emphasis> Pneumocephalus

Background

Spontaneous pneumocephalus in the nontraumatic setting is distinctly unusual. Pneumocephalus from central nervous system infection with Clostridium septicum has been rarely reported, and more commonly reflects a later stage of abscess formation. We present an unusual case of invasive C. septicum infection without an associated diagnosed malignancy presenting with rapidly progressive CNS pathology and resultant early pneumocephalus.

Methods

Medical records, radiologic imaging, and microbiological specimens of a case were reviewed.

Results

A 66-year-old male presented with a history of two witnessed generalized tonic–clonic seizures on awakening. He was found unresponsive at the scene by paramedics and subsequently intubated. There was no reported antecedent symptomatology, such as headache, fever, chills, focal weakness, and speech or gait disturbances. Medical history was remarkable only for diet-controlled hypertension. Computed tomography (CT) head imaging revealed an abnormal right parietal hypodensity. The patient was evaluated per the acute stroke protocol but was not deemed a candidate for intervention or thrombolytic therapy given the uncertainty of his clinical presentation; intravenous antibiotics were administered for possible sepsis. Follow-up CT imaging of the head performed 8 h later revealed right parieto-temporal pneumocephalus with extensive cerebral edema and effacement of basilar cisterns. Neurosurgical intervention was not deemed appropriate given the catastrophic nature of his injury and the patient subsequently expired 14 h after presentation. Blood cultures grew gram-positive rods in three of four bottles identified as C. septicum.

Conclusions

Clostridium septicum is an uncommon and often fatal cause of nontraumatic pneumocephalus. This underscores the need for a high index of clinical suspicion in cases with unexplained pneumocephalus, as early diagnosis remains the key to survival. In survivors of C. septicum infection, subsequent colonoscopy should be considered to exclude undiagnosed or occult gastrointestinal malignancy.

     

The complete chloroplast genome sequence of Chinese wild grape <Emphasis Type="Italic">Vitis amurensis</Emphasis> (Vitaceae: <Emphasis Type="Italic">Vitis</Emphasis> L.)

Vitis amurensis is a species of wild grape with high ecological, medicinal, and economic values. Here, the complete chloroplast genome of this plant was assembled from whole-genome high-throughput sequencing data. The circular double-stranded DNA molecule is 160,953 bp in size, including a pair of inverted repeats (26,354 bp each) separated by large (89,187 bp) and small (19,058 bp) single-copy regions. The chloroplast genome contains 133 genes, including 88 protein-coding genes (80 PCG species), 37 transfer RNA genes (29 tRNA species) and eight ribosomal RNA genes (four rRNA species), 20 of which are duplicated, including eight protein-coding, eight tRNA, and four rRNA genes. The base composition is asymmetric (30.93?% A, 19.07?% C, 18.33?% G, 31.67?% T) with an overall A?+?T content of 62.60?%. A phylogenetic analysis based on complete chloroplast genome sequences showed that V. amurensis is closely related to V. vinifera, V. aestivalis, and V. rotundifolia.     

<Emphasis Type="Italic">CIC</Emphasis> and <Emphasis Type="Italic">FUBP1</Emphasis> mutations in oligodendrogliomas,oligoastrocytomas and astrocytomas

CIC and FUBP1 mutations have recently been detected in oligodendrogliomas but not in oligoastrocytomas. However, allelic losses in the regions on chromosomal arms 19q and 1p harboring CIC and FUBP1 are a common feature of both, oligodendrogliomas and oligoastrocytomas. To resolve this discrepancy, we analyzed CIC and FUBP1 mutations in a set of primary brain tumors including 18 oligodendrogliomas and 42 oligoastrocytomas. In addition, we analyzed 10 astrocytomas and 16 glioblastomas with allelic losses on 19q as well as a set of 12 medulloblastomas for CIC mutations. CIC mutations were found in 15/18 oligodendrogliomas, 14/42 oligoastrocytomas and 3/10 preselected astrocytomas. With the exception of a single case, all CIC mutations occurred in tumors with combined 1p/19q losses. In contrast to oligodendrogliomas where CIC mutations were always detected along with 1p/19q co-deletion, CIC mutations were only found in 52 % of the 1p/19q co-deleted oligoastrocytomas. FUBP1 mutations were detected in 7/61 tumors, all presenting with CIC mutations. FUBP1 mutations appear to cluster in the DNA binding domain spanning exons 5–14. CIC and FUBP1 mutations exclusively occurred in presence of either IDH1 or IDH2 mutations. Our data confirm CIC and FUBP1 mutations in oligodendrogliomas and demonstrate the presence of these mutations in oligoastrocytomas.     

Genetic Variation of the <Emphasis Type="Italic">Kalirin</Emphasis> Gene is Associated with ICAS in the Chinese Population

Alzheimer’s disease (AD) is a neurodegenerative disease that is imposing an increasing burden on society. Currently, AD is the leading cause of senile dementia worldwide. Despite the long existence of AD, there is lack of therapies for AD, suggesting that new and effective treatment strategy must be explored. At present, sirtuin pathway has attracted attention from the researchers due to its promising results in laboratory models of aging. In addition, our understanding in the roles of sirtuin 6 in AD has expanded. It has been identified to be involved in telomere maintenance, DNA repair, genome integrity, energy metabolism, and inflammation, which ultimately regulate life span. Recent findings also demonstrate that sirtuin 6 is lacking in AD patients, proposing that it can be a new potential therapeutic target in AD. Therefore, exploring on how sirtuin 6 is related in AD manifestation may accelerate the research of AD further and benefits future AD patients. Keeping that in mind, this review aims to highlight the possible roles of sirtuin 6 in AD manifestation.     

Significant association of the <Emphasis Type="Italic">arylalkylamine N-acetyltransferase</Emphasis> (<Emphasis Type="Italic">AA-NAT</Emphasis>) gene with delayed sleep phase syndrome

Arylalkylamine N-acetyltransferase (AA-NAT) is a rate-limiting enzyme in melatonin hormone synthesis and participates in daily oscillations of the melatonin level. We studied the association between the AA-NAT gene and delayed sleep phase syndrome (DSPS). Results indicate that there is a significant difference in allele positivity at the single nucleotide polymorphism involved in an amino acid substitution from alanine to threonine at position 129 between patients with DSPS and healthy controls. The frequency of the 129 threonine allele is significantly higher in the patients than in the controls (P=0.0029). The data suggest that AA-NAT could be a susceptibility gene for DSPS. Electronic Publication     

The complete mitochondrial genome of Myanmar warty newt <Emphasis Type="Italic">Tylototriton shanorum</Emphasis> (Salamandridae: <Emphasis Type="Italic">Tylototriton</Emphasis>)

Tylototriton shanorum, an endemic species of Myanmar, is threatened by illegal capture and environmental destruction. Here, the complete mitochondrial genome (mitogenome) of T. shanorum is described. The entire mitogenome sequence of T. shanorum is 17,096 bp long, containing 13 protein coding genes, two ribosomal RNA, 22 transfer RNA genes, one control region. In addition, two additional 3′ Cytb like sequences and two complete tRNA^Thr genes, one pseudo tRNA^Thr, and three noncoding sequences (NC1, NC1′ and NC2) were situated between Cytb and tRNA^Pro genes. The new complete mitogenome sequence of T. shanorum will be useful for conservation genetics, evolutionary biology, phylogeography, as well as phylogenetic relationships studies of this threatened species.     

Ataxia Jackson (<Emphasis Type="Italic">ax</Emphasis><Superscript><Emphasis Type="Italic">J</Emphasis></Superscript>): a genetic model for apoptotic neuronal cell death

Programmed cell death or apoptosis is an important process to form normal adult cytoarchitecture. But in vivo analysis of neuronal apoptosis has not been well advanced. Therefore, apoptotic cell death of a particular neuronal system or anatomical part in a mutant is an invaluable target to learn about a link between a gene and neuronal apoptosis. Ataxia (ax) is an autosomal recessive neurological mutant mouse. We recently investigated brains of homozygotes for ataxia Jackson (ax(J)), an allele of ax, using TUNEL method. A few TUNEL-positive cells were observed in the granular cell layer of the cerebellum, the dentate gyrus, and the olfactory bulb of phenotypically normal littermates (ax(J)/+ or +/+) aged at 23-38 days. In affected ax(J)/ax(J) mice, however, the number of TUNEL-positive cells was significantly increased in the cerebellum, particularly in the granular cell layer (p < 0.05). The ax(J) mouse will be an in vivo unique model for studies on the genetic basis of apoptotic neuronal cell death, and identification of the ax gene is desired to elucidate molecular basis of the apoptosis.