Age Effects on Lactic- and Malic-Acid Dehydrogenases in C57BL/6 Mouse Testes

Author Institution: Department of Biological Sciences, Kent State University, Kent, Ohio 44240There is evidence that lactic-acid-dehydrogenase (LDH) and malic-acid-dehydrogenase (MDH) activities vary with age in several mammalian organs. This study shows that both enzymes in the testes of the C57BL/6 mouse exhibit age-related changes. These changes are most evident when the LDH/MDH ratio is considered. The LDH/MDH ratio decreases to two days before onset of spermatogenesis, remains unchanged to one day before weaning, increases to four or five days prior to breeding activity, and oscillates through the remainder of the 365 days studied. Although these are in vitro results, activity changes occur coincident with physiological changes in the testes

Efficacy of beveled tip aspiration catheter in mechanical thrombectomy for acute ischemic stroke

BACKGROUND: Direct aspiration thrombectomy techniques use large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench top exploration of a novel beveled tip catheter and our experience in treating large vessel occlusions (LVOs) using next-generation aspiration catheters. METHODS: A retrospective analysis from a prospectively maintained database comparing the bevel shaped tip aspiration catheter versus non-beveled tip catheters was performed. Patient demographics, periprocedural metrics, and discharge and 90-day modified Rankin Scale (mRS) scores were collected. Patients were divided into two groups based on which aspiration catheter was used. RESULTS: Our data showed no significant difference in age, gender, IV tissue plasminogen activator administration, admission NIH Stroke Scale score, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, Thrombolysis in Cerebral Infarction (TICI) 2C or better recanalization was more frequent overall (93.2% vs 74.2%, p=0.017), stent retriever usage was lower (9.1% vs 29%, p=0.024), and patients had lower mRS on discharge (median 3 vs 4, p \u3c 0.001) and at 90 days (median 2 vs 4, p=0.008). CONCLUSION: Patients who underwent mechanical thrombectomy with the beveled tip catheter had a higher proportion of TICI 2C or better and had a significantly lower mRS score on discharge and at 90 days

Position-dependent effects of locked nucleic acid (LNA) on DNA sequencing and PCR primers

Genomes are becoming heavily annotated with important features. Analysis of these features often employs oligonucleotides that hybridize at defined locations. When the defined location lies in a poor sequence context, traditional design strategies may fail. Locked Nucleic Acid (LNA) can enhance oligonucleotide affinity and specificity. Though LNA has been used in many applications, formal design rules are still being defined. To further this effort we have investigated the effect of LNA on the performance of sequencing and PCR primers in AT-rich regions, where short primers yield poor sequencing reads or PCR yields. LNA was used in three positional patterns: near the 5′ end (LNA-5′), near the 3′ end (LNA-3′) and distributed throughout (LNA-Even). Quantitative measures of sequencing read length (Phred Q30 count) and real-time PCR signal (cycle threshold, C(T)) were characterized using two-way ANOVA. LNA-5′ increased the average Phred Q30 score by 60% and it was never observed to decrease performance. LNA-5′ generated cycle thresholds in quantitative PCR that were comparable to high-yielding conventional primers. In contrast, LNA-3′ and LNA-Even did not improve read lengths or C(T). ANOVA demonstrated the statistical significance of these results and identified significant interaction between the positional design rule and primer sequence

DC-SIGN (CD209) gene promoter polymorphisms in a Brazilian population and their association with human T-cell lymphotropic virus type 1 infection

This study evaluated four polymorphisms located in the DC-SIGN (CD209) gene promoter region (positions −336, −332 −201 and −139) in DNA samples from four Brazilian ethnic groups (Caucasians, Afro-Brazilian, Asians and Amerindians) to establish the population distribution of these single-nucleotide polymorphisms (SNPs) and correlated DC-SIGN polymorphisms and infection in samples from human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals. To identify CD209 SNPs, 452 bp of the CD209 promoter region were sequenced and the genotype and allelic frequencies were evaluated. This is the first study to show genetic polymorphism in the CD209 gene in distinct Brazilian ethnic groups with the distribution of allelic and genotypic frequency. The results showed that −336A and −139A SNPs were quite common in Asians and that the −201T allele was not observed in Caucasians, Asians or Amerindians. No significant differences were observed between individuals with HTLV-1 disease and asymptomatic patients. However, the −336A variant was more frequent in HTLV-1-infected patients [HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), 80 %; healthy asymptomatic HTLV-1 carriers, 90 %] than in the control group (70 %) [P=0.0197, odds ratio (OR)=2.511, 95 % confidence interval (CI)=1.218–5.179). In addition, the −139A allele was found to be associated with protection against HTLV-1 infection (P=0.0037, OR=0.3758, 95 % CI=0.1954–0.7229) when the HTLV-1-infected patients as a whole were compared with the healthy-control group. These observations suggest that the −139A allele may be associated with HTLV-1 infection, although no significant association was observed among asymptomatic and HAM/TSP patients. In conclusion, the variation observed in SNPs −336 and −139 indicates that this lectin may be of crucial importance in the susceptibility/transmission of HTLV-1 infections

Haplotype Structure of FSHB, the Beta-Subunit Gene for Fertility-Associated Follicle-Stimulating Hormone: Possible Influence of Balancing Selection

Follicle-stimulating hormone (FSH) is essential for human reproduction. The unique functions of this hormone are provided by the FSH receptor-binding beta-subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three European, two Asian and one African population, as well as in the great apes (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB showed deviations from neutrality in all populations suggesting a possible effect of balancing selection. Two core haplotypes were identified (carried by 76-96.6% of each population's sample), the sequences of which are clearly separated from each other. As fertility most directly affects an organism's fitness, the carriers of these haplotypes have apparently had more success in human history to contribute to the next generation. There is a preliminary observation suggesting that the second most frequent FSHB haplotype may be associated with rapid conception success in females. Interestingly, the same haplotype is related to an ancestral FSHB variant shared with the ancestor of the great apes. The determination of the functional consequence of the two core FSHB variants may have implications for understanding and regulating human fertility, as well as in assisting infertility treatments

Comparison of C. elegans and C. briggsae Genome Sequences Reveals Extensive Conservation of Chromosome Organization and Synteny

To determine whether the distinctive features of Caenorhabditis elegans chromosomal organization are shared with the C. briggsae genome, we constructed a single nucleotide polymorphism–based genetic map to order and orient the whole genome shotgun assembly along the six C. briggsae chromosomes. Although these species are of the same genus, their most recent common ancestor existed 80–110 million years ago, and thus they are more evolutionarily distant than, for example, human and mouse. We found that, like C. elegans chromosomes, C. briggsae chromosomes exhibit high levels of recombination on the arms along with higher repeat density, a higher fraction of intronic sequence, and a lower fraction of exonic sequence compared with chromosome centers. Despite extensive intrachromosomal rearrangements, 1:1 orthologs tend to remain in the same region of the chromosome, and colinear blocks of orthologs tend to be longer in chromosome centers compared with arms. More strikingly, the two species show an almost complete conservation of synteny, with 1:1 orthologs present on a single chromosome in one species also found on a single chromosome in the other. The conservation of both chromosomal organization and synteny between these two distantly related species suggests roles for chromosome organization in the fitness of an organism that are only poorly understood presently

Complete Genomic Characterization of a Pathogenic A.II Strain of Francisella tularensis Subspecies tularensis

Francisella tularensis is the causative agent of tularemia, which is a highly lethal disease from nature and potentially from a biological weapon. This species contains four recognized subspecies including the North American endemic F. tularensis subsp. tularensis (type A), whose genetic diversity is correlated with its geographic distribution including a major population subdivision referred to as A.I and A.II. The biological significance of the A.I – A.II genetic differentiation is unknown, though there are suggestive ecological and epidemiological correlations. In order to understand the differentiation at the genomic level, we have determined the complete sequence of an A.II strain (WY96-3418) and compared it to the genome of Schu S4 from the A.I population. We find that this A.II genome is 1,898,476 bp in size with 1,820 genes, 1,303 of which code for proteins. While extensive genomic variation exists between “WY96” and Schu S4, there is only one whole gene difference. This one gene difference is a hypothetical protein of unknown function. In contrast, there are numerous SNPs (3,367), small indels (1,015), IS element differences (7) and large chromosomal rearrangements (31), including both inversions and translocations. The rearrangement borders are frequently associated with IS elements, which would facilitate intragenomic recombination events. The pathogenicity island duplicated regions (DR1 and DR2) are essentially identical in WY96 but vary relative to Schu S4 at 60 nucleotide positions. Other potential virulence-associated genes (231) varied at 559 nucleotide positions, including 357 non-synonymous changes. Molecular clock estimates for the divergence time between A.I and A.II genomes for different chromosomal regions ranged from 866 to 2131 years before present. This paper is the first complete genomic characterization of a member of the A.II clade of Francisella tularensis subsp. tularensis

Patients with Alcohol Problems in the Emergency Department, Part 1: Improving Detection *

Medical and social problems related to alcohol use are frequently seen in the ED. Often, the tempo of emergency medicine practice seems to preclude assessment beyond that required by the acute complaint. However, detection of ED patients with alcohol problems can occur using brief screening tools. This article was developed by members of the SAEM Substance Abuse Task Force, and describes screening tools that have been used successfully to identify atrisk and dependent drinkers. Their brevity, reproducibility, and accuracy vary somewhat, but screening can be realistically performed in the busy ED setting. The early detection of patients with alcohol problems would provide the opportunity for early intervention, and may reduce subsequent morbidity and mortality in this patient population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72559/1/j.1553-2712.1998.tb02696.x.pd