The cAMP-responsive element modulator (CREM) gene plays a pivotal role in the mouse spermatogenesis, but its role in the human infertility has not been fully established. We performed a mutation ...screening in 13 Slovenian men with round spermatid arrest and in six controls. Eleven genetic changes have been identified in the human CREM gene, three novel single-nucleotide polymorphisms within the promoters P1, P3 and intervening sequence 1 (IVS1), one insertion (IVS2) and one non-sense mutation (exon γ). Some infertile patients seem to accumulate potentially harmful genetic changes. We identified a patient with no CREM immunoreactive protein that was homozygous for the nucleotide changes in all promoters, IVS 1, 2, 6, and was heterozygous for the mutation in exon γ. Interestingly, insertion in IVS2 (IVS2-58_55insT) results in a four-fold decrease in binding of nuclear proteins. Computer predictions suggested the presence of a potential novel CREM promoter, however, random amplification of cDNA ends from the human testis cDNA library was not successful in confirming a novel transcription start site of the CREM gene. Screening of a larger number of patients and controls is required to elucidate whether the observed combinations of genetic changes in the CREM gene can explain some forms of male infertility.
Hybrid load-value predictors Burtscher, M.; Zorn, B.G.
IEEE transactions on computers,
07/2002, Letnik:
51, Številka:
7
Journal Article
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Load instructions diminish processor performance in two ways. First, due to the continuously widening gap between CPU and memory speed, the relative latency of load instructions grows constantly and ...the slows program execution. Next, memory reads limit the available instruction-level parallelism as instructions that use the result of a load must wait for the memory access to complete before they can start executing. Load-value predictors alleviate both problems by allowing the CPU to speculatively continue processing without having to wait for load instructions, which can significantly improve the execution speed. In this paper, we investigate the performance of all hybrids that can be built out of a register value, a last value, a stride 2-delta, the last four values, and a finite context method predictor. Our analysis shows that hybrids can deliver 25 percent more speedup than the best single-component predictors. Our hybridization study identified the register value + stride 2-delta predictor as one of the best two-component hybrids. It matches or exceeds the speedup of two-component hybrids from the literature in spite of its substantially smaller and simpler design. Of all the predictors we studied, the register value + stride 2-delta + last four value hybrid performs best.
Education in antimicrobial stewardship (AMS) in veterinary medicine is essential to foster responsible antimicrobial use and control of antimicrobial resistance (AMR) in animals. AMS is listed by the ...EU and international organizations among the basic 'Day One Competences' required of veterinary students upon graduation. Our aim was to evaluate the quality of education of European veterinary students in AMS. We distributed a 27-item survey addressing the perceptions of preparedness and acquired skills on key topics related to AMS to final-year veterinary students in Europe. We collected 3423 complete answers from 89 veterinary schools in 30 countries. Selection of treatment strategies and awareness of emerging AMR problems were markedly different between countries. Overall, only one in four students was familiar with guidelines for antimicrobial use. The students perceived a medium-high impact of veterinary antimicrobial use on AMR in humans. Notably, 75% of the students felt the need for improved teaching on AMS, half of which also demanded more teaching on general antimicrobial therapy. Our results highlight several possible strategies to improve the quality of education, ranging from a better link between clinical rotations and the theory taught in pre-clinical modules, to a more effective introduction into best practices for antimicrobial use.
Efficient replication in vivo is essential for a microparasite to colonize its host and the understanding of the molecular mechanisms by which microbial pathogens grow within host tissues can lead to ...the discovery of novel therapies to treat infection. Here we present evidence that the foodborne bacterial pathogen Listeria monocytogenes, a facultative intracellular parasite, exploits hexose phosphates (HP) from the host cell as a source of carbon and energy to fuel fast intracellular growth. HP uptake is mediated by Hpt, a bacterial homolog of the mammalian translocase that transports glucose-6-phosphate from the cytosol into the endoplasmic reticulum in the final step of gluconeogenesis and glycogenolysis. Expression of the Hpt permease is tightly controlled by the central virulence regulator PrfA, which upon entry into host cells induces a set of virulence factors required for listerial intracellular parasitism. Loss of Hpt resulted in impaired listerial intracytosolic proliferation and attenuated virulence in mice. Hpt is the first virulence factor to be identified as specifically involved in the replication phase of a facultative intracellular pathogen. It is also a clear example of how adaptation to intracellular parasitism by microbial pathogens involves mimicry of physiological mechanisms of their eukaryotic host cells.
A total of 18 men older than 19 years with spinal cord injury was evaluated for fertility potential with testing of semen obtained by rectal probe electroejaculation. After fertility testing, ...including sperm penetration assay, semen cryopreservation and sperm antibody status, 6 of the 18 men proceeded with their partners to use rectal probe electroejaculation in efforts to conceive. Sperm was obtained in 16 of 18 cases. Average ejaculate total sperm count (306 million) was good but motility (22%) was poor. Adequate sperm retrieval after processing yielded a normal sperm penetration assay in 4 of 16 cases (25%) in which sperm were obtained. Favorable semen cryopreservation (greater than 33% of pre-freeze motility noted after thaw) was present in 5 of 16 cases (31%). Live births were achieved in 2 of 6 couples attempting conception. Despite the typically poor sperm motility noted in electroejaculates, rectal probe electroejaculation can result in pregnancies from couples involving spinal cord injured men. The sperm penetration assay data indicate that pregnancy should be achievable in at least 25% of spinal cord injured couples. Achieving these conceptions requires a team approach involving a urologist/andrologist, gynecologist/reproductive endocrinologist and a sperm-processing laboratory.
We report armA in an Escherichia coli pig isolate from Spain. The resistance gene was borne by self-transferable IncN plasmid pMUR050. Molecular analysis of the plasmid and of the armA locus ...confirmed the spread of this resistance determinant.
Genetic basis for dissemination of armA González-Zorn, Bruno; Catalan, Ana; Escudero, Jose A. ...
Journal of antimicrobial chemotherapy,
09/2005, Letnik:
56, Številka:
3
Journal Article
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Objectives and methods: armA is a novel plasmid-borne 16S rRNA methyltransferase that confers high-level resistance to 4,6-disubstituted deoxystreptamines. Recently, we have isolated from a ...high-level broad-spectrum aminoglycoside-resistant Escherichia coli animal isolate a plasmid, pMUR050, that bore the armA gene. In order to elucidate the genetic basis for the spread of armA, we have determined the complete nucleotide sequence of pMUR050. Results: armA was borne by a complex transposon composite flanked by two direct repeats of IS26. The transposon composite included a class one integron with sul1 for resistance to sulphonamides and ant3″9 conferring resistance to spectinomycin–streptomycin, and a macrolide efflux pump and mefE/mel conferring high-level resistance to erythromycin. We identified in GenBank that another plasmid, pCTX-M3, from a Polish Citrobacter freundii human isolate, bore the same genetic structure, including armA. Conclusions: armA is present in human and animal isolates within a novel transposon composite. Further spread of armA between bacteria of diverse origin is to be expected.
BACKGROUND: We investigated whether the psychological stress related to a short war (26 June–7 July, 1991) in Slovenia induced changes in fertility, sex ratio at birth and semen quality ...characteristics. METHODS: Sex ratios i.e. males/(males + females) for 4966 births in the general population of Slovenia and separately for 1565 births in the Slovenian capital, Ljubljana, from January–March 1992 were compared with the sex ratio calculated for the same time period in 1991 and 1993. Semen analyses for 38 normozoospermic men attending an outpatient infertility clinic from May to September 1991 were also evaluated. RESULTS: In the general population in Slovenia there was a significant fall in the sex ratio at birth in 1992, compared with 1991 (0.504 versus 0.518; P = 0.03). In Ljubljana, the decline in sex ratio in 1992 was even more pronounced: 0.483 versus 0.537 in 1991 (P = 0.0001) and 0.483 versus 0.516 in 1993 (P = 0.005). A decrease in the proportion of sperm that were progressively motile from 56% before the war to 52% after it (P = 0.01) and of those that were rapidly motile from 40 to 36% (P = 0.01) was observed. CONCLUSIONS: Acute psychological stress in relation to a short war in Slovenia resulted 6 to 9 months later in a decrease in the observed sex ratio at birth. Negative changes in sperm motility may be involved in the sex ratio modifications.
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