Geographic differences in semen quality of fertile U.S. males.

Although geographic variation in semen quality has been reported, this is the first study in the United States to compare semen quality among study centers using standardized methods and strict quality control. We evaluated semen specimens from partners of 512 pregnant women recruited through prenatal clinics in four U.S. cities during 1999-2001; 91% of men provided two specimens. Sperm concentration, semen volume, and motility were determined at the centers, and morphology was assessed at a central laboratory. Study protocols were identical across centers, and quality control was rigorously maintained. Sperm concentration was significantly lower in Columbia, Missouri, than in New York, New York; Minneapolis, Minnesota; and Los Angeles, California. Mean counts were 58.7, 102.9, 98.6, and 80.8 X 10(6)/mL (medians 53.5, 88.5, 81.8, and 64.8 X 10(6)/mL) in Missouri, New York, Minnesota, and California, respectively. The total number of motile sperm was also lower in Missouri than in other centers: 113, 196, 201, and 162 X 10(6) in Missouri, New York, Minnesota, and California, respectively. Semen volume and the percent morphologically normal sperm did not differ appreciably among centers. These between-center differences remained significant in multivariate models that controlled for abstinence time, semen analysis time, age, race, smoking, history of sexually transmitted disease, and recent fever (all p-values < 0.01). Confounding factors and differences in study methods are unlikely to account for the lower semen quality seen in this mid-Missouri population. These data suggest that sperm concentration and motility may be reduced in semirural and agricultural areas relative to more urban and less agriculturally exposed areas

Detection of xenoestrogens in serum after immunoprecipitation of endogenous steroidal estrogens.

In this article we report a simple and efficient method for detecting nonsteroidal estrogens in a biologic sample. This method uses polyclonal antibodies to estradiol (E2) to immunoprecipitate these major biologically active steroidal estrogens, leaving behind the nonsteroidal estrogens, which are then detected in a cell-based transcriptional activation bioassay for estrogen receptor agonist. The immunoprecipitation method efficiently removed 99% of radiolabeled E2 and estrone (E1) from human serum. In experiments in which supraphysiologic concentrations of E2 and E1 to human serum, all of the immunoreactive estrogens were still removed by the immunoprecipitation protocol. We carried out an in vivo validation study of this method in which we treated female macaques with the xenoestrogen nonylphenol (NP), during the late follicular phase of the menstrual cycle. We used blood samples collected before and after treatment to evaluate and characterize endogenous and exogenous serum estrogens. An immunoassay for E2 did not detect the NP in treated monkeys. The cell-based bioassay also did not detect the estrogenic activity of NP because of its saturation by the endogenous serum steroidal estrogens. However, when steroidal estrogens were removed by immunoprecipitation, we detected the estrogenic activity of NP in the bioassay. Thus, this approach is appropriate for detecting exogenous, nonsteroidal estrogens in serum samples

Semen quality in relation to biomarkers of pesticide exposure.

We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN; Los Angeles, CA; New York, NY). In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3). The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04). No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellent DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously

Bone resorption is affected by follicular phase length in female rotating shift workers.

Stressors as subtle as night work or shift work can lead to irregular menstrual cycles, and changes in reproductive hormone profiles can adversely affect bone health. This study was conducted to determine if stresses associated with the disruption of regular work schedule can induce alterations in ovarian function which, in turn, are associated with transient bone resorption. Urine samples from 12 rotating shift workers from a textile mill in Anqing, China, were collected in 1996-1998 during pairs of sequential menstrual cycles, of which one was longer than the other (28.4 vs. 37.4 days). Longer cycles were characterized by a prolonged follicular phase. Work schedules during the luteal-follicular phase transition (LFPT) preceding each of the two cycles were evaluated. All but one of the shorter cycles were associated with regular, forward phase work shift progression during the preceding LFPT. In contrast, five longer cycles were preceded by a work shift interrupted either by an irregular shift or a number of "off days." Urinary follicle-stimulating hormone levels were reduced in the LFPT preceding longer cycles compared with those in the LFPT preceding shorter cycles. There was greater bone resorption in the follicular phase of longer cycles than in that of shorter cycles, as measured by urinary deoxypyridinoline. These data confirm reports that changes in work shift can lead to irregularity in menstrual cycle length. In addition, these data indicate that there may be an association between accelerated bone resorption in menstrual cycles and changes of regularity in work schedule during the preceding LFPT

Effect of Environmental Tobacco Smoke on Levels of Urinary Hormone Markers

Our recent study showed a dose–response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E(1)C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E(1)C levels in a ±10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E(1)C levels (β= –0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (β= –0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E(1)C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E(1)C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects

Prolonged Antigen Presentation Is Required for Optimal CD8+ T Cell Responses against Malaria Liver Stage Parasites

Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization—a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen

A History of Discrete Event Simulation Programming Languages

The history of simulation programming languages is organized as a progression in periods of similar developments. The five periods, spanning 1955-1986, are labeled: The Period of Search (1955-1960); The Advent (1961-1965); The Formative Period (1966-1970); The Expansional Period (1971-1978); and The Period of Consolidation and Regeneration (1979-1986). The focus is on recognizing the people and places that have made important contributions in addition to the nature of the contribution. A balance between comprehensive and in-depth treatment has been reached by providing more detailed description of those languages which have or have had major use. Over 30 languages are mentioned, and numerous variations are described in the major contributors. A concluding summary notes the concepts and techniques either originating with simulation programming languages or given significant visibility by them

Epsin 1 Promotes Synaptic Growth by Enhancing BMP Signal Levels in Motoneuron Nuclei

We thank Carl-Henrik Heldin (Uppsala University, Sweden) for his generous gift of the PS1 pMad antibody, Hugo Bellen, Corey Goodman, Janis Fischer, Graeme Davis, Guillermo Marques, Michael O'Connor, Kate O'Connor-Giles, and the Bloomington Drosophila Stock Center for flies strains, the Developmental Studies Hybridoma Bank at the University of Iowa for antibodies to Wit and CSP; Marie Phillips for advice on membrane fractionation; Avital Rodal, Kate O'Connor-Giles, Ela Serpe, Kristi Wharton, Mojgan Padash-Barmchi for discussions or comments on the manuscript. We also thank Jody Summers at OUHSC for her generosity in letting us to use her confocal microscope.Conceived and designed the experiments: PAV TRF LRC BZ. Performed the experiments: PAV TRF LRC SMR HB NER BZ. Analyzed the data: PAV TRF LRC SMR HB NER BZ. Wrote the paper: PAV TRF BZ.Bone morphogenetic protein (BMP) retrograde signaling is crucial for neuronal development and synaptic plasticity. However, how the BMP effector phospho-Mother against decapentaplegic (pMad) is processed following receptor activation remains poorly understood. Here we show that Drosophila Epsin1/Liquid facets (Lqf) positively regulates synaptic growth through post-endocytotic processing of pMad signaling complex. Lqf and the BMP receptor Wishful thinking (Wit) interact genetically and biochemically. lqf loss of function (LOF) reduces bouton number whereas overexpression of lqf stimulates bouton growth. Lqf-stimulated synaptic overgrowth is suppressed by genetic reduction of wit. Further, synaptic pMad fails to accumulate inside the motoneuron nuclei in lqf mutants and lqf suppresses synaptic overgrowth in spinster (spin) mutants with enhanced BMP signaling by reducing accumulation of nuclear pMad. Interestingly, lqf mutations reduce nuclear pMad levels without causing an apparent blockage of axonal transport itself. Finally, overexpression of Lqf significantly increases the number of multivesicular bodies (MVBs) in the synapse whereas lqf LOF reduces MVB formation, indicating that Lqf may function in signaling endosome recycling or maturation. Based on these observations, we propose that Lqf plays a novel endosomal role to ensure efficient retrograde transport of BMP signaling endosomes into motoneuron nuclei.Yeshttp://www.plosone.org/static/editorial#pee

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced