Effect of seminal plasma on hipoosmotic swelling test in fresh alpaca spermatozoa

A study was designed with the objective of evaluating the effect of seminal plasma on the response to the hypoosmotic swelling test (HOST) in alpaca spermatozoa, for which three experimental groups were organized as follows: Group 1(n=15) plasma free sperm seminal (obtained from the vas deferens, aspirated in PBS), Group 2(n=15) free seminal plasma sperm reconstituted with seminal plasma (obtained from the vas deferens, aspirated in PBS, mixed in 50/50% with seminal plasma) and Group 3(n=15) whole semen (obtained by artificial vagina), The samples were incubated in a hypoosmotic solution adjusted to 100mOsmol (sodium citrate+fructose+2H2Ocsp 100mL). 0.1mL of semen+0.9mL of hypoosmotic solution was mixed, incubated for 30minutes in a water bath at 37°C and the reaction was stopped with 0.1mL of 4% formaldehyde. A count of at least 200 spermatozoa was performed per sample, using an optical microscope with immersion objective (100X), the vitality was evaluated by supravital eosin staining (0.7%)-nigrosin(1%), the results indicate that it does not exist a detrimental effect of the seminal plasma on the endosmotic response, being, on the contrary, superior in the whole semen; the vitality of the spermatozoa with and without seminal plasma is similar, however it decreases when it is reconstituted with seminal plasma, possibly due to the seminal plasma of another animal; there is no positive correlation between endosmosis and vitality, indicating that the latter would not necessarily reflect the integrity of the membrane, which is why it is recommended to perform this test routinely in alpaca semen exams

Historical trends in Hg, Pb and Zn sedimentation in the central shelf area of Portugal

Temporal records of excess 210Pb, and the determination of major (Al and Ca) and trace elements (Zn, Cr, Ni, Pb, Cu and Hg) in two sediment box-cores, collected in the central area of the Portuguese shelf of North of the Nazaré canyon (offshore from the Lis River), allow evaluation of the deposition of various chemical elements normally associated with anthropogenic activities. In order to compensate for the natural sediment variability, heavy metal contents were normalised to Al. Temporal variations of Hg, Pb and Zn (Al-normalised) show an increasing trend since the beginning of the 1920’s, recording the development of industrial activities. Enrichment factors (EF) were calculated to estimate the level of contamination in these sediments. Mercury is the element with the highest average EF values (EF = 3), followed by Pb (EF = 1.5) and Zn (EF = 1.2). The results indicate that since 1991 64% of total Hg, 44% of total Pb and 24% of total Zn are derived from anthropogenic sources. The average anthropogenic fluxes of Hg, Pb and Zn (0.008, 3, 6 μg cm-2yr-1, respectively) for the last 40 years in a ca. 400 km2 deposition area represent a total accumulation of approximately 30, 12000 and 24400 kg per year of Hg, Pb and Zn, respectively. These results indicate that despite the high-energy conditions and the generally sandy nature of the Portuguese shelf sediments, it is possible to identify significant anthropogenic enrichments in some areas of sediment accumulation. These contaminants are not necessarily related to immediate sources but may instead indicate atmospheric and or marine transport from more distant sources.Los registros temporales del 210Pb en exceso, elementos mayores (Al y Ca), y elementos traza (Zn, Cr, Ni, Pb, Cu y Hg) de 2 box-cores procedentes de la plataforma continental al norte del cañón de Nazaré han permitido caracterizar depósitos de elementos químicos asociados a actividades antropogénicas. Los contenidos de metales pesados han sido normalizados con Al para compensar la variabilidad natural. La variación temporal de Hg, Pb y Zn, normalizados con Al, muestran un incremento desde el inicio de la década de 1920 reflejando el desarrollo de la actividad humana. El nivel de contaminación de los sedimentos ha sido calculado en base a Factores de Enriquecimiento (EF). Los valores medios más altos de FE son de mercurio (EF = 3), seguidos de plomo (EF = 1.5) y zinc (EF = 1.2). Los resultados obtenidos indican que a partir de 1991 el 64% del total de Hg, 44% del total de Pb y 24% del total de Zn son de origen antropogénico. La media para los últimos 40 años de los flujos de Hg, Pb y Zn (0.008, 3, 6 μg cm-2 año-1, respectivamente), en un área de deposición de aproximadamente 400 km2, se traduce en la acumulación de 30, 12000 y 24400 kg por año de Hg, Pb y Zn. Sin embargo, a pesar de las condiciones de alta energía y el carácter arenoso de los sedimentos de la plataforma continental portuguesa, se pueden identificar importantes enriquecimientos antropogénicos en depocentros de sedimentos, no relacionados con fuentes antropogénicas próximas pero que pueden indicar transporte marino y atmosférico de fuentes de contaminación distantes

Particle size distributions in chondritic meteorites: Evidence for pre-planetesimal histories

Magnesium-rich silicate chondrules and calcium-, aluminum-rich refractory inclusions (CAIs) are fundamental components of primitive chondritic meteorites. It has been suggested that concentration of these early-formed particles by nebular sorting processes may lead to accretion of planetesimals, the planetary bodies that represent the building blocks of the terrestrial planets. In this case, the size distributions of the particles may constrain the accretion process. Here we present new particle size distribution data for Northwest Africa 5717, a primitive ordinary chondrite (ungrouped 3.05) and the well-known carbonaceous chondrite Allende (CV3). Instead of the relatively narrow size distributions obtained in previous studies (Ebel et al., 2016, Friedrich et al., 2015, Paque and Cuzzi, 1997, and references therein), we observed broad size distributions for all particle types in both meteorites. Detailed microscopic image analysis of Allende shows differences in the size distributions of chondrule subtypes, but collectively these subpopulations comprise a composite “chondrule” size distribution that is similar to the broad size distribution found for CAIs. Also, we find accretionary ‘dust’ rims on only a subset (∼15–20%) of the chondrules contained in Allende, which indicates that subpopulations of chondrules experienced distinct histories prior to planetary accretion. For the rimmed subset, we find positive correlation between rim thickness and chondrule size. The remarkable similarity between the size distributions of various subgroups of particles, both with and without fine grained rims, implies a common size sorting process. Chondrite classification schemes, astrophysical disk models that predict a narrow chondrule size population and/or a common localized formation event, and conventional particle analysis methods must all be critically reevaluated. We support the idea that distinct “lithologies” in NWA 5717 are nebular aggregates of chondrules. If ≥cm-sized aggregates of chondrules can form it will have implications for planet formation and suggests the sticking stage is where the preferential size physics is operating

A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway

BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also control several signaling processes including proteostasis, apoptosis and transcription. The largest isoform, BAG1L, controls the activity of the androgen receptor (AR) and is upregulated in prostate cancer. Here, we show that BAG1L regulates AR dynamics in the nucleus and its ablation attenuates AR target gene expression especially those involved in oxidative stress and metabolism. We show that a small molecule, A4B17 that targets the BAG domain downregulates AR target genes similar to a complete BAG1L knockout and upregulates the expression of oxidative stress-induced genes involved in cell death. Furthermore, A4B17 outperformed the clinically approved antagonist enzalutamide in inhibiting cell proliferation and prostate tumor development in a mouse xenograft model. BAG1 inhibitors therefore offer unique opportunities for antagonizing AR action and prostate cancer growth

Do sex differences in the prevalence of ECG abnormalities vary across ethnic groups living in the Netherlands? A cross-sectional analysis of the population-based HELIUS study

OBJECTIVES: Major ECG abnormalities have been associated with increased risk of cardiovascular disease (CVD) burden in asymptomatic populations. However, sex differences in occurrence of major ECG abnormalities have been poorly studied, particularly across ethnic groups. The objectives were to investigate (1) sex differences in the prevalence of major and, as a secondary outcome, minor ECG abnormalities, (2) whether patterns of sex differences varied across ethnic groups, by age and (3) to what extent conventional cardiovascular risk factors contributed to observed sex differences. DESIGN: Cross-sectional analysis of population-based study. SETTING: Multi-ethnic, population-based Healthy Life in an Urban Setting cohort, Amsterdam, the Netherlands. PARTICIPANTS: 8089 men and 11 369 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged 18-70 years without CVD. OUTCOME MEASURES: Age-adjusted and multivariable logistic regression analyses were performed to study sex differences in prevalence of major and, as secondary outcome, minor ECG abnormalities in the overall population, across ethnic groups and by age-groups (18-35, 36-50 and >50 years). RESULTS: Major and minor ECG abnormalities were less prevalent in women than men (4.6% vs 6.6% and 23.8% vs 39.8%, respectively). After adjustment for conventional risk factors, sex differences in major abnormalities were smaller in ethnic minority groups (OR ranged from 0.61 in Moroccans to 1.32 in South-Asian Surinamese) than in the Dutch (OR 0.49; 95% CI 0.36 to 0.65). Only in South-Asian Surinamese, women did not have a lower odds than men (OR 1.32; 95% CI 0.96 to 1.84). The pattern of smaller sex differences in ethnic minority groups was more pronounced in older than in younger age-groups. CONCLUSIONS: The prevalence of major ECG abnormalities was lower in women than men. However, sex differences were less apparent in ethnic minority groups. Conventional risk factors did not contribute substantially to observed sex differences

Evening choruses in the Perth Canyon and their potential link with Myctophidae fishes

An evening chorus centered at near 2.2 kHz was detected across the years 2000 to 2014 from seabed receivers in 430-490 m depth overlooking the Perth Canyon, Western Australia. The chorus reached a maximum level typically 2.1 h post-sunset and normally ran for 2.1 h (between 3 dB down points). It was present at lower levels across most of the hours of darkness. Maximum chorus spectrum levels were 74-76 dB re 1 µPa2/Hz in the 2 kHz 1/3 octave band, averaging 6-12 dB and up to 30 dB greater than pre-sunset levels. The chorus displayed highest levels over April to August each year with up to 10 dB differences between seasons. The spatial extent of the chorus was not determined but exceeded the sampling range of 13-15 km offshore from the 300 m depth contour and 33 km along the 300 m depth contour. The chorus comprised short damped pulses. The most likely chorus source is considered to be fishes of the family Myctophidae foraging in the water column. The large chorus spatial extent and its apparent correlation with regions of high productivity suggest it may act as an acoustic beacon to marine fauna indicating regions of high biomass

Corticosteroid co-treatment induces resistance to chemotherapy in surgical resections, xenografts and established cell lines of pancreatic cancer

BACKGROUND: Chemotherapy for pancreatic carcinoma often has severe side effects that limit its efficacy. The glucocorticoid (GC) dexamethasone (DEX) is frequently used as co-treatment to prevent side effects of chemotherapy such as nausea, for palliative purposes and to treat allergic reactions. While the potent pro-apoptotic properties and the supportive effects of GCs to tumour therapy in lymphoid cells are well studied, the impact of GCs to cytotoxic treatment of pancreatic carcinoma is unknown. METHODS: A prospective study of DEX-mediated resistance was performed using a pancreatic carcinoma xenografted to nude mice, 20 surgical resections and 10 established pancreatic carcinoma cell lines. Anti-apoptotic signaling in response to DEX was examined by Western blot analysis. RESULTS: In vitro, DEX inhibited drug-induced apoptosis and promoted the growth in all of 10 examined malignant cells. Ex vivo, DEX used in physiological concentrations significantly prevented the cytotoxic effect of gemcitabine and cisplatin in 18 of 20 freshly isolated cell lines from resected pancreatic tumours. No correlation with age, gender, histology, TNM and induction of therapy resistance by DEX co-treatment could be detected. In vivo, DEX totally prevented cytotoxicity of chemotherapy to pancreatic carcinoma cells xenografted to nude mice. Mechanistically, DEX upregulated pro-survival factors and anti-apoptotic genes in established pancreatic carcinoma cells. CONCLUSION: These data show that DEX induces therapy resistance in pancreatic carcinoma cells and raise the question whether GC-mediated protection of tumour cells from cancer therapy may be dangerous for patients

Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host

Probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. Many of these species are associated with the fermentation of dairy products. Despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. To address this issue, we colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the adult human gut microbiota, and Bifidobacterium longum, a minor member but a commonly used probiotic. Simultaneous whole genome transcriptional profiling of both bacterial species in their gut habitat and of the intestinal epithelium, combined with mass-spectrometric analysis of habitat-associated carbohydrates, revealed that the presence of B. longum elicits an expansion in the diversity of polysaccharides targeted for degradation by B. thetaiotaomicron (e.g., mannose- and xylose-containing glycans), and induces host genes involved in innate immunity. Although the overall transcriptome expressed by B. thetaiotaomicron when it encounters B. longum in the cecum is dependent upon the genetic background of the mouse (as assessed by a mixed analysis of variance [ANOVA] model of co-colonization experiments performed in NMRI and C57BL/6J animals), B. thetaiotaomicron's expanded capacity to utilize polysaccharides occurs independently of host genotype, and is also observed with a fermented dairy product-associated strain, Lactobacillus casei. This gnotobiotic mouse model provides a controlled case study of how a resident symbiont and a probiotic species adapt their substrate utilization in response to one another, and illustrates both the generality and specificity of the relationship between a host, a component of its microbiota, and intentionally consumed microbial species