Dynamic alteration of plasma levels of betatrophin in younger female onset obesity post acute moderate-intensity exercise training

Obesity is a global metabolic disease anchored by a lack of physical activity lipid disturbances. Hitherto, betatrophin is a potential liver-derived hormone that regulates lipid metabolism. A total of 26 selected onset obese individuals (BMI range ± 28–31) were enrolled in this study and given moderate-intensity exercise. Importantly, our data show that acute moderate-intensity interval exercise (MIIE) and acute moderate-intensity continue to exercise (MICE) for 40 min significantly decrease the plasma level of full-length betatrophin respectively (174.18 ± 48.19 ng/mL; 182.31 ± 52.69 ng/mL), compared to the placebo (283.97 ± 32.23 ng/mL) post 10 min and 6 h exercise treatment (p ≤ 0.05). The plasma level of betatrophin was significantly and negatively correlated with BMI (r = ? 0.412, p = 0.037), fasting blood glucose (r = ? 0.390, p = 0.049), and positively correlated with VO_2max (r = 0.456, p = 0.019). In addition, the linear and ordinal logistic regression analysis shows that betatrophin, is a potential predictor for BMI [estimate value = 0.995, p = 0.037 and OR (95 % CI) = 0.992 (0.0984–1.00), p = 0,048]. In summary, our data demonstrate that the circulating levels of betatrophin were decreased after acute moderate-intensity exercise training.     

An assessment of level of heavy metals pollution in the water,sediment and aquatic organisms: A perspective of tackling environmental threats for food security

Pollution is severely threatening the wetland habitats. Heavy metals are one among of the major pollutants in wetland habitats. The cadmium (Cd), copper (Cu), chromium (Cr), cobalt (Co), lead (Pb), mercury (Hg), nickel (Ni) and zinc (Zn), were assessed in the water, sediment, benthic species (polychaetes, mollusc and crustaceans), prawn and fishes. The assessment of heavy metals was done by using double-beam Atomic Absorption Spectrophotometer (AAS). The Hg, Cr and Co were greater in sediment, Ni and Cd were higher in polychaetes and molluscs respectively. However, the Cu and Pb greater in crabs and the Zinc was greater in fishes. The concentration of metals showed significant differences among the various sources examined (P < 0.05) except Cr (P > 0.05). The inter-correlational analysis among the metals assessed from the various sources showed that the Cr and Pb not correlated among the eight metals examined. However, the Cu and Co were correlated with Hg (r = 0.307) and (r = 0.788) respectively. The nickel was correlated with Hg (r = 0.367), Cu (r = 0.362) and Co (r = 0.432). The Zinc was correlated with the Cd (r = 0.331) and Hg (r = 0.737). However, correlation of metals among the different sources shown that the metals of polychaetes correlated with sediment r = 0.637, the metals of crabs correlated with the sediment and polychaetes r = 0.630 and r = 842 respectively, the metals of molluscs was also correlated with sediment (r = 0.636), polychaetes (r = 0.889) and crabs (r = 0.894). In addition to that the metals of prawns was correlated with the polychaetes (r = 839), crabs (r = 0.628) and molluscs (r = 0.634). The metals of fishes correlated with polychaetes (r = 0.529), crabs (r = 0.710), molluscs (r = 0.493) and prawns (r = 0.593). Indeed the multiple regression model explained that the metals of sediments influence the accumulation of metals in biotic species such as polychaetes, molluscs, crustaceans, prawns and fishes with 84% (F = 21.079; p < 0.001).The order of the heavy metals in the water, sediment and biotic species was Hg > Pb > Ni > Cr > Zn > Co > Cu > Cd. The study found that the level of heavy metals at various sources in the sanctuary is showing considerable warning and the sanctuary is required intensive assessment on various aspects of pollution since the Point Calimere Wildlife Sanctuary is supporting several species of migratory and endangered shorebirds seasonally.     

‘Aching to be a boy’: A preliminary analysis of gender assignment of intersex persons in India in a culture of son preference

Intersexuality, particularly in the global South, remains an under-researched field of study. In my in-progress doctoral research project, I explore the cultural, social, and medical discourses that influence how key stakeholders such as healthcare providers make decisions about the sex and gender assignment of the intersex child in India. In this paper I interrogate some of these ideas around gender assignment of intersex people in India, paying particular attention to the context of son preference. I am interested in exploring how decisions of gender assignment by medical professionals are guided by ideas of son preference. Focusing on four qualitative, semi-structured, in-depth interviews across two cities with medical doctors from different specializations, this paper is a preliminary attempt to examine some of the factors that guide medical professionals in making decisions about gender assignment of intersex children and explore the dynamics of the decision-making process. Specifically, I explore the factors that inform doctors’ decision-making and locate these decision-making processes within the broader socio-cultural context of India.     

Protective role of scutellarin on LPS induced – Acute lung injury and regulation of apoptosis,oxidative stress and reduction of mitochondrial dysfunction

Lung fluid accumulation was determined using wet/dry lung mass ratio. Rats subjected to LPS-induced acute lung injury (2.8 ± 0.33, P < 0.05) presented with a significantly higher wet to dry lung weight ration ratio than sham rats (1.6 ± 0.23, P < 0.05). These results demonstrate that acutely inured rats' lungs were oedematous. On the other hand, treatment with scutellarin alone and in combination with a JNK inhibitor, SP600125, both significantly attenuated pulmonary edema as shown via reduced wet/dry lung mass ratios (1.7 ± 0.09 and 1.8 ± 0.23; P < 0.05, respectively). These results showed that the interventions were effective against LPS-induced edema of the lungs. However, the difference between treatment groups' weight ratios was not statistically significant (P > 0.05). In the sham control rats, the levels of ROS and SOD production were maintained at a low and at a high concentration, respectively (P < 0.05). However, following LPS infusion, the ROS levels skyrocketed while that of SOD decreased significantly relative to the control rats (P < 0.05). Furthermore, we noted that pre-treatment with scutellarin reduced the ROS levels in LPS-injured rats while the SOD was increased to near control levels (P < 0.05). Moreover, the combined effect of scutellarin and JNK inhibitor SP600125 on the levels of ROS and the SOD activity followed a similar trend to that of scutellarin alone albeit with a lower magnitude of change. Our results also showed that the combinatorial treatment was not significantly different from scutellarin alone in terms of influence on the levels of ROS production and SOD activity (P > 0.05). The effect of Scutellarin on broncho-alveolar lavage fluid (BALF) cytokine secretion The expression of interleukins-1β, ?18 and ?6 in the broncho-alveolar lavage fluid were significantly upregulated by LPS infusion (P < 0.05). The rise was, however, attenuated via pre-treatment with scutellarin only or in conjunction with SP600125, a JNK inhibitor (all P < 0.05). On the contrary, we observed that LPS injection caused a reduction of interlekins ?4 and ?10 secreted in the BALF. Pre-treatment with scutellarin alone (P < 0.05) and not in combination with SP600125 or SP600125 was able to significantly reverse this noted down-regulation (all P > 0.05).     

Agonistic trials with mirrors do not elicit the same aggressiveness of a real trial in the matrinxã fish,Brycon amazonicus (Spix & Agassiz, 1829)

This study tested the efficacy of mirror trials in studying aggressiveness in the matrinxã fish, Brycon amazonicus. The hypothesis was that a mirror would elicit an aggressive response in B. amazonicus juveniles, but show different behavioral and physiological profiles than those observed in trials with real opponents. Fish were tested using either a mirror trial (n = 7) or a real trial (n = 7), that is, placed alone with a mirror or paired with a same‐sized opponent, respectively. All trials lasted for 20 min and took place in 96‐L aquaria with water temperatures of 28°C. Fish in mirror trials exhibited less locomotion (mirror: 423.3 ± 39.1; real trial: 735.1 ± 31.9; p < .001), rushed less against the opponent (mirror: 3.1 ± 2.3; real trial: 39.6 ± 5.1; p < .001) and showed less escalation of aggressive behavior compared to the winner of a real trial. Regarding the physiological parameters, despite similar cortisol responses (mirror: 84.2 ± 13.8 ng/ml; real trial: 77.2 ± 16.9 ng/ml; p = .757), the fish that fought against a mirror had lower levels of plasma glucose than those of fish that fought against a real opponent (mirror: 76.8 ± 3.6 ng/dl; real trial: 103.8 ± 10.1 ng/ml; p = .037). This lower energy mobilization might be due to a lower cost of the fight in the absence of an opponent that flees from attacks, as the locomotion and number of rush totals were also lower in the mirror trials. This pattern of less locomotion is probably common in mirror trials because the opponent is always limited to one side of the arena. If the energetic cost is one of the factors that can determine the outcome of a fight, and if mirror trials do not evoke the physiological response observed in a real fight, the use of mirror trials must be reviewed in studies that consider the physiological responses.     

Inhibition of Neuron-Specific CREB Dephosphorylation is Involved in Propofol and Ketamine-Induced Neuroprotection Against Cerebral Ischemic Injuries of Mice

Propofol and ketamine may provide certain degree of neuroprotection, but the underlying mechanism remains unclear to date. The cAMP response element-binding protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB) constituted a convergence point involved in neuroprotection. The purpose of this study was to determine whether different dosages of propofol and ketamine could provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)-induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c mice that underwent 6 h MCAO were randomly divided into eight groups: Sham-operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50, 100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine could significantly reduce the infarct volume, edema ratio and neurological deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in peri-infarct region when compared with that of MCAO + saline group (n = 6 per group). In addition, the results of double-labeled immunofluorescent staining showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri-infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice (n = 4 per group). These results suggested that inhibition of neuron-specific P-CREB dephosphorylation in the peri-infarct region is involved in high dose propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.     

Genetic variation within the endangered mangrove species Sonneratia paracaseolaris (Sonneratiaceae) in China detected by inter-simple sequence repeats analysis

Sonneratia paracaseolaris, is a critically endangered mangrove species in China. Using inter-simple sequence repeats (ISSR) markers, we compared the genetic variation of introduced populations with that of natural populations to check whether the genetic diversity has been conserved. At the species level, genetic diversity was relatively high (P = 81.37%, He = 0.2241, and SI = 0.3501). Genetic variation in introduced populations (P = 75.78%, He = 0.2291, and SI = 0.3500) was more than that in natural populations (P = 70.81%, He = 0.1903, and SI = 0.2980). Based on Nei's G_ST value, more genetic differentiation among natural populations was detected (G_ST = 0.3591). Our data show that the genetic diversity of S. paracaseolaris was conserved in introduced populations to some extent, however, owing to the small natural populations and the threats they encountered, more plants should be planted to enlarge and restore the populations.     

Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows

Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at −1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P < 0.01), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) concentrations of P4 than cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P < 0.001), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) P4 than the SAL-IVG group from 12 to 96 hours after trt. Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and the lowest P4 concentrations after treatment among the IVG-treated groups, and all cows presented complete CL regression (defined as P4 <0.4 ng/mL). We conclude that CL regression can be induced through IVG instillation of PGF in lactating dairy cows and that instillation of two IVG doses of 25 mg of PGF 12 hours apart was the most effective strategy.     

Bacteriophage MS2 displays unreported capsid variability assembling T = 4 and mixed capsids

Bacteriophage MS2 is a positive-sense, single-stranded RNA virus encapsulated in an asymmetric T = 3 pseudo-icosahedral capsid. It infects Escherichia coli through the F-pilus, in which it binds through a maturation protein incorporated into its capsid. Cryogenic electron microscopy has previously shown that its genome is highly ordered within virions, and that it regulates the assembly process of the capsid. In this study, we have assembled recombinant MS2 capsids with non-genomic RNA containing the capsid incorporation sequence, and investigated the structures formed, revealing that T = 3, T = 4 and mixed capsids between these two triangulation numbers are generated, and resolving structures of T = 3 and T = 4 capsids to 4 Å and 6 Å respectively. We conclude that the basic MS2 capsid can form a mix of T = 3 and T = 4 structures, supporting a role for the ordered genome in favouring the formation of functional T = 3 virions.     

Contemporary changes in phenotypic variation,and the potential consequences for eco-evolutionary dynamics

Most studies assessing rates of phenotypic change focus on population mean trait values, whereas a largely overlooked additional component is changes in population trait variation. Theoretically, eco-evolutionary dynamics mediated by such changes in trait variation could be as important as those mediated by changes in trait means. To date, however, no study has comprehensively summarised how phenotypic variation is changing in contemporary populations. Here, we explore four questions using a large database: How do changes in trait variances compare to changes in trait means? Do different human disturbances have different effects on trait variance? Do different trait types have different effects on changes in trait variance? Do studies that established a genetic basis for trait change show different patterns from those that did not? We find that changes in variation are typically small; yet we also see some very large changes associated with particular disturbances or trait types. We close by interpreting and discussing the implications of our findings in the context of eco-evolutionary studies.     

Peroxynitrite-induced apoptosis involves activation of multiple caspases in HL-60 cells

In this study, we show that caspases2, 3, 6, and 7 were activated during peroxynitrite-induced apoptosis inhuman leukemia HL-60 cells and that processing of these caspases wasaccompanied by cleavage of poly(ADP-ribose) polymerase and lamin B. Treatment of cells with DEVD-fluoromethyl ketone (FMK), a selectiveinhibitor for caspase 3-like proteases, resulted in a marked diminution of apoptotic cells. VAVAD-FMK, an inhibitor of caspase 2, partially inhibited the apoptotic response to peroxynitrite. However, selective inactivation of caspase 6 by VEID-FMK did not affect apoptosis rates.These data suggest that caspase 3-like proteases and caspase 2, but notcaspase 6, are required for peroxynitrite-induced apoptosis in thiscell type. Moreover, we demonstrate that peroxynitrite treatmentstimulated activation of caspases 8 and 9, two initial caspases in theapoptotic signaling pathway, and preincubation of cells with theirinhibitor, IETD-FMK, inhibited activation of caspase 3-like proteasesand caspase 2 at the concentration that prevents the apoptosis. Theseobservations, together, suggest that caspase 8 and/or caspase 9 mediates activation of caspase 3-like proteases and caspase 2 duringthe apoptosis induced by peroxynitrite in HL-60 cells.

     

Dependence of Forest Structure and Dynamics on Substrate Age and Ecosystem Development

We quantified rates, sizes, and spatial properties of prevailing disturbance regimes in five tropical rain forest landscapes on a substrate-age gradient in Hawaii. By integrating measurements from airborne LiDAR with field studies and statistical modeling, we show that the structure and dynamics of these forests respond to processes that change during the development of ecosystems. On young substrates of 0.3 ky where forests are in primary succession and are limited by N, mean canopy height was 13 m and height decreases more than 1 m occurred in small, isolated events (power-law exponent = 1.69 ± 0.02, n = 61 gaps ha⁻¹). The proportion of the landscape affected by disturbance increased on high-fertility intermediate-aged substrates of 5–65 ky and canopies were heterogeneous. Frequencies of height decreases more than 1 m were n = 14, 18, and 30 gaps ha⁻¹ corresponding to power-law exponents of 2.188 ± 0.02, 2.220 ± 0.03, and 1.982 ± 0.02 on substrates of 5, 20, and 65 ky. There was a substantial difference between forests on a 150 ky substrate and sites of 5–65 ky; trees on the older substrate formed patchworks of stunted cloud-forest and stands of taller-stature trees. The frequency of recent disturbance events more than 1 m was n = 48 gaps ha⁻¹, corresponding to a power-law exponent of 1.638 ± 0.01. Across the substrate-age gradient, the proportion of each landscape that decreased in height by more than 1 m was 0.16, 0.40, 0.41, 0.36, and 0.17, respectively. These findings demonstrate that substrate age and processes associated with ecosystem development can mediate the rates, sizes, and spatial characteristics of disturbance regimes on forested landscapes, and point toward the necessity of large-area samples to obtain robust estimates of natural dynamics.     

Mechanism of Post-Translational Modification by Tyrosine Phosphorylation of Apoptotic Proteins During Hypoxia in the Cerebral Cortex of Newborn Piglets

The present study aims to investigate the mechanism of phosphorylation of apoptotic proteins and tests the hypothesis that the hypoxia-induced increased tyrosine phosphorylation of apoptotic proteins Bcl-2 and Bcl-xl is Ca²⁺-influx-dependent. Piglets were divided in normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic-pretreated with clonidine (Clo + Hx, n = 4) groups. Hypoxic animals were exposed to an FiO₂ of 0.06 for 1 h. Clonidine (12.5 μg/kg, IV) was administered to piglets 30 min prior to hypoxia. Hypoxia was confirmed by ATP and phosphocreatinine (PCr) levels. Cytosol was isolated and separated by 12% SDS–PAGE and probed with tyrosine phosphorylated (p) -Bax, Bad, Bcl-2 and Bcl-xl antibodies and bands were detected. The ATP levels (μmol/g brain) in the Nx, Hx, Clo + Hx were 4.3 ± 1.0 (P < 0.05 vs. Hx, Clo-Hx), 0.9 ± 0.8 and 1.5 ± 0.3, respectively. The PCr levels in the Nx, Hx, Clo + Hx were 2.7 ± 0.7 (P < 0.05 vs. Hx, Clo-Hx), 0.9 ± 0.2 and 0.9 ± 0.9, respectively. Ca²⁺-influx (pmoles/mg protein) was 4.96 ± 0.94 in Nx, 11.11 ± 2.38 in Hx, and 6.23 ± 2.07 in Clo + Hx (P < 0.05 Nx vs. Hx and Hx vs. Clo + Hx). p-Bcl-2 density was 21.1 ± 1.1 Nx, 58.9 ± 9.6 Hx and 29.5 ± 6.4 Clo + Hx (P < 0.05 vs. Hx). p-Bcl-xl density was 29.6 ± 1.5 Nx, 50.6 ± 7.4 Hx and 32.1 ± 0.1 Clo + Hx (P < 0.05 vs. Hx). p-Bax density was 38.6 ± 16.2 Nx, 46.1 ± 5.5 Hx and 41.6 ± 1.9 Clo + Hx groups (P = NS). p-Bad was 66.7 ± 12.8 Nx, 71.2 ± 6.8 Hx and 78.7 ± 22.5 Clo + Hx groups (P = NS). Results showed that clonidine administration prior to hypoxia prevents the hypoxia-induced increased nuclear Ca²⁺-influx and increased phosphorylation of Bcl-2 and Bcl-xl while phosphorylation of Bad and Bax was not altered. We conclude that post-translational modification of anti-apoptotic proteins Bcl-2 and Bcl-xl during hypoxia is nuclear Ca²⁺-influx-dependent. We propose that blockade of nuclear Ca²⁺-influx that prevents phosphorylation of antiapoptotic proteins may become a neuroprotective strategy.     

Influences of ssDNA-RecA Filament Length on the Fidelity of Homologous Recombination

Chromosomal double-strand breaks can be accurately repaired by homologous recombination, but genomic rearrangement can result if the repair joins different copies of a repeated sequence. Rearrangement can be advantageous or fatal. During repair, a broken double-stranded DNA (dsDNA) is digested by the RecBCD complex from the 5′ end, leaving a sequence gap that separates two 3′ single-stranded DNA (ssDNA) tails. RecA binds to the 3′ tails forming helical nucleoprotein filaments. A three-strand intermediate is formed when a RecA-bound ssDNA with L nucleotides invades a homologous region of dsDNA and forms a heteroduplex product with a length ≤ L bp. The homology dependent stability of the heteroduplex determines how rapidly and accurately homologous recombination repairs double-strand breaks. If the heteroduplex is sufficiently sequence matched, repair progresses to irreversible DNA synthesis. Otherwise, the heteroduplex should rapidly reverse. In this work, we present in vitro measurements of the L dependent stability of heteroduplex products formed by filaments with 90 ≤ L ≤ 420 nt, which is within the range observed in vivo. We find that without ATP hydrolysis, products are irreversible when L > 50 nt. In contrast, with ATP hydrolysis when L < 160 nt, products reverse in < 30 seconds; however, with ATP hydrolysis when L ≥ 320 nt, some products reverse in < 30 seconds, while others last thousands of seconds. We consider why these two different filament length regimes show such distinct behaviors. We propose that the experimental results combined with theoretical insights suggest that filaments with 250 ≲ L ≲ 8500 nt optimize DSB repair.     

SIRT2 induces the checkpoint kinase BubR1 to increase lifespan

Mice overexpressing the mitotic checkpoint kinase gene BubR1 live longer, whereas mice hypomorphic for BubR1 (BubR1^H/H) live shorter and show signs of accelerated aging. As wild‐type mice age, BubR1 levels decline in many tissues, a process that is proposed to underlie normal aging and age‐related diseases. Understanding why BubR1 declines with age and how to slow this process is therefore of considerable interest. The sirtuins (SIRT1‐7) are a family of NAD⁺‐dependent deacetylases that can delay age‐related diseases. Here, we show that the loss of BubR1 levels with age is due to a decline in NAD⁺ and the ability of SIRT2 to maintain lysine‐668 of BubR1 in a deacetylated state, which is counteracted by the acetyltransferase CBP. Overexpression of SIRT2 or treatment of mice with the NAD⁺ precursor nicotinamide mononucleotide (NMN) increases BubR1 abundance in vivo. Overexpression of SIRT2 in BubR1^H/H animals increases median lifespan, with a greater effect in male mice. Together, these data indicate that further exploration of the potential of SIRT2 and NAD⁺ to delay diseases of aging in mammals is warranted.     

Association of IL-10-1082 promoter polymorphism with susceptibility to gastric cancer: evidence from 22 case–control studies

Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95% CI = 0.335–0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95% CI = 0.506–0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328–0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527–0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520–0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140–0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374–0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk.     

Multi‐spectroscopic and molecular dynamics simulations investigation of the binding mechanism of polybrominated diphenyl ethers to hen egg white lysozyme

Three PBDEs (BDE25, BDE47, and BDE154) were selected to investigate the interactions between PBDEs and hen egg white lysozyme (HEWL) by molecular modeling, fluorescence spectroscopy, and FT‐IR spectra. The docking results showed that hydrogen bonds were formed between BDE25 and residue TRP63 and between BDE47 and TRP63 with bond lengths of 2.178 Å and 2.146 Å, respectively. The molecular dynamics simulations indicated that van der Waals forces played a predominant role in the binding of three PBDEs to HEWL. The observed fluorescence quenching can be attributed to the formation of complexes between HEWL and PBDEs, and the quenching mechanism is a static quenching. According to Förster's non‐radiative energy transfer theory, the binding distances r were < 7 nm, indicating a high probability of energy transfer from HEWL to the three PBDEs. The synchronous fluorescence showed that the emission maximum wavelength of tryptophan (TRP) residues emerged a red‐shift. FT‐IR spectra indicated that BDE25, BDE47 and BDE154 induced the α‐helix percentage of HEWL decreased from 32.70% ± 1.64% to 28.27% ± 1.41%, 27.50% ± 1.38% and 29.78% ± 1.49%, respectively, whereas the percentage of random coil increased from 26.67% ± 1.33% to 27.60% ± 1.38%, 29.18% ± 1.46% and 30.59% ± 1.53%, respectively.     

Dose-response relationship between plasma epinephrine concentration and alveolar liquid clearance in dogs

Previously, alveolar liquid clearance (ALC) wasobserved to increase in a canine model of neurogenic pulmonary edema(NPE) by adrenal epinephrine (S. M. Lane, K. C. Maender, N. E. Awender, and M. B. Maron. Am. J. Respir. Crit. CareMed. 158: 760-768, 1998). In this study thedose-response relationship between plasma epinephrine concentration andALC was determined in anesthetized dogs by infusing epinephrine toproduce plasma concentrations of 256 ± 37, 1,387 ± 51, 15,737 ± 2,161, and 363,997 ± 66,984 (SE) pg/ml(n = 6 for each concentration) for 4 hand measuring the resultant ALC. The latter was determined by massbalance after instillation of autologous plasma into a lower lung lobe.These plasma concentrations produced ALCs of 14.3 ± 1.2, 20.5 ± 1.9, 30.1 ± 1.5, and 37.9 ± 2.7% of the instilledvolume, respectively. ALC after the lowest infusion rate was notdifferent from that previously observed under baseline conditions(14.1 ± 2.1%), whereas in a previous study of NPE,plasma epinephrine concentration increased to 7,683 ± 687 pg/ml andALC was 30.4 ± 1.6%. These data indicate that, during recoveryfrom canine NPE, ALC is not maximally stimulated and suggest that itmight be possible to pharmacologically produce further increases in therate of resolution of this form of edema.

     

Phytohemagglutinin facilitates the aggregation of blastomere pairs from Day 5 donor embryos with Day 4 host embryos for chimeric bovine embryo multiplication

Multiplication of bovine embryos by the production of aggregation chimeras is based on the concept that few blastomeres of a donor embryo form the inner cell mass (ICM) and thus the embryo proper, whereas cells of a host embryo preferentially contribute to the trophectoderm (TE), the progenitor cells of the embryonic part of the placenta. We aggregated two fluorescent blastomeres from enhanced green fluorescent protein (eGFP) transgenic Day 5 morulae with two Day 4 embryos that did not complete their first cleavage until 27 hours after IVF and tested the effect of phytohemagglutinin-L (PHA) on chimeric embryo formation. The resulting blastocysts were characterized by differential staining of cell lineages using the TE-specific factor CDX2 and confocal laser scanning microscopy to facilitate the precise localization of eGFP-positive cells. The proportions of blastocyst development of sandwich aggregates with (n = 99) and without PHA (n = 46) were 85.9% and 54.3% (P < 0.05), respectively. Epifluorescence microscopy showed that the proportion of blastocysts with eGFP-positive cells in the ICM was higher in the PHA group than in the no-PHA group (40% vs. 16%; P < 0.05). Confocal laser scanning microscopy revealed that the total cell numbers of blastocysts from the PHA group of aggregation chimeras (n = 17; 207.8 ± 67.3 [mean ± standard deviation]) were higher (P < 0.05) than those of embryos without ZP and exposed to PHA (n = 30; 159.6 ± 42.2) and of handling control embryos (n = 19; 176.9 ± 53.3). The same was true for ICM cell counts (56.5 ± 22.0 vs. 37.7 ± 14.2 and 38.7 ± 12.4) and TE cell counts (151.2 ± 58.0 vs. 121.9 ± 37.4 and 138.3 ± 53.0), whereas the ICM/total cell number ratio was not different between the groups. Of the 17 chimeric blastocysts analyzed by confocal laser scanning microscopy, nine had eGFP-positive cells (three of them in the ICM, three in the TE, and three in both lineages). When integration in the ICM occurred, the number of eGFP-positive cells in this compartment was 8.3 ± 2.3 (mean ± standard error of the mean). We conclude that PHA is advantageous for the formation of aggregation chimeras, but the approach tested in the present study with only two donor blastomeres and two host embryos did not result in multiplication of genetically valuable donor embryos.