Levels of selection

Methoxychlor (MXC) reduces fertility in female rodents, decreases antral follicle numbers, and increases atresia through oxidative stress pathways. MXC also inhibits antral follicle growth in vitro. The mechanism by which MXC inhibits growth of follicles is unknown. The growth of follicles is controlled, in part, by cell cycle regulators. Thus, we tested the hypothesis that MXC inhibits follicle growth by reducing the levels of selected cell cycle regulators. Further, we tested whether cotreatment with an antioxidant, N-acetyl cysteine (NAC), prevents the MXC-induced reduction in cell cycle regulators. For in vivo studies, adult cycling CD-1 mice were dosed with MXC or vehicle for 20 days. Treated ovaries were subjected to immunohistochemistry for proliferating cell nuclear antigen (PCNA) staining. For in vitro studies, antral follicles isolated from adult cycling CD-1 mouse ovaries were cultured with vehicle, MXC, and/or NAC for 48, 72 and 96 hrs. Levels of cyclin D2 (Ccnd2) and cyclin dependant kinase 4 (Cdk4) were measured using in vivo and in vitro samples. The results indicate that MXC decreased PCNA staining, and Ccnd2 and Cdk4 levels compared to controls. NAC co-treatment restored follicle growth and expression of Ccnd2 and Cdk4. Collectively, these data indicate that MXC exposure reduces the levels of Ccnd2 and Cdk4 in follicles, and that protection from oxidative stress restores Ccnd2 and Cdk4 levels. Therefore, MXC-induced oxidative stress may decrease the levels of cell cycle regulators, which in turn, results in inhibition of the growth of antral follicles.

Protocells are hypothesised as a transitional phase in the origin of life, prior to the evolution of fully functional prokaryotic cells. The work reported here is being done in the context of the PACE project, which is investigating the fabrication of artificial protocells de novo. We consider here the important open question of whether or how articifial protocells (if or when they are successfully fabricated) might be applied as “computing” devices—what sort of computing might they be suitable for, and how might they be “programmed”? We also ...

During the Minnesota Children's Pesticide Exposure Study (MNCPES), comparisons were made between the insecticide/herbicide loadings obtained with two household dust/insecticide or herbicide samplers: the Edwards and Lioy (EL) press sampler (used for dust collection from carpets or other surfaces) and the Lioy, Wainman and Weisel (LWW) surface wipe sampler. The results were compared with hand rinse levels, and urine metabolite levels obtained from 102 children (ages 3–13). All measurements were made during a 1-week sampling period, and information was obtained on household pesticide use and each child's activities. Of the homes, <5% had recent spot uses of a pesticide but none had recent general applications. The analyses focused primarily on atrazine (a herbicide), and malathion, diazinon, and chlorpyrifos (insecticides). Metabolites were measured for atrazine, malathion and chlorpyrifos. The atrazine levels obtained using the EL indicate that this compound was transporte...

Marketing places though a relatively new activity has grown in importance as countries, regions and individual destinations such as cities compete with one another to attract investment and visitors. Almost every other region or important city will have at least one basic strategy to market itself for one or the other reason: investors or visitors. The dimension of marketing grows complex when a capital city needs being promoted. Recently for Romania, marketing its capital city using its identity and personality is a matter of crucial importance when considering competition. The identity of the capital city of an European country member could prove itself a challenging process given the fact that there are several common grounds, including uniformity, the group member would gave. As a result, individual, independent marketing becomes a necessity in order to differentiate and make the capital city visible and recognisable. Competition is the other aspect requiring clear, visible identity. In order to compete effectively, it is essential to identify the critical success factors and ensure these are incorporated into one's strategic planning. Even from a tourist point of view place and destination marketing indicate that image and identity play an important role in differentiating between similar alternatives. This paper is focusing on action undertaken so far by Bucharest, the capital city of Romania, to market itself and to build a brand. It is also presenting experts opinion and comments on results, assessing the place branding process, discussing its stages and situation as they are at present.

During the Minnesota Children's Pesticide Exposure Study ( MNCPES ) , comparisons were made between the insecticide / herbicide loadings obtained with two household dust / insecticide or herbicide samplers: the Edwards and Lioy ( EL ) press sampler ( used for dust collection from carpets or other surfaces ) and the Lioy, Wainman and Weisel ( LWW ) surface wipe sampler. The results were compared with hand rinse levels, and urine metabolite levels obtained from 102 children ( ages 3 ± 13 ) . All measurements were made during a 1 -week sampling period, and information was obtained on household pesticide use and each child's activities. Of the homes, < 5% had recent spot uses of a pesticide but none had recent general applications. The analyses focused primarily on atrazine ( a herbicide ) , and malathion, diazinon, and chlorpyrifos ( insecticides ) . Metabolites were measured for atrazine, malathion and chlorpyrifos. The atrazine levels obtained using the EL indicate that this compound was transported into the home by an unquantified transport mechanism ( e.g. tracking of soil ) . Two malathion hand rinse values exceeded > 170 ng / cm 2 , suggesting that since indoor surface levels were low, these children had other sources of exposure. Atrazine, chlorpyrifos and malathion were detectable in > 30% of the homes by the EL, LWW or hand rinse. Only chlorpyrifos had detectable levels in !50% of the samples for all types, i.e. compound or metabolite, which is consistent with it being a common household pesticide. The median ( and maximum ) chlorpyrifos levels for the EL surface, EL carpet, LWW surface ( two rooms ) , hand rinse, and urine metabolites were: 0.07 ( 32.6 ) ng / cm 2 ; 0.07 ( 44.5 ) ng / cm 2 ; 0.34 ( 3.64 ) ng / cm 2 ; 0.42 ( 14.4 ) ng / cm 2 ; 0.03 ( 2.14 ) ng / hand and 6.9 ( 59.0 ) g / g, respectively. A strong correlation was found for chlorpyrifos between the EL surface and carpet samples. Chlorpyrifos levels detected by LWW had a different distribution and concentration range than the EL, indicating that it collected more than the surface dislodgeable insecticide. EL was directly comparable to the hand rinse or urine levels, but only the LWW had a weak correlation with hand rinse levels, suggesting that the children had other sources of chlorpyrifos exposure. Thus, mechanistic exposure studies are needed to more accurately establish exposure ± dose relationships in residential settings.

Aerobic vagin itis is a syndrome due to the alteration of the vaginal biota with different bacterial, clinical and immunological characteristics with respect to the classic form of vaginitis. Fro m a clinical point of v iew the infection is characterized by the presence of yello wish, bad-smelling secretions, redness, itching, congestion of the vaginal mucosa and different levels of dyspareunia, to xic leucocytes and parabasal epitheliocytes, negative KOH test, and raised vaginal pH. We studied 243 pregnant women between the 16 th and the 39 th week of gestation who all underwent a vaginal swab and antibiogram. The presence of aerobic vagin itis was found in 147 pregnant wo men who then underwent pharmacological therapy together with their partners. Aerobic vaginit is is one of those diseases that is prevalently transmitted by sexual contact and if it is not diagnosed and treated early, during pregnancy can place the health of both the mother and the fetus at risk as it is associated with preterm birth, pPROM and chorioamn ionitis. It is therefore very important diagnosing it early and treating with a correct pharmacological therapy that, as can be seen from our study, reduces the adverse effects associated with these types of infections.

The aim of this paper was to analyze the levels of selected minerals consumption by the elderly. The investigation was carried out in May and June of 1999 with people between 75 and 80 years of age permanently living in urban and rural areas and small towns of the province of Warmia and Mazury. In total, 160 males and 194 females were examined. The average consumption of nutrients was estimated by the 24-hour interview method. After including the standard loss, it was compared with a consumption norm on a safe level. The average consumption of the selected minerals i.e. Mg, Zn and Cu was compared between the sex and environment groups including the selected classes of norm completion (2/3, 90 and 110%). The average consumption of magnesium, zinc and copper was obtained for 54-59, 61 and 81-96% of the examined people respectively. This indicates the high risk of minerals insufficiency (below 2/3 of the norm). The largest percentage of people (65-91% of the examined) endangered with the insufficiency of the analyzed micro-and macro elements was obtained among the males and the females living in a small town.

Background: Members of the small multidrug resistance (SMR) protein family are integral membrane proteins characterized by four α-helical transmembrane strands that confer resistance to a broad range of antiseptics and lipophilic quaternary ammonium compounds (QAC) in bacteria. Due to their short length and broad substrate profile, SMR proteins are suggested to be the progenitors for larger α-helical transporters such as the major facilitator superfamily (MFS) and drug/metabolite transporter (DMT) superfamily. To explore their evolutionary association with larger multidrug transporters, an extensive bioinformatics analysis of SMR sequences (> 300 Bacteria taxa) was performed to expand upon previous evolutionary studies of the SMR protein family and its origins. Results: A thorough annotation of unidentified/putative SMR sequences was performed placing sequences into each of the three SMR protein subclass designations, namely small multidrug proteins (SMP), suppressor of groEL mutations (SUG), and paired small multidrug resistance (PSMR) using protein alignments and phylogenetic analysis. Examination of SMR subclass distribution within Bacteria and Archaea taxa identified specific Bacterial classes that uniquely encode for particular SMR subclass members. The extent of selective pressure acting upon each SMR subclass was determined by calculating the rate of synonymous to non-synonymous nucleotide substitutions using Syn-SCAN analysis. SUG and SMP subclasses are maintained under moderate selection pressure in comparison to integron and plasmid encoded SMR homologues. Conversely, PSMR sequences are maintained under lower levels of selection pressure, where one of the two PSMR pairs diverges in sequence more rapidly than the other. SMR genomic loci surveys identified potential SMR efflux substrates based on its gene association to putative operons that encode for genes regulating amino acid biogenesis and QAC-like metabolites. SMR subclass protein transmembrane domain alignments to Bacterial/Archaeal transporters (BAT), DMT, and MFS sequences supports SMR participation in multidrug transport evolution by identifying common TM domains. Based on this study, PSMR sequences originated recently within both SUG and SMP clades through gene duplication events and it appears that SMR members may be evolving towards specific metabolite transport.

There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors. Membrane permeability of NNMT inhibitors was characterized using parallel artificial membrane permeability and Caco-2 cell assays. Selectivity was tested against structurally-related methyltransferases and nicotinamide adenine dinucleotide (NAD + ) salvage pathway enzymes. Effects of NNMT inhibitors on lipogenesis and intracellular levels of metabolites, including NNMT reaction product 1-methylnicotianamide (1-MNA) were evaluated in cultured adipocytes. Effects of a potent NNMT inhibitor on obesity measures and plasma lipid were assessed in diet-induced obese mice fed a high-fat diet. Methylquinolinium scaffolds with primary amine substitutions displayed high permeability from passive and active transport across membranes. Importantly, methylquinolinium analogues displayed high selectivity, not inhibiting related SAM-dependent methyltransferases or enzymes in the NAD + salvage pathway. NNMT inhibitors reduced intracellular 1-MNA, increased intracellular NAD

Background Genome-wide association studies (GWAS) based on linkage disequilibrium (LD) provide a promising tool for the detection and fine mapping of quantitative trait loci (QTL) underlying complex agronomic traits. In this study we explored the genetic basis of variation for the traits heading date, plant height, thousand grain weight, starch content and crude protein content in a diverse collection of 224 spring barleys of worldwide origin. The whole panel was genotyped with a customized oligonucleotide pool assay containing 1536 SNPs using Illumina&#39;s GoldenGate technology resulting in 957 successful SNPs covering all chromosomes. The morphological trait &quot;row type&quot; (two-rowed spike vs. six-rowed spike) was used to confirm the high level of selectivity and sensitivity of the approach. This study describes the detection of QTL for the above mentioned agronomic traits by GWAS. Results Population structure in the panel was investigated by various methods and six subgrou...

Aldose reductase (AR) is an enzyme of the polyol pathway implicated in long-term effect of diabetes mellitus. The development of new molecules as drugs for the inhibition of this enzyme is a growing area of research. Several in vivo and in vitro studies have been carried out to test the inhibitory effect of many organic compounds against AR, but the results have been limited due to their weak pharmacokinetic parameters and safety profile. In this study, molecular docking and molecular dynamics (MD) simulation were performed to establish the inhibitory effect of two critical bioactive compounds (astaxanthin and zeaxanthin) that were affirmed to be safe and powerful antioxidants. Docking studies revealed that both astaxanthin and zeaxanthin displays good binding affinity and inhibition to AR with binding energies of -5.88 kcal/mol and -5.63 kcal/mol, respectively. In contrast to epalrestat; the standard inhibitor having a binding energy of -5.62 kcal/mol. Amino acid residue analysis has shown that both compounds, including the standard inhibitor, bind to the same site due to their common interaction with Trp20 and Tyr48 at AR catalytic site. To complement molecular docking results, we performed MD simulations. The results show that the binding energies of the standard inhibitor, astaxanthin, and zeaxanthin are -134.3486 kJ/mol, -186.271 kJ/mol, and -123.557 kJ/mol, respectively. In both cases, astaxanthin displays better inhibition to AR followed by the standard inhibitor and zeaxanthin.

A method to measure genomic response to natural and artificial selection by means of genetic markers in livestock is proposed. Genomic response through several levels of selection was measured using sequential testing for distorted segregation of alleles among selected and nonselected sons, single-sperm typing, and a test with records for growth performance. Statistical power at a significance level of 0.05 was &gt;0.5 for a marker linked to a QTL with recombination fractions 0, 0.10, and 0.20 for detecting genomic responses for gene effects of 0.6, 0.7, and 1.0 phenotypic standard deviations, respectively. Genomic response to artificial selection in six commercial bull sire families comprising 285 half-sib sons selected for growth performance was measured using 282 genetic markers evenly distributed over the cattle genome. A genome-wide test using selected sons was significant (P &lt; 0.001), indicating that selection induces changes in the genetic makeup of commercial cattle popul...

Darwin described forces of selection acting upon individuals, but there remains a great deal of controversy about the exact status and definition of a biological individual. Recently some authors have argued that the individual is dispensable-that an inability to pin it down is not problematic because little rests on it anyway. The aim of this article is to show that there is a real problem of biological individuality, and an urgent need to arbitrate among the current plethora of solutions to it.

Objective: To evaluate the concentrations of metallothionein (MT) in giant mudskippers Periophthalmodon schlosseri (P. schlosseri) and to elucidate their potential use in bio monitoring of coastal environment. Methods: The giant mudskippers were collected from four sampling sites on the west coast of Peninsular Malaysia and analyzed for heavy metals -Cu, Zn and Cd, and MT concentrations in liver, gills and muscle by using an air-acetylene flame atomic absorption spectrophotometer, Perkin Elmer Analyst 800 and UV-Visible Recording Spectrophotometer Shimadzu UV-160 A Model, respectively. Results: One-way analysis of variance (ANOVA) with Duncan multiple comparisons of the measured metals and MT concentrations in the liver, gills and muscle of P. schlosseri were statistically significant (P < 0.05) between the sampling sites. Non-significant difference (P > 0.05) was observed between Cu concentrations in the gills and Cd concentration in the liver, gills, and muscle at all the four sampling sites. Zn concentration in the tissues was significantly different (P < 0.05) among the sampling sites. Statistically significant positive correlation (P < 0.05; r = 0.583) and negative correlation (P < 0.01; r = -0.737) were observed between MT concentration in muscle with Cu and Zn concentrations in muscle, respectively. Conclusions: The highest MT concentrations were found at sampling sites that mostly showed low metals concentrations in the tissues. The use of MT induction in P. schlosseri as a valuable biochemical tool for assessment of metals bioavailability and environmental impact needs further research to explore its feasibility as a biomarker of metal exposure.