Male hamsters discriminate estrous state from vaginal secretions and individuals from flank marks

It is clear that male hamsters discriminate between the odors of individual, conspecific females, as shown by using habituation-dishabituation methods. However, it is not clear from past research whether male hamsters are able to discriminate between the odors of estrous and non-estrous females. A series of habituation-dishabituation experiments was conducted to determine whether males discriminated between different estrous cycle states using two female secretions, those from flank-glands and vaginal secretions. We found that, when habituated to a female flank-gland secretion, males discriminated between this female and a second female on the test trial, whether both were in estrus, both were in diestrus, or one was in estrus and the other in diestrus. There was no difference, however, in the magnitude of their dishabituation response toward flank-gland odors of females in estrus and diestrus. These results suggest that males use flank-gland odors to gain information primarily about individuals. When tested with vaginal secretions in habituation-dishabituation tests, males only showed differences in investigation when the second female was in estrus, indicating that males use vaginal secretions to gain information primarily about reproductive state.     

Can captivity lead to inter-species mating in two Mesocricetus hamster species?

In two closely related species, females generally prefer conspecific males over heterospecific males. We found that estrous (but not diestrous) female Syrian hamsters Mesocricetus auratus prefer the odors of conspecific males to odors of Turkish hamsters Mesocricetus brandti . However, female Syrian hamsters are not aggressive toward male Turkish hamsters and will readily mate with them. We hypothesize that many generations in captivity led to a reduction in females' ability to avoid inter-species mating, possibly related to the heightened sexual receptivity observed in Mesocricetus hamsters in captivity. To test this hypothesis, we replicated a study carried out with female Turkish hamsters soon after the current laboratory stock of this species was established. In that study, female Turkish hamsters showed lordosis toward male Syrian hamsters in only 20% of interactions and attacked heterospecific males in 80% of the pairings. Using animals descended from that original colony (after many generations in captivity and certain episodes of inbreeding), 100% of female Turkish hamsters mated with heterospecific males and none showed aggression toward heterospecific males. Thus female avoidance of inter-specific mating may be affected by captive rearing conditions.     

3-(Arylamino)-3-phenylpropan-2-olamines as a new series of dual norepinephrine and serotonin reuptake inhibitors

A series of 3-(arylamino)-3-phenylpropan-2-olamines was prepared and screened for their ability to inhibit monoamine reuptake. A number of analogues displayed significant dual norepinephrine and serotonin reuptake inhibition. Compounds in this class exhibited minimal affinity for the dopamine transporter.     

Hydroxylation of l-proline to cis-3-hydroxy-l-proline by recombinant Escherichia coli expressing a synthetic l-proline-3-hydroxylase gene

A synthetic gene encoding a Streptomyces l-proline-3-hydroxylase was constructed and used to produce the hydroxylase protein in recombinant Escherichia coli. A fermentation process for growth of this recombinant E. coli for enzyme production was scaled-up to 250 L. A biotransformation process was developed using cell suspensions of the recombinant E. coli and subsequently scaled-up to 10 L for conversion of l-proline to cis-3-hydroxy-l-proline. A reaction yield of 85 M% and d.e. of 99.9% was obtained for cis-3-hydroxy-l-proline.     

Spatial distribution of the active surveillance of sheep scrapie in Great Britain: an exploratory analysis

Background  

This paper explores the spatial distribution of sampling within the active surveillance of sheep scrapie in Great Britain. We investigated the geographic distribution of the birth holdings of sheep sampled for scrapie during 2002 – 2005, including samples taken in abattoir surveys (c. 83,100) and from sheep that died in the field ("fallen stock", c. 14,600). We mapped the birth holdings by county and calculated the sampling rate, defined as the proportion of the holdings in each county sampled by the surveys. The Moran index was used to estimate the global spatial autocorrelation across Great Britain. The contributions of each county to the global Moran index were analysed by a local indicator of spatial autocorrelation (LISA).     

Randomized Trial of a Behavioral Weight Loss Intervention for Low‐income Women: The Weight Wise Program

Low‐income women in the United States have the highest rates of obesity, yet they are seldom included in weight loss trials. To address this research gap, components of two evidence‐based weight loss interventions were adapted to create a 16‐week intervention for low‐income women (Weight Wise Program), which was evaluated in a randomized trial with the primary outcome of weight loss at 5‐month follow‐up. Participants were low‐income women (40–64 years) with a BMI of 25–45. Of 143 participants, 72 were randomized to the Weight Wise Program (WWP) and 71 to the Control Group (CG). Five‐month follow‐up data were obtained from 64 (89%) WWP and 62 (87%) CG participants. With baseline values carried forward for missing data, WWP participants had a weight change of ?3.7 kg compared to 0.7 kg in the CG (4.4 kg difference, 95% confidence interval (CI), 3.2–5.5, P < 0.001). For systolic blood pressure (SBP), change in the WWP was ?6.5 mm Hg compared to ?0.4 mm Hg among controls (6.2 mm Hg difference, 95% CI, 1.7–10.6, P = 0.007); for diastolic BP (DBP), changes were ?4.1 mm Hg for WWP compared to ?1.3 mm Hg for controls (2.8 mm Hg difference, 95% CI, 0.0–5.5, P = 0.05). Of the 72 WWP participants, 64, 47, and 19% lost at least 3, 5, and 7% of their initial body weight, respectively. In conclusion, the WWP was associated with statistically significant and clinically important short‐term weight loss.     

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background

Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world''s population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration.

Methodology/Principal Findings

Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM''s novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H₃₇R_v and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H₃₇R_v with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)thiazole-4-carboxylate inhibited mtFabH with an IC₅₀ of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism.

Conclusions/Significance

These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents.