The competitive cost of antibiotic resistance in Mycobacterium tuberculosis

Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.     

Quantitation of the main constituents of some authentic sesame seed oils of different origin

This paper describes the composition of sesame seed oils obtained from seeds collected from five countries that are major suppliers of traded sesame seed oil. Oils were extracted from the seeds using small-scale industry pressing equipment and analyzed using standard methods for fatty acids, fatty acids in the triglyceride 2-position, tocopherols and tocotrienols, triglycerides, sterols, steradienes, and iodine value. Values for the composition of the sterols, triglycerides, fatty acids, iodine value, and tocopherol composition were generally in good agreement with the results published elsewhere. All of the oils from roasted seeds contained low levels of the sterol degradation products stigmasta-3,5-diene and campesta-3,5-diene, which were probably formed by dehydration of the parent sterols during roasting.     

EPOXI at comet Hartley 2

Understanding how comets work--what drives their activity--is crucial to the use of comets in studying the early solar system. EPOXI (Extrasolar Planet Observation and Deep Impact Extended Investigation) flew past comet 103P/Hartley 2, one with an unusually small but very active nucleus, taking both images and spectra. Unlike large, relatively inactive nuclei, this nucleus is outgassing primarily because of CO(2), which drags chunks of ice out of the nucleus. It also shows substantial differences in the relative abundance of volatiles from various parts of the nucleus.     

Trophic action of leptin on hypothalamic neurons that regulate feeding

In adult mammals, the adipocyte-derived hormone leptin acts on the brain to reduce food intake by regulating the activity of neurons in the arcuate nucleus of the hypothalamus (ARH). Here, we report that neural projection pathways from the ARH are permanently disrupted in leptin-deficient (Lepob/Lepob) mice and leptin treatment in adulthood does not reverse these neuroanatomical defects. However, treatment of Lepob/Lepob neonates with exogenous leptin rescues the development of ARH projections, and leptin promotes neurite outgrowth from ARH neurons in vitro. These results suggest that leptin plays a neurotrophic role during the development of the hypothalamus and that this activity is restricted to a neonatal critical period that precedes leptin's acute regulation of food intake in adults.     

High-pressure creep of serpentine, interseismic deformation, and initiation of subduction

The supposed low viscosity of serpentine may strongly influence subduction-zone dynamics at all time scales, but until now its role could not be quantified because measurements relevant to intermediate-depth settings were lacking. Deformation experiments on the serpentine antigorite at high pressures and temperatures (1 to 4 gigapascals, 200 degrees to 500 degrees C) showed that the viscosity of serpentine is much lower than that of the major mantle-forming minerals. Regardless of the temperature, low-viscosity serpentinized mantle at the slab surface can localize deformation, impede stress buildup, and limit the downdip propagation of large earthquakes at subduction zones. Antigorite enables viscous relaxation with characteristic times comparable to those of long-term postseismic deformations after large earthquakes and slow earthquakes. Antigorite viscosity is sufficiently low to make serpentinized faults in the oceanic lithosphere a site for subduction initiation.     

Amlodipine: One of the main anti-hypertensive drugs in veterinary therapeutics

Amlodipine is a dihydropyridine compound and belongs to the pharmacological family of calcium channel blockers. It is one of the main treatments of systemic arterial hypertension in cats and its validity has been confirmed in several reports. Its beneficial effect on the peripheral and coronary vascular bed is due to immediate vasodilation and to a delayed anti-hypertrophic action. The aim of the present review is to highlight the clinically-relevant characteristics of amlodipine, especially regarding its mechanism of action, and to present the main clinical reports supporting its interest in veterinary cardiology.     

Evaluation of a romifidine constant rate infusion protocol with or without butorphanol for dentistry and ophthalmologic procedures in standing horses

ObjectiveTo compare the clinical usefulness of constant rate infusion (CRI) protocols of romifidine with or without butorphanol for sedation of horses.Study designProspective ‘blinded’ controlled trial using block randomization.AnimalsForty healthy Freiberger stallions.MethodsThe horses received either intravenous (IV) romifidine (loading dose: 80 μg kg^?1; infusion: 30 μg kg^?1 hour^?1) (treatment R, n = 20) or romifidine combined with butorphanol (romifidine loading: 80 μg kg^?1; infusion: 29 μg kg^?1 hour^?1, and butorphanol loading: 18 μg kg^?1; infusion: 25 μg kg^?1 hour^?1) (treatment RB, n = 20). Twenty-one horses underwent dentistry and ophthalmic procedures, while 19 horses underwent only ophthalmologic procedure and buccal examination. During the procedure, physiologic parameters and occurrence of head/muzzle shaking or twitching and forward movement were recorded. Whenever sedation was insufficient, additional romifidine (20 μg kg^?1) was administered IV. Recovery time was evaluated by assessing head height above ground. At the end of the procedure, overall quality of sedation for the procedure was scored by the dentist and anaesthetist using a visual analogue scale. Statistical analyses used two-way anova or linear mixed models as relevant.ResultsSedation quality scores as assessed by the anaesthetist were R: median 7.55, range: 4.9–9.0 cm, RB: 8.8, 4.7–10.0 cm, and by the dentist R: 6.6, 3.0–8.2 cm, RB: 7.9, 6.6–8.8 cm. Horses receiving RB showed clinically more effective sedation as demonstrated by fewer poor scores and a tendency to reduced additional drug requirements. More horses showed forward movement and head shaking in treatment RB than treatment R. Three horses (two RB, one R) had symptoms of colic following sedation.Conclusions and clinical relevanceThe described protocols provide effective sedation under clinical conditions but for dentistry procedures, the addition of butorphanol is advantageous.     

Supra-nutritional dietary intake of selenite and selenium yeast in normal and stressed rainbow trout (Oncorhynchus mykiss): Implications on selenium status and health responses

Commercial salmonid diets are not typically supplemented with selenium (Se) as they naturally contain relatively high levels of this essential trace element; however supplementation may be necessary to meet requirements during physical stress. Adopting an integrated approach by simultaneously determining Se status, various health parameters and interactions with other trace elements, this study aimed to determine the role of supra-supplemented selenite and Se-yeast (Selplex^®) on the growth and health of rainbow trout (Oncorhynchus mykiss), both under normal conditions and after exposure to chronic physical stress. Fish were fed one of seven diets; a basal un-supplemented diet (0.73 mg kg^− 1 Se) or diets supplemented with Se-yeast or sodium selenite to provide 2, 4, or 8 mg kg^− 1 Se for 10 weeks prior to subjection of daily handling and confinement stressors for seven days. Net whole body Se retention was significantly greater for Se-yeast than selenite at all levels. In normal conditions activities of hepatic glutathione peroxidase (GSH-Px) and thioredoxin reductase (Trx-R) indicate that Se requirements were met by the basal diet. Similarly, pre-stress supra-supplementation of selenite and Se-yeast did not affect oxidative status (total antioxidant capacity of serum and hepatic malondialdehyde), immuno-competence (respiratory burst activity, serum lysozyme, and leukocyte counts) or other haematological and growth parameters (nuclear abnormalities in erythrocytes, and specific growth rate). In contrast, the trend towards a higher GSH-Px post-stress in Se supplemented diets over the basal diet, particularly in Se-yeast fed fish, indicates that Se requirements may not be met by the un-supplemented practical diet in stressed fish. Seven days of chronic physical stress decreased whole body Se and increased GSH-Px activity signifying an increased Se utilisation. During stress Se status was more effectively maintained by Se-yeast than selenite. Increased hepatic lipid peroxidation in stressed fish fed 8 mg kg^− 1 selenite indicates a possible pro-oxidant effect of selenite. A positive interaction was observed between dietary selenite and whole body copper, but no such interaction was observed with Se-yeast. This study concludes that physical stressors can result in an elevated Se utilisation and consequently supplementation of commercial diets may be necessary such that Se reserves are available as a contingency for stress.