Capture and medetomidine-ketamine anesthesia of free-ranging wolverines (Gulo gulo)

Capture and anesthesia with medetomidine-ketamine were evaluated in free-ranging wolverines (Gulo gulo) immobilized for marking with radiocollars or intraperitoneal radiotransmitters in Norrbotten, Sweden, during early June 2004 and 2005. Twelve juvenile wolverines were captured by hand and injected with 0.14 +/- 0.03 mg/kg (mean +/- SD) medetomidine and 7.5 +/- 2.0 mg/kg ketamine. Twelve adult wolverines were darted from a helicopter or the ground, or captured by hand. Adults received 0.37 +/- 0.06 mg/kg medetomidine and 9.4 +/- 1.4 mg/kg ketamine. Arterial blood samples were collected between 15 min and 30 min and between 45 min and 60 min after drug administration and immediately analyzed for selected hematologic and plasma variables. Hyperthermia was recorded initially in one juvenile wolverine and 11 adults. Rectal temperature, heart rate, and lactate decreased significantly during anesthesia, whereas hemoglobin oxygen saturation, pH, partial pressure of arterial carbon dioxide, and base excess increased. Adult wolverines darted from a helicopter had a significantly higher rectal temperature, higher glucose and hematocrit values, and a lower heart rate than juveniles captured by hand. Impaired arterial oxygenation was evident in all wolverines. This study provides baseline data on physiologic variables in adult and juvenile wolverines captured with different methods and anesthetized with medetomidine-ketamine.     

High-Fat Diet Reduces the Formation of Butyrate,but Increases Succinate,Inflammation, Liver Fat and Cholesterol in Rats,while Dietary Fibre Counteracts These Effects

Introduction

Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation.

Objective

To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks.

Material and Methods

Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks.

Results and Discussion

Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.     

Frequency Change Detection in Human Auditory Cortex

We offer a model of how human cortex detects changes in the auditory environment. Auditory change detection has recently been the object of intense investigation via the mismatch negativity (MMN). MMN is a preattentive response to sudden changes in stimulation, measured noninvasively in the electroencephalogram (EEG) and the magnetoencephalogram (MEG). It is elicited in the oddball paradigm, where infrequent deviant tones intersperse a series of repetitive standard tones. However, little apart from the participation of tonotopically organized auditory cortex is known about the neural mechanisms underlying change detection and the MMN. In the present study, we investigate how poststimulus inhibition might account for MMN and compare the effects of adaptation with those of lateral inhibition in a model describing tonotopically organized cortex. To test the predictions of our model, we performed MEG and EEG measurements on human subjects and used both small- (<1/3 octave) and large- (>5 octaves) frequency differences between the standard and deviant tones. The experimental results bear out the prediction that MMN is due to both adaptation and lateral inhibition. Finally, we suggest that MMN might serve as a probe of what stimulus features are mapped by human auditory cortex.     

Comparative proteome cataloging of Lactobacillus rhamnosus strains GG and Lc705

The present study reports an in-depth proteome analysis of two Lactobacillus rhamnosus strains, the well-known probiotic strain GG and the dairy strain Lc705. We used GeLC-MS/MS, in which proteins are separated using 1-DE and identified using nanoLC-MS/MS, to generate high-quality protein catalogs. To maximize the number of identifications, all data sets were searched against the target databases using two search engines, Mascot and Paragon. As a result, over 1600 high-confidence protein identifications, covering nearly 60% of the predicted proteomes, were obtained from each strain. This approach enabled identification of more than 40% of all predicted surfome proteins, including a high number of lipoproteins, integral membrane proteins, peptidoglycan associated proteins, and proteins predicted to be released into the extracellular environment. A comparison of both data sets revealed the expression of more than 90 proteins in GG and 150 in Lc705, which lack evolutionary counterparts in the other strain. Differences were noted in proteins with a likely role in biofilm formation, phage-related functions, reshaping the bacterial cell wall, and immunomodulation. The present study provides the most comprehensive catalog of the Lactobacillus proteins to date and holds great promise for the discovery of novel probiotic effector molecules.     

Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects

Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects.     

The C-terminus of dUTPase: observation on flexibility using NMR

The dynamics of the C-terminus of the dUTPases from Escherichia coli and equine infectious anaemia virus (EIAV) were studied by 1H-(15)N nuclear magnetic resonance spectroscopy. The two enzymes differ with regard to flexibility in the backbone of the 15 most C-terminal amino acid residues, some of which are conserved and essential for enzymic activity. In the bacterial enzyme, the residues closest to the C-terminus are highly flexible and display a correlation time in the nanosecond time range. No similar high flexibility could be detected for the C-terminal part of EIAV dUTPase, indicating a different time range of flexibility.