VGLUT2-dependent sensory neurons in the TRPV1 population regulate pain and itch

The natural response to itch sensation is to scratch, which relieves the itch through an unknown mechanism. Interaction between pain and itch has been frequently demonstrated, and the selectivity hypothesis of itch, based on data from electrophysiological and behavioral experiments, postulates the existence of primary pain afferents capable of repressing itch. Here, we demonstrate that deletion of vesicular glutamate transporter (VGLUT) 2 in a subpopulation of neurons partly overlapping with the vanilloid receptor (TRPV1) primary afferents resulted in a dramatic increase in itch behavior accompanied by a reduced responsiveness to thermal pain. The increased itch behavior was reduced by administration of antihistaminergic drugs and by genetic deletion of the gastrin-releasing peptide receptor, demonstrating a dependence on VGLUT2 to maintain normal levels of both histaminergic and nonhistaminergic itch. This study establishes that VGLUT2 is a major player in TRPV1 thermal nociception and also serves to regulate a normal itch response.     

Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor

Imidazo[1,2-a]pyridines were identified via their shape and electrostatic similarity as novel positive allosteric modulators of the metabotropic glutamate 2 receptor. The subsequent synthesis and SAR are described. Potent, selective and metabolically stable compounds were found representing a promising avenue for current further studies.     

Moose summer and winter diets along a large scale gradient of forage availability in southern Norway

Studies on dietary functional responses in large herbivores are traditionally conducted by following individual animals. The method is very time-consuming, and hence, typically provides only a narrow array of forage species compositions. Here we use a range level approach to look at moose (Alces alces) selectivity for and utilization of forage species in relation to availability in both summer and winter. We compare 12 Norwegian ranges representing a large scale gradient in plant communities. The most important forage species in the diet were birches (Betula spp., comprising 43% of all trees browsed in summer and 27% in winter), rowan (Sorbus aucuparia, 25% of trees browsed in summer, 37% in winter), and bilberry (Vaccinum myrtillus, 42% of herbaceous epidermal fragments in summer feces). Selectivity for birches was positively related to its availability and negatively related to availability of rowan, Salix spp., and aspen (Populus tremula) together (all more selected for than birches). Multiple regression models including availability of several forage species were thus superior to single-species models in explaining the diet content of main forage plants. Selectivity for birches was also stronger in summer than in winter, while the opposite pattern was found for rowan. The finding is relevant for our evaluation of the quality of summer and winter ranges, and hence, their relative influence on population productivity. Our study underlines the need to incorporate species composition of available forage when quantifying dietary functional responses in selective herbivores such as moose. Furthermore, care should be taken when extrapolating data on moose diet across ranges or seasons.     

Macronutrient balancing in free‐ranging populations of moose

At northern latitudes, large spatial and temporal variation in the nutritional composition of available foods poses challenges to wild herbivores trying to satisfy their nutrient requirements. Studies conducted in mostly captive settings have shown that animals from a variety of taxonomic groups deal with this challenge by adjusting the amounts and proportions of available food combinations to achieve a target nutrient balance. In this study, we used proportions‐based nutritional geometry to analyze the nutritional composition of rumen samples collected in winter from 481 moose (Alces alces) in southern Sweden and examine whether free‐ranging moose show comparable patterns of nutrient balancing. Our main hypothesis was that wild moose actively regulate their rumen nutrient composition to offset ecologically imposed variation in the nutritional composition of available foods. To test this, we assessed the macronutritional composition (protein, carbohydrates, and lipids) of rumen contents and commonly eaten foods, including supplementary feed, across populations with contrasting winter diets, spanning an area of approximately 10,000 km². Our results suggest that moose balanced the macronutrient composition of their rumen, with the rumen contents having consistently similar proportional relationship between protein and nonstructural carbohydrates, despite differences in available (and eaten) foods. Furthermore, we found that rumen macronutrient balance was tightly related to ingested levels of dietary fiber (cellulose and hemicellulose), such that the greater the fiber content, the less protein was present in the rumen compared with nonstructural carbohydrates. Our results also suggest that moose benefit from access to a greater variety of trees, shrubs, herbs, and grasses, which provides them with a larger nutritional space to maneuver within. Our findings provide novel theoretical insights into a model species for ungulate nutritional ecology, while also generating data of direct relevance to wildlife and forest management, such as silvicultural or supplementary feeding practices.     

Mutations in the Small GTPase Gene RAB39B Are Responsible for X-linked Mental Retardation Associated with Autism, Epilepsy, and Macrocephaly

Human Mental Retardation (MR) is a common and highly heterogeneous pediatric disorder affecting around 3% of the general population; at least 215 X-linked MR (XLMR) conditions have been described, and mutations have been identified in 83 different genes, encoding proteins with a variety of function, such as chromatin remodeling, synaptic function, and intracellular trafficking. The small GTPases of the RAB family, which play an essential role in intracellular vesicular trafficking, have been shown to be involved in MR. We report here the identification of mutations in the small GTPase RAB39B gene in two male patients. One mutation in family X (D-23) introduced a stop codon seven amino acids after the start codon (c.21C > A; p.Y7X). A second mutation, in the MRX72 family, altered the 5′ splice site (c.215+1G > A) and normal splicing. Neither instance produced a protein. Mutations segregate with the disease in the families, and in some family members intellectual disabilities were associated with autism spectrum disorder, epileptic seizures, and macrocephaly. We show that RAB39B, a novel RAB GTPase of unknown function, is a neuronal-specific protein that is localized to the Golgi compartment. Its downregulation leads to an alteration in the number and morphology of neurite growth cones and a significant reduction in presynaptic buttons, suggesting that RAB39B is required for synapse formation and maintenance. Our results demonstrate developmental and functional neuronal alteration as a consequence of downregulation of RAB39B and emphasize the critical role of vesicular trafficking in the development of neurons and human intellectual abilities.     

Discrepancy between the <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>effects of murine mesenchymal stem cells on T-cell proliferation and collagen-induced arthritis

Introduction  

The goal of this study is to analyze the potential immunosuppressive properties of mesenchymal stem cells (MSC) on T cell proliferation and in collagen-induced arthritis (CIA). An additional aim is to investigate the role of interferon-γ (IFN-γ) in these processes.     

Somatic embryogenesis from mature <Emphasis Type="Italic">Bambusa balcooa</Emphasis> Roxburgh as basis for mass production of elite forestry bamboos

A reliable protocol for mass propagation via somatic embryogenesis in mature bamboos has been established using pseudospikelets of Bambusa balcooa. Fourty percent of the explants gave rise to multiple regenerants within 4 months. This conversion rate is sufficiently high to use the process in commercial mass production. Further, shoot apical meristems can also be used as primary explants without lost of efficiency. Regenerated plants were uniform and identical to the mother plant and to plants obtained by axillary branching with respect to growth characteristics and morphology. Furthermore, epigenetic changes could not be detected by Methylation Sensitive AFLP (MSAP). During the complete process no changes in ploidy level could be observed. The process allows for a cost reduction for this tropical bamboo for forestry of up to 57% compared to micropropagation via axillary branching. For the first time, a reliable process based on somatic embryogenesis has been developed that is well suited for commercial micropropagation of elite mature bamboos.     

Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism

In primary hyperparathyroidism (PHPT), excess PTH secretion by adenomatous or hyperplastic parathyroid glands leads to elevated serum [Ca(2+)]. Patients present complex symptoms of muscular fatigue, various neuropsychiatric, neuromuscular, and cardiovascular manifestations, and, in advanced disease, kidney stones and metabolic bone disease. Our objective was to characterize changes in muscle and hematopoietic gene expression in patients with reversible mild PHPT after parathyroidectomy and possibly link molecular pathology to symptoms. Global mRNA profiling using Affymetrix gene chips was carried out in biopsies obtained before and 1 yr after parathyroidectomy in seven patients discovered by routine blood [Ca(2+)] screening. The tissue distribution of PTH receptor (PTHR1 and PTHR2) mRNAs were quantitated using real-time RT-PCR in unrelated persons to define PTH target tissues. Of about 10,000 expressed genes, 175 muscle, 169 hematological, and 99 bone-associated mRNAs were affected. Notably, the major part of muscle-related mRNAs was increased whereas hematological mRNAs were predominantly decreased during disease. Functional and molecular network analysis demonstrated major alterations of several tissue characteristic groups of mRNAs as well as those belonging to common cell signaling and major metabolic pathways. PTHR1 and PTHR2 mRNAs were more abundantly expressed in muscle and brain than in hematopoietic cells. We suggest that sustained stimulation of PTH receptors present in brain, muscle, and hematopoietic cells have to be considered as one independent, important cause of molecular disease in PHPT leading to profound alterations in gene expression that may help explain symptoms like muscle fatigue, cardiovascular pathology, and precipitation of psychiatric illness.     

Mobility of individual roach <Emphasis Type="Italic">Rutilus rutilus</Emphasis> (L.) in three weir-fragmented Belgian rivers

Adult roach Rutilus rutilus (L.) (N = 24; 19.9–36.1 cm FL) from three highly fragmented Belgian rivers were tagged with surgically implanted radio transmitters. Their seasonal movements were observed from March to August 2004 (circum reproduction period) in river stretches delimited by two physical barriers. In the three rivers, roach displayed similar patterns of movements which were mainly influenced by the date of observation (movements increased in late April–May) and water temperature (travel distances were more important when water temperature ranged between 10°C and 14°C). Roach sometimes cleared physical obstacles. The mean distances travelled in each river were relatively short (max. 2.5 km) and mainly influenced by the length of the study reach, which was delimited by physical barriers.