Complementary Roles of the Hippocampus and the Dorsomedial Striatum during Spatial and Sequence-Based Navigation Behavior

We investigated the neural bases of navigation based on spatial or sequential egocentric representation during the completion of the starmaze, a complex goal-directed navigation task. In this maze, mice had to swim along a path composed of three choice points to find a hidden platform. As reported previously, this task can be solved by using two hippocampal-dependent strategies encoded in parallel i) the allocentric strategy requiring encoding of the contextual information, and ii) the sequential egocentric strategy requiring temporal encoding of a sequence of successive body movements associated to specific choice points. Mice were trained during one day and tested the following day in a single probe trial to reveal which of the two strategies was spontaneously preferred by each animal. Imaging of the activity-dependent gene c-fos revealed that both strategies are supported by an overlapping network involving the dorsal hippocampus, the dorsomedial striatum (DMS) and the medial prefrontal cortex. A significant higher activation of the ventral CA1 subregion was observed when mice used the sequential egocentric strategy. To investigate the potential different roles of the dorsal hippocampus and the DMS in both types of navigation, we performed region-specific excitotoxic lesions of each of these two structures. Dorsal hippocampus lesioned mice were unable to optimally learn the sequence but improved their performances by developing a serial strategy instead. DMS lesioned mice were severely impaired, failing to learn the task. Our data support the view that the hippocampus organizes information into a spatio-temporal representation, which can then be used by the DMS to perform goal-directed navigation.     

Effect of structured lipid-enriched total parenteral nutrition in rats bearing yoshida sarcoma

The efficacy of structured lipid, a triacylglycerol of medium and long chain fatty acids, as an element of nutritional support therapies in cancer cachexia was investigated. Using the Yoshida sarcoma to induce cachexia, male Sprague Dawley rats (90 g) were injected subcutaneously with tumor cells (n = 17) or sterile saline (n = 16). Seven days later, rats were randomized to two intravenous diets for 3 days at 220 kcal/kg body weight/d, including 2 g nitrogen/kg body weight/d and 39% of total calories as either structured lipid or long chain triglyceride. Nitrogen balance, tumor growth rate, energy metabolism, and plasma albumin and free fatty acid levels were measured, and whole-body protein kinetics and liver, muscle, and tumor fractional protein synthetic rates were evaluated by adding (14)C-leucine to the diet during the last 4 hours of feeding. Nitrogen balance improved (P < .05) in both tumor and control rats receiving structured lipid-enriched total parenteral nutrition, and was also greater in tumor rats compared with controls. There were no differences in tumor growth or protein kinetics between diet groups. Albumin was lower (P < .05) in tumor rats, but significantly higher in both tumor and control rats given structured lipid-enriched total parenteral nutrition. Free fatty acid was significantly higher in tumor rats versus controls. Whole-body protein kinetics were similar among the four groups. Liver weight, liver weight to body weight ratio, and liver protein synthetic rate were higher in tumor rats. Also, liver weight to body weight ratio was lower in tumor and control animals given structured lipid-enriched total parenteral nutrition. Muscle protein synthetic rate was significantly lower in tumor rats, but higher in tumor and control rats given long chain triglyceride-enriched total parenteral nutrition. The nutritional benefits of structured lipid-enriched total parenteral nutrition favor support of host tissue without promoting tumor growth.     

Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host–helminth system

Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual''s immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host–helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.     

Effect of low-energy microwaves on DNA stability in solution

DNA isolated from liver of healthy and tumor-bearing (sarcoma 45) rats was irradiated in water-salt solution with weak microwaves (64.5 GHz, 50 μW/cm²). The heat stability of DNA increased with irradiation time (a raise of 1.5°C in T _m for “tumor” DNA after 90 min, without changes in ΔT), which may be associated with dehydration of the surrounding Na⁺ ions.     

First account on the larval biology of a Litomosoides filaria,from a bat

Litomosoides filariae are parasites of unrelated groups of hosts, including bats, marsupials, ancient and modern rodents. The four life cycles to-date elucidated, develop in terrestrial mammals and, at least experimentally, in the mite Ornithonyssus bacoti. A batch of mites was fed on an infected bat, Artibeus jamaicensis captured in Costa Rica, and 18 days later one infective larva was recovered. Its morphology was similar to that of other Litomosoides species, with the characteristic long buccal capsule. These first accounts on the larval biology of Litomosoides from Microchiroptera confirm the unity of the genus which supports the view that it has passed from one group of hosts to another by means of captures.     

Processing of viral envelope glycoprotein by the endomannosidase pathway: evaluation of host cell specificity

Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide processing which through its capacity to cleave the internal linkage between the glucose-substituted mannose and the remainder of the polymannose carbohydrate unit can provide an alternate pathway for achieving deglucosylation and thereby make possible the continued formation of complex oligosaccharides during a glucosidase blockade. In view of the important role which has been attributed to glucose on nascent glycoproteins as a regulator of a number of biological events, we chose to further define the in vivo action of endomannosidase by focusing on the well characterized VSV envelope glycoprotein (G protein) which can be formed by the large array of cell lines susceptible to infection by this pathogen. Through an assessment of the extent to which the G protein was converted to an endo-beta-N- acetylglucosaminidase (endo H)-resistant form during a castanospermine imposed glucosidase blockade, we found that utilization of the endomannosidase-mediated deglucosylation route was clearly host cell specific, ranging from greater than 90% in HepG2 and PtK1 cells to complete absence in CHO, MDCK, and MDBK cells, with intermediate values in BHK, BW5147.3, LLC-PK1, BRL, and NRK cell lines. In some of the latter group the electrophoretic pattern after endo H treatment suggested that only one of the two N-linked oligosaccharides of the G protein was processed by endomannosidase. In the presence of the specific endomannosidase inhibitor, Glcalpha1-->3(1- deoxy)mannojirimycin, the conversion of the G protein into an endo H- resistant form was completely arrested. While the lack of G protein processing by CHO cells was consistent with the absence of in vitro measured endomannosidase activity in this cell line, the failure of MDBK and MDCK cells to convert the G protein into an endo H-resistant form was surprising since these cell lines have substantial levels of the enzyme. Similarly, we observed that influenza virus hemagglutinin was not processed in castanospermine-treated MDCK cells. Our findings suggest that studies which rely on glucosidase inhibition to explore the function of glucose in controlling such critical biological phenomena as intracellular movement or quality control should be carried out in cell lines in which the glycoprotein under study is not a substrate for endomannosidase action.      

Influence of language and ancestry on genetic structure of contiguous populations: A microsatellite based study on populations of Orissa

Background

Although cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the severity of disease is highly variable indicating the influence of modifier genes. The intestines of Cftr deficient mice (CF mice: Cftr ^tm1Unc ) are prone to obstruction by excessive mucus accumulation and are used as a model of meconium ileus and distal intestinal obstruction syndrome. This phenotype is strongly dependent on the genetic background of the mice. On the C57Bl/6 background, the majority of CF mice cannot survive on solid mouse chow, have inflammation of the small intestine, and are about 30% smaller than wild type littermates. In this work potential modifier loci of the CF intestinal phenotype were identified.

Results

CF mice on a mixed genetic background (95% C57Bl/6 and 5% 129Sv) were compared to CF mice congenic on the C57Bl/6 background for several parameters of the intestinal CF phenotype. CF mice on the mixed background exhibit significantly greater survival when fed dry mouse chow, have reduced intestinal inflammation as measured by quantitative RT-PCR for marker genes, have near normal body weight gain, and have reduced mucus accumulation in the intestinal crypts. There was an indication of a gender effect for body weight gain: males did not show a significant improvement at 4 weeks of age, but were of normal weight at 8 weeks, while females showed improvement at both 4 and 8 weeks. By a preliminary genome-wide PCR allele scanning, three regions were found to be potentially associated with the milder phenotype. One on chr.1, defined by marker D1Mit36, one on chr. 9 defined by marker D9Mit90, and one on chr. 10, defined by marker D10Mit14.

Conclusion

Potential modifier regions were found that have a positive impact on the inflammatory phenotype of the CF mouse small intestine and animal survival. Identification of polymorphisms in specific genes in these regions should provide important new information about genetic modifiers of the CF intestinal phenotype.     

Glucocorticoid Receptors are Localized to Dendritic Spines and Influence Local Actin Signaling

Glucocorticoids affect learning and memory but the cellular mechanisms involved are poorly understood. The present studies tested if the stress-responsive glucocorticoid receptor (GR) is present and regulated within dendritic spines, and influences local signaling to the actin cytoskeleton. In hippocampal field CA1, 13?% of synapses contained GR-immunoreactivity. Three-dimensional reconstructions of CA1 dendrites showed that GR aggregates are present in both spine heads and necks. Consonant with evidence that GR?? mRNA associates with the translation regulator Fragile X Mental Retardation Protein (FMRP), spine GR levels were rapidly increased by group 1 mGluR activation and reduced in mice lacking FMRP. Treatment of cultured hippocampal slices with the GR agonist dexamethasone rapidly (15?C30?min) increased total levels of phosphorylated (p) Cofilin and extracellular signal-regulated kinase (ERK) 1/2, proteins that regulate actin polymerization and stability. Dexamethasone treatment of adult hippocampal slices also increased numbers of PSD95+ spines containing pERK1/2, but reduced numbers of pCofilin-immunoreactive spines. Dexamethasone-induced increases in synaptic pERK1/2 were blocked by the GR antagonist RU-486. These results demonstrate that GRs are present in hippocampal spines where they mediate acute glucocorticoid effects on local spine signaling. Through effects on these actin regulatory pathways, GRs are positioned to exert acute effects on synaptic plasticity.     

Molecular genetic analysis of the intratumoral clonal heterogeneity of colorectal adenocarcinomas

Molecular genetic analysis of allelic deletions from the loci containing the tumor suppressor genes p16, p15, p19 (9p21), RB1 (13p14), PTEN (10q23), and TP53 (17p13); microsatellite instability; and activating mutations of K-RAS (codons 12 and 13) was performed in four different segments of sporadic colorectal cancer (CRC) in 11 patients. Intratumoral genetic heterogenity was detected in 9 out of 11 (81%) colorectal adenocarcinomas and was morphologically validated. Analysis of different segments of one tumor reported that not only intratumoral heterogeneity, but also the order of the appearance and distribution of molecular anomalies during tumorigenesis in sporadic CRC. K-RAS point mutations and anomalies of the p16-RB1-cyclin D pathway were assumed to occur prior to microsatellite instability and PTEN deletions during tumor progression.     

Base specificity in the interaction of ethidium with synthetic polyribonucleotides.

Base specificity in the interaction of ethidium with double stranded synthetic RNA homopolymers has been studied by means of spectroscopic (UV-visible absorption and fluorescence), microcalorimetric and dilatometric techniques. The results show a strong base specificity in this interaction, the association constant with poly A:poly U being more than three order of magnitude higher than with poly O:poly C. The interaction is mainly enthalpy driven, the differences in affinity being essentially entropic in origin. These evidences along with the dilatometric data suggest that the observed base specificity may arise from the different extent of water release upon intercalation.