Experience dictates stem cell fate in the adult hippocampus

Adult hippocampal neurogenesis has been implicated in cognitive and emotional processes, as well as in response to antidepressant treatment. However, little is known about how the adult stem cell lineage contributes to hippocampal structure and function and how this process is modulated by the animal's experience. Here we perform an indelible lineage analysis and report that neural stem cells can produce expanding and persisting populations of not only neurons, but also stem cells in the adult hippocampus. Furthermore, the ratio of stem cells to neurons depends on experiences of the animal or the location of the stem cell. Surprisingly, social isolation facilitated accumulation of stem cells, but not neurons. These results show that neural stem cells accumulate in the adult hippocampus and that the stem cell-lineage relationship is under control of anatomic and experiential niches. Our findings suggest that, in the hippocampus, fate specification may act as a form of cellular plasticity for adapting to environmental changes.     

Ribosomal protein L11 recruits miR-24/miRISC to repress c-Myc expression in response to ribosomal stress

c-Myc promotes cell growth by enhancing ribosomal biogenesis and translation. Deregulated expression of c-Myc and aberrant ribosomal biogenesis and translation contribute to tumorigenesis. Thus, a fine coordination between c-Myc and ribosomal biogenesis is vital for normal cell homeostasis. Here, we show that ribosomal protein L11 regulates c-myc mRNA turnover. L11 binds to c-myc mRNA at its 3' untranslated region (3'-UTR), the core component of microRNA-induced silencing complex (miRISC) argonaute 2 (Ago2), as well as miR-24, leading to c-myc mRNA reduction. Knockdown of L11 drastically increases the levels and stability of c-myc mRNA. Ablation of Ago2 abrogated the L11-mediated reduction of c-myc mRNA, whereas knockdown of L11 rescued miR-24-mediated c-myc mRNA decay. Interestingly, treatment of cells with the ribosomal stress-inducing agent actinomycin D or 5-fluorouracil significantly decreased the c-myc mRNA levels in an L11- and Ago2-dependent manner. Both treatments enhanced the association of L11 with Ago2, miR-24, and c-myc mRNA. We further show that ribosome-free L11 binds to c-myc mRNA in the cytoplasm and that this binding is enhanced by actinomycin D treatment. Together, our results identify a novel regulatory paradigm wherein L11 plays a critical role in controlling c-myc mRNA turnover via recruiting miRISC in response to ribosomal stress.     

Isolation of a naturally-occurring nickel resistance plasmid from a rare hypersaline estuary (Laguna Madre,Texas, USA) for potential use as a bio-indicator of metal contamination

Metal-resistant bacteria were isolated from sediments of the Laguna Madre, a rare hypersaline estuary impacted by many anthropogenic compounds, including various metals and metalloids. Bacteria were initially isolated on nutrient agar supplemented with NaCl; random isolates (n = 100) were tested for metal resistance toward zinc, nickel, chromium, and cadmium using a pour plate disc assay. Metal-resistant cultures were assayed for plasmids that contained naturally-occurring heavy metal resistance genes. Putative metal-resistance plasmids were tested for metal-resistance efficacy by transforming a metal-sensitive strain of Escherichia coli. Polymerase Chain Reaction (PCR) primers were designed to detect cnrA, part of a nickel–cobalt resistance gene cluster, and restriction endonuclease digests were performed to detect restriction sites within the plasmid. Results showed that many bacterial isolates tested were resistant toward most of the metals used in this study. Among tested bacteria cultures, 34 were resistant to zinc, 64 were resistant to chromium, and 51 resistant to cadmium. Only 8 cultures were resistant to nickel; however, most bacteria were found to be resistant to more than one metal. Several plasmids were found from the bacteria isolates. One plasmid, designated pDZ5, was isolated from a bacterium identified as Bacillus pumilus by 16S rRNA sequencing. Plasmid pDZ5 conferred nickel resistance to the metal-sensitive E. coli strain and was found to contain cnrA as confirmed by PCR amplification. Plasmid pDZ5 was successfully cut with restriction enzymes for potential ligation with reporter genes. The presence, abundance and expression of pDZ5 may prove to be a useful bio-indicator of metal contamination, specifically nickel pollution, in the Laguna Madre due to the fewer number of bacteria that were nickel-resistant compared to other metals.     

Ret signalling integrates a craniofacial muscle module during development

An appropriate organisation of muscles is crucial for their function, yet it is not known how functionally related muscles are coordinated with each other during development. In this study, we show that the development of a subset of functionally related head muscles in the zebrafish is regulated by Ret tyrosine kinase signalling. Three genes in the Ret pathway (gfra3, artemin2 and ret) are required specifically for the development of muscles attaching to the opercular bone (gill cover), but not other adjacent muscles. In animals lacking Ret or Gfra3 function, myogenic gene expression is reduced in forming opercular muscles, but not in non-opercular muscles derived from the same muscle anlagen. These animals have a normal skeleton with small or missing opercular muscles and tightly closed mouths. Myogenic defects correlate with a highly restricted expression of artn2, gfra3 and ret in mesenchymal cells in and around the forming opercular muscles. ret(+) cells become restricted to the forming opercular muscles and a loss of Ret signalling results in reductions of only these, but not adjacent, muscles, revealing a specific role of Ret in a subset of head muscles. We propose that Ret signalling regulates myogenesis in head muscles in a modular manner and that this is achieved by restricting Ret function to a subset of muscle precursors.     

The physiology of the normal human breast: an exploratory study

The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.     

Body image changes associated with participation in an intensive lifestyle weight loss intervention

The primary aim of this study was to test for changes in body image in men and women enrolled in the Look AHEAD trial. Look AHEAD (Action for Health in Diabetes) is a multicenter, randomized controlled trial designed to test whether intentional weight loss reduces cardiovascular morbidity and mortality in overweight individuals with type 2 diabetes. Participants included 157 adults at one site (Pennington Biomedical Research Center (PBRC), Baton Rouge, LA) of the Look AHEAD study. At baseline, the mean BMI of the female participants was 36.4, and the mean BMI for males was 33.5. Following baseline assessment, participants were randomly assigned to the intensive lifestyle intervention (ILI, n = 81) or diabetes support and education (DSE, n = 76). The body morph assessment version 2.0 (BMA 2.0) was used to assess estimates of perceived current body size, ideal body size, acceptable body size, and body image dissatisfaction at baseline and 1 year. Over the 1 year, participants in the ILI group had significantly greater reductions in weight (10.1% for men and 8.9% for women) than those in the DSE group (+ 0.8% for men and -0.2%, for women). Perceived current body size was reduced significantly more in both men and women in the ILI group, relative to DSE. There were also significantly greater reductions in body image dissatisfaction in the ILI group, relative to the DSE group for men and women. The results of this study indicate that body image dissatisfaction improved following participation in an intensive behavioral weight loss program.     

Breeding system and pollination ecology of introduced plants compared to their native relatives

Identifying how plant-enemy interactions contribute to the success of introduced species has been a subject of much research, while the role of plant-pollinator interactions has received less attention. The ability to reproduce in new environments is essential for the successful establishment and spread of introduced species. Introduced plant species that are not capable of autonomous self-fertilization and are unable to attract resident pollinators may suffer from pollen limitation. Our study quantifies the degree of autogamy and pollination ecology of 10 closely related pairs of native and introduced plant species at a single site near St. Louis, Missouri, USA. Most of these species pairs had similar capacities for autogamy; however, of those that differed, the introduced species were more autogamous than their native congeners. Most introduced plants have pollinator visitation rates similar to those of their native congeners. Of the 20 species studied, only three had significant pollen limitation. We suggest that the success of most introduced plant species is because they are highly autogamous or because their pollinator visitation rates are similar to those of their native relatives. Understanding and identifying traits related to pollination success that are key in successful introductions may allow better understanding and prediction of biological invasions.     

Increased endothelial cell adhesion on plasma modified nanostructured polymeric and metallic surfaces for vascular stent applications

Techniques to regenerate the vasculature have risen considerably over the last few decades due to the increased clinical diagnosis of artery narrowing and blood vessel blockage. Although initially re‐establishing blood flow, current small diameter vascular regenerative materials often eventually cause thrombosis and restenosis due to a lack of initial endothelial cell coverage on such materials. The objective of this in vitro study was to evaluate commonly used vascular materials (specifically, polyethylene terephthalate, polytetrafluoroethylene, polyvinyl chloride, polyurethane, nylon, commercially pure titanium, and a titanium alloy (Ti6Al4V)) modified using an ionic plasma deposition (IPD) process and a nitrogen ion implantation plasma deposition (NIIPD) process. Such surface modifications have been previously shown to create nanostructured surface features which mimic the natural nanostructured surface features of blood vessels. The modified and unmodified surfaces were characterized by scanning electron microscopy, atomic force microscopy and surface energy measurements. Furthermore, in vitro endothelial cell adhesion tests (a key first step for vascular material endothelialization) demonstrated increased endothelial cell adhesion on many modified (with IPD and NIIPD + IPD) compared to unmodified samples. In general, endothelial cell adhesion increased with nanoroughness and surface energy but demonstrated a decreased endothelial cell adhesion trend after an optimal coating surface energy value was reached. Thus, results from this study provided materials and a versatile surface modification process that can potentially increase endothelialization faster than current unmodified (conventional) polymer and metallic vascular materials. Biotechnol. Bioeng. 2009;103: 459–471. © 2009 Wiley Periodicals, Inc.