Sodium tungstate (NaW) is an inorganic salt that has proven to be a potent insulin-mimetic agent, although the molecular events seems to differ. Inhibition of hepatic gluconeogenesis is one significant physiological action of insulin, therefore studying the effect of NaW on gluconeogenic enzymes will contribute to understand its elusive mechanism of action. Here, we show that NaW has no inhibitory effect over the gluconeogenic enzyme fructose 1,6-bisphosphatase (FBPase) in vitro, but mimics insulin in the induction of the nuclear translocation of FBPase in rat liver, which may have a negative impact on its activity. Then, at least in part, NaW may inhibit hepatic gluconeogenesis by inducing the proper subcellular distribution of FBPase, without directly interfering with its phosphatase activity.
Addgene • Addgene (http://www.addgene.org) is a nonprofit organization whose mission is to accelerate research and biomedical discovery by facilitating access to useful research materials and information. To fulfill this mission, Addgene maintains a repository that distributes >50,000 plasmids contributed by scientists coming from more than 3,000 different labs all over the world. The repository stores, quality controls, and annotates the data associated with the plasmids. Addgene also recently started providing ready-to-use viral particles produced from select plasmids in the repository. Researchers can use these viral particles directly in their experiments, thereby skipping the viral production process and accelerating their research. All plasmid data is made freely available to the public at Addgene.org. Members of the academic and nonprofit research community can request plasmids from the repository for a small fee. In addition, the organization creates useful educational materials covering topics from basic biology to the therapeutic applications of CRISPR for an audience ranging from undergraduate biologists to tenured professors. Every month Addgene distributes '11,000 plasmids, provides hundreds of viral particles, and publishes posts on a blog receiving >60,000 views per month. Addgene is an essential and global resource for the academic life sciences.
Currently there is limited knowledge as to the morphology of bacteriogenic manganese (Mn)-oxide minerals, making it difficult to identify Mn minerals from geologic deposits as being biotic or abiotically formed. When investigating mineral deposits it is critical to understand what environmental processes lead to mineral formation in order to accurately interpret the information locked inside each mineral. This study aims to characterize the morphology, structural variability, and microbe-mineral association of bacteriogenic Mn(III/IV) oxides produced by Mn(II/III)-oxidizing bacteria, using pure cultures of three known Mn-oxidizing bacteria. Morphology and localization of bacteriogenic Mn-oxides was characterized using high resolution scanning electron (HR-SEM) and transmission electron microscopy (TEM). We found that the morphology of bacteriogenic Mn-oxides varies between bacterial species, and that the localization of Mn oxidizing enzymes determines if Mn-oxides are closely associated with the cellular surface or form in exopolysaccharides (EPS). Knowledge acquired from this study illustrates the complexity of identifying bacteriogenic Mn-oxides and oxidation products from more complex natural environmental settings like ancient geologic deposits.
Mutations in the Schwachman-Bodian diamond syndrome (SBDS) gene—involved in ribosome biogenesis—cause Shwachman-diamond syndrome (SDS), a known bone marrow failure disorder. A dysfunctional ribosome biogenesis is postulated as a cause of phenotypes seen in SDS patients. Recently, lymphocytes from SDS patients with hypomorphic SBDS expression were shown to harbor significantly increased DNA damage and ï§H2AX foci in response to X-rays or gamma rays. Additionally, SBDS knockdown in cells increases ROS (reactive oxygen species) levels and enhances proliferation defects in a p53 dependent manner. These new reports suggest that SBDS may have a novel and a yet unexplored role in DNA repair and damage response pathways. In this short opinion article, I will discuss these recent observations and delineate hypothesis to explain the potential new roles of SBDS.
In our bodies, DNA is damaged for a variety of genotoxic agents including UV radiation in sunlight, and thus DNA-repair systems are fundamental to the maintenance of life. In human cells, this damage is removed exclusively by the nucleotide excision repair mechanism (NER). NER can be divided into two subpathways: global genomic NER (GG-NER or GGR) and transcription coupled NER (TC-NER or TCR). In transcription-coupled repair (TCR), NER occurs most rapidly in the template strand of actively transcribed genes. This work is focused in the use of eXcision repair-sequencing (XR-seq), an excision repair sequencing methodology to map the location of repair sites in different Escherichia coli (E. coli) strains. Using XR-seq, Adebali et al. have dissected the accurate role of two important excision repair proteins, Mfd and UvrD, confirming their role in repair of UV-induced damage. Genome-wide analysis of the transcribed strand/nontranscribed strand (TS/NTS) repair ratio demonstrated that, deletion of mfd globally shifts the distribution of TS/NTS ratios downward by a factor of about 2 on average for the most highly transcribed genes. These results indicate that Mfd-dependent TCR is widespread in the E. coli genome, whereas UvrD plays a role in excision repair by aiding the catalytic turnover of excision repair proteins.
Cancer cell-derived exosomes have recently been implicated in contributing to metastasis. It is expectable that specific membrane trafficking factors would participate in the regulation of exosome formation, transport and release from cells. Recent investigations have revealed certain members belonging to the SNARE, sorting factor and Rab GTPase protein families as being crucial in governing the exosome life cycle. These trafficking components have therefore been primed as new targets potentially modulating cancer progression. This mini-review is focused on the involvement of membrane trafficking components in regulating exosome-related transport and signaling, and in turn influencing clinical outcomes in cancer.
The repertoire of nuclease-guided genome modifications was recently expanded to include homology-independent targeted integration (HITI) of exogenous DNA by a report published in the December 2016 issue of Nature (Suzuki et al. 2016). The key feature distinguishing HITI from homology-based DNA Knock-in is its applicability in post-mitotic cells of non-regenerative tissues, such as the brain and retina. Suzuki et al. demonstrated the therapeutic utility of HITI through genomic knock-in of an exon previously deleted by a naturally occurring mutation that causes blindness in rats. The potential therapeutic impacts are farther-reaching than the replacement of deleted genomic segments. Targeted integration of therapeutic genes in post-mitotic cells in vivo may improve treatments that rely on continued gene augmentation or silencing.
Recently numerous commentators have raised serious concerns over the inability of the academic system to appropriately deal with the rapid growth in the number of postdocs it is training – particularly in light of the far more moderate growth in the number of permanent academic positions. Concomitantly, in the context of an increased emphasis for universities to contribute to economic activity, many commentators have criticized the poor entrepreneurial performance of universities. Here I explore various proposed remedies to the postdoc problem and to the poor entrepreneurial performance of universities. I highlight shared interests in each other’s missions and suggest that a solution to the postdoc problem could be found in the vision of the ‘entrepreneurial university’.
Type I diabetes is characterized by the gradual loss of β cells in the pancreas leading to insulin deficiency, hyperglycemia, and if left untreated, death. Since the 1920’s Type I diabetes has been treated with multiple daily injections of insulin in an attempt to restore glucose metabolism and stave off ketoacidosis - the life-threatening consequence of chronic hyperglycemia. While insulin injections have allowed millions of people to successfully live with Type I diabetes, it is by no means a perfect treatment. Multiple daily injections and the short half-life of insulin combine to cause daily bouts of hypoglycemia and hyperglycemia, which can cause multiple detrimental sequelae including microvascular damage, nerve damage, fat buildup/obesity, and cardiovascular disease (Smith-Marsh and Zeller 2017). Thus, Type I diabetics have been waiting for a new and better therapy to be developed.
Recent studies have demonstrated that leptin can prolong life chronically in rats with poorly-controlled type 1 diabetes (T1D). Multiple explanations have been proposed to explain leptin’s chronic antihyperglycemic effect, including suppression of glucagon release and/or signaling, reductions in hyperphagia and ectopic lipid content, and improvements in insulin sensitivity; it is leptin’s ability to reduce plasma glucose relies on all of these effects. In addition, leptin reverses hyperglycemia and diabetic ketoacidosis (DKA) acutely, within 6 hours of leptin infusion, by suppressing hypothalamic-pituitary-adrenal (HPA) axis activity in insulinopenic rats. Thus current evidence suggests that leptin’s acute, insulin-independent effect to reverse DKA by suppressing HPA axis activity occurs through a different mechanism from its chronic, pleotropic, insulin-dependent effect to reverse hyperglycemia and prolong survival in rodents with T1D. Leptin may therefore represent an attractive therapeutic target to improve glycemic control in humans with poorly-controlled T1D.