Main contents: Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes; Spo11-Accessory Proteins Link Double-Strand Break Sites to the Chromosome Axis in Early Meiotic Recombination; Spo11-Accessory Proteins Link Double-Strand Break Sites to the Chromosome Axis in Early Meiotic Recombination; Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats; Red Meat Consumption and Risk of Type 2 Diabetes: 3 Cohorts of U.S. Adults and an Updated Meta-Analysis; On the growth and form of the gut; Spider Silk-Based Gene Carriers for Tumor Cell-Specific Delivery.
Focus: Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes
1. Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes
【Articles for reference】The Journal of Cell Biology, 2011; 194 (3): 407 DOI:10.1083/jcb.201012049 Rb and p130 control cell cycle gene silencing to maintain the postmitotic phenotype in cardiac myocytes
P. Sdek, P. Zhao, Y. Wang, et al.
The mammalian heart loses its regenerative potential soon after birth. Adult cardiac myocytes (ACMs) permanently exit the cell cycle, and E2F-dependent genes are stably silenced, although the underlying mechanism is unclear. Heterochromatin, which silences genes in many biological contexts, accumulates with cardiac differentiation. H3K9me3, a histone methylation characteristic of heterochromatin, also increases in ACMs and at E2F-dependent promoters. We hypothesize that genes relevant for cardiac proliferation are targeted to heterochromatin by retinoblastoma (Rb) family members interacting with E2F transcription factors and recruiting heterochromatin protein 1 (HP1) proteins. To test this hypothesis, we created cardiac-specific Rb and p130 inducible double knockout (IDKO) mice. IDKO ACMs showed a decrease in total heterochromatin, and cell cycle genes were derepressed, leading to proliferation of ACMs. Although Rb/p130 deficiency had no effect on total H3K9me3 levels, recruitment of HP1-γ to promoters was lost. Depleting HP1-γ up-regulated proliferation-promoting genes in ACMs. Thus, Rb and p130 have overlapping roles in maintaining the postmitotic state of ACMs through their interaction with HP1-γ to direct heterochromatin formation and silencing of proliferation-promoting genes.
【Comments】Unveil the mystery of myocytes loss its proliferation capacity, which could explain why mammalian heart loses its regenerative potential soon after birth. This will be helpful in research of enhancing heart regenerative potential.
2. Spo11-Accessory Proteins Link Double-Strand Break Sites to the Chromosome Axis in Early Meiotic Recombination
【Articles for reference】Cell, 2011; 146 (3): 372-383 DOI:10.1016/j.cell.2011.07.003
Spo11-Accessory Proteins Link Double-Strand Break Sites to the Chromosome Axis in Early Meiotic Recombination
Silvia Panizza, Marco A. Mendoza, Marc Berlinger, et al.
Meiotic recombination between homologous chromosomes initiates via programmed DNA double-strand breaks (DSBs), generated by complexes comprising Spo11 transesterase plus accessory proteins. DSBs arise concomitantly with the development of axial chromosome structures, where the coalescence of axis sites produces linear arrays of chromatin loops. Recombining DNA sequences map to loops, but are ultimately tethered to the underlying axis. How and when such tethering occurs is currently unclear. Using ChIPchip in yeast, we show that Spo11-accessory proteins Rec114, Mer2, and Mei4 stably interact with chromosome axis sequences, upon phosphorylation of Mer2 by S phase Cdk. This axis tethering requires meiotic axis components (Red1/Hop1) and is modulated in a domain-specific fashion by cohesin. Loss of Rec114, Mer2, and Mei4 binding correlates with loss of DSBs. Our results strongly suggest that hotspot sequences become tethered to axis sites by the DSB machinery prior to DSB formation.
【Comments】 This research add information for further understanding the process of reproductive cell formation.
3. Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats
【Articles for reference】Endocrinology, August 9, 2011 DOI: 10.1210/en.2010-1471
Nutrient Responsive Nesfatin-1 Regulates Energy Balance and Induces Glucose-Stimulated Insulin Secretion in Rats
R. Gonzalez, R. L. S. Perry, X. Gao, et al.
Nesfatin-1 is a recently discovered anorexigen, and we first reported nesfatin-like immunoreactivity in the pancreatic β-cells. The aim of this study was to characterize the effects of nesfatin-1 on whole-body energy homeostasis, insulin secretion, and glycemia. The in vivo effects of continuous peripheral delivery of nesfatin-1 using osmotic minipumps on food intake and substrate partitioning were examined in ad libitum-fed male Fischer 344 rats. The effects of nesfatin-1 on glucose-stimulated insulin secretion (GSIS) were examined in isolated pancreatic islets. L6 skeletal muscle cells and isolated rat adipocytes were used to assess the effects of nesfatin-1 on basal and insulin-mediated glucose uptake as well as on major steps of insulin signaling in these cells. Nesfatin-1 reduced cumulative food intake and increased spontaneous physical activity, whole-body fat oxidation, and carnitine palmitoyltransferase I mRNA expression in brown adipose tissue but did not affect uncoupling protein 1 mRNA in the brown adipose tissue. Nesfatin-1 significantly enhanced GSIS in vivo during an oral glucose tolerance test and improved insulin sensitivity. Although insulin-stimulated glucose uptake in L6 muscle cells was inhibited by nesfatin-1 pretreatment, basal and insulin-induced glucose uptake in adipocytes from nesfatin-1-treated rats was significantly increased. In agreement with our in vivo results, nesfatin-1 enhanced GSIS from isolated pancreatic islets at both normal (5.6 mm) and high (16.7 mm), but not at low (2 mm), glucose concentrations. Furthermore, nesfatin-1/nucleobindin 2 release from rat pancreatic islets was stimulated by glucose. Collectively, our data indicate that glucose-responsive nesfatin-1 regulates insulin secretion, glucose homeostasis, and whole-body energy balance in rats.
【Comments】This research further explains the role of Nesfatin-1 in metabolism, which is reducing foot intake and making use of stored fat. Moreover, Nesfatin-1 also stimulates pancreatic β cell secret insulin. This research could be very helpful in treating obesity and diabetics.
4. Red Meat Consumption and Risk of Type 2 Diabetes: 3 Cohorts of U.S. Adults and an Updated Meta-Analysis
【Articles for reference】 American Journal of Clinical Nutrition, August 10, 2011 [Epub ahead of print]
Red Meat Consumption and Risk of Type 2 Diabetes: 3 Cohorts of U.S. Adults and an Updated Meta-Analysis
An Pan, Qi Sun, Adam M. Bernstein, et al.
The relation between consumption of different types of red meats and risk of type 2 diabetes (T2D) remains uncertain.
We evaluated the association between unprocessed and processed red meat consumption and incident T2D in US adults.
We followed 37,083 men in the Health Professionals Follow-Up Study (1986-2006), 79,570 women in the Nurses' Health Study I (1980-2008), and 87,504 women in the Nurses' Health Study II (1991-2005). Diet was assessed by validated food-frequency questionnaires, and data were updated every 4 y. Incident T2D was confirmed by a validated supplementary questionnaire.
During 4,033,322 person-years of follow-up, we documented 13,759 incident T2D cases. After adjustment for age, BMI, and other lifestyle and dietary risk factors, both unprocessed and processed red meat intakes were positively associated with T2D risk in each cohort (all P-trend <0.001). The pooled HRs (95% CIs) for a one serving/d increase of unprocessed, processed, and total red meat consumption were 1.12 (1.08, 1.16), 1.32 (1.25, 1.40), and 1.14 (1.10, 1.18), respectively. The results were confirmed by a meta-analysis (442,101 participants and 28,228 diabetes cases): the RRs (95% CIs) were 1.19 (1.04, 1.37) and 1.51 (1.25, 1.83) for 100 g of unprocessed red meat and for 50 g of unprocessed red meat, respectively. We estimated that substitutions of one serving of nuts, low-fat dairy, and whole grains per day for one serving of red meat per day were associated with a 16-35% lower risk of T2D.
【Comments】 This research proved the relationship between red meat consumption and incidence of diabetics. Similar research would contribute to form a healthy diet, especially for the patient with related disease.
5. On the growth and form of the gut
【Articles for reference】 Nature, 2011; 476 (7358): 57 DOI: 10.1038/nature10277
On the growth and form of the gut
Thierry Savin, Natasza A. Kurpios, Amy E. Shyer, et al.
The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut.
【Comments】 Macromechanics of simple differential growth creates complex organs. Nature creates complicated universe in a simplest and basic way. Seeing through the appearance to perceive the essence is the golden rule to discern nature.
6. Spider Silk-Based Gene Carriers for Tumor Cell-Specific Delivery
【Articles for reference】 Bioconjugate Chemistry, 2011; : 110712095946020 DOI:10.1021/bc200170u
Spider Silk-Based Gene Carriers for Tumor Cell-Specific Delivery
Keiji Numata, Michaela R Reagan, Robert H Goldstein, et al.
The present study demonstrates pDNA complexes of recombinant silk proteins containing poly(l-lysine) and tumor-homing peptides (THPs), which are globular and approximately 150–250 nm in diameter, show significant enhancement of target specificity to tumor cells by additions of F3 and CGKRK THPs. We report herein the preparation and study of novel nanoscale silk-based ionic complexes containing pDNA able to home specifically to tumor cells. Particular focus was on how the THP, F3 (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK), and CGKRK, enhanced transfection specificity to tumor cells. Genetically engineered silk proteins containing both poly(l-lysine) domains to interact with pDNA and the THP to bind to specific tumor cells for target-specific pDNA delivery were prepared using Escherichia coli, followed by in vitro and in vivo transfection experiments into MDA-MB-435 melanoma cells and highly metastatic human breast tumor MDA-MB-231 cells. Non-tumorigenic MCF-10A breast epithelial cells were used as a control cell line for in vitro tumor-specific delivery studies. These results demonstrate that combination of the bioengineered silk delivery systems and THP can serve as a versatile and useful new platform for nonviral gene delivery.
【Comments】 New gene carriers may increase specificity and selectivity, but have little impact on clinical application of gene therapy.