Limits to gene flow in a cosmopolitan marine planktonic diatom

The role of geographic isolation in marine microbial speciation is hotly debated because of the high dispersal potential and large population sizes of planktonic microorganisms and the apparent lack of strong dispersal barriers in the open sea. Here, we show that gene flow between distant populations of the globally distributed, bloom-forming diatom species Pseudo-nitzschia pungens (clade I) is limited and follows a strong isolation by distance pattern. Furthermore, phylogenetic analysis implies that under appropriate geographic and environmental circumstances, like the pronounced climatic changes in the Pleistocene, population structuring may lead to speciation and hence may play an important role in diversification of marine planktonic microorganisms. A better understanding of the factors that control population structuring is thus essential to reveal the role of allopatric speciation in marine microorganisms.     

Noninvasive imaging of cardiac venous anatomy with 64-slice multi-slice computed tomography and noninvasive assessment of left ventricular dyssynchrony by 3-dimensional tissue synchronization imaging in patients with heart failure scheduled for cardiac resynchronization therapy

Objectives of this study were to perform a prospective head-to-head comparison between multi-slice computed tomography (MSCT) venography and invasive venography in cardiac resynchronization therapy (CRT) candidates as well as to evaluate the relation between left ventricular (LV) lead position and effect on LV dyssynchrony and immediate response to CRT. Twenty-one consecutive heart failure patients scheduled for CRT implantation were prospectively enrolled to undergo 64-slice MSCT to visualize the venous system, invasive venography during device implantation, and tri-plane tissue synchronization imaging (TSI) before and after implantation. Excellent agreement between MSCT and invasive venography was noted. No significant differences were observed between both techniques regarding vessel diameters. In 12 patients, a match was observed between the area of latest mechanical activation (on TSI) and LV lead position. These patients showed a significant decrease in LV dyssynchrony (43 +/- 7 ms to 11 +/- 9 ms, p <0.0001) with acute reduction in LV end-systolic volume (188 +/- 54 ml to 162 +/- 48 ml, p <0.01) and improvement in LV ejection fraction (22% +/- 9% to 34% +/- 9%, p <0.01). Patients with a mismatch between area of latest activation and LV lead position remained dyssynchronous without improvement in LV function. In conclusion, visualization of major tributaries of the coronary sinus was comparable between invasive venography and MSCT venography. Optimal LV lead positioning in a vein draining the area of latest mechanical activation (determined from tri-plane TSI) resulted in acute improvement of LV dyssynchrony and systolic function after CRT implantation.     

Iron depletion limits intracellular bacterial growth in macrophages

Many intracellular pathogens infect macrophages and these pathogens require iron for growth. Here we demonstrate in vitro that the intracellular growth of Chlamydia psittaci, trachomatis, and Legionella pneumophila is regulated by the levels of intracellular iron. Macrophages that express cell surface ferroportin, the only known cellular iron exporter, limit the intracellular growth of these bacteria. Hepcidin is an antimicrobial peptide secreted by the liver in response to inflammation. Hepcidin binds to ferroportin mediating its internalization and degradation. Addition of hepcidin to infected macrophages enhanced the intracellular growth of these pathogens. Macrophages from flatiron mice, a strain heterozygous for a loss-of-function ferroportin mutation, showed enhanced intracellular bacterial growth independent of the presence of exogenous hepcidin. Macrophages, from wild-type or flatiron mice, incubated with the oral iron chelator deferriprone or desferasirox showed reduced intracellular bacterial growth suggesting that these chelators might be therapeutic in chronic intracellular bacterial infections.     

Insulin resistance and metabolic syndrome in type 1 diabetes mellitus

Insulin resistance (IR) plays a larger role in the type 1 diabetes mellitus (T1DM) disease process than commonly recognized. Overweight and physical inactivity have increased steadily for the last 20-30 years in children and adolescents in many populations, concurrently with a rising incidence of T1DM. The role of IR in T1DM has only recently been gaining acceptance. This review will focus on how IR influences our current understanding of disease development and metabolic syndrome (MS) in T1DM. Increases in IR by weight gain and sedentarism, associated to decreased beta cell mass by autoimmune process, may disrupt normoglycemia in pre-T1DM individuals. IR may reflect a more aggressive form of autoimmune disease mediated by immuno-inflammatory factors that also mediate beta cell destruction (TNF-alpha and IL-6). These concepts are included in the "accelerator hypothesis". Moreover, family history of T2DM and chronic hyperglycemia (glucotoxicity), occurring after T1DM diagnosis, contribute to decrease peripheral glucose uptake. The onset of diabetic nephropathy (DN) might also contribute to IR and metabolic syndrome (MS) via low-grade inflammation and increased oxidative stress. MS is found between 12 to 40% in T1DM, especially in patients with advanced DN and poor glycemic control. These findings have therapeutic and cardiovascular prognostic implications as children make the transition toward adolescence and young adulthood T1DM.     

Expression of {beta}1 integrin receptors during rat pancreas development--sites and dynamics

The integrin receptors link to extracellular matrix proteins and exert a dynamic role in development by providing the physical basis for cell adhesion and controlling cell growth. In the present study, we examined changes in the expression of beta1 integrins and its associated alpha-subunits to islet cell development in the rat pancreas. A significant increase in protein expression of integrin alpha3, alpha6, and beta1 was observed from fetal to postnatal life. High mRNA levels of these integrin subunits was detected at embryonic d 18 and dropped significantly after birth with relatively low expression throughout postnatal life. Integrins alpha3, alpha5, alpha6, and beta1 were expressed in a cell-specific manner in the pancreas with high integrin immunoreactivity in duct and islet regions during fetal life, and a progressive increase later into postnatal life. The coexpression with islet and putative islet precursor markers during fetal and postnatal development suggest a role for these integrin subunits in differentiation and maturation of islets. Functional studies in vitro showed that anti-beta1 antibody treatment inhibited islet cell adhesion to extracellular matrices and disrupted islet architecture. Blockade of beta1 integrin receptor and knockdown beta1 mRNA resulted in a decrease in the expression of insulin mRNA and increased islet cell death. These results suggest that progression in islet cell development is accompanied by and dependent upon cell adhesion via beta1 integrin and its respective alpha-subunits and suggest that the beta1 family of integrins may play a critical role in islet cell architecture, development, integrity, and function.     

Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health

Treatment of asymptomatic bacteriuria and urinary tract infections in pregnancy can prevent adverse outcome for mother and child. However, antimicrobial resistance can impede effective chemotherapy. From April 1995 to March 1996, urine specimens from 5153 pregnant women in a rural area in northern Tanzania were inoculated on dip slides. Bacterial isolates from 101 positive dip slides were identified and tested for susceptibility to antimicrobial agents by disc diffusion. In total, 107 bacterial isolates were recovered, 71 Gram-negative and 36 Gram-positive. The most frequent isolates were Escherichia coli (n=27) and enterococci (n=15). E. coli isolates showed low rates of resistance to ampicillin (17%), mecillinam (9%), cefalexin (0%), nitrofurantoin (4%), trimethoprim-sulfamethoxazole (0%), trimethoprim (13%) and sulfamethoxazole (0%). Other Gram-negative bacteria displayed higher rates of resistance to these drugs. All enterococcal isolates were sensitive to ampicillin and only 2 were resistant to nitrofurantoin. Growth of E. coli from urine culture was correlated with adverse outcome of pregnancy (relative risk 4.13, 95% confidence interval 1.50-11.38). Antimicrobial susceptibility prevails in urinary isolates of E. coli and enterococci from rural areas of northern Tanzania. Susceptibility data from both rural and urban areas should be taken into account when planning antibiotic policies.     

Microsatellite Analysis of Sporadic Flat and Depressed Lesions of the Colon

Prior studies of molecular and genetic derangements in flat and depressed lesions of the colon have revealed lower frequencies in a number of markers commonly present in exophytic lesions. These and other differences suggest that flat lesions are driven by alternative pathways. We reviewed a database of patients who had undergone endoscopic mucosal resection (EMR) for flat and depressed lesions at the University of Chicago from January 2001 to April 2003. Formalin-fixed and paraffin-embedded colonic samples were retrieved from the tissue bank, and five standardized mononucleotide and dinucleotide microsatellite regions were analyzed for instability (MSI) using fluorescently labeled forward primers in nonmultiplex reactions. Sixteen patients were identified with flat or depressed lesions who had adequate tissue specimens available for MSI analysis. Of these specimens, eight were tubular adenomas, three were tubulovillous adenomas, and five were carcinomas in situ. Four of the lesions were microsatellite unstable, each at a single locus, and one lesion showed probable instability at a second locus. Eleven lesions were microsatellite stable. Aberrations in DNA repair mechanisms do not appear to significantly contribute to the molecular derangements underlying sporadic flat or depressed colonic lesions. The molecular bases that underlie the aggressive behavior of sporadic flat and depressed lesions remain to be determined, and further investigation is warranted.     

Trends in leisure time physical activity,smoking, body mass index and alcohol consumption in Danish adults with and without diabetes: A repeat cross-sectional national survey covering the years 2000 to 2010

Aims

In recent decades there has been an increased focus on non-pharmacological treatment of diabetes. The aim of this study was to investigate trends in leisure time physical activity (PA), smoking, body mass index (BMI), and alcohol consumption reported in 2000, 2005 and 2010 by Danish subjects with diabetes.

Methods

Data comprised level of leisure time PA (inactive; moderate active; medium active; high active); smoking; BMI; and alcohol consumption, provided by The Danish Health and Morbidity Surveys. Participants older than 45 years with or without diabetes were included from cross-sectional analyses from 2000, 2005 and 2010.

Results

In participants with diabetes, leisure time PA levels increased from 2000 to 2010: The percentage of those that were physically active increased from 53.5% to 78.2% (p < 0.001; women) and from 67.8% to 79.1% (p = 0.01; men). The prevalence of daily smokers was reduced from 27.2% to 16.4%, p = 0.015, in women with diabetes. In men with diabetes, BMI increased from 27.2 ± 4.0 to 28.6 ± 5.1 kg m⁻², p = 0.003, and men who exceeded the maximum recommendation for alcohol consumption increased from 9.4% to 19.0%, p = 0.007. The leisure time PA level was reduced in participants with diabetes compared to participants without diabetes throughout the study.

Conclusions

The percentage of physically active Danish participants older than 45 years with diabetes increased from 2000 to 2010, and the most beneficial trends in life style were observed among the women. These trends may have serious implications for cardiovascular risk in Danish patients with diabetes.