Buffer standards for the physiological pH of N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES) from (278.15 to 328.15) K

This paper reports the results for the pH of six buffer solutions free of chloride ion with compositions: (a) BES (0.03 mol·kg(-1)) + NaBES (0.09 mol·kg(-1)); (b) BES (0.02 mol·kg(-1)) + NaBES (0.04 mol·kg(-1)); (c) BES (0.04 mol·kg(-1)) + NaBES (0.08 mol·kg(-1)); (d) BES (0.04 mol·kg(-1)) + NaBES (0.04 mol·kg(-1)) (e) BES (0.05 mol·kg(-1)) + NaBES (0.05 mol·kg(-1)); and (f) (0.06 mol·kg(-1)) + NaBES (0.06 mol·kg(-1)). The remaining eight buffer solutions (g) to (n) have saline media of the ionic strength I = 0.16 mol·kg(-1), matching closely to that of the physiological sample. Conventional pa(H) values, designated as pH(s), for all six buffer solutions (a) - (f) without the chloride ion and eight buffer solutions with the chloride ion (g) - (n) at I = 0.16 mol·kg(-1) from (278.15 K to 328.15) K have been calculated. The operational pH values for five buffer solutions at T = 298.15 K and T = 310.15 K have been determined based on the difference in the values of the liquid junction potentials between the blood phosphate standard and the experimental buffer solutions. Five of these buffers are recommended as secondary standards for the physiological pH range 7.5 to 8.5.     

Candidate genes contributing to the aggressive phenotype of mantle cell lymphoma

Mantle cell lymphoma and small lymphocytic lymphoma are lymphocyte cancers that have similar morphologies and a common age of onset. Mantle cell lymphoma is generally an aggressive B cell lymphoma with a short median survival time, whereas small lymphocytic lymphoma is typically an indolent B cell lymphoma with a prolonged median survival time. Using primary tumor samples in bi-directional suppression subtractive hybridization, we identified genes with differential expression in an aggressive mantle cell lymphoma versus an indolent small lymphocytic lymphoma. “Virtual” Northern blot analyses of multiple lymphoma samples confirmed that a set of genes was preferentially expressed in aggressive mantle cell lymphoma compared to indolent small lymphocytic lymphoma. These analyses identified mantle cell lymphoma-specific genes that may be involved in the aggressive behavior of mantle cell lymphoma and possibly other aggressive human lymphomas. Interestingly, most of these differentially expressed genes have not been identified using other techniques, highlighting the unique ability of suppression subtractive hybridization to identify potentially rare or low expression genes.     

How to discover modules in mind and brain: the curse of nonlinearity, and blessing of neuroimaging. A comment on Sternberg (2011)

Sternberg (2011) elegantly formalizes how certain sets of hypotheses, specifically modularity and pure or composite measures, imply certain patterns of behavioural and neuroimaging data. Experimentalists are often interested in the converse, however: whether certain patterns of data distinguish certain hypotheses, specifically whether more than one module is involved. In this case, there is a striking reversal of the relative value of the data patterns that Sternberg considers. Foremost, the example of additive effects of two factors on one composite measure becomes noninformative for this converse question. Indeed, as soon as one allows for nonlinear measurement functions and nonlinear module processes, even a cross-over interaction between two factors is noninformative in this respect. Rather, one requires more than one measure, from which certain data patterns do provide strong evidence for multiple modules, assuming only that the measurement functions are monotonic. If two measures are not monotonically related to each other across the levels of one or more experimental factors, then one has evidence for more than one module (i.e., more than one nonmonotonic transform). Two special cases of this are illustrated here: a "reversed association" between two measures across three levels of a single factor, and Sternberg's example of selective effects of two factors on two measures. Fortunately, functional neuroimaging methods normally do provide multiple measures over space (e.g., functional magnetic resonance imaging, fMRI) and/or time (e.g., electroencephalography, EEG). Thus to the extent that brain modules imply mind modules (i.e., separate processors imply separate processes), the performance data offered by functional neuroimaging are likely to be more powerful in revealing modules than are the single behavioural measures (such as accuracy or reaction time, RT) traditionally considered in psychology.     

Nitric oxide increases susceptibility of Toll-like receptor-activated macrophages to spreading Listeria monocytogenes

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Highlights? TLR stimulation prevents primary Listeria infection but enhances cell-cell spread ? Spread is enhanced because of nitric oxide-dependent delay in phagolysosome fusion ? NOS2 inhibition reduces Listeria CFU and spread in livers of infected mice     

Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Among these genes, ribosomal protein S19 (RPS19) is mutated most frequently. Generation of animal models for diseases like DBA is challenging because the phenotype is highly dependent on the level of RPS19 down-regulation. We report the generation of mouse models for RPS19-deficient DBA using transgenic RNA interference that allows an inducible and graded down-regulation of Rps19. Rps19-deficient mice develop a macrocytic anemia together with leukocytopenia and variable platelet count that with time leads to the exhaustion of hematopoietic stem cells and bone marrow failure. Both RPS19 gene transfer and the loss of p53 rescue the DBA phenotype implying the potential of the models for testing novel therapies. This study demonstrates the feasibility of transgenic RNA interference to generate mouse models for human diseases caused by haploinsufficient expression of a gene.     

Principles for establishing trust when developing a substance abuse intervention with a Native American community

This article traces the development of a research project with a Native American community. Four principles were used to guide the development of the "Community Partnership to Affect Cherokee Adolescent Substance Abuse" project using a community-based participatory research approach. The principles suggest that establishing trust is key when developing and conducting research with a Native American community.     

Associations of objectively measured sedentary behaviour and physical activity with markers of cardiometabolic health

Aims/hypothesis

The study aimed to examine the associations between objectively measured sedentary time, breaks in sedentary time, moderate-to-vigorous physical activity (MVPA) and total physical activity with markers of cardiometabolic health in a population with known risk factors for type 2 diabetes mellitus.

Methods

This study reports data from two ongoing diabetes prevention programmes. Participants with known risk factors were recruited from primary care practices located within the East Midlands, UK, over the period 2010–2011. ActiGraph GT3X accelerometers (15 s epochs) were used to assess sedentary time (<25 counts per 15 s), MVPA (≥488 counts per 15 s) and total physical activity (total counts). A break was considered as any interruption in sedentary time (≥25 counts per 15 s). Linear regression examined the independent association of sedentary time, breaks in sedentary time, MVPA and total physical activity with markers of cardiometabolic health.

Results

The sample comprised 878 participants; 153 from Project STAND (Sedentary Time And Diabetes) (age 32.9?±?5.6 years, 28.8% male) and 725 from Walking Away from Diabetes (age 63.7?±?7.8 years, 64.8% male). Following adjustment for various covariates, including MVPA and BMI, there were detrimental linear associations of sedentary time with 2 h plasma glucose (standardised beta coefficient) (β?=?0.220, p?<?0.001), triacylglycerol (β?=?0.206, p?=?0.001) and HDL-cholesterol (β?=??0.123, p?=?0.029). Breaks in sedentary time, total physical activity and MVPA were significantly inversely associated with measures of adiposity, but not with any other cardiometabolic variables after adjustment for sedentary time and BMI.

Conclusions/interpretation

In adults at high risk of type 2 diabetes mellitus, time spent sedentary is strongly and adversely associated with cardiometabolic health and may be a more important indicator of poor health than MVPA.     

MGMT and MLH1 methylation in Helicobacter pylori-infected children and adults

AIM:To evaluate the association between Helicobacter pylori(H.pylori) infection and MLH1 and MGMT methylation and its relationship with microsatellite instability(MSI).METHODS:The methylation status of the MLH1 and MGMT promoter region was analysed by methylation specific methylation-polymerase chain reaction(MSPPCR) in gastric biopsy samples from uninfected or H.pylori-infected children(n = 50),from adults with chronic gastritis(n = 97) and from adults with gastric cancer(n = 92).MLH1 and MGMT mRNA expression were measured by real-time PCR and normalised to a constitutive gene(β actin).MSI analysis was performed by screening MSI markers at 4 loci(Bat-25,Bat-26,D17S250 and D2S123) with PCR;PCR products were analysed by single strand conformation polymorphism followed by silver staining.Statistical analyses were performed with either the χ 2 test with Yates continuity correction or Fisher’s exact test,and statistical significance for expression analysis was assessed using an unpaired Student’s t-test.RESULTS:Methylation was not detected in the promoter regions of MLH1 and MGMT in gastric biopsy samples from children,regardless of H.pylori infection status.The MGMT promoter was methylated in 51% of chronic gastritis adult patients and was associated with H.pylori infection(P < 0.05);this region was methylated in 66% of gastric cancer patients,and the difference in the percentage of methylated samples between these patients and those from H.pylori-infected chronic gastritis patients was statistically significant(P < 0.05).MLH1 methylation frequencies among H.pylori-infected and non-infected chronic gastritis adult patients were 13% and 7%,respectively.We observed methylation of the MLH1 promoter(39%) and increased MSI levels(68%) in samples from gastric cancer patients in comparison to samples from H.pylori-infected adult chronic gastritis patients(P < 0.001 and P < 0.01,respectively).The frequency of promoter methylation for both genes was higher in gastric cancer samples than in H.pylori-positiv