Monoclonal origin of B lymphocyte colony-forming cells in spleen colonies formed by multipotential hemopoietic stem cells

Spleen colonies produced by transplanting lethally irradiated mice with either 12 day fetal liver or adult bone marrow cells were found to contain B- lymphocyte colony-forming cells (BL-CFC) . The proportion of BL-CFC positive spleen colonies did not increase substantially between 8 and 14 days after transplantation, the range being 18-45 percent. However, the absolute number of BL-CFC per spleen colony varied considerably (between 1 and 10,318), although the majority of colonies contained less than 200 BL-CFC. Irrespective of the time after transplantation, smaller spleen colonies were found to have a higher frequency of BL-CFC than larger spleen colonies. To determine the possible clonal origin of BL-CFC from spleen colony- forming unit (CFU-S), CBA mice were injected with equal numbers of CBA and CBA T(6)/T(6) fetal liver or adult bone marrow cells. Analysis of 7-15-day spleen colonies demonstrated that 90 percent were either exclusively T(6) positive or T(6) negative and approximately equal numbers ofboth colony types were observed. B-lymphocyte colonies were grown and successfully karyotyped from 19 spleen colonies. When compared with the original spleen colony karyotype the B-lymphocyte colony cells karyotype was identical in all 19 cases. In 3 of the 19 colonies analyzed a mixture of T(6) positive and T(6) negative karyotypes was present and identical proportions of the karyotypes were present in the pooled B-lymphocyte colony cells and spleen colony cells. The data indicate that the B-lymphocyte colony-forming cells detected in spleen colonies are genuine members of the hemopoietic clone derived from the initiating hemopoietic stem cell (CFU-S)

An Acute Bout of Exercise Improves the Cognitive Performance of Older Adults.

There is evidence that an acute bout of exercise confers cognitive benefits, but it is largely 2 unknown what the optimal mode and duration of exercise is and how cognitive performance 3 changes over time after exercise. We compared the cognitive performance of 31 older adults 4 using the Stroop test before, immediately after, and at 30 and 60 minutes after a 10 and 30 5 minute aerobic or resistance exercise session. Heart rate and feelings of arousal were also 6 measured before, during and after exercise. We found that independent of mode or duration of 7 exercise, the participants improved in the Stroop Inhibition task immediately post-exercise. We 8 did not find the exercise influenced the performance of the Stroop Color or Stroop Word 9 Interference tasks. Our findings suggest that an acute bout of exercise can improve cognitive 10 performance, and in particular the more complex executive functioning, of older adults

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. First, we assessed the effect of gestational VPA on fetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses which are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied - inbred Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic generalized epilepsy, and inbred Non-Epileptic Control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Fetuses were extracted via C-section on gestational day 21 (one day prior to birth) and fetal brains were snap frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes down-regulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function, and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic fetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation

TIMI frame count and adverse events in women with no obstructive coronary disease: A pilot study from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Background: TIMI frame count (TFC) predicts outcomes in patients with obstructive coronary artery disease (CAD); it remains unclear whether TFC predicts outcomes in patients without obstructive CAD. Methods: TFC was determined in a sample of women with no obstructive CAD enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study. Because TFC is known to be higher in the left anterior descending artery (LAD), TFC determined in the LAD was divided by 1.7 to provide a corrected TFC (cTFC). Results: A total of 298 women, with angiograms suitable for TFC analysis and long-term (6-10 year) follow up data, were included in this sub-study. Their age was 55±11 years, most were white (86%), half had a history of smoking, and half had a history of hypertension. Higher resting cTFC was associated with a higher rate of hospitalization for angina (34% in women with a cTFC >35, 15% in women with a cTFC ≤35, P<0.001). cTFC provided independent prediction of hospitalization for angina after adjusting for many baseline characteristics. In this cohort, resting cTFC was not predictive of major events (myocardial infarction, heart failure, stroke, or all-cause death), cardiovascular events, all-cause mortality, or cardiovascular mortality. Conclusions: In women with signs and symptoms of ischemia but no obstructive CAD, resting cTFC provides independent prediction of hospitalization for angina. Larger studies are required to determine if resting TFC is predictive of major events in patients without obstructive coronary artery disease. © 2014 Petersen et al

The effect of time constraint on anticipation, decision making, and option generation in complex and dynamic environments

Researchers interested in performance in complex and dynamic situations have focused on how individuals predict their opponent(s) potential courses of action (i.e., during assessment) and generate potential options about how to respond (i.e., during intervention). When generating predictive options, previous research supports the use of cognitive mechanisms that are consistent with long-term working memory (LTWM) theory (Ericsson and Kintsch in Phychol Rev 102(2):211–245, 1995; Ward et al. in J Cogn Eng Decis Mak 7:231–254, 2013). However, when generating options about how to respond, the extant research supports the use of the take-the-first (TTF) heuristic (Johnson and Raab in Organ Behav Hum Decis Process 91:215–229, 2003). While these models provide possible explanations about how options are generated in situ, often under time pressure, few researchers have tested the claims of these models experimentally by explicitly manipulating time pressure. The current research investigates the effect of time constraint on option-generation behavior during the assessment and intervention phases of decision making by employing a modified version of an established option-generation task in soccer. The results provide additional support for the use of LTWM mechanisms during assessment across both time conditions. During the intervention phase, option-generation behavior appeared consistent with TTF, but only in the non-time-constrained condition. Counter to our expectations, the implementation of time constraint resulted in a shift toward the use of LTWM-type mechanisms during the intervention phase. Modifications to the cognitive-process level descriptions of decision making during intervention are proposed, and implications for training during both phases of decision making are discussed

Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films

Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B$^+$) and phosphorous (P$^+$) ions. Different samples, prepared by varying the ion dose in the range $10^{14}$ to 5 x $10^{15}$ and ion energy in the range 150-350 keV, were investigated by the Raman spectroscopy, photoluminescence (PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman results from dose dependent B$^+$ implanted samples show red-shifted and asymmetrically broadened Raman line-shape for B$^+$ dose greater than $10^{14}$ ions cm$^{-2}$. The asymmetry and red shift in the Raman line-shape is explained in terms of quantum confinement of phonons in silicon nanostructures formed as a result of ion implantation. PL spectra shows size dependent visible luminescence at $\sim$ 1.9 eV at room temperature, which confirms the presence of silicon nanostructures. Raman studies on P$^+$ implanted samples were also done as a function of ion energy. The Raman results show an amorphous top SOS surface for sample implanted with 150 keV P$^+$ ions of dose 5 x $10^{15}$ ions cm$^{-2}$. The nanostructures are formed when the P$^+$ energy is increased to 350 keV by keeping the ion dose fixed. The GAXRD results show consistency with the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in SILICON(SPRINGER

Optimal drug combinations and minimal hitting sets

<p>Abstract</p> <p>Background</p> <p>Identifying effective drug combinations that significantly improve over single agents is a challenging problem. Pairwise combinations already represent a huge screening effort. Beyond two drug combinations the task seems unfeasible.</p> <p>Results</p> <p>In this work we introduce a method to uncover drug combinations with a putative effective response when presented to a heterogeneous population of malignant agents (strains), such as cancer cell lines or viruses. Using data quantifying the effect of single drugs over several individual strains, we search for minimal drug combinations that successfully target all strains. We show that the latter problem can be mapped to a minimal hitting set problem in mathematics. We illustrate this approach using data for the NCI60 panel of tumor derived cell lines, uncovering 14 anticancer drug combinations.</p> <p>Conclusion</p> <p>The drug-response graph and the associated minimal hitting set method can be used to uncover effective drug combinations in anticancer drug screens and drug development programs targeting heterogeneous populations of infectious agents such as HIV.</p

Mean Dietary Salt Intake in Urban and Rural Areas in India: A Population Survey of 1395 Persons.

BACKGROUND: The scientific evidence base in support of population-wide salt reduction is strong, but current high-quality data about salt intake levels in India are mostly absent. This project sought to estimate daily salt consumption levels in selected communities of Delhi and Haryana in north India and Andhra Pradesh in south India. METHODS AND RESULTS: In this study, 24-hour urine samples were collected using an age- and sex-stratified sampling strategy in rural, urban, and slum areas. Salt intake estimates were made for the overall population of each region and for major subgroups by weighting the survey data for the populations of Delhi and Haryana, and Andhra Pradesh. Complete 24-hour urine samples were available for 637 participants from Delhi and Haryana and 758 from Andhra Pradesh (65% and 68% response rates, respectively). Weighted mean population 24-hour urine excretion of salt was 8.59 g/day (95% CI 7.68-9.51) in Delhi and Haryana and 9.46 g/day (95% CI 9.06-9.85) in Andhra Pradesh (P=0.097). Estimates inflated to account for the minimum likely nonurinary losses of sodium provided corresponding estimates of daily salt intake of 9.45 g/day (95% CI 8.45-10.46) and 10.41 g/day (95% CI 9.97-10.84), respectively. CONCLUSIONS: Salt consumption in India is high, with mean population intake well above the World Health Organization recommended maximum of 5 g/day. A national salt reduction program would likely avert much premature death and disability