Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis

<p>Abstract</p> <p>Background</p> <p>Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs) and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 were analyzed.</p> <p>Results</p> <p>Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs.</p> <p>Conclusion</p> <p>These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets.</p

Optimised use of Oxford Nanopore Flowcells for Hybrid Assemblies

Hybrid assemblies are highly valuable for studies of Enterobacteriaceae due to their ability to fully resolve the structure of mobile genetic elements, such as plasmids, which are involved in the carriage of clinically important genes (e.g. those involved in antimicrobial resistance/virulence). The widespread application of this technique is currently primarily limited by cost. Recent data have suggested that non-inferior, and even superior, hybrid assemblies can be produced using a fraction of the total output from a multiplexed nanopore [Oxford Nanopore Technologies (ONT)] flowcell run. In this study we sought to determine the optimal minimal running time for flowcells when acquiring reads for hybrid assembly. We then evaluated whether the ONT wash kit might allow users to exploit shorter running times by sequencing multiple libraries per flowcell. After 24 h of sequencing, most chromosomes and plasmids had circularized and there was no benefit associated with longer running times. Quality was similar at 12 h, suggesting that shorter running times are likely to be acceptable for certain applications (e.g. plasmid genomics). The ONT wash kit was highly effective in removing DNA between libraries. Contamination between libraries did not appear to affect subsequent hybrid assemblies, even when the same barcodes were used successively on a single flowcell. Utilizing shorter run times in combination with between-library nuclease washes allows at least 36 Enterobacteriaceae isolates to be sequenced per flowcell, significantly reducing the per-isolate sequencing cost. Ultimately this will facilitate large-scale studies utilizing hybrid assembly, advancing our understanding of the genomics of key human pathogens

Radiation-Driven Shock and Debris Propagation Down a Partitioned Pipe

Two experiments have been performed to measure the effects of pulsed radiation loads on the front of small tubular structures, using as an energy source the X-ray fluence produced by a Z-pinch at the Sandia National Laboratories Z Facility. The project had two major goals: to establish the feasibility of using the Z machine to study the phenomenology associated with debris generation and propagation down tubular structures with partitions; and to use the resultant experimental data to validate numerical hydrocodes (shock physics codes) so that we have confidence in their use in analyzing these types of situations. Two tubular aluminum structures (5 and 10 cm long and 1 cm inside diameter) were prepared, with aluminum partitions located at the front, halfway down the pipe, and at the rear. Interferometry (VISARS) provided multiple velocity histories for all of the partitions. In both experiments, the first barrier, which was exposed directly to the x-ray fluence, was launched into the pipe at a velocity of {approximately}2 km/s, accelerating to give a mean velocity of approximately 2.6 km/s. Loss of plate integrity is inferred from the dispersed launch of the second partition at approx. 1 km/s. Wall shocks propagating at 4.5 km/s were inferred, although strain gage measurements did not succeed. Post-test metallography showed evidence of melting and partial vaporization of the plates, and turbulent mixing with material from the walls. Calculations qualitatively agree with the observed results, but slightly overpredict debris velocity, possibly due to overestimates of total energy fluence. An application for this work is the study of techniques for line-of-sight shock and debris mitigation on high-power pulse-power facilities such as Z and its follow-on machines

Importance of data structure in comparing two dimension reduction methods for classification of microarray gene expression data

BACKGROUND: With the advance of microarray technology, several methods for gene classification and prognosis have been already designed. However, under various denominations, some of these methods have similar approaches. This study evaluates the influence of gene expression variance structure on the performance of methods that describe the relationship between gene expression levels and a given phenotype through projection of data onto discriminant axes. RESULTS: We compared Between-Group Analysis and Discriminant Analysis (with prior dimension reduction through Partial Least Squares or Principal Components Analysis). A geometric approach showed that these two methods are strongly related, but differ in the way they handle data structure. Yet, data structure helps understanding the predictive efficiency of these methods. Three main structure situations may be identified. When the clusters of points are clearly split, both methods perform equally well. When the clusters superpose, both methods fail to give interesting predictions. In intermediate situations, the configuration of the clusters of points has to be handled by the projection to improve prediction. For this, we recommend Discriminant Analysis. Besides, an innovative way of simulation generated the three main structures by modelling different partitions of the whole variance into within-group and between-group variances. These simulated datasets were used in complement to some well-known public datasets to investigate the methods behaviour in a large diversity of structure situations. To examine the structure of a dataset before analysis and preselect an a priori appropriate method for its analysis, we proposed a two-graph preliminary visualization tool: plotting patients on the Between-Group Analysis discriminant axis (x-axis) and on the first and the second within-group Principal Components Analysis component (y-axis), respectively. CONCLUSION: Discriminant Analysis outperformed Between-Group Analysis because it allows for the dataset structure. An a priori knowledge of that structure may guide the choice of the analysis method. Simulated datasets with known properties are valuable to assess and compare the performance of analysis methods, then implementation on real datasets checks and validates the results. Thus, we warn against the use of unchallenging datasets for method comparison, such as the Golub dataset, because their structure is such that any method would be efficient

Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression

<p>Abstract</p> <p>Background</p> <p>We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA).</p> <p>Methods</p> <p>To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for.</p> <p>Results</p> <p>As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan.</p> <p>Conclusions</p> <p>We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation.</p

Review of research to inform California's climate scoping plan: Agriculture and working lands

Agriculture in California contributes 8% of the state's greenhouse gas (GHG) emissions. To inform the state's policy and program strategy to meet climate targets, we review recent research on practices that can reduce emissions, sequester carbon and provide other co-benefits to producers and the environment across agriculture and rangeland systems. Importantly, the research reviewed here was conducted in California and addresses practices in our specific agricultural, socioeconomic and biophysical environment. Farmland conversion and the dairy and intensive livestock sector are the largest contributors to GHG emissions and offer the greatest opportunities for avoided emissions. We also identify a range of other opportunities including soil and nutrient management, integrated and diversified farming systems, rangeland management, and biomass-based energy generation. Additional research to replicate and quantify the emissions reduction or carbon sequestration potential of these practices will strengthen the evidence base for California climate policy

Associations between anthropometric indicators in early life and low-grade inflammation, insulin resistance and lipid profile in adolescence

Background and AimsThe long-term relations between excessive adiposity in early childhood and unfavourable cardiometabolic profiles in later ages are not yet completely understood. We aimed to assess the associations between birth weight (BW) and BMI from 6 months to 6 years of age, with biomarkers indicative of low-grade inflammation, insulin resistance and lipid profiles in adolescence.Methods and ResultsRetrospective school-based study with 415 Portuguese adolescents (220 girls), mean age of 14.08±1.6 years old. Anthropometric data from birth to 6 years old was extracted from individual child health book records. Actual weight and height were measured and BMI calculated. Participants were classified at each time point as normal weight or overweight according to WHO reference values. Biomarkers were obtained from venous blood samples. Linear regressions were used to explore the associations between the biomarkers and early life anthropometric indicators. From 2 years onwards, BMI associated positively with the inflammatory score and HOMA-IR in adolescence. Children who were overweight/obese from 2 to 6 years of age presented significantly higher inflammatory score and HOMA-IR later in adolescence. TC/HDL ratio was also positively associated with BMI from the age of 5 years onwards. The associations between BMI and cardiometabolic outcomes remained positive in adolescence, with overweight adolescents presenting a higher inflammatory score, HOMA-IR and TC/HDL than normal weight adolescents.ConclusionA high BMI from an early age was consistently associated with worse inflammatory and lipid profiles and insulin resistance in adolescence. No associations were found between BW and the same studied outcomes

Subcortical brain atrophy persists even in HAART-regulated HIV disease

The purpose of this study was to determine the pattern and extent of caudate nucleus and putamen atrophy in HIV-infected men with well-controlled immune status and viral replication. 155 men underwent structural brain magnetic resonance imaging; 84 were HIV-infected and 71 were uninfected controls. MRI data were processed using the Fully Deformable Segmentation routine, producing volumes for the right and left caudate nucleus and putamen, and 3-D maps of spatial patterns of thickness. There was significant atrophy in the HIV-infected men in both the caudate and putamen, principally in the anterior regions. The volume of the basal ganglia was inversely associated with the time since first seropositivity, suggesting that either there is a chronic, subclinical process that continues in spite of therapy, or that the extent of the initial insult caused the extent of atrophy

RSPO3 impacts body fat distribution and regulates adipose cell biology in vitro

Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically increase RSPO3 expression in subcutaneous adipocytes. These variants are also associated with reduced lower-body fat, enlarged gluteal adipocytes and insulin resistance. Based on human cellular studies RSPO3 may limit gluteofemoral adipose tissue (AT) expansion by suppressing adipogenesis and increasing gluteal adipocyte susceptibility to apoptosis. RSPO3 may also promote upper-body fat distribution by stimulating abdominal adipose progenitor (AP) proliferation. The distinct biological responses elicited by RSPO3 in abdominal versus gluteal APs in vitro are associated with differential changes in WNT signalling. Zebrafish carrying a nonsense rspo3 mutation display altered fat distribution. Our study identifies RSPO3 as an important determinant of peripheral AT storage capacity

Delta1 Expression, Cell Cycle Exit, and Commitment to a Specific Secretory Fate Coincide within a Few Hours in the Mouse Intestinal Stem Cell System

The stem cells of the small intestine are multipotent: they give rise, via transit-amplifying cell divisions, to large numbers of columnar absorptive cells mixed with much smaller numbers of three different classes of secretory cells - mucus-secreting goblet cells, hormone-secreting enteroendocrine cells, and bactericide-secreting Paneth cells. Notch signaling is known to control commitment to a secretory fate, but why are the secretory cells such a small fraction of the population, and how does the diversity of secretory cell types arise? Using the mouse as our model organism, we find that secretory cells, and only secretory cells, pass through a phase of strong expression of the Notch ligand Delta1 (Dll1). Onset of this Dll1 expression coincides with a block to further cell division and is followed in much less than a cell cycle time by expression of Neurog3 – a marker of enteroendocrine fate – or Gfi1 – a marker of goblet or Paneth cell fate. By conditional knock-out of Dll1, we confirm that Delta-Notch signaling controls secretory commitment through lateral inhibition. We infer that cells stop dividing as they become committed to a secretory fate, while their neighbors continue dividing, explaining the final excess of absorptive over secretory cells. Our data rule out schemes in which cells first become committed to be secretory, and then diversify through subsequent cell divisions. A simple mathematical model shows how, instead, Notch signaling may simultaneously govern the commitment to be secretory and the choice between alternative modes of secretory differentiation