Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic gene panel.

The clinical benefits of the MammaPrint® signature for breast cancer is well documented; however, how these genes are related to cell cycle perturbation have not been well determined. Our single-cell transcriptome mapping (algorithm) provides details into the fine perturbation of all individual genes during a cell cycle, providing a view of the cell-cycle-phase specific landscape of any given human genes. Specifically, we identified that 38 out of the 70 (54%) MammaPrint® signature genes are perturbated to a specific phase of the cell cycle. The MammaPrint® signature panel derived its clinical prognosis power from measuring the cell cycle activity of specific breast cancer samples. Such cell cycle phase index of the MammaPrint® signature suggested that measurement of the cell cycle index from tumors could be developed into a prognosis tool for various types of cancer beyond breast cancer, potentially improving therapy through targeting a specific phase of the cell cycle of cancer cells

The role of GDNF family ligand signalling in the differentiation of sympathetic and dorsal root ganglion neurons

The diversity of neurons in sympathetic ganglia and dorsal root ganglia (DRG) provides intriguing systems for the analysis of neuronal differentiation. Cell surface receptors for the GDNF family ligands (GFLs) glial cell-line-derived neurotrophic factor (GDNF), neurturin and artemin, are expressed in subpopulations of these neurons prompting the question regarding their involvement in neuronal subtype specification. Mutational analysis in mice has demonstrated the requirement for GFL signalling during embryonic development of cholinergic sympathetic neurons as shown by the loss of expression from the cholinergic gene locus in ganglia from mice deficient for ret, the signal transducing subunit of the GFL receptor complex. Analysis in mutant animals and transgenic mice overexpressing GFLs demonstrates an effect on sensitivity to thermal and mechanical stimuli in DRG neurons correlating at least partially with the altered expression of transient receptor potential ion channels and acid-sensitive cation channels. Persistence of targeted cells in mutant ganglia suggests that the alterations are caused by differentiation effects and not by cell loss. Because of the massive effect of GFLs on neurite outgrowth, it remains to be determined whether GFL signalling acts directly on neuronal specification or indirectly via altered target innervation and access to other growth factors. The data show that GFL signalling is required for the specification of subpopulations of sensory and autonomic neurons. In order to comprehend this process fully, the role of individual GFLs, the transduction of the GFL signals, and the interplay of GFL signalling with other regulatory pathways need to be deciphered

Analysis of abdominal training role of strengthening and muscledefinition

El presente documento tiene como objetivo socializar los diferentes métodos de entrenamiento que conllevan a un desarrollo óptimo de la fuerza y la definición abdominal, este músculo debido a sus funciones, apariencia y ubicación dentro del cuerpo, es indispensable tanto en la actividad física y fitness como en el deporte de altos logros en los que la fuerza abdominal ayuda a realizar los gestos deportivos de manera correcta y prevenir lesiones. Además, en los campos dela salud y de la estética, un abdomen delgado y bien definido es fundamental para los parámetros actuales de imagen. Sin embargo, a pesar de su importancia, la mayor parte dela población es reacia al entrenamiento abdominal, debido a su dificultad aparente, al gran esfuerzo y constancia que se debe aplicar para la consecución de los resultados deseados o al desconocimiento de su entrenamiento. Para lograr los resultados es necesario ejercitarlo de manera constante e ir de la mano con una alimentación adecuada para conseguir resultados adecuados y pertinentes.This document aims to socialize the different training methods that lead to optimal development of strengt hand abdominal definition, this muscle due to their functions, appearance and location with in the body, it is essential to both physical activity and fitness as in the sport of high achievements in the abdominal strength that helps to make sports gestures correctly and prevent injuries. Furthermore, in the fields of health and aesthetics, a thin abdomen and it is essential for well defined current imaging parameters. How ever, despite its importance, most of the population is reluctant to abdominal training, because of its apparent difficulty, the great effort and perseverance to be applied to achieve the desired results or lack of training. To achieve the results you need to exercise constantly and go hand in hand with proper nutrition for optimal results.Incluye referencias bibliográfica

Prenatal cocaine exposure reduced NMDA/Glycine and K⁺-depolarization induced BDNF and proBDNF release in hippocampi (a) and PFCX (b).

<p>Hippocampal and PFCX slices prepared from P21 prenatal cocaine- and saline-treated rats were used to determine spontaneous BDNF/proBDNF efflux as well as BDNF and proBDNF release induced by 10-min 10 μM NMDA/1 μM glycine in LMKR or 1-min 65 mM K⁺-depolarization in a superfusion system. BDNF and proBDNF in the perfusate were then immunoprecipitated with immobilized anti- BDNF and determined by Western blotting with anti-BDNF. The brain slices were collected, homogenized and solubilized and the level of β-actin in the brain slices was determined by Western blotting to illustrate equal quantities of tissues. The blots were quantified by densitometric scanning. Data are expressed as means ± s.e.m. of the ratios of BDNF or proBDNF optical intensity to the optical intensity of β-actin. n = 6. **p < 0.05, *p < 0.01 compared to LMKR-treated in the same group. ##p < 0.05, #p < 0.01 compared to respective protein in the saline-treated group.</p

Prenatal cocaine exposure increased BDNF binding affinity for TrkB.

<p>Prenatal cocaine exposure increased BDNF binding affinity for TrkB by 18- and 15- fold (dotted lines) in biotinylated hippocampal and PFCX synaptic membranes, respectively from P21 prenatal cocaine- and saline-treated rats. In the control membranes, there were two BDNF binding sites, a high-affinity site (KD1) and a low-affinity site (KD2) (solid lines). Prenatal cocaine exposure also increased the low-affinity binding of BDNF by 82- and 12-fold. Nonlinear regression data curve fit was performed using Prism. Data points are the means and vertical bars are the s.e.m. derived from 6 independent rats (3 males and 3 females) in each treatment group.</p

<i>Ex vivo</i> exposure to 50–200 ng/ml BDNF did not alter the expression of full-length (145-KDa) and truncated (95-KDa) TrkB and p75NTR in BDNF-incubated hippocampal and prefrontal cortical slices.

<p>The abundance of 145- and 95-KDa TrkB (a, b) as well as p75NTR (c, d) in 50 μg post-mitochondrial synaptosome-enriched fractions prepared from hippocampal and PFCX slices of P21 prenatal cocaine- and saline-exposed rats following 30-min incubation with 50–200 ng/ml BDNF were compared by Western blotting. The blots were stripped and re-probed with anti-β-actin to validate equal loading. Densitometric quantification of blots revealed no discernible differences in 145- and 95-KDa TrkB as well as p75NTR expression levels as a result of incubation with BDNF. n = 4. Data are mean ± s.e.m. of the ratio of 145-, 95-KDa TrkB, p75NTR to β-actin optical intensities.</p

Prenatal cocaine exposure increased 50 ng/ml BDNF-induced TrkB activation in hippocampi and PFCX.

<p>(a) Representative blots showing prenatal cocaine exposure increased 50 ng/ml BDNF-induced TrkB activation in hippocampi and PFCX evidenced by higher activated (tyrosine-phosphorylated [pY]) TrkB. (b) Summary of the densitometric quantification of the pY and total 145- and 95-KDa TrkB. The data are expressed as the ratios of pY- full-length (145-KDa) and truncated TrkB (95-KDa) optical intensity normalized by the optical intensity of total 145- and 95-KDaTrkB, respectively. n = 6 (3 females and 3 males). Data are reported as means ± s.e.m. of the ratio of pY-TrkB to TrkB optical intensities. *p < 0.01, **p < 0.05 compared to respective protein in the saline-treated group.</p

Prenatal cocaine exposure did not alter the expression levels of full-length (145-KDa) and truncated (95-KDa) TrkB, p75^NTR, pro-BDNF and BDNF, Akt1 and ERK2, N-Shc and Shc, as well as NR1 and PLC-γ1 in both hippocampus and prefrontal cortex.

<p>The expression levels of 145- and 95-KDa TrkB (a). P75NTR (b), pro-BDNF and BDNF (c) as well as Akt1 and ERK2(d), Shc and N-Shc (e), NR1 and PLC-γ1(f), in 50 μg post-mitochondrial synaptosome-enriched fractions prepared from hippocampi and PFCX of P21 rats exposed to saline or cocaine <i>in utero</i> were compared by Western blotting. The blots were stripped and re-probed with anti-β-actin to validate equal loading. Densitometric quantification of blots revealed no discernible differences in 145- and 95-KDa TrkB, P75NTR, proBDNF and BDNF, Akt1, ERK2, Shc and N-Shc, NR1 and PLC-γ1 expression levels. n = 4. Data are mean ± s.e.m. of the ratio of 145-, 95-KDa TrkB, p75^NTR, proBDNF, BDNF, Akt1, ERK2, N-Shc, Shc, NR1 or PLC-γ1to β-actins optical intensities.</p