Depletion of Mannose Receptor-Positive Tumor-associated Macrophages via a Peptide-targeted Star-shaped Polyglutamate Inhibits Breast Cancer Progression in Mice.

Unlabelled: Although many studies have explored the depletion of tumor-associated macrophages (TAM) as a therapeutic strategy for solid tumors, currently available compounds suffer from poor efficacy and dose-limiting side effects. Here, we developed a novel TAM-depleting agent ("OximUNO") that specifically targets CD206 TAMs and demonstrated efficacy in a triple-negative breast cancer (TNBC) mouse model. OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX).

Frataxin Deficit Leads to Reduced Dynamics of Growth Cones in Dorsal Root Ganglia Neurons of Friedreich's Ataxia YG8sR Model: A Multilinear Algebra Approach.

Computational techniques for analyzing biological images offer a great potential to enhance our knowledge of the biological processes underlying disorders of the nervous system. Friedreich's Ataxia (FRDA) is a rare progressive neurodegenerative inherited disorder caused by the low expression of frataxin, which is a small mitochondrial protein. In FRDA cells, the lack of frataxin promotes primarily mitochondrial dysfunction, an alteration of calcium (Ca) homeostasis and the destabilization of the actin cytoskeleton in the neurites and growth cones of sensory neurons.

Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation.

Background: Alcohol exposure impairs brain development and leads to a range of behavioural and cognitive dysfunctions, termed as foetal alcohol spectrum disorders. Although different mechanisms have been proposed to participate in foetal alcohol spectrum disorders, the molecular insights of such effects are still uncertain. Using a mouse model of foetal alcohol spectrum disorder, we have previously shown that maternal binge-like alcohol drinking causes persistent effects on motor, cognitive and emotional-related behaviours associated with neuroimmune dysfunctions.

Phosphodiesterase Inhibitors Revert Axonal Dystrophy in Friedreich's Ataxia Mouse Model.

Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by an unstable GAA repeat expansion within intron 1 of the FXN gene and characterized by peripheral neuropathy. A major feature of FRDA is frataxin deficiency with the loss of large sensory neurons of the dorsal root ganglia (DRG), namely proprioceptive neurons, undergoing dying-back neurodegeneration with progression to posterior columns of the spinal cord and cerebellar ataxia. We used isolated DRGs from a YG8R FRDA mouse model and C57BL/6J control mice for a proteomic study and a primary culture of sensory neurons from DRG to test novel pharmacological strategies.

Reversible Axonal Dystrophy by Calcium Modulation in Frataxin-Deficient Sensory Neurons of YG8R Mice.

Friedreich's ataxia (FRDA) is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG) of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux.

Characterization of the new human pleomorphic undifferentiated sarcoma TP53-null cell line mfh-val2.

Pleomorphic undifferentiated sarcoma (PUS), also called malignant fibrous histiocytoma, is a soft tissue sarcoma which occurs predominantly in the extremities. Its origin is a poorly defined mesenchymal cell, which derives to histiocytic and fibroblastic cells. The patient, a 58 year-old man, presented a lesion located in the forearm composed by spindle cells and multinucleated giant cells, which expressed vimentin and adopted a histological pattern formed by irregular-swirling fascicles.

Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features.

The in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY), and hMSC (46, XY)) into a germ cell-like phenotype in vitro.

Comparative RNA-seq analysis of the Tritrichomonas foetus PIG30/1 isolate from pigs reveals close association with Tritrichomonas foetus BP-4 isolate 'bovine genotype'.

Tritrichomonas foetus was described as a commensal of the stomach, caecum and nasal cavity of pigs before it was recognised as the cause of reproductive tract disease of cattle. T. foetus also causes chronic large bowel diarrhoea in domestic cats.

Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.

This study aimed to identify the underlying molecular genetic cause in four Spanish families clinically diagnosed of Retinitis Pigmentosa (RP), comprising one autosomal dominant RP (adRP), two autosomal recessive RP (arRP) and one with two possible modes of inheritance: arRP or X-Linked RP (XLRP). We performed whole exome sequencing (WES) using NimbleGen SeqCap EZ Exome V3 sample preparation kit and SOLID 5500xl platform. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation and the absence in local control population.

Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations.

Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words.

Next maSigPro: updating maSigPro bioconductor package for RNA-seq time series.

Motivation: The widespread adoption of RNA-seq to quantitatively measure gene expression has increased the scope of sequencing experimental designs to include time-course experiments. maSigPro is an R package specifically suited for the analysis of time-course gene expression data, which was developed originally for microarrays and hence was limited in its application to count data.

Results: We have updated maSigPro to support RNA-seq time series analysis by introducing generalized linear models in the algorithm to support the modeling of count data while maintaining the traditional functionalities of the package.

Programmed cell death activated by Rose Bengal in Arabidopsis thaliana cell suspension cultures requires functional chloroplasts.

Light-grown Arabidopsis thaliana cell suspension culture (ACSC) were subjected to mild photooxidative damage with Rose Bengal (RB) with the aim of gaining a better understanding of singlet oxygen-mediated defence responses in plants. Additionally, ACSC were treated with H2O2 at concentrations that induced comparable levels of protein oxidation damage. Under low to medium light conditions, both RB and H2O2 treatments activated transcriptional defence responses and inhibited photosynthetic activity, but they differed in that programmed cell death (PCD) was only observed in cells treated with RB.

Cells, stem cells, and cancer stem cells.

The stem cell field owes a great deal to the previous work conducted by embryologists and researchers devoted to reproductive medicine. The time is coming when this emerging field will pay off in the reproductive sciences by offering new avenues of understanding gametogenesis and early embryonic development. Human embryonic stem cells are pluripotent cells that proliferate in vitro while maintaining an undifferentiated state, and they are capable of differentiating into most cell types under appropriate conditions.

In vitro production of haploid cells after coculture of CD49f+ with Sertoli cells from testicular sperm extraction in nonobstructive azoospermic patients.

Objective: To isolate CD49f+ cells from testicular sperm extraction (TESE) samples of azoospermic patients and induce meiosis by coculturing these cells with Sertoli cells.

Design: Prospective analysis.

Setting: Research center.

Human embryonic stem cells derived in xeno-free conditions.

In this chapter, we describe the derivation and characterization of nine hIn this chapter, we describe the derivation and characterization of nine human embryonic stem cells (hESC) (VAL-3 to -11B) from different developmental embryo stages (inner cell mass from a blastocyst, morula, and blastomere from a 3-day embryo) under xeno-free conditions providing the necessary protocols and techniques to carry out their derivation, characterization, and propagation.

Neuronal polarization is impaired in mice lacking RhoE expression.

Proper development of neuronal networks relies on the polarization of the neurons, thus the establishment of two compartments, axons and dendrites, whose formation depends on cytoskeletal rearrangements. Rnd proteins are regulators of actin organization and they are important players in several aspects of brain development as neurite formation, axon guidance and neuron migration. We have recently demonstrated that mice lacking RhoE/Rnd3 expression die shortly after birth and have neuromotor impairment and neuromuscular alterations, indicating an abnormal development of the nervous system.

Overcoming challenges of ovarian cancer stem cells: novel therapeutic approaches.

Understanding the genetic and molecular mechanisms of ovarian cancer has been the focus of research efforts working toward the greater goal of improving cancer therapy for patients with residual disease after initial treatment with conventional surgery and neoadjuvant chemotherapy. The focus of this review will be centered on new therapeutic strategies based on Cancer Stem Cells studies of chemoresistant subpopulations, the prevention of metastasis, and individualized therapy in order to find the most successful combination of treatments to effectively treat human ovarian cancer. We reviewed recent literature (1993-2011) of novel treatment approaches to ovarian cancer stem cells.

Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is Dependent on Clathrin-mediated Endocytosis.

Unlabelled: Enforced cell transdifferentiation of human cancer cells is a promising alternative to conventional chemotherapy. We previously identified albumin-associated lipid- and, more specifically, saturated fatty acid-induced transdifferentiation programs in human cancer cells (HCCLs). In this study, we further characterized the adipocyte-like cells, resulting from the transdifferentiation of human cancer cell lines MCF-7 and MALME-3M, and proposed a common mechanistic approach for these transdifferentiating programs.

Pkc1 and actin polymerisation activities play a role in ribosomal gene repression associated with secretion impairment caused by oxidative stress.

In Saccharomyces cerevisiae, the cell integrity pathway plays a role in the oxidative stress response. In this study, we show that the Pkc1 protein mediates oxidative signalling by helping to downregulate ribosomal gene expression when cells are exposed to hydrogen peroxide. An active actin cytoskeleton is required for this function, because the cells blocked in actin polymerisation were unable to repress ribosomal gene transcription.

Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain.

The brain is one of the major target organs of alcohol actions. Alcohol abuse can lead to alterations in brain structure and functions and, in some cases, to neurodegeneration. Cognitive deficits and alcohol dependence are highly damaging consequences of alcohol abuse.

Specific unsaturated fatty acids enforce the transdifferentiation of human cancer cells toward adipocyte-like cells.

Differentiation therapy pursues the discovery of novel molecules to transform cancer progression into less aggressive phenotypes by mechanisms involving enforced cell transdifferentiation. In this study, we examined the identification of transdifferentiating adipogenic programs in human cancer cell lines (HCCLs). Our findings showed that specific unsatturated fatty acids, such as palmitoleic, oleic and linoleic acids, trigger remarkable phenotypic modifications in a large number of human cancer cell lines (HCCLs), including hepatocarcinoma HUH-7, ovarian carcinoma SK-OV-3, breast adenocarcinoma MCF-7 and melanoma MALME-3M.

Derivation, characterization, differentiation, and registration of seven human embryonic stem cell lines (VAL-3, -4, -5, -6M, -7, -8, and -9) on human feeder.

Derivation of human embryonic stem cell lines has been a remarkable scientific achievement during the last decade. Human embryonic stem cells are regarded as an unlimited cell source for replacement therapy in regenerative medicine. Clearly, the scientific community requires proper derivation, characterization, and registration with the purpose of making them available for research and future medical applications worldwide.

Developments and challenges in human embryonic stem cell research in Spain.

After years of following the trail of others, Spain is finally making a serious bid in science, specifically in regenerative medicine. In the framework of the European Union, Spain is setting up the basis for a solid collaborative network between public and private institutions, involving basic, translational, applied, technological and clinical researchers. In a society characterised by the idiom "slow but secure", it is still too soon to see the results of the huge economic and infrastructure investment made.

BCL6: somatic mutations and expression in early-stage chronic lymphocytic leukemia.

BCL6 somatic mutations affect normal and tumoral post germinal center B-lymphocytes. Our objective was to analyse expression, mutations and polymorphisms in the BCL6 gene and to correlate those variables with the clinical outcome in early-stage chronic lymphocytic leukemia (CLL). CLL samples were used for characterisation of the mutational status of BCL6/ immunoglobulin variable heavy chain (IGHV) genes, and expression of BCL6 was determined by real time PCR and immunoblot.