Reprogramming to pluripotency using designer TALE transcription factors targeting enhancers.

The modular DNA recognition code of the transcription-activator-like effectors (TALEs) from plant pathogenic bacterial genus Xanthomonas provides a powerful genetic tool to create designer transcription factors (dTFs) targeting specific DNA sequences for manipulating gene expression. Previous studies have suggested critical roles of enhancers in gene regulation and reprogramming. Here, we report dTF activator targeting the distal enhancer of the Pou5f1 (Oct4) locus induces epigenetic changes, reactivates its expression, and substitutes exogenous OCT4 in reprogramming mouse embryonic fibroblast cells (MEFs) to induced pluripotent stem cells (iPSCs).

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study.

Background: Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC.

Methods: Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.

Association of exon 19 and 21 EGFR mutation patterns with treatment outcome after first-line tyrosine kinase inhibitor in metastatic non-small-cell lung cancer.

Background: This study investigated whether there were differential survival outcomes to first-line tyrosine kinase inhibitors (TKI) in patients with metastatic non-small-cell lung cancer harboring different subtypes of exon 19 and exon 21 mutations on epidermal growth factor receptor (EGFR).

Methods: Of 452 patients with stage IIIB and IV non-small-cell lung cancer, 192 patients (42.5%) harbored EGFR mutation and 170 (37.

Columnar cell-like changes in the male breast.

Aims: Columnar cell lesions are known as a link between normal breast and low grade neoplastic lesions in female, but have not been established in the male breast. This study evaluated the presence of ducts showing columnar cell-like features in the male breast.

Methods: Seventy-one consecutive surgical resections from men (6 invasive breast carcinoma of grade 3, 1 atypical ductal hyperplasia and 64 other lesions) were reviewed to identify foci of dilated ducts with columnar epithelial cells, and their morphological features including apical snouts, intraluminal secretions and calcifications were assessed.

CX3CL1 expression is associated with poor outcome in breast cancer patients.

The significance of chemokines in cancer biology has been widely recognized in recent years. CX3CL1 is a unique subclass of chemokine with complex functions, including recruitment of anti-tumor leukocytes and promoting cancer survival, thus affecting cancer progression in both the directions. It is not clear how these different functions interact in breast cancers.

Probing the bonding in nitrogen-doped graphene using electron energy loss spectroscopy.

Precise control of graphene properties is an essential step toward the realization of future graphene devices. Defects, such as individual nitrogen atoms, can strongly influence the electronic structure of graphene. Therefore, state-of-the-art characterization techniques, in conjunction with modern modeling tools, are necessary to identify these defects and fully understand the synthesized material.

Acute refractory hypoxemia after chest trauma reversed by high-frequency oscillatory ventilation: a case report.

Introduction: Polytrauma often results in significant hypoxemia secondary to direct lung contusion or indirectly through atelectasis, systemic inflammatory response, large volume fluid resuscitation and blood product transfusion. In addition to causing hypoxemia, atelectasis and acute lung injury can lead to right ventricular failure through an acute increase in pulmonary vascular resistance. Mechanical ventilation is often applied, accompanied with recruitment maneuvers and positive end-expiratory pressure in order to recruit alveoli and reverse atelectasis, while preventing excessive alveolar damage.

Development and evaluation of a de-identification procedure for a case register sourced from mental health electronic records.

Background: Electronic health records (EHRs) provide enormous potential for health research but also present data governance challenges. Ensuring de-identification is a pre-requisite for use of EHR data without prior consent. The South London and Maudsley NHS Trust (SLaM), one of the largest secondary mental healthcare providers in Europe, has developed, from its EHRs, a de-identified psychiatric case register, the Clinical Record Interactive Search (CRIS), for secondary research.

CD73 expression on extracellular vesicles derived from CD4+ CD25+ Foxp3+ T cells contributes to their regulatory function.

CD4(+)CD25(+)Foxp3(+) Treg cells maintain immunological tolerance. In this study, the possibility that Treg cells control immune responses via the production of secreted membrane vesicles, such as exosomes, was investigated. Exosomes are released by many cell types, including T cells, and have regulatory functions.

Leukemia cell-rhabdovirus vaccine: personalized immunotherapy for acute lymphoblastic leukemia.

Purpose: Acute lymphoblastic leukemia (ALL) remains incurable in most adults. It has been difficult to provide effective immunotherapy to improve outcomes for the majority of patients. Rhabdoviruses induce strong antiviral immune responses.

The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress.

The Center for Human Immunology, Autoimmunity, and Inflammation (CHI) is an exciting initiative of the NIH intramural program begun in 2009. It is uniquely trans-NIH in support (multiple institutes) and leadership (senior scientists from several institutes who donate their time). Its goal is an in-depth assessment of the human immune system using high-throughput multiplex technologies for examination of immune cells and their products, the genome, gene expression, and epigenetic modulation obtained from individuals both before and after interventions, adding information from in-depth clinical phenotyping, and then applying advanced biostatistical and computer modeling methods for mining these diverse data.

Characterization of CACNA2D3 as a putative tumor suppressor gene in the development and progression of nasopharyngeal carcinoma.

Apart from β-catenin accumulation, loss of 3p21 is one of the most frequent genetic alterations in numerous malignancies including nasopharyngeal carcinoma (NPC). Herein, we characterized a novel candidate tumor suppressor gene (TSG) CACNA2D3, a voltage-dependent subunit alpha 2 delta 3 of a calcium channel complex. Downregulation of CACNA2D3 was frequently detected in primary NPCs and NPC cell lines compared with their nontumorigenic counterparts.

From finger pricks to point-and-click.

In this issue of Immunity, Obermoser et al. (2013) systematically analyze and compare the blood-transcriptomic response of the pneumococcal and influenza vaccines in humans over multiple time points spanning hours to tens of days. They then present web-based interactive figures that facilitate exploration of this large, complex data set.

Enhanced degradation of haloacid by heterologous expression in related Burkholderia species.

Haloacids are environmental pollutant and can be transformed to non-toxic alkanoic acids by microbial dehalogenase. Bacterium Burkholderia species MBA4 was enriched from soil for its ability to bioremediate haloacids such as mono-chloroacetate (MCA), mono-bromoacetate (MBA), 2-mono-chloropropionate, and 2-mono-bromopropionate. MBA4 produces an inducible dehalogenase Deh4a that catalyzes the dehalogenation process.

Post-esophagectomy gastric conduit cancers: treatment experiences and literature review.

Esophagectomy remains the mainstay of treatment for esophageal cancer. The stomach is the commonest organ used to restore intestinal continuity after esophagectomy. Metachronous gastric cancer in the gastric conduit after esophagectomy is rare; the etiology remains unclear.

Condition-specific measure was more responsive than generic measure in colorectal cancer: all but social domains.

Objective: To examine the responsiveness of generic and condition-specific instruments based on the anchor of self-reported level of global change in patients with colorectal cancer (CRC).

Study Design And Setting: Three hundred thirty-three patients with CRC were surveyed at two assessments at baseline and follow-up at 6 months from September 2009 to July 2010 using the Short Form-12 Health Survey version 2 (SF-12v2) and Functional Assessment of Cancer Therapy-Colorectal (FACT-C) measures. The responsiveness of the two measures was evaluated using standardized effect size, standardized response mean, responsiveness statistic, and receiver operating characteristic (ROC) curve analysis.

Fibrotic focus in breast carcinomas: relationship with prognostic parameters and biomarkers.

Background: Fibrotic focus (FF) has been observed in breast cancers and is suggested to be an important prognostic marker. However, most of these observations were reported by the same group of investigators with similar sample cohort. The relationship of FF and molecular subtypes as well as its associated prognosis has not been elucidated.

SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer.

In this study, we report the identification of a novel role of SIRT6 in both epirubicin and paclitaxel resistance in breast cancer. We found that SIRT6 protein levels are elevated in paclitaxel- and epirubicin-resistant MCF-7 cells compared with the parental sensitive cells. SIRT6 knockout and depletion sensitized cells to both paclitaxel and epirubicin treatment, whereas SIRT6 ectopic overexpression led to increased resistance to paclitaxel and epirubicin.

Expression of mammaglobin and gross cystic disease fluid protein-15 in breast carcinomas.

Immunohistochemical analysis of gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin (MGB) is frequently used in routine practice for assessment of metastases or regional recurrences of breast origin. Breast cancer is highly heterogeneous. Expression of these 2 markers in various breast cancer subtypes has not been well studied.

Inhibition of TGF-β signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophages.

Inadequate immunity that occurs in a tumor environment is in part due to the presence of M2-type tumor-associated macrophages (TAMs). TGF-β has a multi-functional role in tumor development including modulating the biological activity of both the tumor and TAMs. In this study, using an in vitro TAM/tumor cell co-culture system ligation of TLR7, which is expressed on TAMs but not the tumor cells, in the presence of TGF-β receptor I inhibitor re-programmed the phenotype of the TAMs.

Nerve growth factor receptor (NGFR): a potential marker for specific molecular subtypes of breast cancer.

Aims: Nerve growth factor receptor (NGFR) is a transmembrane receptor for the neurotrophin family. It acts either as tumour suppressor or oncogene depending on cellular context. Its role in breast cancers remained conflicting, possibly due to the heterogeneity of breast cancer subtypes.

Transports of acetate and haloacetate in Burkholderia species MBA4 are operated by distinct systems.

Background: Acetate is a commonly used substrate for biosynthesis while monochloroacetate is a structurally similar compound but toxic and inhibits cell metabolism by blocking the citric acid cycle. In Burkholderia species MBA4 haloacetate was utilized as a carbon and energy source for growth. The degradation of haloacid was mediated by the production of an inducible dehalogenase.

Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is IL-4 dependent.

Background: Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic graft rejection mediated by Th2 cytokines remains ill-defined.

Methodology/principal Findings: Wild type and adiponectin-null mice were used as graft recipients in mouse MHC class II disparate cardiac transplantation (bm12 toB6) and the graft rejection was monitored. In adiponectin-null mice we observed that the cellular infiltrate of eosinophils, CD4(+) and CD8(+) T cells was reduced in grafts compared to the controls as was collagen deposition and vessel occlusion.

Insertion mutations in Helicobacter pylori flhA reveal strain differences in RpoN-dependent gene expression.

Flagellar biogenesis in the gastric pathogen Helicobacter pylori involves a transcriptional hierarchy that utilizes all three sigma factors found in this bacterium (RpoD, RpoN and FliA). Transcription of the RpoN-dependent genes requires the sensor kinase FlgS and response regulator FlgR. It is thought that FlgS senses some cellular cue to regulate transcription of the RpoN-dependent flagellar genes, but this signal has yet to be identified.