Cdc42 induces EGF receptor protein accumulation and promotes EGF receptor nuclear transport and cellular transformation.

Cdc42 is a Ras-related small GTP-binding protein. A previous study has shown that Cdc42 binding to the γ subunit of the coatomer protein complex (γCOP) is essential for Cdc42-regulated cellular transformation, but the molecular mechanism involved is not well understood. Here, we demonstrate that constitutively-active Cdc42 binding to γCOP induced the accumulation of epithelial growth factor receptor (EGFR) in the cells, sustained EGF-stimulated extracellular signal-regulated kinase (ERK), JUN amino-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) signaling and promoted cell division.

Contribution of transcription to animal early development.

In mature gametes and during the oocyte-to-embryo transition, transcription is generally silenced and gene expression is post-transcriptionally regulated. However, we recently discovered that major transcription can occur immediately after fertilization, prior to pronuclear fusion, and in the first cell division of the oocyte-to-embryo transition in the nematode Ascaris suum. We postulate that the balance between transcriptional and post-transcriptional regulation during the oocyte-to-embryo transition may largely be determined by cell cycle length and thus the time available for the genome to be transcribed.

Mitochondrial dynamics regulates hypoxia-induced migration and antineoplastic activity of cisplatin in breast cancer cells.

Mitochondria are high dynamic organelles with frequent fission and fusion. Here, we found hypoxia stimulated Drp1 expression, mitochondrial fission and migration in metastatic MDA-MB‑231 cells, but not in non-metastatic MCF-7 cells. Inhibition of Drp1-dependent mitochondrial fission by Mdivi-1 or silencing Drp1 attenuated hypoxia-induced mitochondrial fission and migration in MDA-MB‑231 cells.

[Role of central venous pressure, global end diastolic volume index and extravascular lung water index in evaluating fluid resuscitation in patients with septic shock].

Objective: To explore the role of central venous pressure (CVP), global end diastolic volume index (GEDI) and extravascular lung water index (ELWI) monitoring in patients with septic shock during fluid resuscitation by pulse induced continuous cardiac output (PiCCO) test.

Methods: Forty-six patients with severe sepsis and septic shock were enrolled in this study. Hemodynamic monitoring was performed during fluid resuscitation and the data including CVP, GEDI and ELWI were collected to analyze their relationship and the clinical values.

MoS2 nanoflowers with expanded interlayers as high-performance anodes for sodium-ion batteries.

MoS2 nanoflowers with expanded interlayer spacing of the (002) plane were synthesized and used as high-performance anode in Na-ion batteries. By controlling the cut-off voltage to the range of 0.4-3 V, an intercalation mechanism rather than a conversion reaction is taking place.

Parascaris univalens--a victim of large-scale misidentification?

The equine ascarid parasite Parascaris equorum is well known as a ubiquitous parasite infecting foals. A sibling species, Parascaris univalens, was first described over 130 years ago, but very little attention has been given to its existence and possible implications for anthelmintic resistance, clinical disease, or host age spectrum. P.

Vacuolar-type H(+)-ATPase subunits and the neurogenic protein big brain are required for optimal copper and zinc uptake.

Copper and zinc homeostasis in polarized epithelial cells requires the correct localization and regulation of membrane-bound transport proteins at the apical and basolateral cell membranes. We have identified a subunit of the vacuolar-type H(+)-ATPase (V-ATPase) complex, vhaPPA1-2, and the Drosophila aquaporin homolog big brain (bib), as being required for the correct localization of the copper uptake transporters Ctr1A and Ctr1B and the zinc uptake protein dZip89B and hence necessary for optimal copper and zinc accumulation in vivo. Knockdown of vhaPPA1-2 or bib resulted in cuticle hypo-pigmentation phenotypes typical of copper deficiency in the fly and induction of midgut Ctr1B expression, a known response to low cellular copper levels.

RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection.

Latent viral infection is a persistent cause of human disease. Although standard antiviral therapies can suppress active viral replication, no existing treatment can effectively eradicate latent infection and therefore a cure is lacking for many prevalent viral diseases. The prokaryotic immune system clustered regularly interspaced short palindromic repeat (CRISPR)/Cas evolved as a natural response to phage infections, and we demonstrate here that the CRISPR/Cas9 system can be adapted for antiviral treatment in human cells by specifically targeting the genomes of latent viral infections.

A quantitative comparison of single-cell whole genome amplification methods.

Single-cell sequencing is emerging as an important tool for studies of genomic heterogeneity. Whole genome amplification (WGA) is a key step in single-cell sequencing workflows and a multitude of methods have been introduced. Here, we compare three state-of-the-art methods on both bulk and single-cell samples of E.

"Father knows best?".

Following fertilization, activation of a complex developmental program requires the differential expression of key genes. In most metazoa, the prevailing view is that early differential gene expression occurs primarily through post-transcriptional regulation of maternally deposited products in the oocyte. Two novel studies published from the Rajewsky laboratory in this issue of add significantly to the emerging notion that this process may be more complex than previously appreciated.

Clinical outcome of ultrasound-guided percutaneous microwave ablation on colorectal liver metastases.

The present study aimed to assess the feasibility, safety and efficiency of ultrasound-guided percutaneous microwave ablation (MWA) on liver metastases from colon or rectal cancer. Patients who received MWA therapy for liver metastases from colon or rectal cancer between June 2009 and May 2012 were enrolled in the study. Follow-up data was collected from the patients in order to statistically analyze the adverse effects, concurrent disease and survival status.

Maintenance of chaperone-mediated autophagy activity in cultured cells expressing mutant huntingtin.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by mutant huntingtin (Htt) with an expanded polyglutamine tract. It has been reported that Htt regulates autophagy. However, it remains unclear whether mutant Htt affects chaperone-mediated autophagy (CMA).

Involvement of Drp1 in hypoxia-induced migration of human glioblastoma U251 cells.

Glioblastoma is one of the most aggressive brain tumors with high morbidity and mortality. Hypoxia is often the common characteristic of tumor microenvironment, and hypoxia-inducible factor-1α (HIF-1α) is an essential factor regulating the migratory activity of cancer cells including glioblastoma. Recently, mitochondrial dynamics was found to be involved in the aggression of cancer cells.

Programmed DNA elimination in multicellular organisms.

Genetic information typically remains constant in all cells throughout the life cycle of most organisms. However, there are exceptions where DNA elimination is an integral, developmental program for some organisms, associated with generating distinct germline versus somatic genomes. Programmed DNA elimination occurs in unicellular ciliates and diverse metazoa ranging from nematodes to vertebrates.

Highly efficient, solution processed electrofluorescent small molecule white organic light-emitting diodes with a hybrid electron injection layer.

Highly efficient, solution-processed, and all fluorescent white organic light-emitting diodes (WOLEDs) based on fluorescent small molecules have been achieved by incorporating a low-conductivity hole injection layer and an inorganic-organic hybrid electron injection layer. The light-emission layer is created by doping a fluorescent π-conjugated blue dendrimer host (the zeroth generation dendrimer, G0) with a yellow-emitting fluorescent dopant oligo(paraphenylenevinylene) derivative CN-DPASDB with a doping ratio of 100:0.15 (G0:CN-DPASDB) by weight.

The phylogenetic and geographic structure of Y-chromosome haplogroup R1a.

R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25,000 (95% CI: 21,300-29,000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800-6800) years.

Transcription in pronuclei and one- to four-cell embryos drives early development in a nematode.

Background: A long-standing view of development is that transcription is silenced in the oocyte until early divisions in the embryo. The point at which major transcription is reactivated varies between organisms, but is usually after the two-cell stage. However, this model may not be universal.

JNK signaling is needed to tolerate chromosomal instability.

Chromosomal instability (CIN), as a common feature of tumors, represents a potential therapeutic target if ways can be found to specifically cause apoptosis in unstably dividing cells. We have previously shown that if signaling through the JNK pathway is reduced, apoptosis is triggered in models of chromosomal instability induced by loss of the spindle checkpoint. Here we identify components upstream and downstream of JNK that are able to mediate this effect, and test the involvement of p53 and DNA damage in causing apoptosis when JNK signaling is reduced in CIN cells.

Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection.

HIV-1 entry into CD4(+) T cells requires binding of the virus to CD4 followed by engagement of either the C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4) coreceptor. Pharmacologic blockade or genetic inactivation of either coreceptor protects cells from infection by viruses that exclusively use the targeted coreceptor. We have used zinc-finger nucleases to drive the simultaneous genetic modification of both ccr5 and cxcr4 in primary human CD4(+) T cells.

How does cancer cell metabolism affect tumor migration and invasion?

Cancer metastasis is the major cause of cancer-associated death. Accordingly, identification of the regulatory mechanisms that control whether or not tumor cells become "directed walkers" is a crucial issue of cancer research. The deregulation of cell migration during cancer progression determines the capacity of tumor cells to escape from the primary tumors and invade adjacent tissues to finally form metastases.

hsa-miR29b, a critical downstream target of non-canonical Wnt signaling, plays an anti-proliferative role in non-small cell lung cancer cells via targeting MDM2 expression.

In non-small cell lung cancer cell lines, activation of β-catenin independent signaling, via Wnt7a/Frizzled9 signaling, leads to reversal of cellular transformation, reduced anchorage-independent growth and induction of epithelial differentiation. miRNA expression profiling on a human lung adenocarcinoma cell line (A549) identified hsa-miR29b as an important downstream target of Wnt7a/Frizzled9 signaling. We show herein that hsa-miR29b expression is lost in non-small cell lung cancer (NSCLC) cell lines and stimulation of β-catenin independent signaling, via Wnt7a expression, in NSCLC cell lines results in increased expression of hsa-miR29b.

Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases.

The HIV-1 coreceptor CCR5 is a validated target for HIV/AIDS therapy. The apparent elimination of HIV-1 in a patient treated with an allogeneic stem cell transplant homozygous for a naturally occurring CCR5 deletion mutation (CCR5(Δ32/Δ32)) supports the concept that a single dose of HIV-resistant hematopoietic stem cells can provide disease protection. Given the low frequency of naturally occurring CCR5(Δ32/Δ32) donors, we reasoned that engineered autologous CD34(+) hematopoietic stem/progenitor cells (HSPCs) could be used for AIDS therapy.

ALDH1A isozymes are markers of human melanoma stem cells and potential therapeutic targets.

Although the concept of cancer stem cells (CSCs) is well-accepted for many tumors, the existence of such cells in human melanoma has been the subject of debate. In this study, we demonstrate the existence of human melanoma cells that fulfill the criteria for CSCs (self-renewal and differentiation) by serially xenotransplanting cells into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. These cells possess high aldehyde dehydrogenase (ALDH) activity with ALDH1A1 and ALDH1A3 being the predominant ALDH isozymes.

Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm.

Meiotic recombination and de novo mutation are the two main contributions toward gamete genome diversity, and many questions remain about how an individual human's genome is edited by these two processes. Here, we describe a high-throughput method for single-cell whole-genome analysis that was used to measure the genomic diversity in one individual's gamete genomes. A microfluidic system was used for highly parallel sample processing and to minimize nonspecific amplification.