Targeting netrin-3 in small cell lung cancer and neuroblastoma.

The navigation cue netrin-1 is well-documented for its key role in cancer development and represents a promising therapeutic target currently under clinical investigation. Phase 1 and 2 clinical trials are ongoing with NP137, a humanized monoclonal antibody against netrin-1. Interestingly, the epitope recognized by NP137 in netrin-1 shares 90% homology with its counterpart in netrin-3, the closest member to netrin-1 in humans, for which little is known in the field of cancer.

Corrigendum: Optical properties of GaN nanowires grown on chemical vapor deposited-graphene (2019 Nanotechnology 30 214005).

no abstract.

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants.

Histone Acetylation Dynamics Integrates Metabolic Activity to Regulate Plant Response to Stress.

Histone lysine acetylation is an essential chromatin modification for epigenetic regulation of gene expression during plant response to stress. On the other hand, enzymes involved in histone acetylation homeostasis require primary metabolites as substrates or cofactors whose levels are greatly influenced by stress and growth conditions in plants. In addition, histone lysine acylation that requires similar enzymes for deposition and removal as histone acetylation has been recently characterized in plant.

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations.

Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis.

Design, Setting, And Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms.

Platelet rich plasma in androgenetic alopecia: A systematic review.

In recent years, dozens of manufacturers and clinics have been promoting the use of platelet rich plasma (PRP) procedures for skin and hair regeneration. Well-designed randomized controlled studies for these procedures are lacking. In this communication, we review the efficacy and safety of PRP procedures for androgenetic alopecia from multiple published peer-reviewed studies.

JUNO, the receptor of sperm IZUMO1, is expressed by the human oocyte and is essential for human fertilisation.

Study Question: Is JUNO protein present at the surface membrane of human oocytes and involved in the fertilisation process?

Summary Answer: JUNO protein is expressed on the plasma membrane of human oocytes and its inhibition by a monoclonal antibody completely blocks gamete fusion.

What Is Known Already: Fusion of gamete membranes is the culminating event of the fertilisation process, but its molecular mechanisms are poorly understood. Until now, three molecules have been shown to be essential: CD9 tetraspanin in the oocyte, Izumo1 protein on the sperm and Juno, its corresponding receptor on the oocyte.

Dynamics and functional interplay of histone lysine butyrylation, crotonylation, and acetylation in rice under starvation and submergence.

Background: Histone lysine acylations by short-chain fatty acids are distinct from the widely studied histone lysine acetylation in chromatin, although both modifications are regulated by primary metabolism in mammalian cells. It remains unknown whether and how histone acylation and acetylation interact to regulate gene expression in plants that have distinct regulatory pathways of primary metabolism.

Results: We identify 4 lysine butyrylation (Kbu) sites (H3K14, H4K12, H2BK42, and H2BK134) and 45 crotonylation (Kcr) sites on rice histones by mass spectrometry.

Radio-sensitization of head and neck cancer cells by a combination of poly(I:C) and cisplatin through downregulation of survivin and c-IAP2.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers. Concurrent radio-chemotherapy is the standard of care for advanced tumors. However, there is a need for more efficient regimens with less side effects resulting from high doses.

Clustering-based preprocessing method for lipidomic data analysis: application for the evolution of newborn skin surface lipids from birth until 6 months.

After life in utero and birth, the skin is submitted to an important process of adaptation to a relatively dry gaseous environment. Skin surface lipids (SSLs) contribute actively to the protection of the skin barrier. Within this context, our objective was to study the evolution of each lipid compound during the postnatal period.

Direct and rapid identification of T315I-Mutated BCR-ABL expressing leukemic cells using infrared microspectroscopy.

Despite the major success obtained by the use of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), resistances to therapies occur due to mutations in the ABL-kinase domain of the BCR-ABL oncogene. Amongst these mutations, the "gatekeeper" T315I is a major concern as it renders leukemic cells resistant to all licenced TKI except Ponatinib. We report here that Fourier transform infrared (FTIR) microspectroscopy is a powerful methodology allowing rapid and direct identification of a spectral signature in single cells expressing T315I-mutated BCR-ABL.

Targeting BCR-ABL+ stem/progenitor cells and BCR-ABL-T315I mutant cells by effective inhibition of the BCR-ABL-Tyr177-GRB2 complex.

Treatment of BCR-ABL+ human leukemia has been significantly improved by ABL tyrosine kinase inhibitors (TKIs), but they are not curative for most patients and relapses are frequently associated with BCR-ABL mutations, warranting new targets for improved treatments. We have now demonstrated that protein expression of human estrogen receptor alpha 36 (ERα36), an alternative splicing variant of human estrogen receptor alpha 66 (ERα66), is highly increased in TKI-insensitive CD34+ chronic myeloid leukemia (CML) cells and BCR-ABL-T315I mutant cells, and is abnormally localized in plasma membrane and cytoplasm. Interestingly, new pre-clinically-validated analogs of Icaritin (SNG162 and SNG1153), which target abnormal ERα36 activity, inhibit cell growth and induce apoptosis of BCR-ABL+ leukemic cells, particularly BCR-ABL-T315I mutant cells.

Toll-like receptor 3 stimulation triggers metabolic reprogramming in pharyngeal cancer cell line through Myc, MAPK, and HIF.

Toll-like receptor 3 (TLR3) has a dual role in cancer; its activation can trigger apoptosis as well as stimulate cancer cell survival, proliferation, and progression. We have shown here that TLR3 activation can induce metabolic reprogramming in a pharyngeal cancer cell line, leading to increased aerobic glycolysis, cell migration, elevated levels of reactive oxidative species (ROS), and decreased anti-oxidative response. Key proteins in these signaling pathways are heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), pyruvate kinase M2 (PKM2), and CD44 variants, which were over-expressed after TLR3 stimulation.

Longitudinal association of antidepressant medication use with metabolic syndrome: Results of a 9-year follow-up of the D.E.S.I.R. cohort study.

Objective: To examine longitudinal associations between antidepressant medication use and the metabolic syndrome (MetS).

Methods: 5014 participants (49.8% were men) from the D.

CXCL12/CXCR4 pathway is activated by oncogenic JAK2 in a PI3K-dependent manner.

JAK2 activation is the driver mechanism in negative myeloproliferative neoplasms (MPN). These diseases are characterized by an abnormal retention of hematopoietic stem cells within the bone marrow microenvironment and their increased trafficking to extramedullary sites. The CXCL12/CXCR4 axis plays a central role in hematopoietic stem cell/ progenitor trafficking and retention in hematopoietic sites.

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study.

Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.

Chronic oxidative stress promotes H2AX protein degradation and enhances chemosensitivity in breast cancer patients.

Anti-cancer drugs often increase reactive oxygen species (ROS) and cause DNA damage. Here, we highlight a new cross talk between chronic oxidative stress and the histone variant H2AX, a key player in DNA repair. We observe that persistent accumulation of ROS, due to a deficient JunD-/Nrf2-antioxidant response, reduces H2AX protein levels.

CAG repeat size in Huntingtin alleles is associated with cancer prognosis.

The abnormal expansion of a ≥36 CAG unit tract in the Huntingtin gene (HTT) leads to Huntington's disease (HD), but has also been associated with cancer: the incidence of cancer is lower in HD patients than in age-matched controls, but HD-causing variants of HTT accelerate the progression of breast tumors and the development of metastases in mouse models of breast cancer. To investigate the relationship between HTT CAGs and cancer, data concerning 2407 women with BRCA1 or BRCA2 mutations that predispose to breast and ovarian cancers and 431 patients with breast cancer without family histories were studied; the size of the CAG expansions on both HTT alleles was determined in each subject. The proportion of individuals carrying a CAG expansion in a pathological range for HD was 10 times more frequent than previously reported in the literature.

A fluorescent nanoprobe for single bacterium tracking: functionalization of silver nanoparticles with tryptophan to probe the nanoparticle accumulation with single cell resolution.

The investigation of the interaction of silver nanoparticles and live bacteria cells is of particular importance for understanding and controlling their bactericidal properties. In this study, the process of internalization of silver nanoparticles in Escherichia coli cells was followed by means of synchrotron excitation deep ultraviolet (DUV) fluorescence imaging. Antimicrobial nanostructures that can absorb and emit light in the UV region were prepared by functionalization of silver nanoparticles with tryptophan amino acid and used as environmentally sensitive fluorescent probes.

Cerebral Blood Flow Improvement after Indirect Revascularization for Pediatric Moyamoya Disease: A Statistical Analysis of Arterial Spin-Labeling MRI.

Background And Purpose: The severity of Moyamoya disease is generally scaled with conventional angiography and nuclear medicine. Arterial spin-labeling MR imaging is now acknowledged for the noninvasive quantification of cerebral blood flow. This study aimed to analyze CBF modifications with statistical parametric mapping of arterial spin-labeling MR imaging in children undergoing an operation for Moyamoya disease.

Substrate-Free InGaN/GaN Nanowire Light-Emitting Diodes.

We report on the demonstration of substrate-free nanowire/polydimethylsiloxane (PDMS) membrane light-emitting diodes (LEDs). Metal-organic vapour-phase epitaxy (MOVPE)-grown InGaN/GaN core-shell nanowires were encapsulated into PDMS layer. After metal deposition to p-GaN, a thick PDMS cap layer was spin-coated and the membrane was manually peeled from the sapphire substrate, flipped upside down onto a steel holder, and transparent indium tin oxide (ITO) contact to n-GaN was deposited.

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation.