Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control.

In the malaria vector Anopheles gambiae, two point mutations in the acetylcholinesterase (ace-1) and the sodium channel (kdr) genes confer resistance to organophosphate/carbamate and pyrethroid insecticides, respectively. The mechanisms of compensation that recover the functional alterations associated with these mutations and their role in the modulation of insecticide efficacy are unknown. Using multidisciplinary approaches adapted to neurons isolated from resistant Anopheles gambiae AcerKis and KdrKis strains together with larval bioassays, we demonstrate that nAChRs, and the intracellular calcium concentration represent the key components of an adaptation strategy ensuring neuronal functions maintenance.

Orthosteric muscarinic receptor activation by the insect repellent IR3535 opens new prospects in insecticide-based vector control.

The insect repellent IR3535 is one of the important alternative in the fight against mosquito-borne disease such as malaria, dengue, chikungunya, yellow fever and Zika. Using a multidisciplinary approach, we propose the development of an innovative insecticide-based vector control strategy using an unexplored property of IR3535. We have demonstrated that in insect neurosecretory cells, very low concentration of IR3535 induces intracellular calcium rise through cellular mechanisms involving orthosteric/allosteric sites of the M1-muscarinic receptor subtype, G protein βγ subunits, background potassium channel inhibition generating depolarization, which induces voltage-gated calcium channel activation.

Zinc-α2-glycoprotein: a proliferative factor for breast cancer? In vitro study and molecular mechanisms.

Zinc-α2-glycoprotein (ZAG) is a new adipokine whose gene expression is downregulated in obese patients. We recently reported ZAG expression in breast tumor or healthy breast tissue and detected this expression at high levels in ductal carcinoma and in normal epithelial adjacent tissue but not in normal tissue of healthy women. In the present study, we used two human breast tumor cell lines (MCF-7 and MDA-MB‑231) and one fibrocystic breast cell line (MCF‑10a) to examine whether recombinant ZAG has an effect on proliferative/apoptotic response in breast cancer cell lines.

Δ160p53 is a novel N-terminal p53 isoform encoded by Δ133p53 transcript.

p53 gene expresses several protein isoforms modulating p53-mediated responses through regulation of gene expression. Here, we identify a novel p53 isoform, Δ160p53, lacking the first 159 residues. By knockdown experiments and site-directed mutagenesis, we show that Δ160p53 is encoded by Δ133p53 transcript using ATG160 as translational initiation site.

Molecular mechanisms of leptin and adiponectin in breast cancer.

Obesity is associated with an increased risk of breast cancer in postmenopausal women. Accumulating evidence suggests that adipose tissue, which is an endocrine organ producing a large range of factors, may interfere with breast cancer development. Leptin and adiponectin are two major adipocyte-secreted hormones.

p53 family members in cancer diagnosis and treatment.

p53 is a much studied transcription factor which has a key role in the maintenance of genetic stability. It belongs to a larger family of genes including two other highly related proteins, p63 and p73. The p53 pathway has a vital role in the prevention of cancer formation and is ubiquitously lost in a high percentage of human cancers.

IL-1 family in breast cancer: potential interplay with leptin and other adipocytokines.

Obesity is associated with an increased risk of breast cancer. interleukin-1 (IL-1), a pro-inflammatory cytokine secreted by adipose tissue, is involved in breast cancer development. There is also convincing evidence that other adipocytokines including leptin not only have a role in haematopoiesis, reproduction and immunity but are also growth factors in cancer.

IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde?

Interleukin-1 receptor antagonist (IL-1ra) has been shown to play a crucial role in the prevention of various inflammatory diseases. There is also convincing evidence that IL-1ra is able to counteract inflammatory effects of IL-1 members implicated in insulin resistance and diabetes. However, the use of knock-out animal models provides evidence to the contrary and the role of IL-1ra in obesity-linked anomalies remains controversial.

A temporal switch in the insulin-signalling pathway that regulates hepatic IGF-binding protein-1 gene expression.

Insulin regulation of hepatic gene transcription is a vital component of glucose homeostasis. Understanding the molecular regulationof thisprocess aids the searchfor the defect(s) that promotesinsulin-resistant states, such asdiabetesmellitus. We havepreviously shownthat the insulin regulationof hepatic IGF-binding protein-1 (IGFBP1) expression requiresthe signalling proteins phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamycin (mTOR).

The expression of migration stimulating factor, a potent oncofetal cytokine, is uniquely controlled by 3'-untranslated region-dependent nuclear sequestration of its precursor messenger RNA.

Migration stimulating factor (MSF) is a truncated oncofetal fibronectin isoform expressed by fetal and tumor-associated cells. MSF mRNA is distinguished from other fibronectin isoforms by its size (2.1 kb) and the inclusion of a specific intronic sequence at its 3' end.