Mesenchymal MAPKAPK2/HSP27 drives intestinal carcinogenesis.

Mesenchymal cells in the microenvironment of cancer exert important functions in tumorigenesis; however, little is known of intrinsic pathways that mediate these effects. MAPK signals, such as from MAPKAPK2 (MK2) are known to modulate tumorigenesis, yet their cell-specific role has not been determined. Here, we studied the cell-specific role of MK2 in intestinal carcinogenesis using complete and conditional ablation of MK2.

Differential effects of 14-3-3 dimers on Tau phosphorylation, stability and toxicity in vivo.

Neurodegenerative dementias collectively known as Tauopathies involve aberrant phosphorylation and aggregation of the neuronal protein Tau. The largely neuronal 14-3-3 proteins are also elevated in the central nervous system (CNS) and cerebrospinal fluid of Tauopathy patients, suggesting functional linkage. We use the simplicity and genetic facility of the Drosophila system to investigate in vivo whether 14-3-3s are causal or synergistic with Tau accumulation in precipitating pathogenesis.

Atypical, non-standard functions of the microtubule associated Tau protein.

Since the discovery of the microtubule-associated protein Tau (MAPT) over 40 years ago, most studies have focused on Tau's role in microtubule stability and regulation, as well as on the neuropathological consequences of Tau hyperphosphorylation and aggregation in Alzheimer's disease (AD) brains. In recent years, however, research efforts identified new interaction partners and different sub-cellular localizations for Tau suggesting additional roles beyond its standard function as microtubule regulating protein. Moreover, despite the increasing research focus on AD over the last decades, Tau was only recently considered as a promising therapeutic target for the treatment and prevention of AD as well as for neurological pathologies beyond AD e.

Vibrational Detection of Odorant Functional Groups by .

A remarkable feature of olfaction, and perhaps the hardest one to explain by shape-based molecular recognition, is the ability to detect the presence of functional groups in odorants, irrespective of molecular context. We previously showed that trained to avoid deuterated odorants could respond to a molecule bearing a nitrile group, which shares the vibrational stretch frequency with the CD bond. Here, we reproduce and extend this finding by showing analogous olfactory responses of to the chemically vastly different functional groups, thiols and boranes, that nevertheless possess a common vibration at 2600 cm.

Drk-mediated signaling to Rho kinase is required for anesthesia-resistant memory in .

Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons.

Minute Impurities Contribute Significantly to Olfactory Receptor Ligand Studies: Tales from Testing the Vibration Theory.

Several studies have attempted to test the vibrational hypothesis of odorant receptor activation in behavioral and physiological studies using deuterated compounds as odorants. The results have been mixed. Here, we attempted to test how deuterated compounds activate odorant receptors using calcium imaging of the fruit fly antennal lobe.

Distinct phenotypes of three-repeat and four-repeat human tau in a transgenic model of tauopathy.

Tau exists as six closely related protein isoforms in the adult human brain. These are generated from alternative splicing of a single mRNA transcript and they differ in the absence or presence of two N-terminal and three or four microtubule binding domains. Typically all six isoforms have been considered functionally similar.

Mesenchymal Cells in Colon Cancer.

Mesenchymal cells in the intestine comprise a variety of cell types of diverse origins, functions, and molecular markers. They provide mechanical and structural support and have important functions during intestinal organogenesis, morphogenesis, and homeostasis. Recent studies of the human transcriptome have revealed their importance in the development of colorectal cancer, and studies from animal models have provided evidence for their roles in the pathogenesis of colitis-associated cancer and sporadic colorectal cancer.

The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species.

Background: The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control.

Sox2: To crest or not to crest?

Precise control of neural progenitor transformation into neural crest stem cells ensures proper craniofacial and head development. In the neural progenitor pool, SoxB factors play an essential role as cell fate determinants of neural development, whereas during neural crest stem cell formation, Sox2 plays a predominant role as a guardian of the developmental clock that ensures precision of cell flow in the developing head.

Differential Electrophysiological Responses to Odorant Isotopologues in Drosophilid Antennae.

Olfaction presents the ultimate challenge to molecular recognition as thousands of molecules have to be recognized by far fewer olfactory receptors. We have presented evidence that Drosophila readily distinguish odorants based on their molecular vibrations using a battery of behavioral assays suggesting engagement of a molecular vibration-sensing component. Here we interrogate electrophysiologically the antennae of four Drosophilids and demonstrate conserved differential response amplitudes to aldehydes, alcohols, ketones, nitriles, and their deuterated isotopologues.

A "Hit and Run" Approach to Inducible Direct Reprogramming of Astrocytes to Neural Stem Cells.

Temporal and spatial control of gene expression can be achieved using an inducible system as a fundamental tool for regulated transcription in basic, applied and eventually in clinical research. We describe a novel "hit and run" inducible direct reprogramming approach. In a single step, 2 days post-transfection, transiently transfected Sox2(FLAG) under the Leu3p-αIPM inducible control (iSox2) triggers the activation of endogenous Sox2, redirecting primary astrocytes into abundant distinct nestin-positive radial glia cells.

Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report.

Purpose: CYLD is a tumor suppressor that has been linked to the development of various human malignancies, including colon cancer. The tumor-suppressing function of CYLD is associated with its deubiquitinating activity, which maps to the carboxyl-terminal region of the protein. In the present study we evaluated the role of intestinal epithelial CYLD in colitis-associated cancer using a conditional mouse CYLD inactivation model.

Angiotensin II inhibitor facilitates epidermal wound regeneration in diabetic mice.

Tissue regeneration and wound healing are severely impaired in diabetes and are associated with poor circulation and dysfunctional blood vessels. Angiotensin II inhibitors are anti-hypertensive drugs used in clinical practice to regulate blood pressure and could affect tissue remodeling. We hypothesize that blocking angiotensin II, using Losartan, could facilitate tissue regeneration in diabetic mice.

Structural and regulatory elements of the interaction between amyloid-β protein precursor and Homer3.

Amyloid-β protein precursor (AβPP) metabolism and the accumulation of its derivative amyloid-β (Aβ) peptide in senile plaques have been considered key players in the development of Alzheimer's disease (AD). However, the mechanisms underlying the generation and the deposition of Aβ are not clear but emphasis has been given in the role of AβPP protein interactions that regulate its processing and offer a means to manipulate Aβ production. We have previously shown that AβPP interacts with members of the Homer protein family, which leads to inhibition of Aβ generation.

Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila.

Abnormally phosphorylated Tau protein, the major component of neurofibrillary tangles, is critical in the pathogenesis of Alzheimer's disease and related Tauopathies. We used Drosophila to examine the role of key disease-associated phosphorylation sites on Tau-mediated neurotoxicity. We present evidence that the late-appearing phosphorylation on Ser(238) rather than hyperphosphorylation per se is essential for Tau toxicity underlying premature mortality in adult flies.

Sox2 acts as a rheostat of epithelial to mesenchymal transition during neural crest development.

Precise control of self-renewal and differentiation of progenitor cells into the cranial neural crest (CNC) pool ensures proper head development, guided by signaling pathways such as BMPs, FGFs, Shh and Notch. Here, we show that murine Sox2 plays an essential role in controlling progenitor cell behavior during craniofacial development. A "Conditional by Inversion" Sox2 allele (Sox2(COIN) ) has been employed to generate an epiblast ablation of Sox2 function (Sox2(EpINV) ).

Neuroprotection requires the functions of the RNA-binding protein HuR.

Alterations in the functions of neuronal RNA-binding proteins (RBPs) can contribute to neurodegenerative diseases. However, neurons also express a set of widely distributed RBPs that may have developed specialized functions. Here, we show that the ubiquitous member of the otherwise neuronal Elavl/Hu family of RNA-binding proteins, Elavl1/HuR, has a neuroprotective role.

Electron spin changes during general anesthesia in Drosophila.

We show that the general anesthetics xenon, sulfur hexafluoride, nitrous oxide, and chloroform cause rapid increases of different magnitude and time course in the electron spin content of Drosophila. With the exception of CHCl3, these changes are reversible. Anesthetic-resistant mutant strains of Drosophila exhibit a different pattern of spin responses to anesthetic.

Fetal exposure to maternal inflammation does not affect postnatal development of genetically-driven ileitis and colitis.

Background: Chronic inflammatory disorders have been increasing in incidence over the past decades following geographical patterns of industrialization. Fetal exposure to maternal inflammation may alter organ functions and the offspring's disease risk. We studied the development of genetically-driven ileitis and colitis in response to maternal inflammation using mouse models.