A common CTRB misfolding variant associated with pancreatic cancer risk causes ER stress and inflammation in mice.

Objective: Genome wide association studies have identified an exon 6 deletion variant that associates with increased risk of pancreatic cancer. To acquire evidence on its causal role, we developed a new mouse strain carrying an equivalent variant in , the mouse orthologue of .

Design: We used CRISPR/Cas9 to introduce a 707bp deletion in encompassing exon 6 ( ).

Endogenous retroviruses shape pluripotency specification in mouse embryos.

The smooth and precise transition from totipotency to pluripotency is a key process in embryonic development, generating pluripotent stem cells capable of forming all cell types. While endogenous retroviruses (ERVs) are essential for early development, their precise roles in this transition remains mysterious. Using cutting-edge genetic and biochemical techniques in mice, we identify MERVL-gag, a retroviral protein, as a crucial modulator of pluripotent factors OCT4 and SOX2 during lineage specification.

The HASTER lncRNA promoter is a cis-acting transcriptional stabilizer of HNF1A.

The biological purpose of long non-coding RNAs (lncRNAs) is poorly understood. Haploinsufficient mutations in HNF1A homeobox A (HNF1A), encoding a homeodomain transcription factor, cause diabetes mellitus. Here, we examine HASTER, the promoter of an lncRNA antisense to HNF1A.

Chronic pancreatitis and lipomatosis are associated with defective function of ciliary genes in pancreatic ductal cells.

Genetic diseases associated with defects in primary cilia are classified as ciliopathies. Pancreatic lesions and ductal cysts are found in patients with ciliopathic polycystic kidney diseases suggesting a close connection between pancreatic defects and primary cilia. Here we investigate the role of two genes whose deletion is known to cause primary cilium defects, namely Hnf6 and Lkb1, in pancreatic ductal homeostasis.

A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies.

By whole exome sequencing, we recently identified a missense mutation (p.R703C) in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals.

Low cadmium concentration in whole blood from residents of northern Sardinia (Italy) with special reference to smoking habits.

Introduction: The present study was initiated to investigate the cadmium concentrations in whole blood of Northern Sardinian, non-occupationally exposed adult subjects. Sardinia is a large Italian island which differs genetically and environmentally from other mainland Italian areas.

Methods: Two hundred and forty-three adults (157 females and 86 males) were selected in the study area from subjects who were undergoing blood collection for laboratory analysis during the period January 2005-May 2005.

BCL6 represses NFkappaB activity in diffuse large B-cell lymphomas.

BCL6 is a transcriptional repressor whose deregulated expression plays a key role in diffuse large B-cell lymphomas (DLBCLs). BCL6 expression characterizes one of the two main subtypes (GC type) of DLBCL, while the other (ABC type) is recognized by increased NFkappaB activation. The mechanistic basis of this distinction remains unclear and the BCL6 targets have been only partially explored.

The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors.

The Ras homolog enriched in striatum, Rhes, is the product of a thyroid hormone-regulated gene during brain development. Rhes and the dexamethasone-induced Dexras1 define a novel distinct subfamily of proteins within the Ras family, characterized by an extended variable domain in the carboxyl terminal region. We have carried this study because there is a complete lack of knowledge on Rhes signaling.

Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum.

Thyroid hormone action on brain development is essentially exerted through regulation of the expression rate of a number of genes some of which have been identified in the past 10 years. In the present work we describe the thyroid hormone regulation of a novel Ras homolog which we have named Rhes (Ras homolog enriched in striatum). The rhes cDNA was previously isolated in subtractive hybridization experiments aimed at identifying cDNA clones corresponding to genes expressed preferentially in the rat striatum.

Computerized tomography in the management and follow-up of extensive periapical lesion.

Radiographs are good diagnostic aids in endodontics, although they have limitations. The purpose of this article is to discuss the use of computerized tomography in differential diagnosis, treatment planning, follow-up and overall clinical management of complex periapical lesions. A clinical case of an extensive symptomatic periapical lesion of the upper jaw is presented, in which the use of computerized tomography allowed evaluation of the true extent of the lesion and its spatial relationship to important anatomical landmarks.

Rhes: A striatal-specific Ras homolog related to Dexras1.

We have characterized an apparently full-length cDNA corresponding to a rat mRNA, SE6C, previously identified by subtractive hybridization as being expressed predominantly in the striatal region of the brain. The SE6C mRNA encodes a 266 amino acid protein with significant similarity to members of the Ras-like GTP-binding protein family; thus, we have chosen the name Rhes, for Ras homolog enriched in striatum. The human homolog was found in a genomic sequence from human chromosome 22q13.

Transcriptional induction of RC3/neurogranin by thyroid hormone: differential neuronal sensitivity is not correlated with thyroid hormone receptor distribution in the brain.

RC3/neurogranin is a calmodulin-binding protein kinase C substrate, located in dendritic spines of forebrain neurons. It has been implicated in post-synaptic signal transduction events involving Ca2+ and calmodulin leading to many forms of synaptic plasticity. RC3 gene expression is under developmental and physiological regulation.

Spontaneous bursting activity of dopaminergic neurons in midbrain slices from immature rats: role of N-methyl-D-aspartate receptors.

Dopamine neurons in midbrain coronal slices from adult rats (40-70 days old) discharged only in pacemaker-like mode. Irregular or bursting mode was never observed. In contrast, dopamine neurons in slices from immature rats (15-21 days old) exhibited not only pacemaker-like firing (53.

Depolarization inactivation of dopamine neurons: an artifact?

A widely accepted theory postulates that, in rats, chronic treatment with neuroleptics causes the depolarization inactivation of the majority of midbrain dopamine (DA) neurons. The present study was aimed to verify whether general anesthesia and/or other factors might contribute to the depolarization inactivation of A9 and A10 DA neurons. To investigate on the possible role played by DA receptor subtypes, three representatives DA antagonists were used: haloperidol (a mixed D1/D2), (-)-sulpiride (a selective D2) and SCH 23390 (a selective D1).

Failure of chronic haloperidol to induce depolarization inactivation of dopamine neurons in unanesthetized rats.

Chronic treatment with neuroleptics has been reported to induce a status of depolarization inactivation of the majority of midbrain dopamine neurons. The present study was aimed at determining whether general anesthesia might be a contributory cause of depolarization inactivation of substantia nigra dopamine neurons. In agreement with previous studies, where neuronal sampling was carried out in animals under chloral hydrate anesthesia, chronic treatment with haloperidol (0.

Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension.

The spectrum of left ventricular geometric adaptation to hypertension was investigated in 165 patients with untreated essential hypertension and 125 age- and gender-matched normal adults studied by two-dimensional and M-mode echocardiography. Among hypertensive patients, left ventricular mass index and relative wall thickness were normal in 52%, whereas 13% had increased relative wall thickness with normal ventricular mass ("concentric remodeling"), 27% had increased mass with normal relative wall thickness (eccentric hypertrophy) and only 8% had "typical" hypertensive concentric hypertrophy (increase in both variables). Systemic hemodynamics paralleled ventricular geometry, with the highest peripheral resistance in the groups with concentric remodeling and hypertrophy, whereas cardiac index was super-normal in those with eccentric hypertrophy and low normal in patients with concentric remodeling.

[Postoperative infections: the use of thymostimulin (TP1) in patients at risk].

The authors report data related to 212 surgical patients at risk because immunocompromised. Patients were divided in two homogeneous groups, one treated with Thymostimulin and the other as a control group, all affected by severe pathologies. Patients presenting postoperative complications directly related to technical reasons were excluded.

[Role of densitometry and scintigraphy in post-traumatic algodystrophy of the arms. Initial diagnosis and monitoring during treatment with carbocalcitonin].

In 24 patients affected with post-traumatic reflex sympathetic dystrophy syndrome (RSDS) with upper limb involvement following humeral fractures, bone mineral density (BMD, mg/cm2) was measured by means of dual-photon absorptiometry in the distal radius of both the affected and the normal contralateral limbs. Subsequently, all patients underwent dynamic and static scintigraphic exams after i.v.

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics.

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors.