The DCR protein TTC3 affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways.

In neuronal cells, actin remodeling plays a well known role in neurite extension but is also deeply involved in the organization of intracellular structures, such as the Golgi apparatus. However, it is still not very clear which mechanisms may regulate actin dynamics at the different sites. In this report we show that high levels of the TTC3 protein, encoded by one of the genes of the Down Syndrome Critical Region (DCR), prevent neurite extension and disrupt Golgi compactness in differentiating primary neurons. These effects largely depend on the capability of TTC3 to promote actin polymerization through signaling pathways involving RhoA, ROCK, CIT-N and PIIa. However, the functional relationships between these molecules differ significantly if considering the TTC3 activity on neurite extension or on Golgi organization. Finally, our results reveal an unexpected stage-dependent requirement for F-actin in Golgi organization at different stages of neuronal differentiation

The sterlet sturgeon genome sequence and the mechanisms of segmental rediploidization.

Sturgeons seem to be frozen in time. The archaic characteristics of this ancient fish lineage place it in a key phylogenetic position at the base of the ~30,000 modern teleost fish species. Moreover, sturgeons are notoriously polyploid, providing unique opportunities to investigate the evolution of polyploid genomes. We assembled a high-quality chromosome-level reference genome for the sterlet, Acipenser ruthenus. Our analysis revealed a very low protein evolution rate that is at least as slow as in other deep branches of the vertebrate tree, such as that of the coelacanth. We uncovered a whole-genome duplication that occurred in the Jurassic, early in the evolution of the entire sturgeon lineage. Following this polyploidization, the rediploidization of the genome included the loss of whole chromosomes in a segmental deduplication process. While known adaptive processes helped conserve a high degree of structural and functional tetraploidy over more than 180 million years, the reduction of redundancy of the polyploid genome seems to have been remarkably random

A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas).

Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes

Fever as a Cause of Hypophosphatemia in Patients with Malaria

Hypophosphatemia occurs in 40 to 60% of patients with acute malaria, and in many other conditions associated with elevations of body temperature. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. To validate our findings, we analyzed a second sample of malaria patients during a subsequent 10-year period. Serum phosphorus correlated inversely with temperature (n = 59, r = −0.62; P<0.0001), such that each 1°C increase in body temperature was associated with a reduction of 0.18 mmol/L (0.56 mg/dL) in the serum phosphorus level (95% confidence interval: −0.12 to −0.24 mmol/L [−0.37 to −0.74 mg/dL] per 1°C). A similar effect was observed among 19 patients who had repeat measurements of serum phosphorus and temperature. In a multiple linear regression analysis, the relation between temperature and serum phosphorus level was independent of blood pH, PCO2, and serum levels of potassium, bicarbonate, calcium, albumin, and glucose. Our study demonstrates a strong inverse linear relation between body temperature and serum phosphorus level that was not explained by other factors known to cause hypophosphatemia. If causal, this association can account for the high prevalence of hypophosphatemia, observed in our patients and in previous studies of patients with malaria. Because hypophosphatemia has been observed in other clinical conditions characterized by fever or hyperthermia, this relation may not be unique to malaria. Elevation of body temperature should be added to the list of causes of hypophosphatemia

Initiator Elements Function to Determine the Activity State of BX-C Enhancers

A >300 kb cis-regulatory region is required for the proper expression of the three bithorax complex (BX-C) homeotic genes. Based on genetic and transgenic analysis, a model has been proposed in which the numerous BX-C cis-regulatory elements are spatially restricted through the activation or repression of parasegment-specific chromatin domains. Particular early embryonic enhancers, called initiators, have been proposed to control this complex process. Here, in order to better understand the process of domain activation, we have undertaken a systematic in situ dissection of the iab-6 cis-regulatory domain using a new method, called InSIRT. Using this method, we create and genetically characterize mutations affecting iab-6 function, including mutations specifically modifying the iab-6 initiator. Through our mutagenesis of the iab-6 initiator, we provide strong evidence that initiators function not to directly control homeotic gene expression but rather as domain control centers to determine the activity state of the enhancers and silencers within a cis-regulatory domain

Determination of olanzapine in rat brain by means of HPLC with coulometric detection

Olanzapine (Zyprexa\uae, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3b][1,5]-benzodiazepine, OLA) is an atypical antipsychotic drug which demonstrates high interaction with serotonin 5-HT2A, 5-HT2C, 5-HT3, dopamine D1, D2, D4, adrenergic, histamine and muscarinic receptors. It has chemical structure and many therapeutic properties (activity against both negative and positive symptoms of schizophrenia) and side effects similar to those of clozapine, yet with the advantage that it seems to not cause agranulocytosis. Brain olanzapine levels are an important index which can verify if pharmacological effects are due to direct receptor occupancy or to secondary modifications due to the therapeutically effective treatment. Aim of the present study is the implementation of a sensitive and selective analytical method for the determination of brain olanzapine levels, based on the use of HPLC with electrochemical coulometric detection. Analyte separation was achieved on a C8 column (150 74.6 mm I.D., 5 \ub5m) using a mobile phase composed of methanol and a pH 3.5 phosphate buffer containing triethylamine (21:79). Analyte detection was carried out using a Coulochem III coulometric detector (working electrode: porous graphite; reference electrode: alpha-hydrogen/palladium, auxiliary electrode: stainless steel). The guard cell was set at 0.000 V; the analytical cell was set at: detector 1, + 0.350 V; detector 2, -0.200 V. Sample pre-treatment was carried out by solid-phase extraction (SPE) on Oasis HLB cartridges, loading 500 \ub5L of brain homogenate, eluting with methanol and obtaining a final sample volume of 125 \ub5L. The extraction yield of this procedure is very good, always higher than 95%. The preliminary results of the method are very promising, with good sensitivity and repeatability. Assays are in progress to fully validate the method