Distribution of UL144, US28 and UL55 genotypes in Polish newborns with congenital cytomegalovirus infections

Human cytomegalovirus (HCMV) is the most common congenital infection. HCMV strains display genetic variability in different regions. Distribution of HCMV genotypes in the population of congenitally infected newborns from Central Poland and viral load in newborns' blood is described and discussed. HCMV isolates were analysed by sequencing at three sites on the genome: the UL144 tumour necrosis factor-alpha (TNFα)-like receptor gene, the US28 beta-chemokine receptor gene and the UL55 envelope glycoprotein B (gB) gene. The newborns' blood was examined for HCMV DNA with a nested (UL144, UL55) or heminested (US28) polymerase chain reaction, and the genotypes were determined by sequence analysis. HCMV DNA was detectable in 25 out of 55 examined newborns born by HCMV-infected mothers (45.5%). The blood viral load in mother-infant pairs was determined. Most of the newborns had identical virus genotype, gB2 (96%), UL144 B1 (88%) and US28 A2 (84%). These genotypes were detected in all newborns with asymptomatic congenital infection. The occurrence of UL144 B1 or US28 A2 genotypes in the babies examined was significant in comparison to other genotypes (p=0.0002 and p=0.040 respectively). There was no association between specific gB subtypes in all patients groups (p=0.463). There was no correlation between HCMV genotypes and the outcome.     

A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia

Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH.     

Proton‐Conducting Properties of Acid‐Doped Poly(glycidyl methacrylate)‐1,2,4‐Triazole Systems

1,2,4‐triazole‐functional PGMA polymers have been synthesized and their anhydrous proton‐conducting properties were investigated after doping with phosphoric acid and triflic acid. PGMA was prepared by solution polymerization and then modified with 1H‐1,2,4‐triazole (Tri) and 3‐amino‐1,2,4‐triazole (ATri). FT‐IR, ¹³C NMR and elemental analysis verify the high immobilization of the triazoles in the polymer chain. Phosphoric‐acid‐doped polymers showed lower T_g and higher proton conductivities. PGMA‐Tri 4 H₃PO₄ showed a maximum water‐free proton conductivity of approximately 10^?2 S · cm^?1 while that of PGMA‐ATri 2 H₃PO₄ was 10^?3 S · cm^?1. The structure and dynamics of the polymers were explored by ¹H MAS and ¹³C CP‐MAS solid‐state NMR.

     

A Simple Route to Rod‐Coil Block Copolymers of Oligo‐ and Polythiophenes with PMMA and Polystyrene

A simple and efficient approach for the preparation of rod‐coil block copolymers comprising oligo‐ and polythiophenes blocks together with PMMA or PS blocks is described. The block copolymers were prepared using a two‐step procedure. α,ω‐dicarboxy‐terminated oligothiophenes and carboxy terminated poly(3‐hexylthiophene) were first prepared. These were then reacted with P₄S₁₀ in a second step to generate the α,ω‐thioester terminated oligothiophenes and poly(3‐hexylthiophene)s which were subsequently used in a one‐pot reaction as RAFT polymerization agents with methylmethacrylate and styrene. The di‐ and tri‐block copolymers hence obtained were fully characterized, both in solution and as thin films.

     

Perinatal and intrafamily transmission of hepatitis B virus in three generations of a low-prevalence population

Family members of 47 hepatitis B virus (HBV)-carrier pregnant women were tested for the presence of hepatitis B surface antigen (HBsAg), other markers of HBV infection, and hepatitis A virus (HAV) antibodies. Eleven members of six families were found to be HBV DNA positive. Five of the anti-HBe-positive persons were found to be HBV DNA carriers, too. The mean age of the HBV DNA carriers was found to be lower than that of Hbe carriers; therefore, it is suggested that seroconversion to HBe occurs before the resolution of HBV DNA carrier state. Superinfection with hepatitis A virus was not found to influence the elimination of HBV-carrier state, as there was no correlation found between the hepatitis A exposure and the hepatitis B virus markers in the families. The low HBV prevalence in the population (0.3%) was in contrast to the high prevalence of the families of the HBV-carrier mothers (27.1%) and family members with HBV markers (50.4%). Significant positive correlation was found in the proportion of HBV-positive children, and the HBV history of their parents. When fathers were shown to be seronegative, the probability of HBV transmission was reduced by a factor of 6 (12.5% instead of 75%) probably due to reduced viral load and possibly by other factors. Several results indicate, that the noncytocidal hepatitis B virus clearing mechanism suggested by Guidotti et al. [1996, 1999] was effective also in the HBV-carrier human population.     

Morphometry,Microstructure, and Wear Pattern of Neornithischian Dinosaur Teeth From the Upper Cretaceous Iharkút Locality (Hungary)

Teeth of iguanodontian ornithopods and ceratopsians could be remarkably similar, thus the referral of isolated dental material to particular neornithischian clades can be highly problematic. These groups are represented by the rhabdodontid Mochlodon vorosi and the basal coronosaurian Ajkaceratops kozmai in the Upper Cretaceous Csehbánya Formation at Iharkút (western Hungary). Whereas teeth of Mochlodon are common elements at the locality, no dental material belonging to Ajkaceratops was identified until now. Here we used mathematical statistical approaches, as well as tooth wear and dental microstructure analysis in order to decide whether the teeth previously referred to Mochlodon can be treated as a homogenous sample, or some remains belong rather to Ajkaceratops. According to our results, there was a striking morphological and structural convergence between the teeth of both taxa. However, the wear study revealed the existence of two different patterns within the sample. One is characterized by straight and parallel microstriations that suggest orthal movements during the jaw closure. This pattern was associated with Mochlodon. The other pattern appeared only on a few teeth, and it can be differentiated by its distinctive curved microstriations that indicate circumpalinal chewing. Because curved striations have never been described in ornithopods, but are found in several neoceratopsians, this pattern was associated here with Ajkaceratops. Here we present the first teeth that can provisionally be referred to the latter genus. We believe that the methodology discussed in this article will facilitate distinguishing ceratopsian and ornithopod teeth in other localities as well. Anat Rec, 300:1439–1463, 2017. © 2017 Wiley Periodicals, Inc.     

Cardiac function and morphology studied by two-dimensional Doppler echocardiography in unsedated newborn pigs

The newborn pig is currently the most used species in animal neonatal research. Valid non-invasive monitoring is important in particular for long-term survival of unsedated animals. In the unsedated newborn pig (n = 35, median age 24 h, range 7-48 h) we standardized two-dimensional Doppler echocardiography and determined the normal ranges for cardiac function. Probe positioning had to be adjusted to the V-shaped thorax and the mid-line position of the heart. Six out of the sixteen animals < 20 h had a patent ductus arteriosus compared with one of the twenty animals > 20 h old. One atrial septal defect (5 mm) and one small ventricular septal defect were diagnosed. The average heart size was 0.7-0.9% of body weight which is similar to human infants of the same size. The mean aortic diameter was 6.0 +/- 0.5 mm (mean +/- S.D.) and cardiac output was 0.38 +/- 0.08 l min-1; both correlate with body weight (r = 0.80 and 0.73, respectively). Tricuspid regurgitation velocity was 3.0 +/- 0.4 m s-1 (mean +/- S.D.), giving an estimated pressure gradient across the tricuspid valve of 37 +/- 9.7 mmHg. The aortic diameter and the heart weight per kg body weight are comparable to those reported for preterm neonates. The cardiac output and velocities across the four valves are more comparable with term neonates.     

Nicotine Exerts an Anti-inflammatory Effect in a Murine Model of Acute Lung Injury

Activation of the cholinergic anti-inflammatory pathway through direct activation of nicotinic acetylcholine receptors on immune cells can inhibit pro-inflammatory chemokine and cytokine release and thereby protect in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against acute lung inflammation. Mice challenged with intratracheal lipopolysaccharide (LPS, 50 μg) were treated with nicotine (0.2 or 0.4 mg/kg, sc). After 24 h, bronchoalveolar lavage fluid (BALF) was obtained to measure leukocyte infiltration, lung edema, and pro-inflammatory chemokine (MIP-1α, MIP-2, and eotaxin) and cytokine (IL-1, IL-6, and TNF-α) levels. Nicotine treatment reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by decreased BALF inflammatory cells, myeloperoxidase, and protein. Nicotine also downregulated lung production of pro-inflammatory chemokines and cytokines. These data support the proposal that activation of the cholinergic anti-inflammatory pathway may represent a useful addition to the therapy of acute respiratory distress syndrome.     

Successfully overcoming the inhibitory impact of the "forget" instruction: A voxel-based morphometric study of directed forgetting

In directed-forgetting studies, test items are followed by an instruction either to "remember" or to "forget" (F). Many to-be-forgotten (TBF) stimuli are not retrieved at the recognition phase. However, some subjects are able to correctly recollect a high number of TBF stimuli. We examined whether this ability is reflected in the structure of brain regions involved in memory and the control of retrieval processes. In subjects with high recognition rates for TBF stimuli, voxel-based morphometry revealed increased gray matter (GM) volume in the left ventrolateral prefrontal cortex (VLPFC) and the right hippocampus (H). GM volume in these regions correlated positively with the TBF recognition rate. No significant differences were detected in subjects who forgot many TBF stimuli. Our findings indicate that the right H and left VLPFC are of particular relevance in releasing TBF items from inhibition caused by the F instruction.