Linkage of human cytomegalovirus glycoprotein gO variant groups identified from worldwide clinical isolates with gN genotypes, implications for disease associations and evidence for N-terminal sites of positive selection

Previously, we identified the glycoprotein gO gene, UL74, as a hypervariable locus in the human cytomegalovirus (HCMV) genome [Virology 293 (2002) 281]. Here, we analyze gO from 50 isolates from congenitally infected newborns, transplant recipients, and HIV/AIDS patients from Italy, Australia, and UK. These are compared to four gO groups described from USA transplantation patients [J. Virol. 76 (2002) 10841]. Phylogenetic analyses identified seven genotypes. Divergence between genotypes was up to 55% and within 3%. Discrete linkage was shown between seven hypervariable gO and gN genotypes, but not with gB. This suggests interactions, while gN and gO are known to form complexes with distinct conserved glycoproteins gM, gH/gL, respectively, both are involved in fusogenic entry and exit. Codon-based maximum likelihood models showed evidence for sites of positive selection. Further analyses of disease relationships should take into account these newly defined gO/gN groups.     

小鼠IgE抗体生成的免疫调节——对半抗原-载体蛋白质IgE抗体应答的研究

众所周知,半抗原具有两个特性:(1)无免疫原性;(2)具有反应原性。当半抗原与载体蛋白质结合后便可获得免疫原性,而成为完全抗原。在Ⅰ型变态反应实验动物研究中广为应     

Electrochemical release testing of nickel-titanium orthodontic wires in artificial saliva using thin layer activation

Alloys based on Ni–Ti intermetallics generally exhibit special shape memory and pseudoelastic properties, which make them desirable for use in the dental field as orthodontic wires. The possibility of nickel release from these materials is of high concern, because the allergenicity of this element. The aim of this study was to test pseudoelastic Ni–Ti wires in simulated physiological conditions, investigating the combined effect of strain and fluoridated media: the wires were examined both under strained (5% tensile strain) and unstrained conditions, in fluoridated artificial saliva at 37 °C. Real time electrochemical nickel release testing was performed using a novel application of a radiotracer based method, thin layer activation (TLA). TLA was validated, in unstrained conditions, against adsorptive stripping voltammetry methodology. Control tests were also performed in non-fluoridated artificial saliva. From our research it transpired that the corrosion behaviour of Ni–Ti alloy is highly affected by the fluoride content, showing a release of 4.79 ± 0.10 μg/cm²/day, but, differently from other biomaterials, it does not seem to be affected by elastic tensile strain. The application of the TLA method in the biomedical field appears a suitable technique to monitor in real time the corrosion behaviour of biomedical devices.     

Effects of sex and estrous cycle on modulation of the acoustic startle response in mice

Potential sex differences in amplitude, habituation, prepulse inhibition (PPI) and prepulse facilitation (PPF) of the acoustic startle response (ASR) were investigated using male and female mice from the two different inbred mouse strains C57BL/6J (C57) and C3H. Furthermore, the effects of the estrous cycle were tested. The estrous cycle appeared to have no effect on ASR amplitude, habituation, PPF and PPI, the latter being in contrast to results in rats and humans. While sex had no effect on PPI or PPF, males exhibited higher startle amplitudes than females, irrespective of strain, which we discuss to be due to increased male anxiety. In addition, long-term habituation was stronger in C57 males and short-term habituation was weaker in C3H males with respect to females. These results provide evidence for influence of the reproductive hormones on startle reactivity and startle habituation; we therefore conclude that future studies involving genetic influences on behavior using inbred strains are only complete if both sexes are included.     

A strain gauge device for measuring feeding or drinking in laboratory rats

The details of mechanical construction and electronic circuitry of a strain gauge system for continuously measuring food and water ingestion in laboratory rats are described. The system has been reliably tested over a number of years. It is eminently suitable for investigating daily rhythms in rat feeding and drinking behavior, where a large volume of data is collected over extended periods of time.     

Teratological studies on the TCDD congener 3,3′,4,4′-tetrachloroazoxybenzene in sensitive and nonsensitive mouse strains: Evidence for direct effect on embryonic tissues

The teratogenicity of 3,3,4,4-tetrachloroazoxybenzene (TCAOB), a TCDD congener, was studied in Ah-responsive (C57BL and NMRI) and non-responsive (DBA/2J and AKR/NBom) strains of mice. In the responsive strains, the TCAOB produced cleft palate and hydronephrosis in 50–90% of the offspring at a dose level of 6–8 mg/kg b.w. in the absence of apparent maternal toxicity. Day 11 was shown to be the day of highest sensitivity (palatal closure occurs at day 14) in the C57BL strain. Higher doses (16 mg/kg b.w.) produced high rate of fetal death both in responsive (C57BL; 60%) and non-responsive (DBA; 40%) strains. These doses induced cleft palate in 95% of the surviving C57BL fetuses but failed to do so in the DBA strain. The non-sensitivity of the DBA and AKR strains appeared to segregate as a dominant trait. Backcrosses between NMRI x DBA F₁ generation and NMRI showed an intermediate sensitivity. It was shown that the genotype of the embryo was of ultimate importance for the development of cleft palate. There appeared however to be an additional host (maternal) factor as well, because the offspring of NMRI females mated with NMRI x DBA F₁ males showed a higher rate of cleft palate as compared to those of the crossing between NMRI x DBA F₁ females and NMRI males. Light and scanning electron microscopy indicated that the apical epithelial cells of the secondary palates failed to follow the normal pattern of programmed cell death, suggesting a similar mechanism of pathogenesis as previously described for TCDD.     

Role of shear wave elastography measured in the flaccid state in predicting arteriogenic erectile dysfunction

The gold-standard method for diagnosing arteriogenic erectile dysfunction (AED) is the penile Doppler ultrasonography. We proposed a novel method for predicting AED using ultrasonic shear wave elastography (SWE) considering that the former was invasive and variable. A total of 98 male patients were enrolled in our study, referred for ED between December 2018 and October 2020. For comparison, we also included 42 volunteers from the Healthy Physical Examination Center of our hospital. The Penile Doppler Ultrasonography (PDU) and SWE were performed for all patients with the intracavernosal injection (ICI). We named three groups as AED group, nonvascular ED group and healthy controls group. No statistically significant differences were found among the three groups in terms of demographic and clinical characteristics. There were no significant differences in IIEF-5 between AED and nonvascular ED. A significant (r = 0.642, p < 0.0001) positive correlation between flaccid and erectile SWE was observed. With a cut-off value of 13.45 KPa, the area under curve, specificity, and sensitivity of the SWE values under the flaccid state in distinguishing AED from healthy subjects were 0.867, 0.786 and 0.896 respectively. The SWE value in the flaccid state can distinguish the AED from healthy subjects.     

超声技术在肝纤维化诊断中的应用进展

肝纤维化是临床上各类慢性肝病进行性发展的重要病理过程之一,可进一步发展为肝硬化甚至肝癌。肝纤维化的早期诊断对预防各类肝病发展为肝硬化及肝癌具有重要意义。肝穿刺活检是诊断肝纤维化的“金标准”,但其具有创伤性,易引起多种并发症,目前无法作为常规筛查手段。近年来,超声检查技术作为一种无创性肝纤维化诊断方法在临床上得到越来越多的应用,并取得了诸多进展。本文就超声技术在肝纤维化诊断方面的研究现状作一综述。     

Vaccines against Neisseria meningitidis serogroup B strains – What does genomics reveal on the Portuguese strain’s coverage

In Portugal, Neisseria meningitidis serogroup B (MenB) is the most common serogroup causing invasive meningococcal disease. To protect against MenB disease two protein based MenB vaccines are available in Portugal, the 4CMenB that was licenced in 2014 and included in the routine immunization program in October 2020, and the bivalent rLP2086 vaccine licensed in 2017. The aim of this study was to predict the coverage of the 4CMenB and rLP2086 vaccines against Portuguese isolates of Neisseria meningitidis sampled between 2012 and 2019 and to evaluate the diversity of vaccine antigens based on genomic analysis.Whole-genome sequence data from 324 Portuguese Neisseria meningitidis isolates were analysed. To predict strain coverage by 4CMenB and rLP2086, vaccine antigen reactivity was assessed using the MenDeVar index available on the PubMLST Neisseria website.This study included 235 (75.6%) MenB isolates of all invasive MenB strains reported between 2012 and 2019. Moreover, 89 non MenB isolates sampled in the same period, enrolling 68 from invasive disease and 21 from healthy carriers, were also studied.The predicted strain coverage of MenB isolates was 73.5% (95% CI: 64.8%–81.2%) for 4CMenB and 100% for rLP2086. Predicted strain coverage by 4CMenB in the age group from 0 to 4 years old, was 73.9%. Most of MenB isolates were covered by a single antigen (85.4%), namely fHbp (30.3%), P1.4 (29.2%), and NHBA (24.7%).In Portugal, the most prevalent peptides in MenB isolates were: P1.4 (16.2%), NHBA peptide 2 (14.0%), and fHbp peptide 14 (7.2%), from 4CMenB and fHbp peptide 19 (10.6%) from rLP2086. No significant temporal trends were observed concerning the distribution and diversity of vaccine antigen variants.4CMenB and rLP2086 vaccines showed potential coverage for isolates regardless serogroup.The use of both vaccines should be considered to control possible outbreaks caused by serogroups with no vaccine available.     

An empirical study of the structure of the patrol/marking motivational system in the rat

The existence and structure of an hypothesized motivational system of patrol/marking was supported and elucidated by a behavioral study on untrained highly inbred laboratory rats. One rat (the "runner") was placed into a test chamber containing a wire-mesh running wheel flanked by two chambers, one of which contained another rat (the "target"). Four conditions of runners (socially-isolated males, socially-housed males, non-estrous females, and estrous females) were exposed to four types of targets (socially-housed males, non-estrous females, estrous females, and blank targets consisting of any empty target chamber). Also placed in the chamber was a Petri dish containing scent-markings of the target rat. The experiment was designed in a counterbalanced way with 10 replications and repeated two times in two separate years. As predicted from the hypothesis, scent-marking, sniffing the dish, locomotion (number of wheel revolutions), and approach (differential running towards the target) were all correlated with each other and varied in the same way as a function of the hormonal and experiential condition of the runner and the type of target. They were interpreted to reflect motor patterns of a single unitary patrol/marking motivational system. Grooming, on the other hand, did not correlate with the other behaviors and facial gland secretion was, therefore, rejected as a motor pattern of patrol/marking.