Soluble HLA-G and HLA-A,-B,-C serum levels in patients with allergic rhinitis

Background: Allergic rhinitis (AR) is characterized by Th2‐polarized immune response. Soluble HLA (sHLA) molecules play an immunomodulatory activity. So far, however, no study investigated them in AR. Objective: The aim of this study was to evaluate sHLA‐G and sHLA‐A,‐B,‐C serum levels in AR patients with pollen allergy and in a group of healthy controls. Methods: Forty‐nine AR patients were enrolled. A group of healthy nonallergic subjects was considered as control. sHLA‐G and sHLA‐A,‐B,‐C serum levels were determined by immunoenzymatic method. The study was conducted during the winter, such as outside the pollen season. Results: Allergic patients had significantly higher levels of both sHLA‐G (P < 0.0001) and sHLA‐A,‐B,‐C (P = 0.011) molecules than normal controls. Moreover, there was a significant relationship between these two soluble molecules (r = 0.69) in allergic patients. Conclusion: The present study provides the first evidence that both sHLA‐G and sHLA‐A,‐B,‐C serum levels are significantly increased in AR patients with pollen allergy.     

Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes.

The autoimmune attack in type 1 diabetes is not only targeted to beta cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA-IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, beta-cell antibody status (ICA, GADA, IA2A) and HLA-DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 +/- 16 years; duration: 9 +/- 8 years) were tested for ICA, PCA, AAA and EmA-IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase-65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA-IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (beta = - 1.15, P = 0.002), age (beta = 0.02, P = 0.01) and GADA + (beta = 1.06, P = 0.02), but not by HLA-DQ type or IA2A status. Dysthyroidism (P < 0.0001) was more frequent in aTPO + subjects. PCA status was determined by age (beta = 0.03, P = 0.002). We also observed an association between PCA + and GADA + (OR = 1.9, P = 0.049), aTPO + (OR = 1.9, P = 0.04) and HLA DQA1*0501-DQB1*0301 status (OR = 2.4, P = 0.045). Iron deficiency anaemia (OR = 3.0, P = 0.003) and pernicious anaemia (OR = 40, P < 0.0001) were more frequent in PCA + subjects. EmA-IgA + was linked to HLA DQA1*0501-DQB1*0201 + (OR = 7.5, P = 0.039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501-DQB1*0301 and EmA-IgA + with HLA DQA1*0501-DQB1*0201.     

Integration of Pig-a, micronucleus, chromosome aberration, and Comet assay endpoints in a 28-day rodent toxicity study with 4-nitroquinoline-1-oxide

As part of the Stage III Pig‐a multilaboratory validation trial, we examined the induction of CD59‐negative reticulocytes and total red blood cells (RET^CD59? and RBC^CD59?, respectively) in male Sprague Dawley® rats treated with 4‐nitroquinoline‐1‐oxide (4NQO), for 28 consecutive days by oral gavage, at doses of 1.25, 2.50, 3.75, 5.00, and 7.50 mg kg^?1 day^?1 (the high dose group was sacrificed on Day 15 due to excessive morbidity/mortality). Animals also were evaluated for: micronucleated reticulocytes (mnRET) by flow cytometry; DNA damage in peripheral blood, liver, and stomach using the Comet assay; and chromosome aberrations (CAb) in peripheral blood lymphocytes (PBL). All endpoints were analyzed at two or more timepoints where possible. Mortality, body and organ weights, food consumption, and clinical pathology also were evaluated, and demonstrated that the maximum tolerated dose was achieved at 5.00 mg kg^?1 day^?1. The largest increases observed for the genetic toxicology endpoints (fold‐increase compared to control, where significant; all at 5.00 mg kg^?1 day^?1 on Day 29) were: RET^CD59? (21X), RBC^CD59? (9.0X), and mnRET (2.0X). In contrast, no significant increases were observed for the CAb or Comet response, in any tissue analyzed, at any timepoint. Because 4NQO is a well known mutagen, clastogen, and carcinogen, the lack of response for these latter endpoints was unexpected. These results emphasize the extreme care that must betaken in dose and endpoint selection when incorporating genotoxicity endpoints into routine toxicity studies as has been recommended or is under consideration by various regulatory and industrial bodies. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.     

Laboratory testing of SARS‐CoV,MERS‐CoV,and SARS‐CoV‐2 (2019‐nCoV): Current status,challenges, and countermeasures

Emerging and reemerging infectious diseases are global public concerns. With the outbreak of unknown pneumonia in Wuhan, China in December 2019, a new coronavirus, SARS‐CoV‐2 has been attracting tremendous attention. Rapid and accurate laboratory testing of SARS‐CoV‐2 is essential for early discovery, early reporting, early quarantine, early treatment, and cutting off epidemic transmission. The genome structure, transmission, and pathogenesis of SARS‐CoV‐2 are basically similar to SARS‐CoV and MERS‐CoV, the other two beta‐CoVs of medical importance. During the SARS‐CoV and MERS‐CoV epidemics, a variety of molecular and serological diagnostic assays were established and should be referred to for SARS‐CoV‐2. In this review, by summarizing the articles and guidelines about specimen collection, nucleic acid tests (NAT) and serological tests for SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2, several suggestions are put forward to improve the laboratory testing of SARS‐CoV‐2. In summary, for NAT: collecting stool and blood samples at later periods of illness to improve the positive rate if lower respiratory tract specimens are unavailable; increasing template volume to raise the sensitivity of detection; putting samples in reagents containing guanidine salt to inactivate virus as well as protect RNA; setting proper positive, negative and inhibition controls to ensure high‐quality results; simultaneously amplifying human RNase P gene to avoid false‐negative results. For antibody test, diverse assays targeting different antigens, and collecting paired samples are needed.     

DNA adducts of 1,3-butadiene in humans: relationships to exposure, GST genotypes, single-strand breaks, and cytogenetic end points

The modulation of 1,3-butadiene (BD)-induced DNA adducts by occupational exposure, glutathione S-transferase (GST) genotypes, single-strand breaks, and cytogenetic end points was studied in 15 workers and 11 controls. The exposed group consisted of 8 smokers and 7 nonsmokers, whereas the control group consisted of 7 nonsmokers and 4 smokers. Among all subjects, the adduct levels in workers lacking GSTM1 were significantly higher than in those who were GSTM1 positive (P = 0.026), and individuals with combined GSTM1(-) and GSTT1(+) genotype had elevated level of adducts compared to that of persons with GSTM1(+) and GSTT1(+) (P = 0.049). The increase in BD-DNA adduct levels in all subjects was significantly related to BD exposure and GSTM1 genotype (linear multiple regression analysis, P = 0.001; P = 0.035). The results suggest that DNA adducts serve as a sensitive and specific biomarker, integrating exposure and host metabolic capacity, although the data are limited to a small number of subjects.     

Conjugated Silole and Carbazole Copolymers: Synthesis,Characterization, Single‐Layer Light‐Emitting Diode,and Field Effect Carrier Mobility

Summary: Soluble conjugated random and alternating copolymers (PCz‐PSP) derived from N‐hexyl‐3,6‐carbazole (Cz) and 1,1‐dimethyl‐2,3,4,5‐tetraphenylsilole (PSP) were synthesized by palladium(0)‐catalyzed Suzuki coupling reactions. The feed ratios of Cz to PSP were 95:5, 90:10, 80:20, 70:30, and 50:50. Chemical structures and optoelectronic properties of the copolymers were characterized by ¹H NMR, ¹³C NMR, UV absorption, cyclic voltammetry, photoluminescence, electroluminescence, and field effect transistor. HOMO levels of the copolymers are between −5.15 and −5.34 eV. Single‐layer devices with a configuration of ITO/copolymer/Ba/Al were fabricated and the copolymer with PSP content of 20% displayed the highest external quantum efficiency of 0.77%. Field effect transistors with tantalum pentoxide‐polyacrylonitrile double insulators demonstrated that hole mobilities of the copolymers decreased with their PSP contents, and the hole mobility up to 9.3 × 10⁻⁶ cm² · (V · s)⁻¹ could be achieved.

Synthesis of coplymers derived from 3,6‐carbazole and silole.     

Self‐compassion,self‐forgiveness,suicidal ideation,and self‐harm: A systematic review

Self‐compassion has been implicated in the aetiology and course of mental health with evidence suggesting an association between greater self‐compassion and lower emotional distress. However, our understanding of the nature and extent of the relationship between self‐compassion and self‐harm (self‐injury regardless of suicidal intent) or suicidal ideation remains unclear. This review, therefore, aimed to critically evaluate the extant literature investigating this relationship. To do so, a systematic search, including terms synonymous with self‐compassion, was conducted on three main psychological and medical databases (Web of Science, PsycINFO, and Medline). Only studies investigating self‐compassion or self‐forgiveness and self‐harm or suicidal ideation were found to be relevant to the review. Eighteen studies were included in the final narrative synthesis. Heterogeneity of studies was high, and the majority of studies were quantitative and cross‐sectional (n = 16) in design. All studies reported significant associations between higher levels of self‐forgiveness or self‐compassion and lower levels of self‐harm or suicidal ideation. Several studies suggested that self‐compassion or self‐forgiveness may weaken the relationship between negative life events and self‐harm. In conclusion, this review highlights the potential importance of self‐compassion in the aetiology of suicidal thoughts and self‐harm. We discuss the clinical and research implications.     

Psychopathology,GABA, and the Rubinstein‐Taybi syndrome: A review and case study

An adult female with congenital Rubinstein‐Taybi syndrome (RTS) and severe mental retardation is described, who presented with symptoms of severe over‐activity, short attention span, mood lability, and aggressive outbursts in a cyclical pattern, suggestive of recurrent manic‐like episodes. These symptoms improved significantly with divalproex (Depakote) monotherapy. Review of the existing studies showed that 10–76% of persons with RTS may be identified with similar behavioral symptoms. We postulate other persons with RTS may respond to divalproex, and there may be some relationship between the chromosome 16p13.3 deletion and γ‐aminobutyric acid (GABA) receptor or neurotransmitter abnormalities. Recent molecular genetic studies suggest a linkage of this region to bipolar mood disorder and autism, both of which were diagnosed in this patient. Further prospective study is needed of RTS persons regarding behavioral problems, comorbid psychiatric diagnoses, and treatment responses, correlated with genetic abnormalities. © 2002 Wiley‐Liss, Inc.     

Transmission route and introduction of pandemic SARS‐CoV‐2 between China,Italy, and Spain

We present a phylodynamic and phylogeographic analysis of this new severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus in this report. A tree of maximum credibility was constructed using the 72 entire genome sequences of this virus, from the three countries (China, Italy, and Spain) available as of 26 March 2020 on the GISAID reference frame. To schematize the current SARS‐CoV‐2 migration scenario between and within the three countries chosen, using the multitype bearth‐death model implemented in BEAST2. Bayesian phylogeographic reconstruction shows that SARS‐CoV‐2 has a rate of evolution of 2.11 × 10^?3 per sites per year (95% highest posterior density: 1.56 × 10^?3 to 3.89 × 10^?3), and a geographic origin in Shanghai, where time until the most recent common ancestor (tMRCA) emerged, according to the analysis of the molecular clock, around 13 November 2019. While for Italy and Spain, there are two tMRCA for each country, which agree with the assumption of several introductions for these countries. That explains also this very short period of subepidermal circulation before the recent events. A total of 8 (median) migration events occurred during this short period, the largest proportion of which (6 events [75%]) occurred from Shanghai (China) to Spain and from Italy to Spain. Such events are marked by speeds of migration that are comparatively lower as compared with that from Shanghai to Italy. Shanghai's R₀ and Italy's are closer to each other, though Spain's is slightly higher. All these results allow us to conclude the need for an automatic system of mixed, molecular and classical epidemiological surveillance, which could play a role in this global surveillance of public health and decision‐making.     

Kazrin, and its binding partners ARVCF- and delta-catenin, are required for Xenopus laevis craniofacial development

The novel adaptor protein Kazrin associates with multifunctional entities including p120-subfamily members (ARVCF-, delta-, and p0071-catenin). Critical contributions of Kazrin to development or homeostasis are indicated with respect to ectoderm formation, integrity and keratinocyte differentiation, whereas its presence in varied tissues suggests broader roles. We find that Kazrin is maternally loaded, is expressed across development and becomes enriched in the forming head. Kazrin's potential contributions to craniofacial development were probed by means of knockdown in the prospective anterior neural region. Cartilaginous head structures as well as eyes on injected sides were reduced in size, with molecular markers suggesting an impact upon neural crest cell establishment and migration. Similar effects followed the depletion of ARVCF (or delta-catenin), with Kazrin:ARVCF functional interplay supported upon ARVCF partial rescue of Kazrin knockdown phenotypes. Thus, Kazrin and its associating ARVCF- and delta-catenins, are required to form craniofacial tissues originating from cranial neural crest and precordal plate.     

Synthesis,Characterization, and Photopolymerization of Novel Phosphonated Resins, 2

New phosphonated cross‐linked polymers were synthesized from telomers obtained by reaction between 10‐undecenol and dialkyl hydrogenphosphonates. Telomers were studied using MALDI‐TOF MS. It was proven that side products were produced, corresponding to cross‐esterification reactions of dialkyl hydrogenphosphonate on telomers and to radical additions of telomer on 10‐undecenol. The same behavior was also observed with allyl alcohol. Telomers were then converted to resins by methacrylation reactions. Finally, photopolymerization of the different resins synthesized was achieved and influence of the nature of the phosphonate group (diester, monoacid and diacid) was also evaluated.

     

Altered expression of zinc finger proteins,ADAMs, and integrin-related proteins following treatment of cultured human cells with a low concentration of N-methyl-N'-nitro-N-nitrosoguanidine

Proteomic analysis is an important approach to characterize the proteome and study protein functions. It is also a powerful screening method for detecting unexpected alterations in protein expression that may be overlooked by conventional biochemical techniques. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is an alkylating agent that can induce nontargeted mutagenesis in treated cells, although the mechanism remains unclear. Using an efficient proteomic method, we identified several cellular proteins that are responsive to low-concentration MNNG treatment in human FL cells. After MNNG treatment, whole cellular proteins were separated using two-dimensional gel electrophoresis and visualized by silver staining; the digitized images then were analyzed with 2D analysis software. More than 60 proteins showed significant changes in MNNG-treated cells compared to control cells (DMSO treatment). Thirty-one proteins only detected in MNNG-treated or control cells were subjected to in-gel digestion with trypsin and identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry using peptide mass fingerprinting. Eighteen of theses proteins have been identified, including several zinc finger proteins, two members of the ADAMs (a disintegrin and metalloprotease domain) family, and two integrins. Most of these proteins have unknown functions and their involvement in the cellular responses to alkylating agents have not been reported. Therefore, our findings may offer new insights into the mechanisms of low-concentration MNNG-induced nontargeted mutagenesis and these proteins may serve as new biomarkers for detecting exposure of human populations to environmental carcinogens.