Emergence of SARS-CoV-2 B.1.1.7 Lineage at Outpatient Testing Site,Berlin, Germany,January–March 2021

Within 5 weeks in 2021, B.1.1.7 became the dominant severe acute respiratory syndrome coronavirus 2 lineage at an outpatient testing site in Berlin, Germany. Compared with outpatients with wild-type virus infection, patients with B.1.1.7 had similar cycle threshold values, more frequent sore throat and travel history, and less frequent anosmia/ageusia.     

Vaccine protection against lethal homologous and heterologous challenge using recombinant AAV vectors expressing codon-optimized genes from pandemic swine origin influenza virus (SOIV)

The recent H1N1 influenza pandemic and the inevitable delay between identification of the virus and production of the specific vaccine have highlighted the urgent need for new generation influenza vaccines that can preemptively induce broad immunity to different strains of the virus. In this study we have produced AAV-based vectors expressing the A/Mexico/4603/2009 (H1N1) hemagglutinin (HA), nucleocapsid (NP) and the matrix protein M1 and have evaluated their ability to induce specific immune response and protect mice against homologous and heterologous challenge. Each of the vaccine vectors elicited potent cellular and humoral immune responses in mice. Although immunization with AAV-M1 did not improve survival after challenge with the homologous strain, immunization with the AAV-H1 and AAV-NP vectors resulted in survival of all mice, as did inoculation with a combination of all three vectors. Furthermore, trivalent vaccination also conferred partial protection against challenge with the highly heterologous and virulent A/PR/8/34 strain of H1N1 influenza.     

Racial/Ethnic differences in smoking, drinking, and illicit drug use among American high school seniors, 1976-89.

BACKGROUND. This paper reports racial/ethnic differences in the use of licit and illicit drugs by high school seniors in the United States. METHODS. The study uses questionnaire data from annual, nationally representative surveys of seniors from 1976 through 1989. Combined sample sizes were 57,620 for 1976-79; 75,772 for 1980-84; and 73,527 for 1985-89. RESULTS. Native American had the highest prevalence rates for cigarettes, alcohol, and most illicit drugs; White students had the next highest rates for most drugs. Asian Americans had the lowest prevalence rates, and Black students had levels nearly as low except for marijuana. Prevalence rates for the Hispanic groups were mostly in the intermediate ranges except for relatively high cocaine use among the males. Trend patterns for most forms of drug use were similar across subgroups, although cigarette use declined more sharply for Black than White seniors, resulting in greater Black-White differences in recent years. CONCLUSIONS. This study, other school-based studies, and general population surveys all show relatively low levels of drug use by most non-White youth, especially Black Americans and Asian Americans. Multivariate analyses indicate that such subgroup differences in high school seniors' drug use are not primarily attributable to family composition, parents' education, region, or urban-rural distinctions.     

Intronic sequence motifs of HLA-DQB1 are shared between humans, apes and old world monkeys, but a retroviral LTR element (DQLTR3) is human specific

Long terminal repeats (LTRs) of the human endogenous retrovirus K (HERV-K) family have been found at several sites within the human genome, of which one is located in the vicinity of HLA-DQB1. Since this DQLTR3 is only present on some haplotypes, we performed a linkage analysis in 130 Caucasian families. In order to date the integration event we also investigated the presence of this DQLTR3 in apes and Old World monkeys. Additionally, we sequenced the adjacent region of DQLTR3-positive and -negative haplotypes in humans, apes and old world monkeys to elucidate their evolution. Linkage analysis revealed a differential integration of DQLTR3 on specific HLA-DQ haploypes: there was a high frequency of this LTR on haplotypes containing HLA-DQB1*0302 (0.96) and a moderate frequency on HLA-DQB1*0402 (0.78), HLA-DQB1*0303 (0.44), HLA-DQB1*0502 (0.38) and HLA-DQB1*0301 (0.35). HLA-DQB1*0201 (0.18), HLA-DQB1*0503 (0.15), HLA-DQB1*0603 (0.15), HLA-DQB1*0602 (0.04), HLA-DQB1*0501 (0.03) and HLA-DQB1*0604 were rarely positive or devoid of DQLTR3. In apes and Old World primates there was no DQLTR3 rendering it a human specific insertion. Sequence analysis of the adjacent region showed two different motifs in humans corresponding to either presence or absence of DQLTR3. Two different motifs were observed within three sequences of Macaca mulatta: One motif is closely related to the sequence from Macaca nemestrina and Macaca fascicularis whereas the other sequence is more closely related with that of Papio papio and Cercopithecus aethiops. Therefore the analysis of retroviral elements as well as intronic sequences of MHC-DQB1 could help to clarify the evolution of this gene region as well the phylogenic relationship between humans, apes and Old World monkeys.     

Multiparameter analysis of four human renal cell carcinoma xenografts in nude mice

Four human renal cell carcinoma xenografts (RC2, RC14, RC43, NC65), maintained in nude mice for several years, were investigated in a multi - disciplinary study, using (immuno) histochemical, biochemical and ultrastructural techniques. Histological, cellular, nuclear and biological characteristics were investigated. All tumors showed histologically recognizable features of human renal cell carcinomas, although marked differences between the four tumors were seen, both at the histological and ultrastructural level. Flowcytometric analysis of tumor cell suspensions allowed DNA quantification as well as the detection of subpopulations. Immunohistochemical staining procedures using tissue specific antibodies against intermediate filament proteins revealed two populations of tumor cells. Most tumor cells in three of the xenografts coexpressed cytokeratins and vimentin, while in RC43 most of the tumor cells expressed only vimentin. Northern blot analysis showed a higher expression of vimentin mRNA in all tumors as compared to normal kidney tissue. RC43 showed a three-fold higher level of vimentin mRNA than the other xenografts. Growth potential in the human tumor cloning system was evaluated by temporal growth pattern analysis. These experiments showed that the xenografts resemble human primary renal cell tumors in different ways, and reflect different characteristics that can be present in human renal cell carcinoma.     

Glutathione conjugation of electrophilic metabolites of 1-nitronaphthalene in rat tracheobronchial airways and liver: identification by mass spectrometry and proton nuclear magnetic resonance spectroscopy.

1-Nitronaphthalene (1-NN) is a mutagenic nitroaromatic which has been detected in emissions from both heavy- and light-duty diesel engines, as well as in urban airborne particles. 1-NN is a cytochrome P450-bioactivated, nonciliated bronchiolar epithelial (Clara) cell cytotoxicant. These studies examined the metabolism of 1-NN to electrophilic metabolites which were trapped as glutathione conjugates in highly susceptible (lung) and less susceptible (liver) tissues of the rat. Significant depletion of reduced glutathione was observed at all levels of tracheobronchial airways of rats treated with 200 mg/kg 1-NN, ip. This observation of depleted glutathione was consistent with the HPLC radioactivity profiles demonstrating six glutathione conjugates isolated from liver and lung microsomal incubations with 1-NN, [(3)H]glutathione, and glutathione S-transferase. Mass spectrometry of all six metabolites in electrospray positive ion mode yielded an ion of m/z 497 (M + H), and daughter ions of m/z 479 (loss of water), m/z 306 (glutathione), and m/z 177 (loss of the nitro group and formation of hydroxy naphthalene thiolate ion), demonstrating the formation of hydroxy-dihydroglutathionyl derivatives presumably via intermediate epoxide(s). Proton nuclear magnetic resonance spectroscopy identified four different regioisomeric conjugates from lung and liver microsomal incubations: 1-nitro-7-glutathionyl-8-hydroxy-7, 8-dihydronaphthalene, 1-nitro-7-hydroxy-8-glutathionyl-7, 8-dihydronaphthalene, 1-nitro-5-hydroxy-6-glutathionyl-5, 6-dihydronaphthalene, and 1-nitro-5-glutathionyl-6-hydroxy-5, 6-dihydronaphthalene. HPLC radioactivity profiles demonstrated that major conjugates generated in the lung were derived from the C(7), C(8)-epoxide, whereas the most prominent metabolites in the liver were derived from the C(5),C(6)-epoxide.     

Taste preferences in human obesity: environmental and familial factors

Taste-response profiles influence food selection and may help distinguish among potential subgroups of obese individuals. A representative community-based sample of 61 obese and 31 lean adults tasted five sucrose solutions and nine fat-containing solid stimuli resembling cake icings. Solid stimuli contained 15-35% fat and 20-70% sucrose (by weight). No significant differences in taste responsiveness were observed between obese and lean groups. Obese subjects were then divided into subgroups based on age at onset of obesity and past fluctuations in body weight. Obese subjects characterized by large weight fluctuations showed elevated preferences for sugar and fat mixtures compared with the stable subgroup. In contrast, early age at onset of obesity (less than 10 y), thought to be a measure of familial risk, had no significant effects on taste preferences. Environmental as opposed to familial factors may be more immediate determinants of taste preferences and food choice.     

Complete nucleotide sequence of a simian immunodeficiency virus from African green monkeys: a novel type of intragroup divergence

We have determined the entire nucleotide sequence of a full-length molecular clone, termed SIVagm3, which is infectious in vitro and in vivo. The genomic organization was found to be similar to other immunodeficiency viruses of human and simian origin. Comparison of SIVagm3 with SIVagmTYO-1, the only other completely sequenced molecular SIVagm clone, revealed a novel type of intragroup divergence, which is characterized by (1) an unusually high degree of variability in pol in relation to gag and env and (2) a high degree of divergence in the rev and tat genes. Thus, since SIVagm3 and SIVagmTYO-1 evolved from their common ancestor, they diverged in a different manner than human immunodeficiency viruses. Hypervariable regions in env were defined and shown to be relatively restricted in comparison to HIV-1 and HIV-2.