Widespread natural variation in murine natural killer T-cell number and function

Natural killer T (NKT) cells comprise a novel T-lymphocyte subset that can influence a wide variety of immune responses through their ability to secrete large amounts of a variety of cytokines. Although variation in NKT-cell number and function has been extensively studied in autoimmune disease-prone mice, in which it has been linked to disease susceptibility, relatively little is known of the natural variation of NKT-cell number and function among normal inbred mouse strains. Here, we demonstrate strain-dependent variation in the susceptibility of C57BL/6J and BALB/cJ mice to NKT-mediated airway hyperreactivity, which correlated with significant increases in serum interleukin-4 (IL-4) and IL-13 elicited by the synthetic glycosphingolipid alpha-galactosylceramide. Examination of NKT-cell function revealed a significantly greater frequency of cytokine-producing NKT cells in C57BL/6J versus BALB/cJ mice as well as significant differences in the kinetics of NKT-cell cytokine production. Extension of this analysis to a panel of inbred mouse strains indicated that variability in NKT-cell cytokine production was widespread. Similarly, an examination of NKT-cell frequency revealed a significantly greater number of liver NKT cells in the C57BL/6J mice versus BALB/cJ mouse livers. Again, examination of a panel of inbred mouse strains revealed that liver NKT-cell numbers were quite variable, spanning over a 100-fold range. Taken together, these results demonstrate the presence of widespread natural variation in NKT-cell number and function among common inbred mouse strains, which may have implications for the examination of the influence of NKT cells in immune responses and disease pathogenesis among different genetic backgrounds.     

Neurophobia and its implications: evidence from a Caribbean medical school

Background  

Neurology is regarded as a difficult component of the medical curriculum. This has been so marked that the term neurophobia and its effects are being investigated. Given the impact of neurological disorders worldwide, neurophobia has the potential to affect the diagnosis and management of such cases.     

Growth and molecular evolution of vesicular stomatitis serotype New Jersey in cells derived from its natural insect-host: evidence for natural adaptation

In this study we evaluated the growth and molecular evolution of a natural isolate of VSV-NJ (89GAS) from sand flies in cells derived from sand flies (LL5), mosquitoes (C6/36) or hamsters (BHK21). Two VSV-NJ natural isolates of mammalian origin were used for comparison. For each virus we measured: (i) ability to grow in one-step growth curve or after serial passage on each cell type; (ii) ability to induce persistent infection, and (iii) genetic stability of the glycoprotein gene (G) after serial passage in each cell type. Sand fly virus 89GAS grew to higher titers in insect cells compared with viruses of mammalian origin and showed increasing titers with each passage only in C6/36 cells. All viruses established productive persistent infections in both mosquito and sand fly cells but only LL5 cells yielded sustained high virus titers for periods of up to 81 days. Analyses of the consensus sequences of the G gene from each virus after 0, 10 or up to 25 passages in each cell line showed nucleotide substitution rates between 1.39 x l0(-4) and 6.95 x l0(-5). The majority of these changes were non-synonymous, suggesting positive selection. We did not detect increased nucleotide substitution rates on the G gene of 89GAS after passage in cell lines of mosquito or mammalian origin, nor in viruses of mammalian origin after passage in insect cells. This indicates that although VSV G is positively selected in vitro by the insect cell environment, this does not fully explain VSV natural adaptation. This is the first evidence of naturally occurring adaptation of VSV to cells derived from its natural host.     

Use of transgenic animals for carcinogenicity testing: considerations and implications for risk assessment

Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA-/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.     

Stability and instability of childhood traits: implications for personality development of animals

Concepts of animal personality and human temperament are nearly identical, both emphasizing overt behaviors rather than conscious processes, and assuming a primary role of biology in shaping individual differences. A point of divergence is emphasis on development among temperament scholars. Whereas most definitions of personality and temperament emphasize differential continuity-the maintenance of individual differences in behavioral tendencies over time-several behaviors demonstrate absolute discontinuity-age-related changes in mean levels. Attention to species-wide changes in behaviors may generate insight regarding the forces that govern individual differences. Differential continuity may also be heterotypic, with an inferred genotypic attribute being manifest in different behaviors at different ages. Structural continuity-persistence of correlational patterns among variables at different ages-represents a tool for identifying coherence in the common underpinnings of these diverse behaviors. This article describes research exemplifying these forms of continuity in humans, and suggests potential implications for animal personality investigations.     

Airborne endotoxin in homes with domestic animals: implications for cat-specific tolerance

BACKGROUND: Although endotoxin is known to increase symptoms in allergic individuals, early exposure might decrease sensitization. Similarly, the presence of an animal in the home has been associated with decreased sensitization to animal allergens. It has been suggested that the effect of animals could be explained by increased endotoxin exposure. OBJECTIVE: We sought to investigate the effects of domestic animals on airborne endotoxin. METHODS: By using a silent particle collector, air was sampled over 24 hours in homes with or without animals. The total volume sampled was approximately 1000 m3, which provides quantities of allergen and endotoxin that can easily be measured with standard assays. RESULTS: The quantity of endotoxin ranged from less than 0.5 to more than 500 pg/m3, whereas cat and dog allergen ranged from less than 0.002 to more than 5 ng/m3. Overall, the quantity of airborne endotoxin was not higher in homes with at least one animal. However, airborne endotoxin levels were significantly lower in homes with a cat compared with homes with a dog (P < .001). In keeping with this, there was a significant correlation between airborne Can f 1 and airborne endotoxin (r = 0.50, P < .01) but not between endotoxin and Fel d 1 (r = 0.17, P = .27). CONCLUSIONS: The results demonstrate that endotoxin is present in the air of almost all homes. Although higher levels were seen in homes with a dog, similar levels might be present in homes with no animals. The results argue that the effects of cat ownership cannot be explained by increased exposure to endotoxin.     

SARS-CoV-2 and natural infection in animals

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease (COVID-19) pandemic, which has caused serious challenges for public health systems worldwide. Due to the close relationship between animals and humans, confirmed transmission from humans to numerous animal species has been reported. Understanding the cross-species transmission of SARS-CoV-2 and the infection and transmission dynamics of SARS-CoV-2 in different animals is crucial to control COVID-19 and protect animal health. In this review, the possible animal origins of SARS-CoV-2 and animal species naturally susceptible to SARS-CoV-2 infection are discussed. Furthermore, this review categorizes the SARS-CoV-2 susceptible animals by families, so as to better understand the relationship between SARS-CoV-2 and animals.     

Vegetative incompatibility in Neurospora: its effect on horizontal transfer of mitochondrial plasmids and senescence in natural populations

We have investigated the horizontal transfer of two mitochondrial plasmids and the Kalilo senescence phenotype in the fungus Neurospora without the use of heterokaryon-forcing markers. The Kalilo senescent state was only transferred between fully-compatible N. crassa strains, but not between strains differing at any of the loci het-c, het-d, het-e or mating-type. However, the linear plasmid kalDNA and the circular plasmid Han-2 were transferred following incompatible vegetative interactions. Our data suggest that vegetative incompatibility due to allelic differences at het-c is more effective in preventing transfer than that due to het-d, het-e or mating-type. Based on these observations we have developed a novel test for assessing vegetative incompatibility between Kalilo and non-Kalilo field isolates of N. intermedia. In this procedure combinations of Kalilo and non-Kalilo field isolates of N. intermedia were grown together and tested for senescence. Compatibility is inferred if the young non-Kalilo strain dies along with the senescent Kalilo strain, whereas incompatibility is inferred when the Kalilo strain dies without imposing its senescent state onto the non-Kalilo strain. Our results suggest that each of the nine Kalilo strains tested is incompatible with each of 20 non-Kalilo isolates from the same N. intermedia population of the Hawaiian island of Kauai. However, the observed incompatibility did not completely prevent cytoplasmic exchange, and in several cases plasmid transfer could be detected.     

Widespread transfer of resistance genes between bacterial species in an intensive care unit: implications for hospital epidemiology

A transferable plasmid encoding SHV-12 extended-spectrum beta-lactamase, TEM-116, and aminoglycoside resistance was responsible for two sequential clonal outbreaks of Enterobacter cloacae and Acinetobacter baumannii bacteria. A similar plasmid was present among isolates of four different bacterial species. Recognition of plasmid transfer is crucial for control of outbreaks of multidrug-resistant nosocomial pathogens.     

Asthma management: evidence based studies and their implications for cost-efficacy

This review attempts to infer a cost-effective strategy for the management of bronchial asthma based on evidence from randomized controlled trials. Acute severe asthma should be treated with short-acting inhaled beta-agonists followed by a short course of oral steroids. Decisions on hospital admission should be made within 1 to 2 hours and prolonged treatment in emergency departments avoided. A comprehensive educational and drug optimizing program will prevent chronic illness and relapse. Educational programs should be brief but intensive, supervised by asthma specialists and incorporate self monitoring of symptoms plus written action plans. Peak expiratory flow monitoring should not be mandated for all patients. Inhaled corticosteroids (ICS) are the most cost-effective drugs for the long term prevention of asthma. ICS should be started at low doses. If the symptoms of asthma are not well controlled by moderate doses of ICS, high dose ICS treatment should be avoided and add on medication prescribed instead. Oral bronchodilators are less expensive add on medication than long-acting inhaled beta-agonists.     

The evidence of mtDNA haplogroup F in a European population and its ethnohistoric implications

Mitochondrial DNA polymorphism was analysed in a sample of 108 Croatians from the Adriatic Island isolate of Hvar. Besides typically European varieties of human maternal lineages, haplogroup F was found in a considerable frequency (8.3%). This haplogroup is most frequent in southeast Asia but has not been reported before in Europe. The genealogical analysis of haplogroup F cases from Hvar suggested founder effect. Subsequent field work was undertaken to sample and analyse 336 persons from three neighbouring islands (Brac, Korcula and Krk) and 379 more persons from all Croatian mainland counties and to determine if haplogroup F is present in the general population. Only one more case was found in one of the mainland cities, with no known ancestors from Hvar Island. The first published phylogenetic analysis of haplogroup F worldwide is presented, applying the median network method, suggesting several scenarios how this maternal lineage may have been added to the Croatian mtDNA pool.     

Hepatitis B and C in the context of HIV disease: implications for incarcerated populations

HIV-infected inmates are often co-infected with hepatitis B and/or hepatitis C virus. To describe the burden of HIV in the incarcerated population today, one must consider the impact of co-infection. HIV may dramatically modify the course of viral hepatitis infection, especially chronic hepatitis C. The converse is uncertain: chronic hepatitis does not seem to accelerate HIV disease progression. In this article, we offer guidelines for selecting appropriate candidates for treatment among co-infected inmates.     

造血干细胞衰老及其机理的研究

机体衰老是干细胞水平衰老,造血干细胞衰老经历了数量减少和质量的下降。其机制研究表明造血干细胞端粒缩短、mtDNA损伤、p16INK4a基因表达上调、细胞记忆相关蛋白表达的改变等参与造血干细胞衰老的调控。本文就以上内容综述造血干细胞衰老及可能的调控机制。     

Origins and consequences of antimicrobial-resistant nontyphoidal Salmonella: implications for the use of fluoroquinolones in food animals

Human Salmonella infections are common; most infections are self-limiting, however severe disease may occur. Antimicrobial agents, while not essential for the treatment of Salmonella gastroenteritis, are essential for the treatment of thousands of patients each year with invasive infections. Fluoroquinolones and third-generation cephalosporins are the drugs-of-choice for invasive Salmonella infections in humans; alternative antimicrobial choices are limited by increasing antimicrobial resistance, limited efficacy, and less desirable pharmacodynamic properties. Antimicrobial-resistant Salmonella results from the use of antimicrobial agents in food animals, and these antimicrobial resistant Salmonella are subsequently transmitted to humans, usually through the food supply. The antimicrobial resistance patterns of isolates collected from persons with Salmonella infections show more resistance to antimicrobial agents used in agriculture than to antimicrobial agents used for the treatment of Salmonella infections in humans. Because of the adverse health consequences in humans and animals associated with the increasing prevalence of antimicrobial-resistant Salmonella, there is an urgent need to emphasize non-antimicrobial infection control strategies, such as improved sanitation and hygiene, to develop guidelines for the prudent usage of antimicrobial agents, and establishment of adequate public health safeguards to minimize the development and dissemination of antimicrobial resistance and dissemination of Salmonella resistant to these agents.     

Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design.

The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration. Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1-TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules. In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules. The immune response to TBP1 was also host species dependent. Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1-TBP2 complex but detected broadly cross-reactive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum. Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies to TBP2 but no anti-TBP1 antibodies, when examined on Western blots. However, on dot immunoblots, the same patients' sera, as well as the mouse anti-whole cell and the rabbit anti-TBP1-TBP2 complex sera, reacted with purified biologically active TBP1 of strain SD. This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes. These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens. Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded.     

Serological evidence of human adenovirus infections in animals

Twenty-two individual avian and mammalian sera from a zoo were investigated by the haemagglutination inhibition (HAI) and virus neutralization (VN) tests for the presence of specific antibodies to common and less common human adenovirus serotypes, viz. types 5 (Ad 5) and 8 (Ad 8), respectively. Sera positive by both tests were considered to contain presumptive antibody to the adenovirus. One serum contained HAI and VN activities for both viruses; 11 sera were positive by both tests for Ad 5 and three for Ad 8. Four sera were positive for Ad 5 by either test and were of uncertain serological status. Two hundred and forty-three individual farm animals and stray dogs from a rural environment were similarly investigated in the HAI test and three were seropositive for Ad 5; further examination by VN showed that only one of these was positive.     

Behavioral functions and hippocampal cell types: evidence for two nonoverlapping populations in the rat

Extracellular recordings of individual hippocampal neurons in behaving rats were classified by several different electrophysiological criteria as theta (theta-) or complex spike cells. The firing characteristics of each cell were studied in two different behavioral contexts, each of which contained experimental conditions in which firing correlates of these cells have been demonstrated previously. Forty-eight theta-cells and 68 complex spike cells were classified and studied electrophysiologically as animals performed an operant auditory discrimination task or freely explored an open platform environment for water reward. Spontaneous discharge characteristics, as well as electrically evoked firing patterns following stimulation of hippocampal fiber pathways, consistently differentiated theta-cells from complex spike cells. In agreement with previous reports, these results indicate that theta-cells and complex spike cells represent electrophysiologically and possibly morphologically different types of hippocampal neurons. A clear dichotomy also emerged between the firing correlates of identified theta-cells and complex spike cells in the two behavioral tests. During auditory-discrimination learning and performance, time-locked theta-cell discharges to tone onset were correlated with the emergence of conditioned behavioral responding. Increased activity of theta-cells was also observed during locomotion in the spatial exploration task. Time-locked increases in firing to the tone stimulus were restricted to identified theta-cells. Complex spike cells, in contrast to theta-cells, did not increase activity during any phase of tone-discrimination learning or performance. The same cells, however, fired at markedly increased rates coincident with the animals' presence in specific spatial locations during exploration of the platform but did not fire during other overt behaviors on the platform such as grooming, drinking, or locomotion. Complex spike cells qualified on the basis of positive collision tests and antidromic criteria as hippocampal output neurons. "Spatial firing" was unique to complex spike cells and was not observed from theta-cells recorded from the same animal. Twenty-one theta-cells and 31 complex spike cells studied in both behavioral contexts showed mutually exclusive and nonoverlapping electrophysiological firing correlates. No cell was observed in either category which exhibited spatial and tone discrimination related firing correlates.(ABSTRACT TRUNCATED AT 400 WORDS)     

Transmission efficiency of the sigma virus in natural populations of its host,Drosophila melanogaster

Summary A study of the viral samples collected in French natural populations ofDrosophila melanogaster since 1969, indicates that natural populations include, as expected, both stabilized and non stabilized infected individuals. In agreement with previous observations made on other characters of the virus, the viral samples collected appear to be homogeneous for the efficiency of the hereditary transmission. However, this efficiency is greater than the average value observed with virus perpetuated in infected laboratory fly strains. One sample collected in Gabon and three in the U.S.A. appear to differ from the French samples for one at least of the traits studied in these experiments.With 6 Figures