The immunology of infection Gilchrist, James J.; MacLennan, Calman A.
Medicine (Abingdon. 1995, UK ed.),
October 2017, 2017-10-00, Letnik:
45, Številka:
10
Journal Article
Recenzirano
The human immune system is composed of a collection of specialized cells and secreted proteins that allows the identification and removal of an invading pathogen, and in doing so limits host injury ...or death. This system is composed of innate and adaptive branches. It is important to recognize that although the innate and adaptive branches of the immune system differ fundamentally in their mechanisms of pathogen recognition, neither branch functions in isolation. In this article, we address how the innate and adaptive immune systems sense the presence of a pathogen, how the immune system then coordinates anti-pathogen effector functions to remove the pathogen, and finally how immunological memory functions to better protect its host against subsequent exposure to the same pathogen.
Gilchrist et al discuss an identification of a trait-associated SNP, rs8060947 in VAC14. rs8060947 is an expression quantitative trait locus for VAC14 RNA expression and carriage of the A allele is ...associated with reduced VAC14 RNA and protein expression and increased invasion of S. Typhi. VAC14-associated inhibition of S. Typhi invasion is mediated by a reduction in host cell membrane cholesterol.
Invasive nontyphoidal Salmonella (iNTS) disease is a major cause of deaths among children and HIV-infected individuals in sub-Saharan Africa. Acquisition of IgG to iNTS lipopolysaccharide (LPS) ...O-antigen in Malawi in early childhood corresponds with a fall in cases of iNTS disease suggesting that vaccines able to induce such antibodies could confer protection. To better understand the acquisition of IgG to iNTS in other African settings, we performed a cross-sectional seroepidemiological study using sera from 1090 Ugandan individuals aged from infancy to old age. Sera were analysed for IgG to LPS O-antigen of S. Typhimurium and S. Enteritidis using an in-house ELISA. Below 18 months of age, most children lacked IgG to both serovars. Thereafter, specific IgG levels increased with age, peaking in adulthood, and did not wane noticeably in old age. There was no clear difference in antibody levels between the sexes and the few HIV-infected individuals in the study did not have obviously different levels from uninfected subjects. While IgG to iNTS is acquired at a younger age in Malawian compared with Ugandan children, it is not clear whether this is due to differences in the populations themselves, their exposure to iNTS, or variations between assays used. In conclusion, there is a need to develop a harmonised method and standards for measuring antibodies to iNTS across studies and to investigate acquisition of such antibodies with age across different sites in sub-Saharan Africa.
Remembering Frank Balotti Strine, Leo E., Jr; Hanks, James J., Jr; Olson, John F ...
The Business lawyer,
06/2017, Letnik:
72, Številka:
3
Journal Article
Foreword: Remembering Frank Balotti Hanks, James J; Olson, John F; Sparks, A Gilchrist ...
The Business Lawyer,
07/2017, Letnik:
72, Številka:
3
Trade Publication Article
Recenzirano
Frank Balotti was well known and respected in Wilmington and Delaware, of course; but he was also well known and respected throughout the United States for his participation in many of the most ...celebrated corporate law cases of his time and, of course, for his and Jesse Finkelstein's multi-volume Balotti & Finkelstein on The Delaware Law of Corporations & Business Organizations. For some or all of us, knowing and working with Frank often led to other joint adventures-teaching, writing, speaking, the ABA Corporate Laws Committee, advising the post-apartheid Government of South Africa on revising its incorporation process and Companies Law, and teaching law together at Cornell Law School, his beloved alma mater. Frank was a legendary litigator in both Delaware state and federal courts. Long after mourning his passing, we shall miss him. * The authors are lawyers and good friends of the late R. Franklin Balotti who have worked...
OBJECTIVES:To estimate the lifetime risk, prevalence, incidence, and mortality of the principal clinical syndromes associated with frontotemporal lobar degeneration (FTLD) using revised diagnostic ...criteria and including intermediate clinical phenotypes.
METHODS:Multisource referral over 2 years to identify all diagnosed or suspected cases of frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), or corticobasal syndrome (CBS) in 2 UK counties (population 1.69 million). Diagnostic confirmation used current consensus diagnostic criteria after interview and reexamination. Results were adjusted to the 2013 European standard population.
RESULTS:The prevalence of FTD, PSP, and CBS was 10.8/100,000. The incidence and mortality were very similar, at 1.61/100,000 and 1.56/100,000 person-years, respectively. The estimated lifetime risk is 1 in 742. Survival following diagnosis varied widelyfrom PSP 2.9 years to semantic variant FTD 9.1 years. Age-adjusted prevalence peaked between 65 and 69 years at 42.6/100,000the age-adjusted prevalence for persons older than 65 years is double the prevalence for those between 40 and 64 years. Fifteen percent of those screened had a relevant genetic mutation.
CONCLUSIONS:Key features of this study include the revised diagnostic criteria with improved specificity and sensitivity, an unrestricted age range, and simultaneous assessment of multiple FTLD syndromes. The prevalence of FTD, PSP, and CBS increases beyond 65 years, with frequent genetic causes. The time from onset to diagnosis and from diagnosis to death varies widely among syndromes, emphasizing the challenge and importance of accurate and timely diagnosis. A high index of suspicion for FTLD syndromes is required by clinicians, even for older patients.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
The Xenopus mid-blastula transition (MBT) marks the onset of large-scale zygotic transcription, as well as an increase in cell cycle length and a loss of synchronous cell divisions. Little is known ...about what triggers the activation of transcription or how newly expressed genes interact with each other. Here, we use high-resolution expression profiling to identify three waves of gene activity: a post-fertilisation wave involving polyadenylation of maternal transcripts; a broad wave of zygotic transcription detectable as early as the seventh cleavage and extending beyond the MBT at the twelfth cleavage; and a shorter post-MBT wave of transcription that becomes apparent as development proceeds. Our studies have also allowed us to define a set of maternal mRNAs that are deadenylated shortly after fertilisation, and are likely to be degraded thereafter. Experimental analysis indicates that the polyadenylation of maternal transcripts is necessary for the establishment of proper levels of zygotic transcription at the MBT, and that genes activated in the second wave of expression, including Brachyury and Mixer, contribute to the regulation of genes expressed in the third. Together, our high-resolution time series and experimental studies have yielded a deeper understanding of the temporal organisation of gene regulatory networks in the early Xenopus embryo.
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