bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ageing and the Immune System
Authors: Aspinall Richard , Lang Pierre Olivier 
Published: September 2015

Abstract

Recognising invading foreign organisms, preventing their spread and ultimately clearing them from the body throughout life is the central role of the immune system. In a healthy adult, the immune system is composed of approximately 10
12
cells which interact with each other to produce both effector molecules and cells which defend the tissues of the body against potential pathogens.

Unfortunately, like all biological systems, there is normal wear and tear, and with advancing age, the immune system shows a gradual loss of function. However, because each individual differs in their genetic makeup and has been exposed to a different range of environmental factors, this functional decline is not uniform and predictable. There is no certain age at which this process begins and no defined pathway or identifiable sequence of loss of function. The result is considerable variation within the aged population in the ability of an individual to respond productively to potential pathogens and vaccines. Current work is directed at mapping the changes in the immune system with age with a view to identifying any common triggers of deterioration in function. This in turn might lead to an opportunity to reverse the degradation process and thus to extend the period of fully effective protection.

Key Concepts

Low‐grade systemic inflammation is a feature which characterises the ageing process in many individuals.

Evidence from epidemiology studies shows that the susceptibility to infectious diseases increases with age.

Studies on responses to vaccines reveal that many older individuals fail to produce the responses seen in younger individuals, which is associated with protection from the disease.

Some change in the function of cells of the innate immune system (NK cells, neutrophils, macrophages and dendritic cells) has been noted in a number of older individuals.

All older individuals show an accumulation of fat in the primary lymphoid organs, which is associated with functional decline and a reduction in their ability to produce new lymphocytes.

The thymus atrophies with age, and there is a reduction in the areas of active thymopoeisis and in the output of naïve T cells.

The area of active (red) bone marrow declines with age, and the number of naïve B cells emerging from the marrow shows a reduction with age.

A successful T cell‐mediated immune response results in the generation of both T and B memory cells, and as survival depends on successful responses, there is an increase in the number of memory cells with age.

Infections with persistent viruses such as the human herpes virus group can lead to the expansion of specific clones amongst which are cells at, or close to, their replicative limit.

The expansion of some clones within the memory cell pool may also be linked with the loss of other clones and the appearance of ‘holes’ in the repertoire.
Hereditary Breast Cancer Syndromes: Molecular Pathogenesis and Diagnostics
Authors: Vos S , Van der Groep P , Van der Wall E , Van Diest Paul J 
Published: September 2015

AbstractBreast cancer is a major cause of morbidity and mortality worldwide. Approximately, 20% of breast cancer cases are due to a familial predisposition. Most of these familial breast cancers are due to mutations in well‐known genes linked to breast cancer, such asBRCA1,BRCA2,TP53,CHEK2,PTEN,CDH1,STK11/LKB1,RAD50,BRIP1andPALB2. Some of these cancers are, however, due to (a combination of) mutations in lower penetrance genes or some cancers show no relationship with known susceptibility genes. In this article, we describe the function of recently known breast cancer susceptibility genes, the molecular pathogenesis and the histopathology of these hereditary breast cancer syndromes. This may provide a better understanding and classification of hereditary breast cancer and may offer tools for better diagnosis and selection of patients sensitive to specific targeted therapies.Key ConceptsBreast cancer is the most frequent cancer diagnosed in women worldwide.In 5–10% of total breast cancer cases, there is familial breast cancer susceptibility.Hereditary breast cancer is familial breast cancer with a clear Mendelian inheritance pattern.Breast cancer susceptibility genes can be divided into high‐, intermediate‐ and low‐risk genes, of which the high‐risk genesBRCA1andBRCA2are the best known.Breast cancer susceptibility genes mostly involve DNA repair mechanisms.The discovery of breast cancer susceptibility genes has improved our knowledge of breast carcinogenesis, including the morphological, immunohistochemical and molecular characterisation of familial breast cancer.Moreover, knowledge of the biological processes underlying familial breast cancer offers tools for cancer screening, prevention and management.
Chromosomal Rearrangements in Primates
Authors: Ruiz‐Herrera Aurora 
Published: September 2015

Abstract

Primates are characterised by the non‐specialist nature of their morphological features that, together with the plasticity of their behaviours, have allowed them to exploit a wide variety of ecological niches. The study of the mechanisms involved in karyotype evolution in Primates is fundamental to our understanding of mammalian genome organisation and its role in adaptation. The combined use of comparative genomics and molecular cytogenetics has contributed to the finer dissection of chromosomal rearrangements in Primates, providing new insights into the dynamics of genome reshuffling that characterise this group. These approaches have permitted the characterisation of large‐scale genomic changes (i.e. inversions, fusions, fissions and translocations) as well as the chromosomal regions involved. This has contributed to refine Primate genomic architecture and evolutionary relationships among species. Here the different evolutionary patterns that have been described in Primates will be investigated together with the most plausible hypotheses for ancestral karyotypes that have been inferred for each specific lineage.

Key Concepts

Primates are classified into six major groups: lemurids, lorisids, tarsiers, New‐World monkeys, Old‐World monkeys and apes.

The diversity of Primate species is exemplified by the variety of diploid numbers that characterise the group, ranging from 2n = 16 (i.e.
Callicebus lugens
) to 2n = 72 (i.e. some
Cercopithecus
species).

Comparative chromosomal studies among species are now possible, thanks to the combined use of different methodological approaches such whole‐genome comparative studies and FISH using either whole‐chromosome paintings or DNA‐specific probes.

Chromosomal evolution within Primates is highly intricate, as each major taxonomic group has followed a different pattern of reorganisations.

The family Hominidae, which includes orang‐utans, gorillas, chimpanzee and humans, has suffered few large‐scale chromosomal reorganisations since their common ancestor, most of them being lineage‐specific inversions.

Lesser apes are characterised by an extremely high rate of chromosomal reshuffling, including lineage‐specific fissions, fusions, inversions and translocations.

The group Catarrhini shows a general pattern of moderate rate of chromosomal changes, whereas Platyrrhini represents a highly diverse group with diploid numbers ranging from 2n = 16 in
Callicebus
to 2n = 62 in
Lagothrix
, in which inter‐ and intra‐specific chromosomal reorganisations are abundant.

The general view is that the putative karyotype of the last common ancestor of Primates consists of 50 chromosomes, with the following homologies with human chromosomes: 1, 2p‐q, 2q, 3/21, 4, 5, 6, 7b, 7a/16p, 8, 9, 10p, 10q, 11, 12a/22a, 12b/22b, 13, 14/15, 16q, 17, 18, 19p, 19q, 20, X and Y.
TGF‐β in the Immune Response
Authors: Nakatsukasa Hiroko , Tu Eric , Chia Cheryl Pei Zhi , Chen WanJun 
Published: September 2015

AbstractTransforming growth factor‐β (TGF‐β) is a highly evolutionally conserved cytokine that is critical for embryogenesis, cancer and matrix formation and immune responses. Three distinct isoforms, TGF‐β1, 2 and 3, are found in mammals. TGF‐β is secreted by immune and nonhematopoietic cells and acts on virtually all cell types through ubiquitously expressed receptors, which transduce the TGF‐β signal through canonical Smad‐dependent pathway and noncanonical Smad‐independent pathways. In particular, TGF‐β plays a crucial role in immune tolerance and maintains immune homeostasis by inhibiting proliferation, differentiation, activation and effector function of immune cells. On the other side of the coin, TGF‐β can display proinflammatory properties, depending on the context. The more complete understanding of the various functions of TGF‐β in the immune system, especially in tolerance, will enable us to design more specific and effective therapies for immune disorders.Key ConceptsTGF‐β is a multifunctional cytokine that mainly suppresses immune responses to maintain immune homeostasis.TGF‐β signalling is transduced via not only its unique protein, Smad, but also via Smad‐independent pathways.T cells are the major targets of TGF‐β in immune system and its activation/proliferation, apoptosis and differentiation are regulated by TGF‐β.TGF‐β is a key mediator for the regulation of autoimmune diseases.
H
enipaviruses
Authors: Aljofan Mohamad 
Published: September 2015

Abstract

Henipaviruses are the deadliest human pathogens of the
Paramyxoviridae
family. The genus
Henipavirus
includes two closely related, zoonotic, and highly pathogenic paramyxoviruses, Nipah virus (NiV) and Hendra virus (HeV), which cause high morbidity and mortality in animals and humans. There are no approved therapeutics to treat or prevent henipavirus infections in humans. The bat species
Pteropus
are the natural reservoir of henipaviruses, and zoonotic transmission can occur directly or through an intermediate host; horses for HeV and pigs for NiV. The unavailability of a treatment for these infections, the recent detection of HeV antibodies in family pets and the emergence of NiV infections in new geographic areas (Philippines) are an illustration of the risk that these viruses possess and their momentum of becoming a global threat. Unless an effective therapeutic against these viruses is developed, they will continue to emerge and cause significant challenges and threats in the coming years.

Key Concepts

The newly established genus
Henipavirus
of
Paramyxoviridae
family has three members Hendra, Nipah and Cedar viruses.

Fruit bats of the genus
Pteropus
have been identified as the natural reservoir for henipaviruses.

Both Nipah and Hendra viruses are highly pathogenic agents that cause acute encephalitis and respiratory illness with high mortality rate in humans, pigs and horses.

There is no approved therapeutics for the treatment of henipaviruses, and they continue to pose a threat in Australia (Hendra virus) and East and Southeast Asia (Nipah virus) with a great potential to spread beyond these regions.

M 102.4 is an experimental monoclonal antibody that targets the viral entry stage of
Henipavirus
and was proven to treat henipavirus infections in animals.
J
ean
B
rachet (1909–1988)
Authors: Rheinberger Hans‐Jörg 
Published: September 2015

Abstract
This article gives a short account of the work and life of the Belgian molecular embryologist and cytologist Jean Brachet (1909–1988). Jean Brachet was born in Belgium and educated as a physician at the Free University of Brussels. Still while studying, he started to do cytological experiments in the laboratory of Albert Dalcq, looking into the cellular distribution of nucleic acids (DNA (deoxyribonucleic acid) and RNA (ribonucleic acid)). During the 1940s, he established, together with his colleagues Raymond Jeener and Hubert Chantrenne, and under difficult political and material circumstances, the view that RNA is implicated in protein synthesis. Moreover, he identified the cellular granules then called microsomes (today's ribosomes) as the sites of the fabrication of proteins. After the Second World War, he became the leading figure of the Brussels (Rouge Cloître) school of molecular biology. Together with Adrienne Ficq, he developed a potent method of cyto‐autoradiography. On a science policy level, he was instrumental in establishing molecular biology in Belgium and in creating the European Molecular Biology Organization and Laboratory. Throughout his life, Brachet's experimental efforts aimed at understanding organismic development at a molecular level.
Flavoenzymes: Covalent versus Noncovalent
Authors: Starbird Chrystal A , Maklashina Elena , Cecchini Gary , Iverson TM 
Published: September 2015

AbstractThe use of nonprotein cofactors by enzymes expands the range of biological chemistries supported in nature. Flavins, which are derivatives of vitamin B2, are highly conjugated rings that are particularly useful for oxidoreduction and group transfer reactions. Most flavins are noncovalently associated with their enzymes, but around 10% of flavoproteins have the flavin covalently attachedin vivo. Extensive research has investigated how the presence of the covalent bond between enzyme and flavin cofactor influences enzymatic catalysis. This work identified that the primary roles of the covalent flavin are to allow catalysis of more thermodynamically challenging reactions and to prevent the cofactor from disassociating from the enzyme. Major questions in the field now include the mechanism of covalent flavinylation. The earliest studies on a subset of covalent flavoproteins suggested that cofactor attachment could be an autocatalytic posttranslational process. However, the recent identification of assembly factors that promote covalent flavinylation identifies that ancillary proteins may be important for covalent flavinylationin vivo.Key ConceptsCovalent flavin attachment increases stability of the holoenzyme and increases the enzyme's redox potential.Covalent flavinylation may occur either through an entirely autocatalytic mechanism, or be assisted by assembly factors.Enzyme‐associated flavin can promote a variety of chemistries.Flavoenzymes can have covalent or noncovalent flavin.Covalent flavinylation can occur on multiple sites of the protein and flavin molecule.
M
Cells
Authors: Mabbott Neil A , Sehgal Anuj , Donaldson David S 
Published: September 2015

Abstract

The mucosal immune system in the gastrointestinal tract helps protect against orally acquired pathogens. To efficiently do this, the mucosal immune system must be able to sample the gut lumenal contents to enable it to generate protective immune responses against pathogens. The transport of luminal antigens across mucosal epithelia is a key initial step in the induction of an efficient mucosal immune response. Here, we discuss how a unique population of epithelial cells termed M cells (or ‘microfold’ cells) enables the mucosal immune system to efficiently sample the intestinal contents. We describe the characteristic features of M cells; describe the molecular and cellular factors that influence their differentiation and functional maturation; discuss how lumenal antigens are sampled by M cells and also how the specific targeting of antigens to M cells may represent a novel method to induce antigen‐specific mucosal immunity.

Key Concepts

The mucosal immune system in the gastrointestinal and respiratory tracts acts to protect against pathogens acquired by ingestion and inhalation, respectively.

The transport of luminal antigens across mucosal epithelia is a key initial step in the induction of an efficient mucosal immune response.

M cells are a unique population of epithelial cells which are specialised for the transcytosis of a broad range of materials such as particulate antigens, soluble macromolecules, pathogens and secretory IgA across the gut epithelium into the gut‐associated lymphoid tissues.

The efficient transcytosis of antigens by M cells is an important first step in the induction of efficient mucosal immune responses to certain pathogenic microorganisms.

M cells derive from Lgr5
+
stem cells in the intestinal crypts.

Stimulation via the cytokine RANKL and the subsequent intrinsic expression of distinct transcription factors specifically trigger the differentiation of the Lgr5
+
stem‐cell‐derived proliferative daughter cells into mature, functional M cells.

The sampling of lumenal antigens by M cells may occur in a nonselective manner (e.g. via constitutive micropinocytosis). However, M cells also appear to express a range of ‘immunosurveillance’ receptors suggesting that some antigens are acquired specifically via receptor‐mediated endocytosis.

The specific targeting of vaccine antigens may represent novel strategies to develop mucosal vaccines and induce mucosal immunity.

Aging has a dramatic influence on the functional maturation of M cells.
Genomics and Behavioral Evidence
Authors: Bernet William 
Published: September 2015

Abstract
This article summarizes the history and current status of testimony regarding behavioral genetics and genomics. Depending on the case specifics, testimony regarding a person's genetic make‐up may constitute evidence of a particular psychiatric diagnosis, may simply support the diagnosis in a general way, or may help explain the person's behavior. In criminal trials, testimony regarding behavioral genomics—including gene and environment interactions—is most likely to be relevant as mitigation in sentencing hearings. Ordinarily, genotyping a defendant is only one part of a comprehensive psychiatric and psychological forensic evaluation.
Synthesis of Pyridoisoindoles through Diazotization Followed by Intramolecular Cyclization from Pyridinylarylacetates in One Pot
Authors: Kim Cheol‐Eui , Baek Yonghyeon , Kim Sung Hong , Lee Phil Ho 
Published: September 2015

AbstractA robust synthetic method for a variety of pyridoisoindoles from pyridinylarylacetates has been developed through diazotization using 4‐methylbenzenesulfonyl azide and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene followed by intramolecular cyclization via elimination of a nitrogen molecule under copper(II) trifluoromethanesulfonate‐catalyzed conditions in a one‐pot process. The intramolecular cyclization also took place efficiently with diazo substrates to produce pyridoisoindoles in good to excellent yields under metal‐free conditions or catalytic conditions [1.0 mol% copper(II) trifluoromethanesulfonate, 25 °C].magnified image
A panel data analysis of the probability of childbirth in aJapanese sample: New evidence of the two‐child norm
Authors: Morita Masahito , Ohtsuki Hisashi , Hiraiwa‐Hasegawa Mariko 
Published: September 2015

ObjectivesTo reveal the conditions that could facilitate childbirth in modern humans, it is necessary to analyze not only cross‐sectional surveys but also panel data that track the same person for a long period. In this study, we analyzed factors that would influence the probability of childbirth.MethodsWe analyzed Japanese panel data with a Cox proportional hazard model. Subjects of our analysis were married women and their childbirth records from 2004 to 2009.ResultsContrary to the predictions based on the theory of behavioral ecology, we found no positive relationship between good parental conditions for childcare, such as high income, increase in income, or coresidence with parents (i.e., grandparents of children), and the occurrence of childbirth. We found that the number of existing children had a significant impact on the probability of childbirth. The likelihood of further childbirth by couples with one child was nearly equal to that of childless ones. However, the corresponding likelihood of couples with two children was about five times lower than that of childless ones.ConclusionsThe total fertility rates in modern developed societies are quite low and couples prefer having two children. This trend is known as the two‐child norm, but it is a paradoxical phenomenon in terms of fitness maximization. Our result provided new quantitative evidence of this norm. This study revealed that the number of existing children being less than two was one of the factors associated with further childbearing in our Japanese sample. Am. J. Hum. Biol. 28:220–225, 2016. © 2015 Wiley Periodicals, Inc.
Rapid Access to New Thiazepinyl and Oxazepinyl Phosphonates through a Green Pudovik Reaction
Authors: Saha Debasmita , Kaur Tanpreet , Singh Neetu , Singh Udai P. , Sharma Anuj 
Published: September 2015

AbstractA simple, facile, and efficient microwave‐assisted synthetic protocol for the preparation of novel dibenzothiazepinyl and dibenzoxazepinyl phosphonates has been reported. The present Pudovik approach works without a catalyst or solvent to furnish cyclic α‐amino phosphonates by using dibenzothia‐ and dibenzoxazepines as imine substrates. This method has a greener edge and is amenable to large‐scale production.
Quantitative assessment of skin, hair, and iris variation in a diverse sample of individuals and associated genetic variation
Authors: Norton Heather L. , Edwards Melissa , Krithika S. , Johnson Monique , Werren Elizabeth A. , Parra Esteban J. 
Published: September 2015

ABSTRACTObjectivesThe main goals of this study are to 1) quantitatively measure skin, hair, and iris pigmentation in a diverse sample of individuals, 2) describe variation within and between these samples, and 3) demonstrate how quantitative measures can facilitate genotype‐phenotype association tests.Materials and MethodsWe quantitatively characterize skin, hair, and iris pigmentation using the Melanin (M) Index (skin) and CIELab values (hair) in 1,450 individuals who self‐identify as African American, East Asian, European, Hispanic, or South Asian. We also quantify iris pigmentation in a subset of these individuals using CIELab values from high‐resolution iris photographs. We compare mean skin M index and hair and iris CIELab values among populations using ANOVA and MANOVA respectively and test for genotype‐phenotype associations in the European sample.ResultsAll five populations are significantly different for skin (P <2 × 10−16) and hair color (P <2 × 10−16). Our quantitative analysis of iris and hair pigmentation reinforces the continuous, rather than discrete, nature of these traits. We confirm the association of three loci (rs16891982, rs12203592, and rs12913832) with skin pigmentation and four loci (rs12913832, rs12203592, rs12896399, and rs16891982) with hair pigmentation. Interestingly, the derived rs12203592 T allele located within the IRF4 gene is associated with lighter skin but darker hair color.DiscussionThe quantitative methods used here provide a fine‐scale assessment of pigmentation phenotype and facilitate genotype‐phenotype associations, even with relatively small sample sizes. This represents an important expansion of current investigations into pigmentation phenotype and associated genetic variation by including non‐European and admixed populations. Am J Phys Anthropol 160:570–581, 2016. © 2015 Wiley Periodicals, Inc.