bluuebunny/crossref_metadata_2025 huggingface dataset:
STORED PRODUCTS, AND THE INSECTS INFESTING THEM AS EXAMPLES OF THE LOGARITHMIC SERIES
Authors: HARRISON J. L.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
ORTHOGONAL PARTITIONS OF THE 5 × 5 LATIN SQUARES
Authors: FINNEY D. J.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
NEW ZEALAND BLOOD‐TYPE DISTRIBUTIONS: PRELIMINARY INVESTIGATIONS
Authors: PADDOCK R. F.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
CROSSING‐OVER IN A PEDIGREE CONTAINING HAEMOPHILIC AND COLOUR‐BLIND INDIVIDUALS
Authors: RIDDELL W. J. B.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
AN INVESTIGATION OF 171 POSSIBLE LINKAGE RELATIONSHIPS IN MAN
Authors: KLOEPFER H. W.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
The Etiology of Deaf‐Mutism, with special reference to heredity. By H. Lindenov
Authors: KALMUS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
BLOOD‐GROUP FREQUENCIES IN NEW ZEALAND AND MAORI SOLDIERS
Authors: GODLEY E. J.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
SCORES FOR RANKED DATA IN SCHOOL EXAMINATION PRACTICE
Authors: SANDON FRANK
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A PEDIGREE OF SEX‐LINKED ICHTHYOSIS VULGARIS
Authors: HARRIS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
The Advanced Theory of Statistics. Vol. ii. By Maurice G. Kendall
Authors: Smith Cedric A. B.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
HEREDITARY ONYCHOGRYPHOSIS
Authors: VIDEBÆK AAGE
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A SEX‐LIMITING MODIFYING GENE IN DIAPHYSIAL ACLASIS (MULTIPLE EXOSTOSES)
Authors: HARRIS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A PEDIGREE SHOWING SOME RARE Rh GENOTYPES
Authors: LAWLER SYLVIA D. , BERTINSHAW DOREEN
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A TEST FOR HOMOGENEITY OF RECORDS OF FAMILIAL ABNORMALITIES
Authors: HALDANE J. B. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A FURTHER NOTE ON DISCRIMINATORY ANALYSIS
Authors: QUENOUILLE M. H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE MEASUREMENT OF TASTE SENSITIVITY TO PHENYLTHIOUREA (P.T.C.)
Authors: HARRIS H. , KALMUS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
CHEMICAL SPECIFICITY IN GENETICAL DIFFERENCES OF TASTE SENSITIVITY
Authors: HARRIS H. , KALMUS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A PEDIGREE OF HEREDITARY PROGRESSIVE MUSCULAR DYSTROPHY
Authors: BOYES J. W. , FRASER F. C. , LAWLER SYLVIA D. , MACKENZIE HELEN J.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
DATA RELATING TO SEVEN GENETICAL CHARACTERS IN SIX ENDOGAMOUS GROUPS IN BOMBAY
Authors: SANGHVI L. D. , KHANOLKAR V. R.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
The Trend of Scottish Intelligence: A Comparison of the 1947 and 1932 Surveys of the Intelligence of Eleven‐year‐old Pupils. Scottish Council for Research in Education. Univ. of London Press Ltd. 1949. Pp. 151 + xxviii. Price 7s. 6d
Authors: Penrose L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
MEASUREMENTS OF INFANTS AT BIRTH
Authors: LOW ALEX.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
BLOOD‐GROUP FREQUENCIES IN A MOTHER AND INFANT SAMPLE OF THE AUSTRALIAN POPULATION
Authors: BRYCE LUCY M. , JAKOBOWICZ RACHEL , McARTHUR NORMA , PENROSE L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A COMPARATIVE QUANTITATIVE STUDY OF THE FINGER‐PRINTS OF MONGOLIAN IMBECILES AND NORMAL INDIVIDUALS
Authors: HOLT SARAH B.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
TWO PEDIGREES OF ECTRODACTYLY
Authors: MacKENZIE HELEN J. , PENROSE L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
CHANGES IN SEX INCIDENCE OF DIABETES MELLITUS (1912–1947)
Authors: HARRIS H. , McARTHUR NORMA
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
TASTE THRESHOLDS OF FURTHER EIGHTEEN COMPOUNDS AND THEIR CORRELATION WITH P.T.C. THRESHOLDS
Authors: BARNICOT N. A. , HARRIS H. , KALMUS H.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
TASTE SENSITIVITY TO PHENYLTHIOUREA IN DENMARK
Authors: MOHR JAN
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE CHROMOSOME COMPLEMENT IN A MONGOLIAN IMBECILE
Authors: MITTWOCH URSULA
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
A PEDIGREE OF HUNTINGTON'S CHOREA
Authors: LEESE STEPHANIE M. , POND D. A. , SHIELDS J.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
TASTE‐DEFICIENCY IN LAPPISH AND FINNISH POPULATIONS
Authors: ALLISON A. C. , NEVANLINNA H. R.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
THE BLOOD TYPING OF CASES OF MONGOLISM, THEIR PARENTS AND SIBS
Authors: LANG‐BROWN HELEN , LAWLER SYLVIA D. , PENROSE L. S.
Published: April 2011

The articles published by the Annals of Eugenics (1925–1954) have been made available online as an historical archive intended for scholarly use. The work of eugenicists was often pervaded by prejudice against racial, ethnic and disabled groups. The online publication of this material for scholarly research purposes is not an endorsement of those views nor a promotion of eugenics in any way.
Glucuronic Acid Epimerase is Associated with Plasma Triglyceride and High‐Density Lipoprotein Cholesterol Levels in Turks
Authors: Hodoğlugil Uğur , Williamson David W. , Yu Yi , Farrer Lindsay A. , Mahley Robert W.
Published: April 2011

We narrowed chromosome 15q21–23 linkage to plasma high‐density lipoprotein cholesterol (HDL‐C) levels in Turkish families by fine mapping, then focused on glucuronic acid epimerase (GLCE), a heparan sulfate proteoglycan (HSPG) biosynthesis enzyme. HSPGs participate in lipid metabolism along with apolipoprotein (apo) E. Of 31 SNPs in the GLCE locus, nine analyzed by haplotype were associated with HDL‐C and triglyceride levels (permuted p = 0.006 and 0.013, respectively) in families. Of five tagging GLCE SNPs in two cohorts of unrelated subjects, three (rs16952868, rs11631403, and rs3865014) were associated with triglyceride and HDL‐C levels in males (nonpermuted p < 0.05). The association was stronger in APOE 2/3 subjects (apoE2 has reduced binding to HSPGs) and reached multiple‐testing significance (p < 0.05) in both males and females (n= 2612). Similar results were obtained in the second cohort (n= 1164). Interestingly, at the GLCE locus, bounded by recombination hotspots, Turks had a minor allele frequency of SNPs resembling Chinese more than European ancestry; adjoining regions resembled the European pattern. Studies of glce+/−apoe−/− mice fed a chow or high‐fat diet supported a role for GLCE in lipid metabolism. Thus, SNPs in GLCE are associated with triglyceride and HDL‐C levels in Turks, and mouse studies support a role for glce in lipid metabolism.
Writings on Genetic Linkage in the Annals
Authors: Ott Jurg
Published: April 2011

From its inception in 1925 through the almost 30 years that it carried the title of Annals of Eugenics, this journal published numerous articles on the statistical aspects of genetic linkage analysis and its applications to family pedigree data. This overview discusses 40 papers on linkage analysis published in the Annals.
Spray‐drying for the production of dried cultures
Authors: SILVA JOANA , FREIXO RICARDO , GIBBS PAUL , TEIXEIRA PAULA
Published: April 2011

This review emphasises the importance of spray‐drying as an under‐used but promising technique to preserve viable and active starter cultures and also, potentially, probiotic cultures. The knowledge concerning the production of spray‐dried starter cultures is discussed. Different drying techniques and micro‐organisms have been investigated for their survival through the drying process. During drying and subsequent storage in the dried state, bacteria are subjected to several stresses, which have already been described as causing damage to cells, leading to the loss of cellular viability and activity. Some studies found that several factors/strategies can confer improved cellular viability.
The effect of varying casein/fat ratio on physicochemical and sensory qualities of Feta‐type cheese made using buffalo milk
Authors: KUMAR SANJEEV , KANAWJIA SURESH K , KUMAR SURYAMANI
Published: April 2011

The Feta‐type cheese was prepared with different casein/fat (C/F) ratios of buffalo milk using microbial rennet. The manufactured Feta cheeses were subjected to physicochemical and sensory quality at 15‐day interval up to 60 days of ripening. Sensory analysis discriminated the different level of C/F ratio of buffalo milk cheeses predominantly by age. There was no significant difference (P < 0.01) observed in cheese made from C/F ratio of 0.6–0.7 in terms of flavour. The titratable acidity (TA), soluble protein and free fatty acid appear to be age‐dependent and increased throughout the ripening in all experimental cheeses.
Evaluation of the chemical, microbiological and volatile aroma characteristics of Ispir Kaymak, a traditional Turkish dairy product
Authors: CAKMAKCI SONGUL , HAYALOGLU ALI A
Published: April 2011

The gross chemical composition, microbiological quality and volatile aroma composition of Ispir Kaymak, a Turkish creamy dairy product, were investigated in 10 samples. The chemical composition of the samples varied widely: dry matter content ranged from 70.8% to 91.3% and fat varied between 43.0% and 63.0%; probably due to the lack of standardised production in practice. The microbiological counts were found to be (as mean values): 4.02, 3.06, 0.33, <2 log cfu/g for aerobic plate count, yeast and mould, coliform and Staphylococcus aureus, respectively. The sample quality showed that the production and storage conditions should be controlled and the hygienic quality of this product should be improved. A total of 73 volatile compounds, including esters, acids, ketones, aldehydes, alcohols, terpenes and miscellaneous compounds, were identified in the volatile fraction of the samples by gas chromatography–mass spectrometry (GC–MS) using a solid‐phase microextraction technique (SPME/GC–MS). Esters were the main volatiles in Ispir Kaymak, and ketones, alcohols and terpenes were found at high levels; however, the levels of acids were low in all samples.
Sustainability in the Face of Recurring Threats and Disaster
Authors: Menck Claire
Published: April 2011

[sustainability, Gulf Coast, Deepwater Horizon, oil spill, Grand Isle, ecology, environment]
Anthropology's Voice in the Public Policy Process
Authors: Fiske Shirley J
Published: April 2011

[public affairs, views on policy policy process, applied anthropology]

Pam Putenney is the contributing editor of Views on Policy, the AN column of the AAA Committee on Public Policy.
Effect of plastic‐covered ultrasonic scalers on titanium implant surfaces
Authors: Mann M. , Parmar D. , Walmsley A. D. , Lea S. C.
Published: April 2011

Objectives: Maintaining oral health around titanium implants is essential. The formation of a biofilm on the titanium surface will influence the continuing success of the implant. These concerns have led to modified ultrasonic scaler instruments that look to reduce implant damage while maximising the cleaning effect. This study aimed to assess the effect of instrumentation, with traditional and modified ultrasonic scalers, on titanium implant surfaces and to correlate this with the oscillations of the instruments.

Materials and methods: Two ultrasonic insert designs (metallic TFI‐10 and a plastic‐tipped implant insert) were selected. Each scaler probe was scanned using a scanning laser vibrometer, under loaded and unloaded conditions, to determine their oscillation characteristics. Loads were applied against a titanium implant (100g and 200 g) for 10 s. The resulting implant surfaces were then scanned using laser profilometry and scanning electron microscopy (SEM).

Results: Insert probes oscillated with an elliptical motion with the maximum amplitude at the probe tip. Laser profilometry detected defects in the titanium surface only for the metallic scaler insert. Defect widths at 200 g high power were significantly larger than all other load/power conditions (P<0.02). Using SEM, it was observed that modifications to the implant surface had occurred following instrumentation with the plastic‐tipped insert. Debris was also visible around the defects.

Conclusions: Metal scalers produce defects in titanium implant surfaces and load and power are important factors in the damage caused. Plastic‐coated scaler probes cause minimal damage to implant surfaces and have a polishing action but can leave plastic deposits behind on the implant surface.

To cite this article: Mann M, Parmar D, Walmsley AD and Lea SC. Effect of plastic covered ultrasonic scalers on titanium implant surfaces. Clin. Oral Impl. Res. 23, 2012; 76–82 doi: 10.1111/j.1600‐0501.2011.02186.x
The influence of alendronate on osseointegration of nanotreated dental implants in New Zealand rabbits
Authors: Tsetsenekou Efstathia , Papadopoulos Triantafillos , Kalyvas Demos , Papaioannou Nikos , Tangl Stefan , Watzek Georg
Published: April 2011

Objectives: Growing clinical demands for stronger and faster bone bonding to the implant have motivated the development of methods enhancing osseointegration. Lately, the application of bisphosphonates (bis) in order to optimize bone healing has become a topic of great interest. N‐containing bis, such as alendronate (ALN), are the more potent drugs of this class. It was the aim of this study to determine the effect of ALN on the osseointegration of a well‐documented nanotreated implant system in a rabbit femoral condyle model.

Material and methods: Thirty‐two adult female New Zealand White rabbits received one implant (3.25 mm in diameter and 10 mm in length) in their left femoral condyle, a week after they were ovariectomized. Half of them were saline treated (control, group A) and the other half were ALN treated (group B). Rabbits from both groups were euthanized after 6 and 12 weeks, respectively.

Results: The specimens were evaluated histologically and histomorphometrically. Upon histological evaluation, no obvious differences were found between the control and the treatment group. Implants showed good integration into the bone tissue surrounding them. There were also no statistically significant differences in bone‐to‐implant contact and the amount of bone tissue in the immediate neighborhood of the implant at both healing periods.

Conclusions: The systemic administration of ALN was not found to affect histological osseointegration of implants in animals with a hormonal status resembling that of postmenopausal healthy women. Further research will be needed to investigate this approach.
For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection
Authors: Dorhoi Anca , Reece Stephen T. , Kaufmann Stefan H. E.
Published: April 2011

Summary:  Tuberculosis (TB) is a complex disease, and the success of the bacterium as an intracellular pathogen is the outcome of its close and longstanding coevolution with the mammalian host. The dialogue between Mycobacterium tuberculosis and the host is becoming understandable at the molecular, cellular, and tissue level. This has led to the elucidation of the (i) interaction between pattern recognition receptors and pathogen‐associated molecular patterns, (ii) cross‐talk between immune cells, and (iii) mechanisms underlying granuloma development. Disease as an eventual but not a necessary consequence of infection results from a sensitive balance between protective immunity and destructive pathology. Early events, governed largely by conserved mechanisms of host recognition, impact not only on type and course of adaptive immunity but also on lung parenchymal function. New interpretations of how these responses shape the lung environment and direct granuloma development emphasize that the disease results from pathologic consequences of non‐resolving inflammation. We review recent advances in TB research within the context of this ambitious view of TB.
Armed response: how dying cells influence T‐cell functions
Authors: Ferguson Thomas A. , Choi Jayoung , Green Douglas R.
Published: April 2011

Summary:  Immune responses during infection, injury, and cancer proceed in the presence of tissue injury and cell death. Consequently, the system must deal with its own dead cells while it determines the appropriate response to the invader. As apoptotic cells are known to induce immune tolerance and necrotic cells can be potent stimulators of immunity, this decision becomes more complex. The key to understanding the immunologic choices made during cell death is to examine the mechanisms of tolerance induction by dying cells and then relate them to the mechanisms of immunity. Ideally, immunogenic cell death should be directed toward tumor cells and infected cells, whereas tolerogenic cell death should be associated with preventing unwanted immune responses to self. In this review, we discuss how the decision is made by focusing on the biochemical process of cell death and how its key components can influence both tolerance and immunity.
Molecular mechanisms of T‐cell tolerance
Authors: Nurieva Roza I. , Liu Xindong , Dong Chen
Published: April 2011

Summary:  CD4+ T cells are the master regulators of adaptive immune responses, and many autoimmune diseases arise due to a breakdown of self‐tolerance in CD4+ T cells. Activation of CD4+ T cells is regulated by not only the binding of peptide‐major histocompatibility complexes to T‐cell receptor but also costimulatory signals from antigen‐presenting cells. Recently, there has been progress in understanding the extracellular and intracellular mechanisms that are required for implementation and maintenance of T‐cell tolerance. Understanding of the molecular mechanisms underlying T‐cell tolerance will lead to development of pharmacological approaches either to promote the tolerance state in terms of autoimmunity or to break tolerance in cancer.
Immunologic unresponsiveness to alloantigen in vivo: a role for regulatory T cells
Authors: Wood Kathryn J. , Bushell Andrew , Jones Nick D.
Published: April 2011

Summary:  Exposure to alloantigen in vivo or in vitro induces alloantigen reactive regulatory T cells that can control transplant rejection. The mechanisms that underpin the activity of alloantigen reactive regulatory T cells in vivo are common with those of regulatory T cells that prevent autoimmunity. The identification and characterization of regulatory T cells that control rejection and contribute to the induction of immunologic unresponsiveness to alloantigens in vivo has opened up exciting opportunities for new therapies in transplantation. Findings from laboratory studies are informing the design of clinical protocols using regulatory T cells as a cellular therapy.
Dendritic cell control of tolerogenic responses
Authors: Manicassamy Santhakumar , Pulendran Bali
Published: April 2011

Summary:  One of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body’s own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. A fundamental role for the innate immune system, particularly dendritic cells (DCs), in orchestrating immunological tolerance has been appreciated, but emerging studies have highlighted the nature of the innate receptors and the signaling pathways that program DCs to a tolerogenic state. Furthermore, several studies have emphasized the major role played by cellular interactions and the microenvironment in programming tolerogenic DCs. Here, we review these studies and suggest that the innate control of tolerogenic responses can be viewed as different hierarchies of organization, in which DCs, their innate receptors and signaling networks, and their interactions with other cells and local microenvironments represent different levels of the hierarchy.
Immune tolerance in multiple sclerosis
Authors: Goverman Joan M.
Published: April 2011

Summary:  Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously activated by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T‐cell tolerance to myelin antigens and to understand how some myelin‐specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin‐specific T cells, as most myelin‐specific T cells are eliminated by clonal deletion in the thymus. Self‐reactive T cells that escape central tolerance are generally capable only of low‐avidity interactions with antigen‐presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin‐specific T cells have been identified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin‐specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin‐specific T cells.
Early healthcare utilization and welfare interventions among children of mothers with alcohol and substance abuse: a retrospective cohort study
Authors: Sarkola Taisto , Gissler Mika , Kahila Hanna , Autti‐Rämö Ilona , Halmesmäki Erja
Published: April 2011

Aim:  Early childhood healthcare utilization, mortality and welfare interventions were studied among children of mothers with identified gestational alcohol and/or substance abuse.

Methods:  Register‐based retrospective cohort study. The exposed cohort consisted of 638 children born to 524 women followed up antenatally 1992–2001 at special outpatient clinics in the capital area of Finland. Nonexposed children (n = 1914) born to control women were matched for maternal age, parity, number of foetuses, month of birth and delivery hospital of the index child. Postnatal data of both cohorts were collected from national registers until 2007.

Results:  The exposed cohort displayed twice the amount of in‐ and outpatient hospital care episodes compared with nonexposed children. Differences attributable to exposure were found in categories of conditions originating in the perinatal period, mental and behavioural disorders, and nonspecific factors influencing health status and contact with health services. This was reflected in amounts of reimbursements for drugs of the central nervous system, as well as special care allowances and rehabilitation for mental and behavioural disorders. The highest degree of healthcare utilization was observed among exposed children placed in out‐of‐home care. One‐third of these children received outpatient care and one‐tenth required inpatient care for a mental and behavioural disorder. No significant differences were found in early mortality.

Conclusion:  The exposed children displayed significant neonatal and early mental and behavioural healthcare utilization, and need for significant psychosocial support during their first decade of life.
Association between sarcopenia and mortality in healthy older people
Authors: Bunout Daniel , de la Maza María P , Barrera Gladys , Leiva Laura , Hirsch Sandra
Published: April 2011

Aim:  To evaluate the association between loss of fat‐free mass and mortality among older people.

Methods:  Information of healthy Chilean older people evaluated by dual energy X‐ray absorptiometry was used, identifying those who died in a period of 12 years. A Cox proportional hazards model was used to identify mortality predictors. Life tables were constructed calculating survival using predictive variables.

Results:  Information from 1413 participants aged 74.3 ± 5.6 years (1001 women), was obtained. During the follow‐up (median 1594 days), 221 participants died. The Cox model identified age and appendicular fat‐free mass as predictors of death (hazard ratios 1.08 and 0.85, respectively). According to life tables, participants in the lower sex‐specific quartile for appendicular fat‐free mass/height had significantly higher mortality. This association was significant among participants aged over 73 years.

Conclusion:  A low fat‐free mass was predictive of mortality in older people.
Heme binding to the second, lower‐affinity site of the global iron regulator Irr from Rhizobium leguminosarum promotes oligomerization
Authors: White Gaye F. , Singleton Chloe , Todd Jonathan D. , Cheesman Myles R. , Johnston Andrew W. B. , Le Brun Nick E.
Published: April 2011

The iron responsive regulator Irr is found in a wide range of α‐proteobacteria, where it regulates many genes in response to the essential but toxic metal iron. Unlike Fur, the transcriptional regulator that is used for iron homeostasis by almost all other bacterial lineages, Irr does not sense Fe2+ directly, but, rather, interacts with a physiologically important form of iron, namely heme. Recent studies of Irr from the N2‐fixing symbiont Rhizobium leguminosarum (IrrRl) showed that it binds heme with submicromolar affinity at a His‐Xxx‐His (HxH) motif. This caused the protein to dissociate from its cognate DNA regulatory iron control element box sequences, thus allowing expression of its target genes under iron‐replete conditions. In the present study, we report new insights into the mechanisms and consequences of heme binding to Irr. In addition to the HxH motif, Irr binds heme at a second, lower‐affinity site. Spectroscopic studies of wild‐type Irr and His variants show that His46 and probably His66 are involved in coordinating heme in a low‐spin state at this second site. By contrast to the well‐studied Irr from Bradyrhizobium japonicum, neither heme site of IrrRl stabilizes ferrous heme. Furthermore, we show that heme‐free IrrRl exists as a mixture of dimeric and larger, likely hexameric, forms and that heme binding promotes IrrRl oligomerization. Bioanalytical studies of IrrRl variants showed that this property is not dependent on the HxH motif but is associated with heme binding at the second site.

Structured digital abstract

Irr
 binds to irrby molecular sieving (View Interaction 1, 2)

Irr
 binds to irrby cosedimentation in solution (View interaction)
Bacitracin inhibits the reductive activity of protein disulfide isomerase by disulfide bond formation with free cysteines in the substrate‐binding domain
Authors: Dickerhof Nina , Kleffmann Torsten , Jack Ralph , McCormick Sally
Published: April 2011

The peptide antibiotic bacitracin is widely used as an inhibitor of protein disulfide isomerase (PDI) to demonstrate the role of the protein‐folding catalyst in a variety of molecular pathways. Commercial bacitracin is a mixture of at least 22 structurally related peptides. The inhibitory activity of individual bacitracin analogs on PDI is unknown. For the present study, we purified the major bacitracin analogs, A, B, H, and F, and tested their ability to inhibit the reductive activity of PDI by use of an insulin aggregation assay. All analogs inhibited PDI, but the activity (IC50) ranged from 20 μm for bacitracin F to 1050 μm for bacitracin B. The mechanism of PDI inhibition by bacitracin is unknown. Here, we show, by MALDI‐TOF/TOF MS, a direct interaction of bacitracin with PDI, involving disulfide bond formation between an open thiol form of the bacitracin thiazoline ring and cysteines in the substrate‐binding domain of PDI.
Intrinsic local disorder and a network of charge–charge interactions are key to actinoporin membrane disruption and cytotoxicity
Authors: Pardo‐Cea Miguel A. , Castrillo Inés , Alegre‐Cebollada Jorge , Martínez‐del‐Pozo Álvaro , Gavilanes José G. , Bruix Marta
Published: April 2011

Actinoporins are a family of sea anemone proteins that bind to membranes and produce functional pores which result in cell lysis. Actinoporin variants with decreased lytic activity usually show a reduced affinity for membranes. However, for some of these mutant versions there is no direct correlation between the loss of binding affinity and the decrease in their overall lytic activity, suggesting that other steps in pore formation may be hampered or facilitated by the mutations. To test this hypothesis on the mechanism of pore formation by this interesting family of proteins, structural and dynamic NMR studies have been carried out on two disabled variants of the actinoporin Sticholysin II, R29Q and Y111N. It is shown that their lytic activity is not only related to their membrane affinity but also to their conformational mechanism for membrane insertion. Alterations in their activities can be explained by structural, electrostatic and dynamic differences in a cluster of aromatic moieties and the N‐terminus. In addition, the dynamic properties of some segments located at the C‐terminus of the R29Q variant suggest a relevant role for this region in terms of protein–protein interactions. On the basis of all these results, we propose that R29 anchors a network of electrostatic interactions crucial for the actinoporin’s approach to the membrane and that Y111 induces a necessary disorder in the loop regions that bind to membranes.
Attenuation of Fatty Liver and Prevention of Hypercholesterolemia by Extract of Curcuma longa through Regulating the Expression of CYP7A1, LDL‐Receptor, HO‐1, and HMG‐CoA Reductase
Authors: Yiu Wing‐Fat , Kwan Pui‐Long , Wong Cho‐Yee , Kam Tsz‐Shan , Chiu Sin‐Ming , Chan Shun‐Wan , Chan Robbie
Published: April 2011

Abstract:  The extract of Curcuma longa, better known as turmeric, was orally administered to experimental rats that were fed a high‐cholesterol diet to investigate whether it could regulate plasma lipids and cholesterol levels and possibly improve hepatic conditions. With turmeric supplements, rats showed a significant decrease in total plasma cholesterol and low‐density lipoprotein cholesterol but an increase in high‐density lipoprotein cholesterol when compared with rats that were fed a high‐cholesterol diet alone. Fatty liver developed in hypercholesterolemic rats with the high‐cholesterol diet treatment, and this condition was markedly improved when rats were provided with turmeric supplements at 100 mg/kg or 300 mg/kg of body mass. The turmeric treatment resulted in a significant decrease in the total amount of hepatic lipid. Histological staining of liver tissues with Sudan III and hematoxylin showed that rats fed with a high‐cholesterol diet alone had more and larger granular fat bodies than rats having turmeric extract supplementation in their high‐cholesterol diet. Reverse‐transcription polymerase chain reaction was used to assess the expression levels of enzymes involved in fat metabolism and cellular homeostasis in experimental rat livers. The results showed that rats fed a high‐cholesterol diet supplemented with turmeric extract had a significant increase in the expression of cholesterol 7 α‐hydroxylase, hemeoxygenase 1, and low‐density lipoprotein receptors but a significant decrease in 3‐hydroxy‐3‐methyl‐glutaryl‐CoA reductase level when compared with rats fed a normal or high‐cholesterol diet, showing that turmeric prevents hypercholesterolemia and the formation of fatty liver by the modulation of expressions of enzymes that are important to cholesterol metabolism.

Practical Application:  Turmeric may be considered a functional food for regulating plasma cholesterol levels and preventing the development of fatty liver in people who frequently consume a high‐cholesterol diet.
Physicochemical, Nutritional, and Antimicrobial Properties of Wine Grape (cv. Merlot) Pomace Extract‐Based Films
Authors: Deng Qian , Zhao Yanyun
Published: April 2011

Abstract:  Wine grape pomace (WGP) (cv. Merlot) extract‐based films were studied in terms of their physicochemical, mechanical, water barrier, nutritional, and antibacterial properties. Pomace extract (PE) was obtained by hot water extraction and had a total soluble solid of 3.6% and pH 3.65. Plant‐based polysaccharides, low methoxyl pectin (LMP, 0.75% w/w), sodium alginate (SA, 0.3% w/w), or Ticafilm® (TF, 2% w/w), was added into PE for film formation, respectively. Elongation at break and tensile strength were 23% and 4.04 MPa for TF‐PE film, 25% and 1.12 MPa for SA‐PE film, and 9.89% and 1.56 MPa for LMP‐PE film. Water vapor permeability of LMP‐PE and SA‐PE films was 63 and 60 g mm m−2 d−1 kPa, respectively, lower than that of TF‐PE film (70 g mm m−2 d−1 kPa) (P < 0.05). LMP‐PE film had higher water solubility, indicated by the haze percentage of water after 24 h of film immersion (52.8%) than that of TF‐PE (25.7%) and SA‐PE (15.9%) films, and also had higher amount of released phenolics (96.6%) than that of TF‐PE (93.8%) and SA‐PE (80.5%) films. PE films showed antibacterial activity against both Escherichia coli and Listeria innocua, in which approximate 5‐log reductions in E. coli and 1.7‐ to 3.0‐log reductions in L. innocua were observed at the end of 24 h incubation test compared with control. This study demonstrated the possibility of utilizing WGP extracts as natural, antimicrobial, and antioxidant promoting film‐forming material for various food applications.

Practical Application:  WGP extract‐based edible films with the addition of a small amount of commercial polysaccharides showed attractive color and comparable mechanical and water barrier properties to other edible films. The films also demonstrated their potential antioxidant and antimicrobial functions. Hence, they may be used as colorful wraps or coatings for food, pharmaceutical, or other similar applications.
How Micro‐Phase Separation Alters the Heating Rate Effects on Globular Protein Gelation
Authors: Leksrisompong Phanin N. , Foegeding Edward Allen
Published: April 2011

Abstract:  This study was conducted to determine how the combination of heating rate and pH can be used to alter viscoelastic properties and microstructure of egg white protein and whey protein isolate gels. Protein solutions (1% to 7% w/v protein, pH 3.0 to 8.5) were heated using a range of heating rates (0.2 to 60 °C/min) to achieve a final temperature of 80 °C. The gelation process and viscoelastic properties of formed gels were evaluated using small strain rheology. Single phase or micro‐phase separated solution conditions were determined by confocal laser scanning microscopy. In the single phase region, gels prepared by the faster heating rates had the lowest rigidity at 80 °C; however, a common G′ was achieved after holding for 4 h at 80 °C . On the other hand, under micro‐phase separation conditions, faster heating rates allowed phase separated particles to be frozen in the network prior to precipitation. Thus, gels produced by slower heating rates had lower rigidities than gels produced by faster heating rates. The effect of heating rate appears to depend on if the solution is under single phase or micro‐phase separated conditions.

Practical Application:  The effect of heating rate and/or time on protein gel firmness can be explained based on protein charge. When proteins have a high net negative charge and form soluble aggregates, there is no heating rate effect and gels with equal firmness will be formed if given enough time. In contrast, when electrostatic repulsion is low, there is a competition between protein precipitation and gel formation; thus, a faster heating rate produces a firmer gel.
Interaction of Phosphatidylcholine and α‐Tocopherol on the Oxidation of Sunflower Oil and Content Changes of Phosphatidylcholine and Tocopherol in the Emulsion under Singlet Oxygen
Authors: Lee Yoosung , Choe Eunok
Published: April 2011

Abstract:  Interaction of phosphatidylcholine (PC) and α‐tocopherol (α‐Toc) on the oxidation of oil in the emulsion consisting of sunflower oil and water under singlet oxygen at 25 °C was studied by determining peroxide value (PV) and conjugated dienoic acid (CDA) contents. Singlet oxygen was produced by chlorophyll b under 1700 lux. Single addition of PC or α‐Toc decreased the values of peroxides and CDAs of oil in the emulsion via singlet oxygen quenching. PC and α‐Toc showed simply additive interaction in decreasing the singlet oxygen oxidation of oil in the emulsion. α‐Toc was a physical quencher of singlet oxygen in the emulsion, but PC involved chemical quenching in the antioxidant action. Chlorophyll and PC contents were decreased in the emulsion under singlet oxygen, while α‐Toc was not. α‐Toc protected chlorophyll and PC from degradation, and was a more important component than PC in the oil oxidation under singlet oxygen in the emulsion.