THE SYNTHESIS, KINETIC CHARACTERIZATION AND APPLICATION OF A NOVEL BIOTINYLATED AFFINITY LABEL FOR CATHEPSIN-B

In this study we report on the synthesis, kinetic characterization and application of a novel biotinylated and active-site-directed inactivator of cathepsin B. Thus the peptidyliazomethane biotinyl-Phe-Ala-diazomethane has been synthesized by a combination of solid-phase and solution methodologies and has been shown to be a very efficient inactivator of bovine and human cathepsin B. The respective apparent second-order rate constants (k0bs./[I]) for the inactivation of the human and bovine enzymes by this reagent, namely approximately 5.4 x 10(4) M-1 and approximately 7.8 x 10(4) M-1, compare very favourably with those values determined for the urethane-protected analogue benzloxycarbonyl-Phe-Ala-chloromethane first described by Green & Shaw [(1981) J.Biol. Chem. 256, 1923-1928], thus demonstrating that the presence of the biotin moiety at the P3 position is compatible with inhibitor effectiveness. The utilization of this reagent for the detection of cathepsin B in electrophoretic gels, using Western blotting and in combination with a streptavidin/alkaline phosphatase detection system, is also demonstrated. Given that the peptidydiazomethanes exhibit a pronounced reactivity towards cysteine proteinases, we feel that the present label may well constitute the archetypal example of a wide range of reagents for the selective labelling of this class of proteinase, even in a complex biological milieu containing additional classes of proteinases.

Escaping the Holocaust: human and health capital of refugees to the United States, 1940-42

The large-scale persecution of Jews during World War II generated massive refugee movements. Using data from 20,441 predominantly Jewish passengers from 19 countries traveling from Lisbon to New York between 1940 and 1942, we analyze the last wave of refugees escaping the Holocaust and verify the validity of height as a proxy for human and health capital. We further show this episode of European migration displays well-known features of migrant self-selection: early migrants were taller than late migrants; a large migrant stock reduces migrant selectivity; and economic barriers to migration
apply. Our findings show that Europe experienced substantial losses in human and health capital while the US benefitted from the immigration of European refugees.

Casualties distribution in human and natural hazards

Catastrophic events, such as wars and terrorist attacks, big tornadoes and hurricanes, huge earthquakes, tsunamis, floods, and landslides, are always accompanied by a large number of casualties. The size distribution of these casualties have separately been shown to follow approximate power law (PL) distributions. In this paper, we analyze the number of victims of catastrophic phenomena, in particular, terrorism, and find double PL behavior. This means that the data set is better approximated by two PLs instead of one. We have plotted the two PL parameters corresponding to all terrorist events occurred in every year, from 1980 to 2010. We observe an interesting pattern in the chart, where the lines, that connect each pair of points defining the double PLs, are roughly aligned to each other.

When orthologs diverge between human and mouse.

Despite the common assumption that orthologs usually share the same function, there have been various reports of divergence between orthologs, even among species as close as mammals. The comparison of mouse and human is of special interest, because mouse is often used as a model organism to understand human biology. We review the literature on evidence for divergence between human and mouse orthologous genes, and discuss it in the context of biomedical research.

Structure of the extracellular domains of human and Xenopus Fn14: implications in the evolution of TWEAK and Fn14 interactions.

TWEAK (TNF homologue with weak apoptosis-inducing activity) and Fn14 (fibroblast growth factor-inducible protein 14) are members of the tumor necrosis factor (TNF) ligand and receptor super-families. Having observed that Xenopus Fn14 cross-reacts with human TWEAK, despite its relatively low sequence homology to human Fn14, we examined the conservation in tertiary fold and binding interfaces between the two species. Our results, combining NMR solution structure determination, binding assays, extensive site-directed mutagenesis and molecular modeling, reveal that, in addition to the known and previously characterized β-hairpin motif, the helix-loop-helix motif makes an essential contribution to the receptor/ligand binding interface. We further discuss the insight provided by the structural analyses regarding how the cysteine-rich domains of the TNF receptor super-family may have evolved over time. DATABASE: Structural data are available in the Protein Data Bank/BioMagResBank databases under the accession codes 2KMZ, 2KN0 and 2KN1 and 17237, 17247 and 17252. STRUCTURED DIGITAL ABSTRACT: TWEAK binds to hFn14 by surface plasmon resonance (View interaction) xeFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction) TWEAK binds to xeFn14 by surface plasmon resonance (View interaction) hFn14 binds to TWEAK by enzyme linked immunosorbent assay (View interaction).

Development of CHH family recombinant hormones and RNAi for induced maturation of Penaeus monodon

About 80 years ago, the neurosecretory eyestalk structures and their role in endocrine regulation was recognized in crustaceans. After the recognition it took half a century to identify the first peptide hormone. Till date a large number of homologous peptides of crustacean hyperglycaemic hormone and moult-inhibiting hormone have been identified, consequently they are called the CHH family hormones. This family comprises of highly multifunctional peptides which according to sequences and precursor structures can be divided into two subfamilies, type-I (CHH/ITP) and II (MIH, MOIH, VIH/GIH) (Webster et al., 2012). The XO-SG complex has been the major site of the two subfamilies. The advent of molecular techniques resulted in the characterization of different precursors of CHH, MIH and GIH; these hormones consist of a signal peptide, but only the preprohormone of CHHs contain a precursor- related peptide (CPRP) located between the signal and the mature hormone (Weidemann et al., 1989; Klein et al., 1993b; De Kleijn and Van Herp, 1995). The essentialities of the gene structure comply with the functions of the CHH family hormones. The CHH family hormone functions are inhibitory as well as stimulatory in the process of reproduction and maturation

Characterization of human and instrument related measurement errors

Measurement is the act or the result of a quantitative comparison between a given quantity and a quantity of the same kind chosen as a unit. It is generally agreed that all measurements contain errors. In a measuring system where both a measuring instrument and a human being taking the measurement using a preset process, the measurement error could be due to the instrument, the process or the human being involved. The first part of the study is devoted to understanding the human errors in measurement. For that, selected person related and selected work related factors that could affect measurement errors have been identified. Though these are well known, the exact extent of the error and the extent of effect of different factors on human errors in measurement are less reported. Characterization of human errors in measurement is done by conducting an experimental study using different subjects, where the factors were changed one at a time and the measurements made by them recorded. From the pre‐experiment survey research studies, it is observed that the respondents could not give the correct answers to questions related to the correct values [extent] of human related measurement errors. This confirmed the fears expressed regarding lack of knowledge about the extent of human related measurement errors among professionals associated with quality. But in postexperiment phase of survey study, it is observed that the answers regarding the extent of human related measurement errors has improved significantly since the answer choices were provided based on the experimental study. It is hoped that this work will help users of measurement in practice to better understand and manage the phenomena of human related errors in measurement.

Human and Raptor Interactions in the Context of a Nomadic Society

This research project focuses on contemporary eagle-taming falconry practice of the Altaic Kazakhs animal herding society in Bayan Ulgii Province in Western Mongolia. It aims to contributing both theoretical and empirical criteria for cultural preservation of Asian falconry. This cultural as well as environmental discourse is illustrated with concentrated field research framed by ecological anthropology and ethno-ornithology from the viewpoint of “Human-Animal Interaction (HAI)” and “Human-Animal Behavior (HAB)”. Part I (Chapter 2 & 3) explores ethno-archaeological and ethno-ornithological dimensions by interpretive research of archaeological artefacts which trace the historical depth of Asian falconry culture. Part II (Chapter 4 & 5) provides an extensive ethnographic narrative of Altaic Kazakh falconry, which is the central part of this research project. The “Traditional Art and Knowledge (TAK)” in human-raptor interactions, comprising the entire cycle of capture, perch, feeding, training, hunting, and release, is presented with specific emphasis on its relation to environmental and societal context. Traditional falconry as integral part of a nomadic lifestyle has to face some critical problems nowadays which necessitate preventing the complete disappearance of this outstanding indigenous cultural heritage. Part III (Chapter 6 & 7) thus focuses on the cultural sustainability of Altaic Kazakh falconry. Changing livelihoods, sedentarisation, and decontextualisation are identified as major threats. The role of Golden Eagle Festivals is critically analysed with regard to positive and negative impact. This part also intends to contribute to the academic definition of eagle falconry as an intangible cultural heritage, and to provide scientific criteria for a preservation master plan, as well as stipulate local resilience by pointing to successive actions needed for conservation. This research project concludes that cultural sustainability of Altaic Kazakh falconry needs to be supported from the angles of three theoretical frameworks; (1) Cultural affairs for protection based on the concept of nature-guardianship in its cultural domain, (2) Sustainable development and improvement of animal herding productivity and herder’s livelihood, (3) Natural resource management, especially supporting the population of Golden Eagles, their potential prey animals, and their nesting environment.

Human and social biology for CSEC. Teacher's support material.

Recurso para el profesor que acompaña al libro de texto del alumno para preparar el Certificado de Educación Secundaria en el Caribe (CSEC). Trata de los organismos vivos y el medio ambiente, los procesos de vida, la herencia y la variación, la enfermedad y su impacto en los seres humanos; el impacto de las prácticas de salud en el medio ambiente. Tiene notas para el profesor y hojas de trabajo para los alumnos.