Application of Animal Modeling to Biodefense Research

The use of biological agents to attack enemies has substantial historical precedent,and includes documented attempts tocontaminate the wells andreservoirs of enemies withcadavers and animal carcasses;and attemptstoinfect Native Ameri-cans with smallpox via contaminated blankets offered as gifts.Awareness and concern over biological weapons has in-creased greatly as the technological sophistication required to produce related agents has become more global.That theuse of biological agents as a m…     

Zoological Research Call for papers The 1st issue,2013,"Special Issue for Primates and Animal Models of Human Diseases"

To whom it may concern:Co-organized by the Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province and Zoological Research,two special issues for Primates and Animal models of Human diseases [32(1),2011 & 33(1),2012] have been released.The first special issue [32(1),2011] has significantly increased the journal hits on PubMed(500 times more than last month) and during the next couple of months,the editorial office     

The State of Research on Human–Animal Relations: Implications for Human Health

ABSTRACT

Since the late 1970s, scientific evidence has accumulated showing that pet ownership can have positive effects on people’s physical and mental wellbeing. This paper reviews the current state of affairs regarding the relationship between companion animals and human health, focusing on both the physical and psychological health outcomes related to human–animal interactions. Although designed to set the general scene on the link between animals and human wellbeing, research specific to older adults is highlighted where relevant. A particular emphasis is placed on disorders prevalent in modern-day society, notably cardiovascular disease and depression. The possible mechanisms by which companion animals might be able to enhance human wellbeing and quality of life are discussed, focusing on routes including, amongst others, the provision of companionship, social lubrication, and improvements to physical fitness. The role of the social bonding hormone, oxytocin, in facilitating attachment to our pets and the implications for human health is also discussed. Inconsistencies in the literature and methodological limitations are highlighted throughout. It is concluded that future human–animal interaction experiments should aim to account for the confounding variables that are inherent in studies of this nature.     

The First Symposium on Frontiers of Biomedical Sciences Organized by Cell Research "Epigenetics in Development and Diseases"

This is the First Symposium on Frontiers of Biomedical Science organized by Cell Research, a peerreviewed journal supported by the Chinese Academy of Sciences. In recent years, epigenetics have shown its growing importance for the understanding of life processes and the control of human diseases in the genome era. I do hope that this timely symposium will     

The Concept of Mainstream Medicine for All Californians—Part I Fifth Progress Report of the Committee on Role of Medicine in Society

This Fifth Progress Report is to be printed in three parts in California Medicine. Following the appearance of Part III the report will be bound in a pamphlet which may be ordered at $1 a copy from 693 Sutter Publications, Inc., 693 Sutter Street, San Francisco, California 94102.     

The Concept of Mainstream Medicine for All Californians—Part II Fifth Progress Report of the Committee on Role of Medicine in Society

This Fifth Progress Report is being printed in three parts in California Medicine. Following the appearance of Part III the report will be bound in a pamphlet which may be ordered at $1 a copy from 693 Sutter Publications, Inc., 693 Sutter Street, San Francisco, California 94102.     

Proteomic basics — quantification and post-translational modifications of proteins: The 3rd European Summer School in Kloster Neustift

The field of proteomics is rapidly evolving and has emerged as a routine application in many laboratories. It covers not only the identification of proteins but also the quantification and analysis of post-translational protein modifications. During the last few years a series of summer schools teaching comprehensive knowledge in proteomic research and applied techniques have been held. Various research areas were dealt with by international experts in lectures and workshops. The summer schools were addressed to master's and graduate students as well as young post-docs currently moving into the field of proteomics. Here, we give a report on the third European Summer School “Quantification and Post-translational Modifications of Proteins” held at the monastery in Neustift, Brixen/Bressanone, South Tyrol, Italy from August 2 to 9, 2009.     

The eIF3 complex of Leishmania—subunit composition and mode of recruitment to different cap-binding complexes

Eukaryotic initiation factor 3 (eIF3) is a multi-protein complex and a key participant in the assembly of the translation initiation machinery. In mammals, eIF3 comprises 13 subunits, most of which are characterized by conserved structural domains. The trypanosomatid eIF3 subunits are poorly conserved. Here, we identify 12 subunits that comprise the Leishmania eIF3 complex (LeishIF3a-l) by combining bioinformatics with affinity purification and mass spectrometry analyses. These results highlight the strong association of LeishIF3 with LeishIF1, LeishIF2 and LeishIF5, suggesting the existence of a multi-factor complex. In trypanosomatids, the translation machinery is tightly regulated in the different life stages of these organisms as part of their adaptation and survival in changing environments. We, therefore, addressed the mechanism by which LeishIF3 is recruited to different mRNA cap-binding complexes. A direct interaction was observed in vitro between the fully assembled LeishIF3 complex and recombinant LeishIF4G3, the canonical scaffolding protein of the cap-binding complex in Leishmania promastigotes. We further highlight a novel interaction between the C-terminus of LeishIF3a and LeishIF4E1, the only cap-binding protein that efficiently binds the cap structure under heat shock conditions, anchoring a complex that is deficient of any MIF4G-based scaffolding subunit.     

Physical Medicine and Rehabilitation: Late Effects of Poliomyelitis—An Update on Fatigue and Weakness

The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in physical medicine and rehabilitation. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in physical medicine and rehabilitation that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another.The items of progress listed below were selected by the Advisory Panel to the Section on Physical Medicine and Rehabilitation of the California Medical Association, and the summaries were prepared under its direction.     

The Era of Immune Checkpoint Therapy: From Cancer to Viral Infection——A Mini Comment on the 2018 Medicine Nobel Prize

正The 2018 Medicine Nobel Prize was awarded jointly to two immunologists, James P. Allison at the University of Texas MD Anderson Cancer Center in Houston and Tasuku Honjo at Kyoto University in Japan, who pioneered a new way to treat cancers (Ledford et al. 2018). Both Laureates have shown how so called ‘‘immune checkpoints’’ on T cells can be used to manipulate the immune responses so     

The mobile receptor hypothesis and “cooperativity” of hormone binding. Application to insulin

The mobile receptor hypothesis has been proposed to describe the process by which hormone receptor binding initiates a biological response; it states that receptors, which can diffuse independently in the plane of the membrane, reversibly associate with effectors to regulate their activity. The affinity for effector is greater when the receptor is occupied by hormone.A mathematical expression of the mobile receptor hypothesis is used to show that: (1) The predicted kinetics of hormone receptor binding may be indistinguishable from “negative cooperativity”. (2) Receptor occupancy and biological response may be coupled in a non-linear fashion.By choosing specific parameters, most of the existing data on insulin binding and biological responses can be explained in terms of the mobile receptor hypothesis. Thus, the following are easily explained: (1) A single homogeneous receptor may appear kinetically to be composed of two classes (of high and low affinity) of receptors. (2) Occupancy of the apparent class of high affinity receptors is related linearly to the biological response. (3) The same receptor in different tissues may appear to have different affinity. (4) The binding of different biologically active insulin analogues may exhibit different degrees of “cooperatively.” These considerations may also be pertinent to intepretations of other hormone-receptor systems and of various ligand-macromolecule interactions.     

Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma — Prognostic and Translational Implications

Renal cell carcinoma (RCC) is characterized by a profound disruption of proapoptotic signaling networks leading to chemo- and radioresistance. A key mediator of DNA damage-induced apoptosis is the BH3-only protein PUMA. Given its central role in proapoptotic signaling, we analyzed a series of more than 600 precision-annotated primary RCC specimens for PUMA protein expression. We found a reduced expression of PUMA in 22.6% of RCCs analyzed. Unexpectedly, however, PUMA deficiency was not associated with more aggressive tumor characteristic as expected. Instead, a reduced PUMA expression was associated with a lower TNM stage, lower histopathologic grade, and more favorable cancer-specific patient survival. A direct correlation in a separate patient cohort revealed a profound disconnection between PUMA expression and apoptosis as exemplified by the fact that the tumor with the highest level of apoptotic cells was PUMA deficient. In a series of in vitro studies, we corroborated these results and discovered the highest propensity to undergo apoptosis in an RCC cell line with virtually undetectable PUMA expression. At the same time, PUMA expression was not necessarily associated with stronger apoptosis induction, which underscores the striking functional heterogeneity of PUMA expression and apoptosis in RCC. Collectively, our findings suggest that PUMA-independent mechanisms of cell death exist and may play an important role in suppressing malignant progression. They underscore the functional heterogeneity of RCCs and suggest that PUMA expression alone may not be a suitable predictive biomarker. A better understanding of alternative proapoptotic pathways, however, may help to design novel therapeutic strategies for patients with advanced RCC.     

90Y-resin particles—Animal experiments on pigs with regard to the introduction of superselective embolization therapy

Resin particles (diameter 45–75 μm) were labelled with ⁹⁰Y, suspended in a glucose/dextran solution and infused into the kidneys of 3-month-old pigs (tumour model). Both kidneys of each animal were embolized with particles, but only one with active (⁹⁰Y loaded) particles and the other, for comparison, with inactive particles. The organ measurements showed < 1% of injected activity in bone, bone marrow, liver and lung compared to > 99% retention by the kidneys. Only minimal shunted activity was found in blood (<0.27%) and urine (<0.07%). There was a clear shrinkage of the ⁹⁰Y-treated kidneys with a reduction in weight of up to 50%. Histologically, the ischaemic lesions (infarcts and atrophy) were clearly more pronounced and extensive in the ⁹⁰Y-embolized kidneys than in the non-radioactive embolized kidneys. Furthermore, severe arterial wall changes and fibrotic necrosis due to radiation damage were observed in the ⁹⁰Y-treated kidneys. It is concluded that with intra-arterially applied particles a dose of about 100 Gy is sufficient to completely destroy tissue-specific structures. Complications due to acute necrosis or inflammatory reactions were not observed, and there were no shunt related alterations seen in the liver or lungs. The ⁹⁰Y-loaded resin particles are considered suitable for a super selective intra-arterial radioembolization.