Defining the Range of Cellular Components, Including Internal Antigens, That Can Serve as Targets of Graft Rejection

The mechanisms underlying rejection of grafted neural tissue are still being defined. Mechanisms relevant to genetically engineered cells are of current interest. To date, attention has focused on major histocompatibility complex (MHC) antigens as targets of graft rejection. Yet even when there is no MHC disparity, as when the patient's own cells are genetically altered, there is still a potential for graft rejection, directed against the novel antigens. We illustrate this in a rat model

Expression of Class I and II Major Histocompatibility Complex (MHC) Antigens in the Developing CNS

The clinical potential of neural transplantation depends upon the feasibility of allogenenic or xenogeneic transplants, particularly of fetal tissue. This, in turn, is influenced by donor cell expression of MHC antigens. MHC expression in the developing CNS in situ had not been defined. Here, a panel of antibodies was used to define MHC expression in the developing rat embryo

Monoclonal antibodies in neuro-oncology: Getting past the blood-brain barrier

Monoclonal antibodies (mAbs) are used with increasing success against many tumors, but for brain tumors the blood-brain barrier (BBB) is a special concern. The BBB prevents antibody entry to the normal brain; however, its role in brain tumor therapy is more complex. The BBB is closest to normal at micro-tumor sites; its properties and importance change as the tumor grows. In this review, evolving insight into the role of the BBB is balanced against other factors that affect efficacy or interpretation when mAbs are used against brain tumor targets. As specific examples, glioblastoma multiforme (GBM), primary central nervous system lymphoma (PCNSL) and blood-borne metastases from breast cancer are discussed in the context of treatment, respectively, with the mAbs bevacizumab, rituximab and trastuzumab, each of which is already widely used against tumors outside the brain. It is suggested that success against brain tumors will require getting past the BBB in two senses: physically, to better attack brain tumor targets, and conceptually, to give equal attention to problems that are shared with other tumor sites

Extreme Makeover: Bending the Rules to Reduce Risk Rewriting Complex Systems

Abstract. We describe our experience using XP to reimplement sophisticated, high-performance imaging software in a research environment. We focus espe-cially on practices we used to derive value from the existing software, notably reimplementation by ransacking and conversion as learning. Our experience suggests that some of the classic 12 practices which define XP should be ad-justed when there is a existing, well-structured system to serve as a guide.

Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere

Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.NIH grants: (GM082989, CA186430, GM008275, GM008216, GM007229); American Heart Association predoctoral fellowship; American Cancer Society postdoctoral fellowship; NSF grant: (agreement DMR-0944772)

Common Representation of Information Flows for Dynamic Coalitions

We propose a formal foundation for reasoning about access control policies within a Dynamic Coalition, defining an abstraction over existing access control models and providing mechanisms for translation of those models into information-flow domain. The abstracted information-flow domain model, called a Common Representation, can then be used for defining a way to control the evolution of Dynamic Coalitions with respect to information flow

Alzheimer\u27s, angiotensin IV and an aminopeptidase

The angiotensin AT4 receptor was originally defined as the specific, high affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT4 receptor. Central administration of Ang IV or LVV-hemorphin 7 (LVV-H7) markedly enhances learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The high affinity binding site has a broad distribution in the brain including areas such as the hippocmapus that are involved in memory processing. The high affinity Ang IV binding site (AT4 receptor) has been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). Insulin-regulated aminopeptidase is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and in insulin-responsive cells colocalizes with GLUT4 in specific intra-cellular vesicles. Both Ang IV and LVV-H7 are competitive inhibitors of IRAP catalytic activity and are not substrates of the enzyme.<br /

Esperanto for histones : CENP-A, not CenH3, is the centromeric histone H3 variant

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres