HLA-G expression in melanoma: A way for tumor cells to escape from immunosurveillance

Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies.

The middle way

Mesoscopic organization in soft, hard, and biological matter is examined in the context of our present understanding of the principles responsible for emergent organized behavior (crystallinity, ferromagnetism, superconductivity, etc.) at long wavelengths in very large aggregations of particles. Particular attention is paid to the possibility that as-yet-undiscovered organizing principles might be at work at the mesoscopic scale, intermediate between atomic and macroscopic dimensions, and the implications of their discovery for biology and the physical sciences. The search for the existence and universality of such rules, the proof or disproof of organizing principles appropriate to the mesoscopic domain, is called the middle way.

Black holes in the Milky Way Galaxy

Extremely strong observational evidence has recently been found for the presence of black holes orbiting a few relatively normal stars in our Milky Way Galaxy and also at the centers of some galaxies. The former generally have masses of 4–16 times the mass of the sun, whereas the latter are “supermassive black holes” with millions to billions of solar masses. The evidence for a supermassive black hole in the center of our galaxy is especially strong.

Gardenification of tropical conserved wildlands: Multitasking, multicropping, and multiusers

Tropical wildlands and their biodiversity will survive in perpetuity only through their integration into human society. One protocol for integration is to explicitly recognize conserved tropical wildlands as wildland gardens. A major way to facilitate the generation of goods and services by a wildland garden is to generate a public-domain Yellow Pages for its organisms. Such a Yellow Pages is part and parcel of high-quality search-and-delivery from wildland gardens. And, as they and their organisms become better understood, they become higher quality biodiversity storage devices than are large freezers. One obstacle to wildland garden survival is that specific goods and services, such as biodiversity prospecting, lack development protocols that automatically shunt the profits back to the source. Other obstacles are that environmental services contracts have the unappealing trait of asking for the payment of environmental credit card bills and implying delegation of centralized governmental authority to decentralized social structures. Many of the potential conflicts associated with wildland gardens may be reduced by recognizing two sets of social rules for perpetuating biodiversity and ecosystems, one set for the wildland garden and one set for the agroscape. In the former, maintaining wildland biodiversity and ecosystem survival in perpetuity through minimally damaging use is paramount, while in the agroscape, wild biodiversity and ecosystems are tools for a healthy and productive agroecosystem, and the loss of much of the original is acceptable.

Web-based distance continuing education: a new way of thinking for students and instructors

As people have more difficulty taking time away from work to attend conferences and workshops, the idea of offering courses via the Web has become more desirable. Addressing a need voiced by Medical Library Association membership, the authors developed a Web-based continuing-education course on the subject of the librarian's role in evidence-based medicine. The aim of the course was to provide medical librarians with a well-constructed, content-rich learning experience available to them at their convenience via the Web. This paper includes a discussion of the considerations that need to be taken into account when developing Web-based courses, the issues that arise when the information delivery changes from face-to-face to online, the changing role of the instructor, and the pros and cons of offering Web-based versus traditional courses. The results of the beta test and future plans for the course are also discussed.

Programmed cell death: a way of life for plants.

Cell death in higher plants has been widely observed in predictable patterns throughout development and in response to pathogenic infection. Genetic, biochemical, and morphological evidence suggests that these cell deaths occur as active processes and can be defined formally as examples of programmed cell death (PCD). Intriguingly, plants have at least two types of PCD, an observation that is also true of PCD in animals [Schwartz, L. M., Smith, W.W., Jones, M. E. E. & Osborne, B. A. (1993) Proc. Natl. Acad. Sci. USA 90, 980-984]. Thus, in plants, PCD resembles either a common form of PCD seen in animals called apoptosis or it resembles a morphologically distinct form of cell death. The ubiquitous occurrence and necessity of PCD for plant development and defense suggest that the underlying mechanisms of regulation and execution of these processes merit further examination.

Crystal structure of a DNA decamer showing a novel pseudo four-way helix-helix junction.

The crystal structure of the decanucleotide d(CGCAATTGCG)2 has been solved by a combination of molecular replacement and heavy-atom procedures and has been refined to an R factor of 20.2% at 2.7 A. It is not a fully base-paired duplex but has a central core of eight Watson-Crick base pairs flanked by unpaired terminal guanosines and cytosines. These participate in hydrogen-bonding arrangements with adjacent decamer duplexes in the crystal lattice. The unpaired guanosines are bound in the G+C regions of duplex minor grooves. The cytosines have relatively high mobility, even though they are constrained to be in one region where they are involved in base-paired triplets with G.C base pairs. The 5'-AATT sequence in the duplex region has a narrow minor groove, providing further confirmation of the sequence-dependent nature of groove width.