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.

Neutrinos

Neutrinos represent a new “window” to the Universe, spanning a large range of energy. We discuss the science of neutrino astrophysics and focus on two energy regimes. At “lower” energies (≈1 MeV), studies of neutrinos born inside the sun, or produced in interactions of cosmic rays with the atmosphere, have allowed the first incontrovertible evidence that neutrinos have mass. At energies typically one thousand to one million times higher, sources further than the sun (both within the Milky Way and beyond) are expected to produce a flux of particles that can be detected only through neutrinos.

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.

Analysis of six prophages in Lactococcus lactis IL1403: different genetic structure of temperate and virulent phage populations

We report the genetic organisation of six prophages present in the genome of Lactococcus lactis IL1403. The three larger prophages (36–42 kb), belong to the already described P335 group of temperate phages, whereas the three smaller ones (13–15 kb) are most probably satellites relying on helper phage(s) for multiplication. These data give a new insight into the genetic structure of lactococcal phage populations. P335 temperate phages have variable genomes, sharing homology over only 10–33% of their length. In contrast, virulent phages have highly similar genomes sharing homology over >90% of their length. Further analysis of genetic structure in all known groups of phages active on other bacterial hosts such as Escherichia coli, Bacillus subtilis, Mycobacterium and Streptococcus thermophilus confirmed the existence of two types of genetic structure related to the phage way of life. This might reflect different intensities of horizontal DNA exchange: low among purely virulent phages and high among temperate phages and their lytic homologues. We suggest that the constraints on genetic exchange among purely virulent phages reflect their optimal genetic organisation, adapted to a more specialised and extreme form of parasitism than temperate/lytic phages.

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.