[escepticos] SCIENCE-WEEK August 8, 1997

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>Subject: SCIENCE-WEEK August 8, 1997
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>SCIENCE-WEEK
>
>A Free Weekly Digest of the News of Science
>
>SCIENCE-WEEK is the abridged version of SCIENCE-REPORT.
>See the Notices section below.
>
>New: All back issues of SCIENCE-WEEK are available
>free at http://members.aol.com/sciweek
>
>August 8, 1997
>---------------------------------------------
>
>"One thing I have learned in a long life: that all
>our science, measured against reality, is primitive
>and childlike -- and yet it is the most precious
>thing we have." -- Albert Einstein, Physicist
>
>---------------------------------------------
>
>Reported in This Issue:
>
>Xenotransplantation Conflict Between Surgeons and Virologists
>Dating of a 100-Km-Diameter Terrestrial Impact Crater
>Protein-Folding Mechanisms in Prokaryotes vs. Eukaryotes
>Biochemists Intrigued by DNA Knots
>Sequencing of Complete Genome of Ulcer-Causing Bacterium
>A New Method to Block Rejection of Transplanted Organs
>
>--------------------------------------------
>
>XENOTRANSPLANTATION CONFLICT BETWEEN SURGEONS AND VIROLOGISTS
>Xenostransplantation involves the surgical replacement of
>defective human organs by animal organs. There are at present two
>primary concerns in this area: 1) The use of genetically
>engineered animal organs is of great appeal because human organs
>are usually rejected by the human immune system, and a patient
>receiving a human organ must be on a lifetime regimen of immune-
>system-suppressant drugs; and 2) the possibility that the genome
>of the animal cells may contain the sequences of endogenous
>viruses, and these sequences may result in the appearance of
>pathogenic viral forms dormant in the animal but suddenly active
>in the human, and then be transmitted from human to human with
>pandemic consequences. This week the U.S. Food and Drug
>Administration hosted a meeting to reduce an apparent conflict
>between surgeons and virologists over how to proceed. In brief,
>the surgeons want accelerated research to produce genetically
>engineered animal organs that will not be rejected by the human
>immune system, while the virologists are not at all happy with
>the idea, and are urging extreme caution in the use of animal
>tissues in transplantation surgery. The animal organs of most
>relevance are those from the pig, and it has already been
>demonstrated that pig retrovirus can be infectiously transmitted
>to human cells. On the other hand, it has also been demonstrated
>that the surfaces of pig cells can be easily genetically
>engineered so that organ rejection can might be eliminated.
>Despite the conflict, and the real danger of endogenous virus
>infections, the need for artificial organs is so great there is a
>consensus that the field of xenotransplantation will move forward
>no matter what the obstacles. (Nature 31 July)
>
>DATING OF A 100-KM-DIAMETER TERRESTRIAL IMPACT CRATER
>In geology and paleobiology, the Eocene epoch is a period from
>about 58 million years ago to about 36 million years ago. The
>Eocene, which lasted 22 million years, is bordered on the near
>side by the Oligocene (duration 11 million years), and on the far
>side by the Paleocene (duration 5 million years), and the
>Paleocene and Eocene were the epochs during which the original
>mammals appeared, the ancestors of the mammals presently on
>Earth. There is a consensus that 65 million years ago a great
>impact occurred, probably associated with the 180 to 310 km
>diameter Chicxulub crater in Yucatan, and that one important
>consequence of that impact was the end of the age of dinosaurs,
>and the emergence 2 million years later, during the Paleocene, of
>the first mammals. But there have been other large impacts, as
>evidenced by craters, and for obvious reasons these have been of
>great interest to paleobiologists, and accurate dating of these
>impacts is an important research objective. The 100-km-diameter
>Popigai crater in Siberia is considered the 5th largest impact
>crater identified, but its age has never been known with any
>specificity beyond a time bracket of 65 to 25 million years ago.
>This week Richard Bottomley et al (various installations in CA
>and RU) report the first accurate dating, using Argon
>radioisotope methods applied to impact melt rocks, of the Popigai
>crater at 35.7 million years, which puts the Popigai impact near
>the end of the Eocene. This has produced excitement among
>paleobiologists, because the 85-km-diameter Chesapeake Bay impact
>crater off the Virginia shore has already been dated at 35.5
>million years ago, and if all the dating is valid one must
>conclude that near the end of the Eocene the Earth was subjected
>to two enormous impacts within 200,000 years of each other, a
>double blow which may have had an important effect on the
>evolution of life forms. (Nature 24 July)
>
>PROTEIN-FOLDING MECHANISMS IN PROKARYOTES VS. EUKARYOTES
>In biological systems, proteins are the molecules that do most of
>the biological work, and the various proteins are the ultimate
>expression of the genome of any organism. As polymers, proteins
>are similar to the polymers known to polymer chemists, but the
>chemical activities of proteins (and their biological functions)
>depend mostly on higher-order folding into specific configur-
>ations rather than on quasi-crystalline backbone arrays, as is
>often the case in non-biological polymer chemistry. It is these
>specific configurations that are responsible for the important
>specificity and high catalytic power of the proteins that are
>enzymes. The configurations, in turn, are an ultimate result of
>amino acid sequences which form the backbone of proteins,
>sequences which are not simple, as are the backbone sequences of
>most non-biological polymers, but are specific, cryptic (coded),
>and heterogenous. It is now recognized that complex proteins
>usually have more than one folding domain, each involving a
>sequence of 100 to 300 amino acids. The entire folding
>architecture of a complex protein must be precisely constructed
>in order for protein functionality to exist. Which provokes the
>question of how the specific folding of particular proteins is
>ensured by the biological system. The answer is evident for
>simple proteins in vitro: the final configuration is
>predetermined by the amino acid sequence, there being a single
>energetically favored configuration that will always be attained
>at equilibrium. This is Anfinsen's Rule, first proposed by the
>protein biochemist C. B. Anfinsen more than 30 years ago. In
>vivo, however, and particularly for complicated proteins, the
>situation is more involved. This week W. J. Netzer and F. U.
>Hartl (Sloan Kettering Cancer Center, NY US; Max Planck Inst.
>Biochemistry, Martinsried DE) report an analysis of the
>differences between protein folding in prokaryotes (organisms,
>such as bacteria, without membrane-bound organelles such as the
>nucleus) and eukaryotes (organisms with membrane-bound
>organelles). Perhaps the most interesting difference is that in
>prokaryotes protein folding is delayed until translation (final
>synthesis by the ribosome) is completed (post-translational
>folding), while in eukaryotes folding of each protein domain
>occurs as each domain is translated (co-translational folding).
>One result is that new prokaryote proteins can often be
>misfolded. There are helper proteins at work in both prokaryotes
>and eukaryotes to chaperon the proteins to their final
>configurations, but there is still more possibility for errors in
>the prokaryotes. One important consequence of this analysis is
>that when bacteria are genetically engineered to synthesize human
>protein for clinical use, the susceptibility of prokaryote
>protein synthesis to folding errors must be considered. 
>(Nature 24 July)
>
>BIOCHEMISTS INTRIGUED BY DNA KNOTS
>Replication of the genome of any cell, be it prokaryote or
>eukaryote, involves not only the DNA of the cell, but also a
>cluster of enzymes and helper proteins, and the entire set of
>entities can be said to be involved in one of the most elegant
>molecular ballets found anywhere in nature. In prokaryotes, such
>as bacteria, the genome is in the form of a closed loop of DNA.
>If this loop is twisted into a supercoil, or knotted, or
>catenated, these derivative forms must be altered and the relaxed
>open loop restored before replication of the loop can begin.
>There are enzymes involved in these processes, and those that
>have been identified are called topoisomerases, the topo- prefix
>indicating an enzyme that catalyzes topological change. The
>ability of topoisomerases to do their work, to alter the unwanted
>linked states of DNA, is essential for cell survival, and this
>work of untying the knot or knots of a huge looped double-helical
>strand (in prokaryotes), or a linear double-helical strand (in
>eukaryotes) is quite remarkable. In brief, what these enzymes,
>the topoisomerases, do is apparently first recognize the entire
>topology of the DNA molecule, the supercoils, the knots, the
>catenanes, and then move in to precise points to cleave and pass
>and splice so that a relaxed double-helix of DNA is obtained,
>linear in eukaryotes and a closed loop in prokaryotes, all of
>this a precursor to the main part of the ballet, the replication
>process. This week V. V. Rybenkov et al (University of California
>Berkeley, US; New York University, US) report studies of
>eukaryotic and prokaryotic topoisomerases which indicate that not
>only can these enzymes recognize and undo a knot in a DNA circle
>many times their own size, but that the process results in
>forcing tangled DNA into an untangled state apparently far from
>equilibrium. These studies will soon be amplified by others. As
>one commentator put it, "The fun has just begun."
>(Science 1 August)
>
>SEQUENCING OF COMPLETE GENOME OF ULCER-CAUSING BACTERIUM
>Gastritis, stomach ulcers, and stomach cancers are a complex of
>pathologies that are difficult to categorize and often difficult
>to diagnose. Until recently, the consensus was that most cases of
>gastritis and stomach ulcers involved stress-induced acid
>secretion into the stomach, which in the absence of food would
>result in a corrosive action of the acid on the wall of stomach.
>Then, in 1983, came the startling self-experiments and
>conclusions of two Australian physicians, Barry Marshall and
>Robert Warren, who proposed that the bacterium Helicobacter
>pylori, a spiral organism present in half the world's population,
>was the cause of most gastritis and stomach ulcers and perhaps
>stomach cancers as well. The initial report was, to put it
>bluntly, derided by most gastroenterologists, but during the past
>decade most gastroenterologists have in fact come around to agree
>with Marshall and Warren. This week, at the non-profit Institute
>for Genomic Research (Rockville MD US) headed by J. Craig Venter,
>Jean-Francois Tomb et al report the first complete sequencing of
>the genome of Helicobacter pylori. Venter's group is publishing
>the entire genome, giving it away free, partly in protest against
>a corporate entity (Genome Therapeutics, Waltham MA US) that
>claimed two years ago that it had sequenced the genome but would
>not publish it because of its proprietary value and a contract
>with Astra AB of Sweden. Now the complete genome of H. pylori is
>available to everyone. The cost to the Venter and Tomb group was
>apparently $1 to $2 million out of its own funds. The bacterium
>has 1,667,867 base pairs of DNA in a single circular chromosome
>organized into coding sequences for 1,590 genes. The Venter and
>Tomb group have already started comparing various sequences of
>the H. pylori genome with known sequences of other organisms to
>identify what proteins are expressed and for which functions.
>This is only the 5th bacterial genome to be published, and it is
>an important step in molecular medicine. (Nature 7 August)
>
>A NEW METHOD TO BLOCK REJECTION OF TRANSPLANTED ORGANS
>The human immune system orchestrates a complex response to any
>invasion by foreign proteins, or foreign cells, or the
>transformation of the body's own cells into cancer cells after
>genome alteration. One of the key players in the immune response
>is the T-cell, or T-lymphocyte. The "T" prefix relates to the
>fact that at one point in their history, these cells congregate
>in the thymus gland. The basic T-cell immune response consists of
>two stages. In the first stage there is recognition of foreign or
>cancerous pathogenic cells or parts of cells, and the encoding of
>the recognition in the T-cell genome. The second stage involves
>the rapid proliferation of cloned T-cells containing the new
>recognition factor. With the assistance of other cells in the
>immune system, and various secretion products as messengers, the
>entire immune system then does battle against the invader. All of
>this is the basis for what is called "organ rejection", the bane
>of transplantation surgeons. If one wants to replace a damaged
>organ with a healthy organ donated by another person, the central
>problem that has to be overcome is the drive by the recipient
>immune system to reject the donor organ as foreign material. The
>rejection process involves a systematic obliteration of the cells
>of the donor organ, until the organ ceases to function. At the
>present time, the most widely used method to solve this problem
>is to suppress the recipient's immune system with various
>pharmacological agents, but these drugs need to be used for the
>rest of the recipient's life, and their effects are complex and
>often deleterious. In general then, transplantation surgery is a
>difficult affair. One path of research is to genetically engineer
>animal organs so that they will not be rejected, and use such
>organs in human recipients (xenotransplantation: see report above
>on same). Another path of research is to find ways to fine-tune
>the recipient's immune system's response to a transplanted organ,
>a more delicate tinkering as opposed to the more general
>suppression methods that are now used. This week David M. Harlan
>et al (Naval Medical Research Institute, Bethesda MD US) reports
>that in monkeys given kidney transplants a combination of two
>proteins injected periodically for 28 days shuts down the immune
>system rejection of the transplanted organs without affecting the
>immune system's general ability to fight off infections. Although
>the work needs to be replicated, and much research still needs to
>be done, transplantation surgeons are calling the results a
>breakthrough. (Proc. U.S. Natl. Acad. Sci. 6 August)
>
>---------------------------------------------
>NOTICES
>
>---------------------------------------------
>SCIENCE-REPORT is the full science digest: more news, more
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>---------------------------------------------
>CONFERENCE: Vancouver (BC CA)
>SYMPOSIUM ON FLUORINE CHEMISTRY (August 3 - 8)
>Sponsor: University of British Columbia
>contact: aubke en chem.ubc.ca
>---------------------------------------------
>TWO CONFERENCES: Genoa (IT)
>CANCER GENETICS (September 25 - 30)
>TECHNICAL DEVELOPMENTS IN CANCER RESEARCH (September 30)
>Contact: Fondazione Intl. Menarini, Piazza del Carmine, 4,
>20121 Milan, IT. Phone: (39) 2-874932
>---------------------------------------------
>CONFERENCE: San Francisco (CA US)
>THERAPEUTIC ANTIBODY TECHNOLOGY (September 21 - 24)
>Sponsor: Palo Alto Institute of Molecular Medicine
>contact: paimm en netgate.net
>---------------------------------------------
>Science http://www.sciencemag.org
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>Nature http://www.nature.com
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>American Chemical Society http://www.acs.org
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>U.S. National Institutes of Health http://www.nih.gov
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>New England Journal of Medicine http://www.nejm.org
>---------------------------------------------
>---------------------------------------------
>
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