Chiasma interference as a function of genetic distance

For many organisms, meiotic double crossing over is less frequent than expected on the assumption that exchanges occur at random with respect to each other. This "interference," which can be almost total for nearby intervals, diminishes as the intervals in which the double crossovers are scored are moved farther apart. Most models for interference have assumed, at least implicitly, that the intensity of interference depends inversely on the physical distance separating the intervals. However, several observations suggest that interference depends on genetic distance (Morgans) rather than physical distance (base pairs or micrometers). Accordingly, we devise a model in which interference is related directly to genetic distance. Its central feature is that recombinational intermediates (C's) have two fates--they can be resolved with crossing over (Cx) or without (Co). We suppose that C's are distributed at random with respect to each other (no interference); interference results from constraints on the resolution of C's. The basic constraint is that each pair of neighboring Cx's must have between them a certain number of Co's. The required number of intervening Co's for a given organism or chromosome is estimated from the fraction of gene conversions that are unaccompanied by crossover of flanking markers. The predictions of the model are compared with data from Drosophila and Neurospora.     

Bypass surgery for vascular disease of the carotid system

A series of 58 operations on 56 patients, in whom a branch of the superficial temporal artery was anastomosed to a branch of the middle cerebral artery (STA-MCA bypass or Yasargil procedure), is reviewed. These operations were performed chiefly for occlussions or for inaccessible stenotic lesions of the internal carotid or middle cerebral arteries. Patency in eight patients operated on from April 1971 through November 1973 was low (25%). Patency in patients operated on since July 1974 has been high (95%). There have been no deaths and no major ischemic strokes attributable to the surgery. The rationale for this procedure is considered in relationship to the anatomy and physiology of the cerebral circulation and the pathogenesis of syndromes of cerebral ischemia. The operation appears to have a low morbidity in good-risk patients. The role of this operation in managing common manifestations of cerebral vascular disease such as focal transient cerebral ischemic attacks (TIAs) and amaurosis fugax, although not fully established, appears encouraging. The procedure seems useful for orthostatic cerebral ischemia caused by multiple occlusions of major extracranial (and intracranial) vessels and, occasionally, for progressing strokes related to internal carotid artery occlusion, both of which are relatively uncommon manifestations of cerebral vascular occlusive disease. It may have application in the rare "slow stroke." The procedure is probably of limited value, if any, in the management of large completed infarcts but may be indicated in selected patients with small infarctions who have preserved most of their cerebral function and who have had evidence of subsequent focal ischemic events. The procedure is useful for bypassing giant aneurysms or basofrontal tumors invading major vessels. It may have a role in the management of fibromuscular disease of the internal carotid artery.     

Identification of genes expressed in the rat prostate that are modulated differently by castration and Finasteride treatment

In mammals, testosterone and 5alpha-dihydrotestosterone (DHT) are the principal male hormones (androgens). Testosterone is the most abundant circulating androgen, and is converted in specific tissues to DHT by the 5alpha-reductase enzymes. Although each of these androgens binds to the same receptor protein (androgen receptor, AR), each exerts biologically distinct effects. Theories to explain the specific effects of testosterone and DHT have centered on kinetic differences of binding of androgens to the receptor or differences in the metabolic fates of the two hormones. In the current experiments, differential display PCR (ddPCR) was used to identify genes regulated differently by testosterone and DHT. Adult male rats were treated as follows: castrated, treated with Finasteride (an inhibitor of 5alpha-reductase) or left intact for ten days. RNA was prepared from the dissected prostates of these animals and used for ddPCR. Genes exhibiting four distinct patterns of regulation were observed among the mRNAs. Class 1 genes showed equivalent expression in intact and Finasteride-treated animals, but were absent in castrated animals (mRNAs D1, D2, D6, D10). Class 2 genes showed higher expression in intact animals, intermediate levels following Finasteride treatment, but were absent in castrated animals (mRNA D8). Two classes of gene were particularly intriguing: class 3 showed gene expression only in the intact animal (mRNA D7, D9) and class 4 showed increased gene expression following Finasteride treatment (mRNA D3). While the patterns observed for some of these genes (e.g. D8) suggest that the different biological effects of testosterone and DHT may be due to the lower affinity of the AR for testosterone and limiting tissue concentrations of androgen, our results also suggest that some genes expressed in the rat prostate may be regulated in fundamentally different ways in response to testosterone and DHT.     

Release into ventriculo-cisternal perfusate of beta-endorphin- and Met-enkephalin-immunoreactivity: effects of electrical stimulation in the arcuate nucleus and periaqueductal gray of the rat

To examine the resting and evoked release of the endogenous opioid peptides beta-endorphin and Met-enkephalin from brain, we examined the levels of the respective immunoreactivities in the lateral ventricle-cisterna magna perfusate of the halothane-anesthetized rat. Ten Hz but not 100 Hz stimulation in the arcuate nucleus (ARC) of the hypothalamus released beta-endorphin immunoreactivity (beta-EPir) to the perfusate, whereas 100 Hz but not 10 Hz stimulation in the periaqueductal gray (PAG) of the mid brain released Met-enkephalin immunoreactivity (MEir). MEir was not released by stimulation in ARC and beta-EPir was not released by stimulation in PAG. Characterization of the released beta-EPir and MEir by high performance liquid chromatography showed that authentic beta-endorphin and Met-enkephalin were the major constituents of beta-EPir and MEir, respectively. Systemic administration of the dopaminergic antagonist haloperidol increased plasma, but not perfusate levels of beta-EPir. Both the opioid antagonist naloxone and the NMDA antagonist MK-801 failed to affect beta-EPir or MEir release. ARC and PAG stimulated inhibited a nociceptive reflex (tail-dip in 52.5 degrees C water), and naloxone did not reliably reverse this inhibition. These data support the previously suggested possibility of opioid mediation of stimulation induced analgesia, although we were unable to confirm the theory by naloxone reversibility in this study. Furthermore, the data support the assumption that measurement of opioid peptides in cerebrospinal fluid is a relevant approach in research aimed at elucidating the physiological and pathophysiological roles of endogenous opioid peptides.     

Recombination in phage lambda: one geneticist's historical perspective

Several features of bacteriophage lambda suit it for the study of genetic recombination. Central among them are those that make it possible to correlate inheritance of DNA with the inheritance of information encoded by DNA through density-label equilibrium centrifugation. Such studies have revealed relationships between DNA replication and recombination, have identified roles for double-strand breaks in the initiation of recombination, and have elucidated the role of the recombination-stimulating sequence, chi.     

Orientation in operator algebras

A concept of orientation is relevant for the passage from Jordan structure to associative structure in operator algebras. The research reported in this paper bridges the approach of Connes for von Neumann algebras and ourselves for C*-algebras in a general theory of orientation that is of geometric nature and is related to dynamics.     

Modifications of carbohydrate residues and ZP2 and ZP3 glycoproteins in the mouse zona pellucida after fertilization

Oligosaccharide side chains of zona pellucida (ZP) glycoproteins play a key role in the sperm-egg interaction phenomena during fertilization. In the present study, modifications of the ZP glycoproteins during the fertilization process in the mouse were studied by the lectin-gold technique and immunocytochemistry in conjunction with quantitative analysis. Binding of PNA, RCA I, DSA, LFA, MAA, AAA, and anti-ZP2 and anti-ZP3 antibodies was observed throughout the ZP of both unfertilized and fertilized eggs. However, HPA and BSAIB4 labeling was found only in the inner region of the ZP. After neuraminidase treatment (Neu), HPA showed an affinity for the entire ZP. Labeling by LFA, WGA, MAA, PNA, BSAIB4, and AAA decreased in the ZP of fertilized eggs; however, there was an increase in the binding of RCA I. HPA and Neu-HPA increased only in the inner region of the ZP. Immunoreactivity to antibodies against ZP2 and ZP3 also decreased after fertilization. The present results demonstrate that 1) terminal carbohydrate residues contained in the ZP glycoproteins are modified after fertilization and 2) inner and outer regions of the ZP contain different oligosaccharide side chains.