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Biomedical subjects

K D Rose

Publications and source records attributed to K D Rose.

At least 19 recordsLinked to original sources

Mutagenesis by human immunodeficiency virus reverse transcriptase: incorporation of O6-methyldeoxyguanosine triphosphate.

The high frequency of incorporation of non-complementary nucleotides by HIV-1 reverse transcriptase is likely to be a major factor in the exceptionally rapid accumulation of viral mutations during the course of AIDS infections. To investigate whether this high level of infidelity is also associated with the incorporation of nucleotide analogs, we analyzed O6-methyldeoxyguanosine triphosphate and compared the incorporation of this analog by HIV-1 reverse transcriptase to that catalyzed by other DNA synthesizing enzymes. Our results indicate that O6-methyldeoxyguanosine triphosphate serves as a substrate for DNA synthesized in vitro by HIV-1 RT on both DNA and RNA templates. The product DNA contains the modified purine; it is sensitive to the repair enzyme, O6-methylguanine methyltransferase, which specifically reacts with DNA containing methylated guanines at the O6 position. Using a forward mutation assay we demonstrated that the nucleotide analog incorporated by HIV-1 RT is mutagenic. The mutations produced are single-base substitutions opposite template thymidines and result in A:T --> G:C transitions. The incorporation of a mutagenic nucleotide by HIV-1 RT highlights the possibility of increasing the rate of mutagenesis of HIV by the use of nucleotides that form non-complementary base pairs at high frequency.

Base Sequence

Mammal extinctions, body size, and paleotemperature.

There is a general inverse relationship between the natural logarithm of tooth area (a body size indicator) of some fossil mammals and paleotemperature during approximately 2.9 million years of the early Eocene in the Bighorn Basin of northwest Wyoming. When mean temperatures became warmer, tooth areas tended to become smaller. During colder times, larger species predominated; these generally became larger or remained the same size. Paleotemperature trends also markedly affected patterns of local (and, perhaps, regional) extinction and immigration. New species appeared as immigrants during or near the hottest (smaller forms) and coldest (larger forms) intervals. Paleotemperature trend reversals commonly resulted in the ultimate extinction of both small forms (during cooling intervals) and larger forms (during warming intervals). These immigrations and extinctions mark faunal turnovers that were also modulated by sharp increases in sediment accumulation rate.

Animals

The nicotine patch.

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Administration, Cutaneous

Climbing adaptations in the early eocene mammal Chriacus and the origin of artiodactyla.

A virtually complete articulated skeleton of the arctocyonid Chriacus, recently found in northern Wyoming, is one of the most intact early Eocene mammal skeletons ever found. It exhibits numerous adaptations characteristic of mammals that climb, including strong bony crests and processes (reflecting powerful musculature), ability for considerable forearm supination, a highly mobile ankle joint, plantigrade feet, curved and transversely compressed claws, and a long, possibly semiprehensile tail. These features contrast sharply with those of the oldest artiodactyls and indicate that Chriacus or a similar arctocyonid was not ancestral to the Artiodactyla, as has been proposed.

Adaptation, Physiological

The skeleton of early Eocene Cantius, oldest lemuriform primate.

A recently discovered partial skeleton of the adapid Cantius trigonodus from the early Eocene Willwood Formation of the Bighorn Basin, Wyoming, documents substantial new information about the anatomy of the oldest lemuriform primates. It is very similar in all features to its descendant, middle Eocene Notharctus, and both exhibit numerous resemblances to certain extant Malagasy lemurs, particularly Lepilemur, Propithecus, Lemur, and Hapalemur griseus. Like these forms, Cantius had relatively long hind limbs and short forelimbs. Forelimb traits (prominent brachialis flange of the humerus, well-developed olecranon process of the ulna, and strong shafts of the ulna and radius) suggest active use of the forelimbs in progression. Specializations in the hind limb (e.g., expanded articular surface of the femoral head, narrow and elevated patellar trochlea and prominent lateral trochlear ridge, posteriorly oriented femoral and tibial condyles, narrow and elongate talus, and hallucal metatarsal with prominent peroneal tubercle) indicate capabilities for leaping and for powerful grasping with an opposable hallux. Cantius was presumably primitive in having a relatively long ischium and much more distal inferior tibial tuberosity than most extant lemurs--traits suggesting that powerful extension of the thigh and flexion at the knee were important in its locomotion and posture. We interpret Cantius as an active arboreal quadruped with a propensity for leaping. The existence of this skeletal structure in one of the oldest primates of modern aspect suggests that it represents the primitive lemuriform morphology.

Animals

Transdermal administration of nicotine.

The physiological response to nicotine topically applied to the skin was measured in an adult male volunteer. Nicotine base (9 mg) was applied in a 30% aqueous solution to intact skin on the underside of the forearm. Salivary nicotine, heart rate and blood pressure were monitored for 12 h after application of the nicotine. Within 30 min a significant level of nicotine was detected in the saliva (50 ng/ml), pulse had risen by 15 beats/min and systolic blood pressure had risen 10 mmHg. Nicotine levels remained elevated for 2 h and were comparable to levels of nicotine produced by cigarette smoking. Because previous research has shown nicotine to suppress smoking behavior, it may be fruitful to examine transdermal administration of nicotine as a smoking reduction and cessation aid.

Administration, Topical

Function of the mandibular tooth comb in living and extinct mammals.

Among the most interesting mammalian dental specialization is the mandibular 'tooth comb' or 'tooth scraper' that evolved independently in certain primates and other mammals. Its occurrence is most widely known in lemurs and lorises, where it is comprised of the long, slender, procumbent incisors (one or two pairs) and incisiform canines (Fig. 1). In non-primates to canines are not incorporated into the comb. Some tree shrews (Tupaiidae) possess a tooth comb consisting of the four central incisors, and some early Tertiary arctocyonid condylarths had a similar structure composed of all six lower incisors. The extant flying lemurs (Dermoptera: Cynocephalus) also have a dental 'comb' but it is very different from the ones already mentioned, consisting of two pairs of pectinate incisors, each tooth modified into a comb with as many as 15 tines. This condition, although sometimes said to be similar to that in lemurs, is unique to Cynocephalus. One of the principal functions of the tooth comb in primates is to comb the fur, and we present here indirect evidence that condylarths used this structure in the same way, millions of years before tooth combs evolved in prosimians. We also show that the comb-like incisors of Cynocephalus, contrary to popular belief, probably do not function to comb the fur.

Animals

Differentiated perceptions of exertion: part I. mode of integration of regional signals.

The mode of sensory integration of differentiated perceptions of exertion from the legs and chest was determined during sub-maximal cycle ergometer exercise. 50 male subjects performed three separate cycle ergometer tests. Power output was held constant at 840 kpm/min., while pedalling rate was randomly set at 40, 60, or 80 rpm. The over-all rating of perceived exertion was significantly lower than the rating for the legs and higher than that for the chest at each pedalling rate. Local signals from the legs dominated the sensory process. Central signals were less pronounced. The mean of the ratings for the legs and chest was slightly but significantly higher than the over-all rating at each pedalling rate. Therefore, the integration process at the superordinate level of sensory processing appeared as a weighted average of the involved regional signals.

Adult

Differentiated perceptions of exertion: part II. relationship to local and central physiological responses.

Differentiated ratings of perceived exertion in the legs and chest were compared to local and central physiological adjustments during submaximal cycle ergometer exercise. 50 male subjects performed three separate cycle ergometer tests. Power output was held constant at 840 kpm/min., while pedalling rate was randomly set at 40, 60, or 80 rpm. Differentiated reports of exertion from the legs were considered to be local signals and reports from the chest to be central signals. Ratings of exertion for the legs, chest and over-all body were each significantly higher at 40 rpm than 60 or 80 rpm. Heart rate, oxygen uptake, ventilation and respiratory rate were also higher at 40 rpm. Lactic acid, pH, and pCO2 were similar between pedalling rates. Lactic acid did not operate differentially to influence local perceptual signals from the legs. Central measures of respiratory and aerobic metabolic adjustments were consistent with the more intense regional report of chest exertion at 40 rpm.

Adult

Perceived exertion and the field-independence--dependence dimension.

Perceived exertion responses were compared between field-independent and field-dependent perceivers at three cycle-ergometer pedalling rates. 50 male subjects were classified according to mode of field approach on the basis of their performance on an embedded-figures test. Power output was held constant at 840 kpm/min., while pedalling rate was randomly set at 40, 60, or 80 rpm. Significant differences between the field-independent and -dependent groups were not found at the three pedalling rates for any of the physiological variables or for over-all, legs and chest ratings of perceived exertion. The extent of differentiated psychological functioning did not account for individual differences in perceptual reactance during muscular exertion.

Adult

Perceived exertion and stimulus intensity modulation.

Perceptual augmentation and reduction were considered contrasting styles of Stimulus Intensity Modulation. Differences in perceived exertion between augmenters and reducers were determined for three cycle ergometer work loads. Subjects were 20 males having similar physiological characteristics. Stimulus Intensity Modulation was determined by kinesthetic figural aftereffect. Augmenters rated their perceptions of physical exertion to be more intense than reducers at 450, 750 and 1050 kpm/min. Differences in physiological responses between augmenters and reducers were not significant at the three work loads. Style of Stimulus Intensity Modulation appeared differentially to influence perceived exertion at the work levels studied.

Blood Chemical Analysis

New early tertiary primates and a reappraisal of some Plesiadapiformes.

A new study of specimens of paromomyid and microsyopid primates clarifies evolution in these primates and reuslts in new concepts of each family. The paromomyid Phenacolemur and its former synonym, Ignacius, are distinct genera, each with new Early Wasatchian species, Plesiolestes, Palaechthon, Torrejonia, Palenochtha, Navajovius, Micromomys, and Tinimomys are removed from the Paromomyidae and transferred to the Microsyopidae. The Plesiadapiformes are classified in three groups which may be differentiated on incisor and molor structure: Plesiadapoidea (Plesiadapidae, Carpolestidae, and Saxonellidae), Microsyopidae, and Paromomyidae. The Paromomyidae, Microsyopidae (and its two subfamilies), and several genera are rediagnosed in the light of new comparative evidence.

Animals