Cryptococcus neoformans STE12alpha regulates virulence but is not essential for mating.

The Cryptococcus neoformans STE12alpha gene, a homologue of Saccharomyces cerevisiae STE12, exists only in mating type (MAT)alpha cells. In S. cerevisiae, STE12 was required for mating and filament formation. In C. neoformans, haploid fruiting on filament agar required STE12alpha. The ability to form hyphae, however, was not affected by deletion of STE12alpha when convergently growing MATa strains were present. Furthermore, ste12alpha disruptants were fertile when mated with MATa strains, albeit with reduced mating frequency. Most importantly, the virulence of a ste12alpha disruptant of serotype D strain was significantly reduced in a mouse model. When the ste12alpha locus was reconstituted with the wild-type allele by cotransformation, virulence was restored. Histopathological analysis demonstrated a reduction in capsular size of yeast cells, less severe cystic lesions, and stronger immune responses in meninges of mice infected with ste12alpha cells than those of mice infected with STE12alpha cells. Using reporter gene constructs, we found that STE12alpha controls the expression of several phenotypes known to be involved in virulence, such as capsule and melanin production. These results demonstrate a clear molecular link between mating type and virulence in C. neoformans.

The relationship between European genetic admixture and body composition among Hispanics and Native Americans.

Previous studies have shown a relationship between health-related phenotypes and the degree of African, European, or Native American genetic admixture, indicating that there may be a genetic component to these phenotypes. However, these relationships may be driven to a large extent by the environmental differences that co-vary with admixture differences between and within groups. In this study, we examine the relationship between genetic admixture and two phenotypic measurements that are potentially related to health: body mass index (BMI) and percent body fat (PBF). In addition to admixture proportions, we attempt to assess the influence of some environmental covariates by examining how the phenotypes vary with self-reported household income, education of parents, and physical activity level. Genetic, anthropometric, and environmental data were collected from 170 self-reported Hispanic and Native American university students in Albuquerque, NM. We examine the relationships between genetic admixture, phenotype, and environment in both the full sample, as well as in Hispanics and Native Americans separately. Among Hispanics, we find no significant relationship between genetic admixture and body composition. Among Native Americans, despite a small sample size, we find a statistically significant, negative relationship between European genetic admixture and PBF and BMI, after adjusting for other predictor variables. We compare our findings to previous research, and discuss their implications for understanding health disparities within and between ethnic groups.

Virulence of catalase-deficient aspergillus nidulans in p47(phox)-/- mice. Implications for fungal pathogenicity and host defense in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare genetic disorder in which phagocytes fail to produce superoxide because of defects in one of several components of the NADPH oxidase complex. As a result, patients develop recurrent life-threatening bacterial and fungal infections. The organisms to which CGD patients are most susceptible produce catalase, regarded as an important factor for microbial pathogenicity in CGD. To test the role of pathogen-derived catalase in CGD directly, we have generated isogenic strains of Aspergillus nidulans in which one or both of the catalase genes (catA and catB), have been deleted. We hypothesized that catalase negative mutants would be less virulent than the wild-type strain in experimental animal models. CGD mice were produced by disruption of the p47(phox) gene which encodes the 47-kD subunit of the NADPH oxidase. Wild-type A. nidulans inoculated intranasally caused fatal infection in CGD mice, but did not cause disease in wild-type littermates. Surprisingly, wild-type A. nidulans and the catA, catB, and catA/catB mutants were equally virulent in CGD mice. Histopathological studies of fatally infected CGD mice showed widely distributed lesions in the lungs regardless of the presence or absence of the catA and catB genes. Similar to the CGD model, catalase-deficient A. nidulans was highly virulent in cortisone-treated BALB/c mice. Taken together, these results indicate that catalases do not play a significant role in pathogenicity of A. nidulans in p47(phox)-/- mice, and therefore raise doubt about the central role of catalases as a fungal virulence factor in CGD.

Mate choice turns cognitive.

Evolutionary psychology has revolutionized research on human mate choice and sexual attraction in recent years, combining a rigorous Darwinian framework based on sexual selection theory with a loosely cognitivist orientation to task analysis and mechanism modelling. This hard Darwinian, soft computational approach has been most successful at revealing the adaptive logic behind physical beauty, demonstrating that many sexual cues computed from face and body shape are not arbitrary, but function as reliable indicators of phenotypic and genetic quality. The same approach could be extended from physical to psychological cues if evolutionary psychology built stronger ties with personality psychology, psychometrics and behavioral genetics. A major challenge for mate choice research is to develop more explicit computational models at three levels, specifying: (1) the perceptual adaptations that register sexual cues given sensory input, (2) the judgment adaptations that integrate multiple cues into assessments of overall attractiveness, and (3) the search strategies that people follow in trying to form mutually attracted pairs. We describe both recent efforts and possible extensions in these directions. The resulting confluence between evolutionary principles, cognitive models and game-theoretic insights can put mate choice research at the vanguard of an emerging `evolutionary cognitive science' more concerned with domain-specific mental adaptations than with domain-general intelligence.

IFN-gamma is effective in reducing infections in the mouse model of chronic granulomatous disease (CGD).

Chronic granulomatous disease (CGD) is a genetic disorder characterized by recurrent bacterial and fungal infections and tissue granuloma formation. CGD phagocytes are unable to generate superoxide because of mutations in any of four proteins of the phagocyte NADPH oxidase. Prophylactic recombinant human interferon-gamma (IFN-gamma) has been shown to reduce the frequency and severity of infections in CGD patients, but its mechanism(s) remains undefined, and its benefit has been questioned. We investigated the prophylactic effect of IFN-gamma in the mouse model of the major autosomal recessive (p47(phox)) form of CGD. In a prospective, randomized, placebo-controlled study, we compared IFN-gamma, 20,000 U administered subcutaneously (s.c.) three times weekly, to placebo in 118 p47(phox-/-) mice. By 6 weeks of study, there were 3 infections in the IFN-gamma group compared with 13 infections in the placebo group (77% reduction in infections, p<0.01). By 18 months of study, there were 7 infections in the IFN-gamma group compared with 18 infections in the placebo group (39% reduction in infections, p<0.01). Two animals receiving IFN-gamma had seizures after 7 months in the study. No other toxicities were observed. Peripheral blood phagocytes from IFN-gamma treated p47(phox-/-) mice produced no superoxide, excluding restoration of the oxidative burst as a mechanism for the IFN-gamma effect. There were no differences in either peritoneal macrophage nitrate production or thioglycollate-induced peritoneal exudate between treatment groups. This animal model demonstrates a prophylactic benefit of IFN-gamma similar to that seen in humans and provides an opportunity to investigate the mechanism(s) of action for IFN-gamma in CGD.

Fatigue rates of vastus medialis oblique and vastus lateralis during static and dynamic knee extension.

Fatigue rates of the vastus medialis oblique and vastus lateralis muscles were compared from static and dynamic exercise. Based upon clinical observations, it was expected that the vastus medialis oblique would demonstrate greater fatigability than the vastus lateralis. However, based upon physiological and morphological considerations, it was expected that the vastus lateralis would exhibit greater fatigability than the vastus medialis oblique. In the static exercise condition, nine subjects--having no history of knee problems--maintained an isometric knee extension torque at 30 and 60% of their maximum value until exhaustion, during which time electromyography (EMG) data were collected every 10 s. The knee angle was 20 degrees flexion. In the dynamic exercise condition, a different group of seven subjects performed exercise sets consisting of eight cycles of concentric-eccentric knee extension, with a resistance equal to 40% of the maximum isometric value. The range of motion was restricted to the terminal 30 degrees of knee extension. Each set of eight repetitions was followed by a 1 s 50% maximum isometric knee extension, during which time EMG data were collected. The raw EMG data were numerically processed to extract the median frequency of the power density spectrum, which has been shown to reflect the metabolic processes associated with fatigue. Linear regression generated a slope coefficient representing the rate of change of the median frequency, with respect to contraction duration for each subject, muscle, and condition. Analyses of variance, with repeated measures from both exercise conditions suggest that "short-arc" quadriceps exercise did not selectively fatigue either the vastus medialis oblique or vastus lateralis, thereby supporting neither clinical nor physiological expected outcomes. Therefore, the clinical contention that short-arc quadriceps exercises selectively strengthen the vastus medialis oblique is questioned.

An objective criterion for apparent motion based on phase discrimination.

Studies of visual apparent motion have relied on observers' subjective self-reports of experienced motion, for which there is no objective criterion of right or wrong. A new method of phase discrimination is reported that may offer an objective indicator of apparent motion. Ss discriminated the direction of an objective 75-ms phase shift, away from strict temporal alternation of 2 stimulus dots. Accuracy increased from 50% to 100% correct as rate of alternation and distance between the dots was decreased, in conformity with Korte's third law of apparent motion. This and additional evidence suggests that phase discrimination may be mediated by asymmetries between the experienced strengths of leftward and rightward motion. Phase discrimination may also be adaptable to the study of apparent motion and related phenomena in other sensory modalities and other animal species.

Shoulder impingement in front-crawl swimming: I. A method to identify impingement.

PURPOSE: The impingement of subacromial structures has been proposed as a major cause of the shoulder problems experienced by athletes who use repetitive overhead actions. The purpose of this study was to develop a noninvasive method to identify instances at which the shoulder was experiencing impingement during front-crawl swimming. METHODS: Shoulder impingement has been reported to occur when an arm is: (a) elevated above shoulder height while being rotated internally; and (b) forcibly elevated at, or beyond, the maximum active elevation angle. In this study shoulder configurations that satisfied the above two conditions were sought throughout the functional range of each shoulder; and a boundary that distinguished configurations that would cause shoulder impingement was defined. The shoulder movements exhibited during performance of the front-crawl stroke were measured using three-dimensional videography and compared with the boundary defined for each shoulder. The shoulder was considered to experience impingement if the shoulder configuration observed exceeded the boundary defined for that shoulder. RESULTS: For a male collegiate swimmer, impingement occurred for 12% of the stroke time for each shoulder. CONCLUSIONS: The analysis permitted the identification of the instances at which the shoulders were experiencing impingement during the front-crawl swimming. In this study, the measurement of the boundary was based entirely upon the mechanism of impingement described in the literature. Further studies are needed to confirm the occurrence of impingement by means of advanced visualization techniques, such as magnetic resonance imaging (MRI) and ultrasonogram.

Further evidence against a direct automatic neuromotor link between the ACL and hamstrings.

The purpose of this experiment was to determine whether reflexive, or more broadly, automatic hamstrings excitation could be elicited during isometric, maximum effort, step increases in knee extension torque. Eight healthy subjects without lower extremity dysfunction or injury performed maximum effort isometric knee extension at 15 and 85 degrees of knee flexion in minimum elapsed time. Surface electromyography was used to record medial (semimembranosis and semitendinosis) and lateral (biceps femoris--long head) hamstrings excitation that was subsequently normalized to the excitation during maximum isometric knee flexion. To assess whether automatic hamstrings excitation was elicited, the amplitude of the EMG signals was analyzed and compared for 50 ms prior to peak knee extension torque, and three consecutive 50 ms windows following peak knee extension torque. The amplitude of the EMG subsequent to the peak knee extension torque failed to support the contention of an automatic hamstrings excitation mediated by neural circuitry from the ACL. The present results, in conjunction with previous work, suggest that a protective automatic hamstrings contraction is not normally elicited in response to conditions subjecting the anterior cruciate ligament to strain.

Coordination of index finger movements.

The purpose of this investigation was to describe the patterns of coordination among the joint motions of the index finger, and among the EMGs of index finger muscles. Index finger movements involving all three joints were varied in speed and direction. Joint motions were recorded along with fine-wire EMG from all the muscles that insert into the index finger. We observed nearly linear relationships for angular position between the two interphalangeal (IP) joints, and between the metacarpophalangeal (MP) and proximal IP (PIP) joints regardless of movement, speed and direction. The activities of the extrinsic flexors were of similar magnitude and were highly correlated when they acted as agonists but were poorly correlated when they acted as antagonists to the movement. Extrinsic extensor muscles behaved in this way also. The activation patterns of the intrinsic musculature correlated weakly except for extension movements voluntarily limited to the IP joints. We conclude that the highly coordinated action of the extrinsic flexors during flexion contribute importantly to the linked motions of the IP joints in part because these muscles span two or all the three index finger joints. Hence, interjoint movement patterns appear not to arise solely from restraints imposed by passive tissues, especially for fast flexion movements. The weakly correlated intrinsic muscle activity does not uncouple the flexion motions at the PIP and DIP joints because these muscles exert extensor torques at both IP joints. However, the actions of the intrinsic muscles are necessary for stabilizing the MP joint in flexion postures during IP motion and in producing motions voluntarily limited to the MP joint.

Addition of penicillamine, hypotaurine and epinephrine (PHE) or bovine oviductal epithelial cells (BOEC) alone or in combination to bovine in vitro fertilization medium increases the subsequent embryo cleavage rate.

The cleavage rate of in vitro-matured bovine oocytes was compared after fertilization in 1) TALP medium alone (control); 2) in TALP+BOEC; 3) in TALP+PHE; or 4) in TALP+BOEC and PHE. The overall cleavage rate at 45 h post insemination was greater for embryos in Treatments 2 (52%), 3 (55%) and 4 (66%) than for Treatment 1 (32%). The oocyte cleavage rates for Treatments 2 and 3 were similar, but were lower than that of Treatment 4. Addition of PHE or BOEC, alone or in combination, to the fertilization medium resulted in more embryos at the 3- or 4-cell stage than the 2-cell stage by 45 h post insemination. After 5 d of co-culture with BOEC in M-199 medium, 21, 28, 25 and 35% of the cleaved embryos in Treatments 1, 2, 3 and 4, respectively, developed to the morula or blastocyst stage. The rate of development to morulae and blastocysts was similar among Treatments 1, 2 and 3, and between Treatments 2 and 4. Across treatments, a correlation of 0.98 was noted between the portion of embryos that had reached the 3- or 4-cell stage by 45 h post insemination and the percentage of embryos in each treatment that continued to develop to the morula or blastocyst stage in vitro.

Effects of protein source and co-culture on bovine embryo development in synthetic oviductal fluid medium.

Experiment 1 compared the development of 2- to 4-cell bovine embryos cultured in synthetic oviductal fluid with 20% fetal calf serum or 3.2% BSA and in the presence of oviductal cells, cumulus cells, or medium alone. More embryos developed in medium with serum, regardless of culture method (P=0.063). Oviductal cell co-culture resulted in more embryos developing to at least the morula stage (Por=0.400). Addition of serum to oviductal cell co-culture medium increased the number of excellent or good quality embryos (P=0.019). Experiment 2 further compared the development of 2-cell or 3- to 4-cell embryos co-cultured with oviductal cell suspensions in serum-supplemented synthetic oviductal fluid or M-199 medium. More 3- to 4-cell than 2-cell embryos developed to at least the morula stage (P<0.001). More embryos developed to at least the morula stage in synthetic oviductal fluid (P=0.083). Neither initial embryo cell stage nor medium type influenced the percentage of developing embryos that achieved the blastocyst stage or final morphological quality of embryos (P>or=0.535).

In vitro development of bovine embryos as affected by different lots of bovine serum albumin and citrate.

The effect of bovine serum albumin (BSA) lots on the development of in vitro-derived bovine embryos in synthetic oviductal fluid was investigated. Citrate concentration was determined for each lot of BSA, and then correlated with differences noted in the ability of BSA lots to support embryo development. Development of bovine embryos to the blastocyst stage was also compared after culture in chemically-defined medium with varying levels of citrate. There were distinct differences in the ability of the different BSA lots to support embryo development to the blastocyst stage (P

Colitis in a female tamarin (Saguinus mystax).

An adult wild-caught female tamarin (Saguinus mystax) housed in a biomedical research facility was found moribund and extremely dehydrated, with severe diarrhea. She initially responded to supportive therapy but died 3 days later. Necropsy findings included hyperemia of the colonic mucosa, mesenteric lymphadenopathy, acanthocephalid parasites (Prosthenorchis elegans) embedded in the mucosa of the terminal ileum and cecum, and free filarid nematodes (Dipetalonema sp.) in the abdominal cavity. Campylobacter sp. was recovered from the colon. With the exception of changes associated with the parasites, significant histologic changes were limited to the colon. Changes consistent with acute enteric viral infection were found against a background of chronic inflammation. Enterocytes were variably hypertrophied, degenerate, and attenuated. Numerous epithelial syncytial cells were present, and some affected cells (uni- as well as multinucleated) contained intranuclear inclusions. Lymphoid follicles were mildly depleted and contained rare syncytia. Measles (Morbillivirus) infection was confirmed by using immunohistochemistry, reverse transcriptase polymerase chain reaction, and Southern blot analysis. In contrast to the cutaneous rash, respiratory involvement, and low mortality characteristic of Old World monkeys with measles, severe diarrhea with high mortality occurs in New World monkeys with this disease. In addition, our case differs from previous reports of measles in New World monkeys in that syncytial cell formation apparently was limited to the colon of our animal.

Mate choice: from sexual cues to cognitive adaptations.

Evolutionary psychologists have successfully combined sexual selection theory and empirical research to compile lists of sexual attractiveness cues used in human mate choice. But a list of inputs is not the same as a normative or descriptive model of a psychological adaptation. We need to shift from cataloguing sexual cues to modelling cognitive adaptations for mate choice. This theoretical chapter addresses how to make this transition in three parts. The introduction discusses four general problems with cue cataloguing as an evolutionary psychology research strategy: animals' promiscuous flexibility of cue use; cue use being marginal to cognition; cue use being marginal to the hard game-theoretical aspects of mate choice; and cue use being uninformative about the exact adaptive functions of mate choice. The middle section develops six critiques of current mate choice research: the obsession with sex difference; the over-emphasis on physical rather than behavioural cues; the assumption of weighted linear models of cue integration; the avoidance of game-theoretical problems of mutual choice and assortative mating; the neglect of co-evolution between mate choice heuristics and the cues that they select; and the failure to understand that mate choice is only worth doing if potential mates show significant genetic variance. The conclusion outlines a new normative and descriptive framework for mate choice, centred on the use of brutally efficient search heuristics that exploit the informational structure of human genotypes, phenotypes and populations to make good mate choices.