A mutation in aspergillus nidulans that blocks the transition from interphase to prophase

In order to develop a method for obtaining mitotic synchrony in aspergillus nidulans, we have characterized previously isolated heat-sensitive nim mutations that block the nuclear division cycle in interphase at restrictive temperature. After 3.5 h at restrictive temperature the mitotic index of a strain carrying one of these mutations, nimA5, was 0, but when this strain was subsequently shifted from restrictive to permissive temperature the mitotic index increased rapidly, reaching a maximum of 78 percent after 7.5 min. When this strain was examined electron-microscopically, mitotic spindles were absent at restrictive temperature. From these data we conclude that at restrictive temperature nimA5 blocks the nuclear division cycle at a point immediately preceding the initiation of chromosomal condensation and mitotic microtubule assembly, and upon shifting to permissive control over the initiation of microtubule assembly and chromosomal condensation in vivo through a simple temperature shift and, consequently, nimA5 should be a powerful tool for studying these processes. Electron-microscopic examination of spindles of material synchronized in this manner reveals that spindle formation, although very rapid, is gradual in the sense that spindle microtubule numbers increase as spindle formation proceeds.     

An outbreak of blastomycosis in Eastern Tennessee

Most cases of blastomycosis are sporadic and only nine outbreaks representing a total of 112 cases have previously been reported. Less than half of these have been culture proven cases. Outbreaks have previously occurred in North Carolina, Minnesota, Illinois, Wisconsin and Virginia. We report three culturally confirmed cases of blastomycosis from Elizabethton, Tennessee, who had onset of illness within a one-week span of time. The patients presented with fever, chest pain, weight loss, poor appetite and myalgia. Each initially had a dry cough which became productive of purulent sputum as the illness progressed. Mild hemoptysis occurred during each patient's course. Serologic testing by immunodiffusion and enzyme immunoassay were positive and testing by complement fixation was negative in each case. The diagnosis was made by histopathology on transbronchial biopsy or transthoracic needle aspiration material. Each patient improved on ketoconazole therapy.     

Bombesin increases dopamine function in rat brain areas

Bombesin is a tetradecapeptide heterogenously distributed in the mammalian brain. Bombesin (45 micrograms) given intracisternally (IC) to unanesthetized rats increased the accumulation of dihydroxyphenylalanine (DOPA) in striatum, olfactory tubercles and hypothalamus after DOPA-decarboxylase inhibition, thus indicating an increased dopamine synthesis. A dose-dependent increase in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the principal dopamine metabolites, was seen in several brain areas 1 hr after IC injection of bombesin (0-60 micrograms). In striatum and olfactory tubercles HVA increased more than DOPAC with a maximal increase after 30-45 micrograms. In a time-course experiment a biphasic change of dopamine metabolites was observed in the olfactory tubercles with an actual decrease in metabolite levels 4 hr after 60 micrograms IC bombesin injection. Co-administration of bombesin and naloxone (8 mg/kg IP) or ethanol (2.25 g/kg IP) did not affect the increase in dopamine metabolites seen after bombesin alone. The action of IC administered bombesin on dopamine function was most pronounced in hypothalamus indicating a neuroendocrine regulatory of the peptide.     

Visual edge orientation shapes free-flight behavior in Drosophila

Insects rely on visual cues to estimate and control their distance to approaching objects and their flight speed. Here we show that in free-flight, the motion cues generated by high-contrast vertical edges are crucial for these estimates. Within a visual environment dominated by high-contrast horizontal edges, flies fly unusually fast and barely avoid colliding with the walls of the enclosure. The disruption of flight behavior by horizontal edges provides insight into the structure of visually-mediated control algorithms.     

Twenty-four-hour ghrelin is elevated after calorie restriction and exercise training in non-obese women

Objective: The purpose of this study was to determine whether chronic energy deficiency achieved with caloric restriction combined with exercise is associated with changes in the 24‐hour profile of ghrelin in non‐obese, pre‐menopausal women. Research Methods and Procedures: Twelve non‐obese (BMI = 18 to 25 kg/m²), non‐exercising women (age, 18 to 24 years) were randomly assigned to a non‐exercising control group or a diet and exercise group. The 3‐month diet and exercise intervention yielded a daily energy deficit of ?45.7 ± 12.4%. Serial measurements were made of body composition, energy balance, and feelings of fullness. Repeated blood sampling over 24 hours to measure ghrelin occurred before and after the study. Results: Significant decreases in body weight, body fat, and feelings of fullness were observed in only the energy‐deficit group (p < 0.05); significant changes in the following ghrelin features were found in only the deficit group (p < 0.05): elevations in baseline (+353 ± 118 pg/mL), lunch peak (+370 ± 102 pg/mL), dinner peak (+438 ± 149 pg/mL), nocturnal rise (+269 ± 77 pg/mL), and nocturnal peak (+510 ± 143 pg/mL). In addition, we found a larger dinner decline (?197 ± 52 pg/mL) and negative correlations between changes in the ghrelin dinner profile and changes in body weight (R = 0.784), 24‐hour intake (R = 0.67), energy deficiency (R = 0.762), and feelings of fullness (R = 0.648; p < 0.05). Discussion: Changes in ghrelin concentrations across the day after weight loss are closely associated with other physiological adaptations to energy deficiency, further supporting the role of ghrelin as a countermeasure to restore energy balance.     

Myc regulates keratinocyte adhesion and differentiation via complex formation with Miz1

Myc plays a key role in homeostasis of the skin. We show that Miz1, which mediates Myc repression of gene expression, is expressed in the epidermal basal layer. A large percentage of genes regulated by the Myc-Miz1 complex in keratinocytes encode proteins involved in cell adhesion, and some, including the alpha6 and beta1 integrins, are directly bound by Myc and Miz1 in vivo. Using a Myc mutant deficient in Miz1 binding (MycV394D), we show that Miz1 is required for the effects of Myc on keratinocyte responsiveness to TGF-beta. Myc, but not MycV394D, decreases keratinocyte adhesion and spreading. In reconstituted epidermis, Myc induces differentiation and loss of cell polarization in a Miz1-dependent manner. In vivo, overexpression of beta1 integrins restores basal layer polarity and prevents Myc-induced premature differentiation. Our data show that regulation of cell adhesion is a major function of the Myc-Miz1 complex and suggest that it may contribute to Myc-induced exit from the epidermal stem cell compartment.     

Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats

Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts that were empty or contained flutamide were applied directly to the dorsal hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in the open field, elevated plus maze, or defensive freezing tasks. GDX rats exhibited significantly more anxiety-like behaviors than intact or DHT-replaced rats. Intact and DHT-replaced rats administered flutamide to the hippocampus showed significantly more anxiety-like behavior than did intact and DHT-replaced controls. However, flutamide alone did not increase anxiety-like behavior of GDX rats. Together, these findings suggest that androgens can decrease anxiety-like behavior of male rats in part through DHT's actions at androgen receptors in the hippocampus.