Digest: Female-limited X chromosome evolution in Drosophila melanogaster.

Sexual dimorphism can cause sexual antagonism of phenotypic traits. Lund-Hansen and colleagues (2020) investigated female-limited X chromosome evolution in Drosophila melanogaster using forced matrilineal inheritance. Body size and developmental time evolved toward their female optima, but reproductive fitness and locomotion remained unchanged. These findings imply that some sexually antagonized loci may be distributed across the genome and that some phenotypes may have already reached their female optima in nature.

Lrrk2 alleles modulate inflammation during microbial infection of mice in a sex-dependent manner.

Variants in the leucine-rich repeat kinase-2 (LRRK2) gene are associated with Parkinson's disease, leprosy, and Crohn's disease, three disorders with inflammation as an important component. Because of its high expression in granulocytes and CD68-positive cells, LRRK2 may have a function in innate immunity. We tested this hypothesis in two ways. First, adult mice were intravenously inoculated with Salmonella typhimurium, resulting in sepsis. Second, newborn mouse pups were intranasally infected with reovirus (serotype 3 Dearing), which induced encephalitis. In both mouse models, wild-type Lrrk2 expression was protective and showed a sex effect, with female Lrrk2-deficient animals not controlling infection as well as males. Mice expressing Lrrk2 carrying the Parkinson's disease-linked p.G2019S mutation controlled infection better, with reduced bacterial growth and longer animal survival during sepsis. This gain-of-function effect conferred by the p.G2019S mutation was mediated by myeloid cells and was abolished in animals expressing a kinase-dead Lrrk2 variant, p.D1994S. Mouse pups with reovirus-induced encephalitis that expressed the p.G2019S Lrrk2 mutation showed increased mortality despite lower viral titers. The p.G2019S mutant Lrrk2 augmented immune cell chemotaxis and generated more reactive oxygen species during virulent infection. Reovirus-infected brains from mice expressing the p.G2019S mutant Lrrk2 contained higher concentrations of α-synuclein. Animals expressing one or two p.D1994S Lrrk2 alleles showed lower mortality from reovirus-induced encephalitis. Thus, Lrrk2 alleles may alter the course of microbial infections by modulating inflammation, and this may be dependent on the sex and genotype of the host as well as the type of pathogen.

Comparison of acquired bilateral nevus of Ota-like macules in men and women.

BACKGROUND: The clinical and histopathological characteristics of acquired bilateral nevus of Ota-like macules in men are poorly documented due to its rarity. AIMS: To compare the clinical and histopathological characteristics of acquired bilateral nevus of Ota-like macules in men with the condition in women. METHODS: We studied 11 men and 62 women, all with a clinical diagnosis of acquired bilateral nevus of Ota-like macules. Biopsies were taken from 5 men and 10 women and their clinical and histopathological features were compared. RESULTS: The most frequently affected site in men was the forehead [8 (73%) out of 11 patients]. Lesions on the forehead were more common in men than women (P = 0.001). In contrast to women, there was no apparent tendency of the lesions to become more blue with age in men. Concurrent melasma was observed in 14 (23%) out of 62 women, but not in men. Extra-facial acquired dermal melanocytosis was noted in 2 (18%) out of 11 men and in none of the 62 women. CONCLUSION: Significant differences were noted between men and women in the appearance of concurrent pigmentary lesions and the distribution of lesions. Extra-facial acquired dermal melanocytosis was noted in men.

Sexually dichromatic coloration reflects size and immunocompetence in female Spanish terrapins, Mauremys leprosa.

Many studies have shown the importance of colorful ornamentation in mate choosiness or intrasexual conflict. However, research on color ornaments has focused mainly on birds, lizards or fish, but remains practically unknown in other animal groups such as turtles. In addition, female ornaments and their relation with sexual selection also remain almost unknown. Here, we measured the coloration of the shell and the limb stripes of male and female Spanish terrapins Mauremys leprosa and explored the existence of sexual dichromatism and the relation of color characteristics with body size and health state estimated from the immune response to the injection of an antigen (phytohaemagglutinin test). Our results showed that shell coloration, which could be constrained by natural selection to be cryptic, changed with body size, but did not differ between sexes. In contrast, females had brighter and less ultraviolet-saturated and more orange-saturated limb stripes than males. In females, interindividual variation in limb stripe coloration was related with body size and immune response suggesting that this coloration may inform honestly about multiple traits that could be important in sexual selection. In contrast, coloration of limb stripes of males was duller than in females, and was not related with any trait suggesting that coloration is not important in sexual selection for males.

Clinical evidence of pharmacokinetic changes in thalidomide therapy.

The teratogenic effects of thalidomide have been studied for more than 50 years. However, there have been few studies of the pharmacokinetic changes occurring during thalidomide therapy. Thalidomide was originally developed as a sedative. However, thalidomide induces multiple birth defects when used in pregnant women. Thalidomide is now used in the treatment of multiple myeloma (MM) and erythema nodosum leprosum (ENL) in Japan. Rational use of thalidomide is problematic due to a lack of basic research regarding its mechanism of action and serum concentration/effect relationships. There are a number of hypotheses for pharmacokinetic changes in thalidomide therapy. Genetic factors including single nucleotide polymorphisms (SNPs) that change cytochrome P450 (CYP) activity and epigenetic regulation that modifies CYP expression levels may contribute to the changes in pharmacokinetics and adverse drug reactions (ADRs) of thalidomide. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver and kidney diseases do not play important roles in pharmacokinetic changes or ADRs in thalidomide therapy. To date, most research has focused on teratogenic activity, while the impact of polymorphisms in genes encoding drug metabolic enzymes and drug-drug interactions could mediate ADRs. Here, we discuss clinical evidence of pharmacokinetic changes in thalidomide therapy.

Is sexual body shape dimorphism consistent in aquatic and terrestrial chelonians?

Comparisons between aquatic and terrestrial species provide an opportunity to examine how sex-specific adaptations interact with the environment to influence body shape. In terrestrial female tortoises, selection for fecundity favors the development of a large internal abdominal cavity to accommodate the clutch; in conspecific males, sexual selection favors mobility with large openings in the shell. To examine to what extent such trends apply in aquatic chelonians we compared the body shape of males and females of two aquatic turtles (Chelodina colliei and Mauremys leprosa). In both species, females were larger than males. When controlled for body size, females exhibited a greater relative internal volume and a higher body condition index than males; both traits potentially correlate positively with fecundity. Males were more streamlined (hydrodynamic), and exhibited larger openings in the shell providing more space to move their longer limbs; such traits probably improve mobility and copulation ability (the males chase and grab the female for copulation). Overall, although the specific constraints imposed by terrestrial and aquatic locomotion shape the morphology of chelonians differently (aquatic turtles were flatter, hence more hydrodynamic than terrestrial tortoises), the direction for sexual shape dimorphism remained unaffected. Our main conclusion is that the direction of sexual shape dimorphism is probably more consistent than sexual size dimorphism in the animal kingdom.

Molecular exploration of the first-century Tomb of the Shroud in Akeldama, Jerusalem.

The Tomb of the Shroud is a first-century C.E. tomb discovered in Akeldama, Jerusalem, Israel that had been illegally entered and looted. The investigation of this tomb by an interdisciplinary team of researchers began in 2000. More than twenty stone ossuaries for collecting human bones were found, along with textiles from a burial shroud, hair and skeletal remains. The research presented here focuses on genetic analysis of the bioarchaeological remains from the tomb using mitochondrial DNA to examine familial relationships of the individuals within the tomb and molecular screening for the presence of disease. There are three mitochondrial haplotypes shared between a number of the remains analyzed suggesting a possible family tomb. There were two pathogens genetically detected within the collection of osteological samples, these were Mycobacterium tuberculosis and Mycobacterium leprae. The Tomb of the Shroud is one of very few examples of a preserved shrouded human burial and the only example of a plaster sealed loculus with remains genetically confirmed to have belonged to a shrouded male individual that suffered from tuberculosis and leprosy dating to the first-century C.E. This is the earliest case of leprosy with a confirmed date in which M. leprae DNA was detected.

Hematologic and biochemical reference intervals of free-living Mediterranean pond turtles (Mauremys leprosa).

Reference intervals of hematologic and biochemical blood profiles were obtained from 56 male and 58 female Mediterranean pond turtles (Mauremys leprosa) captured from the wild in different periods of their annual cycle. Mean (or median in nonnormal distributions) values of leukocyte differential were 53.8% and 58.5% heterophils, 35.3% and 32.6% eosinophils, 6.3% and 5.8% lymphocytes, 4.3% and 2% monocytes, and 0% and 0% basophils in males and females, respectively. Biochemical values did not differ from other chelonians, but values were generally higher in females than in males.

Pupil cycle time in leprosy patients without clinically apparent ocular pathology.

The pupil cycle time (PCT) was estimated in 384 leprosy patients whose eyes looked normal on clinical examination and in an equal number of healthy controls. A statistically significant increase in PCT (p < 0.05) was noticed in leprosy patients, and corroborates the view that the ocular autonomic system may be affected without any visible clinical pathology in the eye. The clinical value and application of this finding is uncertain since the difference is only a few milliseconds. Young females with leprosy showed a conspicuous lengthening of PCT for which no plausible explanation is offered. There was a general trend for the PCT to increase as the spectrum of disease moved toward the lepromatous pole and a significantly higher PCT (p < 0.01) was found among multibacillary patients compared to paucibacillary patients. Patients who had had erythema nodosum leprosum (ENL) reactions showed a higher PCT than did those who had not had ENL. Patients who had had reversal reactions showed a decrease in PCT, which may be a statistical oddity in this hospital-based study. Patients whose duration of the disease was over 10 years showed a higher PCT, while smear positivity of a patient did not alter the PCT significantly.

Epidemiologic characteristics of leprosy reactions.

An 8-year prospective study of a cohort of 176 newly diagnosed leprosy patients was conducted to examine the possible influence of age, sex, multidrug therapy (MDT), and duration of illness on the risk of either type 1 or type 2 reactions. Patients were enrolled over a 5-year period (1984-1989) and followed for a minimum of 3 years. All reactions studied were severe enough to warrant hospital admission. Overall, 45% of this cohort developed a reaction; 32% of patients considered at risk developed type 1 reactions, and 37% of patients considered at risk developed type 2 reactions. Despite the predominance of men among the leprosy patients, type 1 reactions occurred with significantly greater frequency in women, and did not appear to be influenced by age of onset of leprosy. Individuals experiencing one type 1 reaction were not likely to experience a recurrence, suggesting that the immunologic mechanisms of this reaction may be limited or regulated by genetic or immunologic factors. Type 2 reactions, on the other hand, occurred with equal frequency in both males and females, but were highly associated with onset of leprosy in the second decade of life. Individuals who experienced type 2 reactions often had one or more recurrence of the reaction. No increased risk was seen for either reaction with longer duration of leprosy or longer duration of treatment. The mechanisms by which these differences relate to the pathogenesis of leprosy reactions remains unclear, but future studies of clinical and immunological parameters of leprosy reactions may benefit from stratification of data by gender and age of onset of leprosy in addition to the routine grouping of results by leprosy classification.

Ritanserin and voluntary alcohol intake in rats.

In a previous study (Rammsayer & Vogel, 1991), rats selectively bred for high and low catecholamine responses to stress showed a selective response to the 5-HT2 receptor blocker ritanserin. However, it remained unclear whether selective breeding resulted in a decrease in 5-HT responsivity, as suggested by the lack of an effect in high stress responding rats, or in an increase in 5-HT responsivity, as suggested by ritanserin-induced reduction in alcohol intake in low-responding rats. To answer this question, nonselectively bred rats were forced to drink a 5% alcohol solution for 10 days. For the subsequent six days, animals were injected subcutaneously with 2.5 mg/kg/2 ml ritanserin or vehicle only, and both a 5% solution of alcohol and water were presented to the animals. Ritanserin neither affected alcohol nor total fluid intake suggesting that in the general population of N/NIH (Hansen) rats as well as in rats of the same strain selectively bred for high catecholamine responses, mesolimbic dopaminergic activity is not effectively modulated by specific blockade of 5-HT2 receptors. However, a very pronounced ritanserin induced difference in daily water intake between nonbred male and female rats became evident.