Megabase Length Hypermutation Accompanies Human Structural Variation at 17p11.2

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Evaluating seasonal patterns of female aggression: Case study in a cavity‐nesting bird with intense female–female competition

Seasonal plasticity in aggression is likely to be shaped by the contexts in which aggression is beneficial, as well as the constraints inherent in its underlying mechanisms. In males, seasonal plasticity in testosterone (T) secretion is thought to underlie seasonal plasticity in conspecific aggression, but it is less clear how and why female aggression may vary across different breeding stages. Here, we integrate functional and mechanistic perspectives to begin to explore seasonal patterns of conspecific aggression in female tree swallows (Tachycineta bicolor), a songbird with intense female–female competition and T‐mediated aggression. Female tree swallows elevate T levels during early breeding stages, coinciding with competition for nest boxes, after which time T levels are roughly halved. However, females need to defend ownership of their nesting territory throughout the breeding season, suggesting it may be adaptive to maintain aggressive capabilities, despite low T levels. We performed simulated territorial intrusions using 3D‐printed decoys of female tree swallows to determine how their aggressive response to a simulated intrusion changes across the breeding season. First, we found that 3D‐printed decoys produce data comparable to stage‐matched studies using live decoys, providing researchers with a new, more economical method of decoy construction. Further, female aggressiveness remained relatively high through incubation, a period of time when T levels are quite low, suggesting that other mechanisms may regulate conspecific female aggression during parental periods. By showing that seasonal patterns of female aggression do not mirror the established patterns of T levels in this highly competitive bird, our findings provide a unique glimpse into how behavioural mechanisms and functions may interact across breeding stages to regulate plasticity.     

A molecular marker confirms that the rate of adult maturation is largely independent of the rate of pre-adult development in Drosophila melanogaster

The separation of adult from pre-adult life seen with animals such as Drosophila melanogaster, which are holometabolous and undergo complete metamorphosis, provides the opportunity to examine the contribution of pre-adult rate of development on the rate of maturation and aging of the adult. Recent work has shown that when ambient temperature is used to alter the rate of development there is little effect on adult life span. From this work it has been concluded that the rate of aging is largely independent of the rate of pre-adult development. However, the techniques used to examine life span did not allow for the examination of the earliest events of adult life. Our experimental design used a molecular marker linked to life span as a sensitive measure of determining physiological age. In this way, we were able to evaluate the effect of pre-adult rate of development on the earliest events of adult life. Using ambient temperature to alter both the rate of development in the pre-adult and the rate of aging in the adult independently, we were able to show that it is the ambient temperature at which the adults are living that is the principle determinant of the rate of maturation and aging of the adult. Little effect was seen on the rate of adult maturation in response to an acceleration or a slowing down of the rate of pre-adult development as measured by our molecular marker. These data support the conclusions drawn by others who examined the effect of the rate of development on adult life expectancy. The timing mechanisms at work during pre-adult and adult life appear to be largely regulated separately. If there is such a thing as a physiological clock, it appears to be reset upon eclosion. © 1996 Wiley-Liss, Inc.     

Screening the pandemic response box identified benzimidazole carbamates,Olorofim and ravuconazole as promising drug candidates for the treatment of eumycetoma

Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma.     

Dynamics of cytokine production during coccidial infections in chickens: colony-stimulating factors and interferon

Abstract We assayed two classes of immunoregulatory cytokines, colony-stimulating factors (CSF) and interferon (IFN), during and immediately after a primary coccidial infection in chickens. Coccidial infection induces significant alterations in serum colony-stimulating activity (CSA) and these alterations immediately precede the characteristic biphasic leukocytosis. CSA rose sharply during the first 24 h post-inoculation (PI), but returned to control levels by 48 h PL. At this time, we detected an increase in peripheral blood leukocytes which peaked at 96 h PI. A second phase of CSA increase began 96 h PI and peaked at 120–144 h PI which again preceded the second phase of leukocytosis. We also examined the production of IFN during the first 20 days PI. Splenic T cells from Eimeria maxima -infected chickens produced significantly less IFN on day 5 PI compared to T cells from the coccidia-free controls. By days 10 and 15 PI, there was no significant difference in IFN production between the T cells of infected and non-infected chickens. However, by day 20 PI, IFN production by the T cells of the infected birds produced significantly more IFN than the control T cells. The results of our studies indicated the differential production of two different cytokines by chickens during and following a primary coccidial infection. Based on these experiments, CSF may be some of the first cytokines produced during an E. maxima -infection, while IFN may be one of the later cytokines produced.     

Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus

Increased levels of B lymphocyte stimulator (BLyS) are associated with systemic autoimmunity in animal models of spontaneous autoimmune disease, and transgenic animals expressing BLyS develop typical autoimmune disease. Here, we demonstrate significant elevations of BLyS in the patients with systemic lupus erythematosus (SLE). The BLyS isolated from the sera of SLE patients had the same m.w. as the natural soluble form and was able to stimulate B cell activation in vitro. Increased BLyS in SLE patients was partially associated with higher levels of anti-dsDNA Ab of the IgG, IgM, and IgA classes, but not associated with the disease activity. Our results suggest that BLyS may be a useful marker for early activation of an autoimmune diathesis and likely plays a critical role in triggering activation of self-Ag-driven autoimmune B cells in human SLE. BLyS may provide an effective therapeutic target in systemic autoimmunity.     

Predation, behavior, and attachment by Chrysoperla plorabunda larvae on Brassica oleracea with different surface waxblooms

Predation by Chrysoperla plorabunda (Fitch) (Chrysopidae) first instars on Plutella xylostella (L.) (Plutellidae) neonates was measured on nine Brassica oleracea L. types with different surface wax crystal morphology. Forty-eight-hour survival of P. xylostella caged on leaves was significantly reduced by C. plorabunda on plants expressing glossy mutations that reduce surface waxbloom, but not on plants with normal waxbloom. During 5-min observations, C. plorabunda spent more time walking and less time scrambling (moving the legs with no locomotion) on glossy types than on the normal-wax types. Adhesive force produced by C. plorabunda on plant surfaces was 20 to 200-fold greater on glossy types than on normal-wax types. All the glossy types provided an advantage to C. plorabunda over normal-wax types by increasing the force of attachment to the leaf suface by the larvae, which in turn increased time allocated to walking, leading to greater predation of P. xylostella larvae. Among glossy and normal wax types together, attachment force and time allocated to walking were significantly correlated with predation by C. plorabunda. Within glossy or normal-wax types, however, these correlations were not significant. Neither time allocated to walking, nor attachment to the leaf surface was a predictor of predation by C. plorabunda within glossy or normal-wax types. Although diverse mechanisms therefore contribute to differences in predation, the results show that reduction in waxbloom can substantially affect the mobility and effectiveness of this generalist predator.