Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions

In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2 ^−/− mutants. However, the developmental ontogeny and cellular identity of these “thymic” PTH–expressing cells is unknown. We found that the lethality of aparathyroid Gcm2 ^−/− mutants was affected by genetic background without relation to serum PTH levels, suggesting a need to reconsider the physiological function of thymic PTH. We identified two sources of extra-parathyroid PTH in wild-type mice. Incomplete separation of the parathyroid and thymus organs during organogenesis resulted in misplaced, isolated parathyroid cells that were often attached to the thymus; this was the major source of thymic PTH in normal mice. Analysis of thymus and parathyroid organogenesis in human embryos showed a broadly similar result, indicating that these results may provide insight into human parathyroid development. In addition, medullary thymic epithelial cells (mTECs) express PTH in a Gcm2-independent manner that requires TEC differentiation and is consistent with expression as a self-antigen for negative selection. Genetic or surgical removal of the thymus indicated that thymus-derived PTH in Gcm2 ^−/− mutants did not provide auxiliary endocrine function. Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant “thymic PTH.”     

Balanced dispersal or source–sink–do both models describe wood mice in farmed landscapes?

Plant responses to browsing can affect root and shoot morphology, which is important to subsequent herbivory, nutrient acquisition and competition. This paper examines the above- and below-ground responses of three browse species, with different growth strategies, to simulated browsing damage at different times of year. Saplings were grown in pots in sand culture to enable whole sapling analysis. At winter dormancy or budburst, 50% of previous year's shoots (and associated leaves/buds) were clipped. Subsequent sapling growth and morphology was compared with that of unclipped control saplings. Treatment differences in growth parameters of each species were observed, including changes in branching patterns, shoot lengths, diameters and ratios, leaf sizes and end-of-season bud numbers. Some responses were damage-induced per se; others differed according to timing of damage. Compensatory growth by the two deciduous species ( Betula pendula , Sorbus aucuparia ) resulted in few biomass differences by the end of the year of damage as compared to controls, but both above- and below-ground growth of clipped Pinus sylvestris was poor, particularly those damaged at budburst, giving strong differences between control, dormant, and budburst clipped saplings.     

Atypical memory phenotype T cells with low homeostatic potential and impaired TCR signaling and regulatory T cell function in Foxn1Delta/Delta mutant mice

Foxn1Delta/Delta mutants have a block in thymic epithelial cell differentiation at an intermediate progenitor stage, resulting in reduced thymocyte cellularity and blocks at the double-negative and double-positive stages. Whereas naive single-positive thymocytes were reduced >500-fold in the adult Foxn1Delta/Delta thymus, peripheral T cell numbers were reduced only 10-fold. The current data shows that Foxn1Delta/Delta peripheral T cells had increased expression of activation markers and the ability to produce IL-2 and IFN-gamma. These cells acquired this profile immediately after leaving the thymus as early as the newborn stage and maintained high steady-state proliferation in vivo but decreased proliferation in response to TCR stimulation in vitro. Single-positive thymocytes and naive T cells also had constitutively low alphabetaTCR and IL7R expression. These cells also displayed reduced ability to undergo homeostatic proliferation and increased rates of apoptosis. Although the frequency of Foxp3+CD4+CD25+ T cells was normal in Foxn1Delta/Delta mutant mice, these cells failed to have suppressor function, resulting in reduced regulatory T cell activity. Recent data from our laboratory suggest that T cells in the Foxn1Delta/Delta thymus develop from atypical progenitor cells via a noncanonical pathway. Our results suggest that the phenotype of peripheral T cells in Foxn1Delta/Delta mutant mice is the result of atypical progenitor cells developing in an abnormal thymic microenvironment with a deficient TCR and IL7 signaling system.     

Crystal structure of murine CstF-77: dimeric association and implications for polyadenylation of mRNA precursors

Cleavage stimulation factor (CstF) is a heterotrimeric protein complex essential for polyadenylation of mRNA precursors. The 77 kDa subunit, CstF-77, is known to mediate interactions with the other two subunits of CstF as well as with other components of the polyadenylation machinery. We report here the crystal structure of the HAT (half a TPR) domain of murine CstF-77, as well as its C-terminal subdomain. Structural and biochemical studies show that the HAT domain consists of two subdomains, HAT-N and HAT-C domains, with drastically different orientations of their helical motifs. The structures reveal a highly elongated dimer, spanning 165 A, with the dimerization mediated by the HAT-C domain. Light-scattering studies, yeast two-hybrid assays, and analytical ultracentrifugation measurements confirm this self-association. The mode of dimerization and the relative arrangement of the HAT-N and HAT-C domains are unique to CstF-77. Our data support a role for CstF dimerization in pre-mRNA 3' end processing.     

Aging and factors related to running economy

The purpose of this study was to investigate the relationship that age has on factors affecting running economy (RE) in competitive distance runners. Fifty-one male and female subelite distance runners (Young [Y]: 18-39 years [n = 18]; Master [M]: 40-59 years [n = 22]; and Older [O]: 60-older [n = 11]) were measured for RE, step rate, lactate threshold (LT), VO2max, muscle strength and endurance, flexibility, power, and body composition. An RE test was conducted at 4 different velocities (161, 188, 215, and 241 m·min(-1)), with subjects running for 5 minutes at each velocity. The steady-state VO2max during the last minute of each stage was recorded and plotted vs. speed, and a regression equation was formulated. A 1 × 3 analysis of variance revealed no differences in the slopes of the RE regression lines among age groups (y = 0.1827x - 0.2974; R2 = 0.9511 [Y]; y = 0.1988x - 1.0416; R2 = 0.9697 [M]; y = 0.1727x + 3.0252; R2 = 0.9618 [O]). The VO2max was significantly lower in the O group compared to in the Y and M groups (Y = 64.1 ± 3.2; M = 56.8 ± 2.7; O = 44.4 ± 1.7 mlO2·kg(-1)·min(-1)). The maximal heart rate and velocity @ LT were significantly different among all age groups (Y = 197 ± 4; M = 183 ± 2; O = 170 ± 6 b·min(-1) and Y = 289.7 ± 27.0; M = 251.5 ± 32.9; O = 212.3 ± 24.6 m·min(-1), respectively). The VO2max @ LT was significantly lower in the O group compared to in the Y and M groups (Y = 50.3 ± 2.0; M = 48.8 ± 2.9; O = 34.9 ± 3.2 mlO2·kg(-1)·min(-1)). The O group was significantly lower than in the Y and M groups in flexibility, power, and upper body strength. Multiple regression analyses showed that strength and power were significantly related to running velocity. The results from this cross-sectional analysis suggest that age-related declines in running performance are associated with declines in maximal and submaximal cardiorespiratory variables and declines in strength and power, not because of declines in running economy.     

Significance of source and size in the mechanical response of human cerebral blood vessels

Cerebral blood vessels are frequently damaged in traumatic brain injury. Mechanical properties of fresh human cerebral vessels obtained through surgeries have been reported. Because surgical sources of human specimens are rare and produce a limited amount of material, we sought to compare the properties of more readily available cerebral arteries and veins obtained from cadavers to fresh vessel data. Additionally, because the previous study was limited to small vessels available in surgery, it was unknown how generally applicable the results were to larger cerebral arteries and veins. In the current study, large and small cerebral vessels from autopsy were stretched axially. Data from these and similar tests on fresh vessels were combined to determine the significance of source and size on mechanical properties. Structural comparisons of histological samples were additionally utilized to characterize differences. Results indicate that specimens from autopsy and surgery behave similarly except that vessels from autopsy tend to be less extensible. While tests on large vessels were limited, small arteries obtained from autopsy tended to be slightly stiffer than large arteries. In contrast, bridging veins from cadavers were typically stiffer and stretched less before structural failure than cortical veins from the same source. These effects are, however, secondary to differences identified between arteries and veins in the previous study.     

Russian honey bee (Hymenoptera: Apidae) colonies: Acarapis woodi (Acari: Tarsonemidae) infestations and overwintering survival

Honey bee, Apis mellifera L. (Hymenoptera: Apidae), colonies infested by parasitic mites are more prone to suffer from a variety of stresses, including cold temperature. We evaluated the overwintering ability of candidate breeder lines of Russian honey bees, most of which are resistant to both Varroa destructor Anderson & Trueman and Acarapis woodi (Rennie), during 1999-2001. Our results indicate that Russian honey bee colonies (headed by original and supersedure queens) can successfully overwinter in the north, even during adverse weather conditions, owing to their frugal use of food stores and their resistance to tracheal mite infestations. In contrast, colonies of Italian honey bees consumed more food, had more mites, and lost more adult bees than Russian honey bees, even during unusually mild winter conditions.