Experimental estrogen-induced hyperprolactinemia results in bone-related hearing loss in the guinea pig

Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135-138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, in that study, it was not possible to determine whether hyperprolactinemia was a cause or an effect of the symptoms. To investigate the effect of hyperprolactinemia on inner ear function, we first developed a model of hyperprolactinemia in estrogen-primed Fischer 344 rats and then performed functional studies on pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, a hearing loss of approximately 30-40 dB across all frequencies, as indicated by the compound action potential audiogram. During the 3rd mo, the hearing loss continued to deteriorate. The threshold shifts were more substantial in males than in females. Observations under a dissection microscope revealed bone dysmorphology of the bulla and the cochlea. Light microscopy observations of cryostat sections confirmed bone-related pathology of the bony cochlear bulla and the cochlear wall and revealed morphopathology of the stria vascularis and spiral ligament. Scanning electron microscopy revealed loss of hair cells and stereocilia damage, in particular in the upper three cochlear turns and the two outermost hair cell rows. The data provide the first evidence of otic capsule and hair cell pathology associated with estrogen-induced prolonged hyperprolactinemia and suggest that conditions such as pregnancy, anti-psychotic drug treatment, aging, and/or stress might lead to similar ear dysfunctions.     

Common Avian Infection Plagued the Tyrant Dinosaurs

Background

Tyrannosaurus rex and other tyrannosaurid fossils often display multiple, smooth-edged full-thickness erosive lesions on the mandible, either unilaterally or bilaterally. The cause of these lesions in the Tyrannosaurus rex specimen FMNH PR2081 (known informally by the name ‘Sue’) has previously been attributed to actinomycosis, a bacterial bone infection, or bite wounds from other tyrannosaurids.

Methodology/Principal Findings

We conducted an extensive survey of tyrannosaurid specimens and identified ten individuals with full-thickness erosive lesions. These lesions were described, measured and photographed for comparison with one another. We also conducted an extensive survey of related archosaurs for similar lesions. We show here that these lesions are consistent with those caused by an avian parasitic infection called trichomonosis, which causes similar abnormalities on the mandible of modern birds, in particular raptors.

Conclusions/Significance

This finding represents the first evidence for the ancient evolutionary origin of an avian transmissible disease in non-avian theropod dinosaurs. It also provides a valuable insight into the palaeobiology of these now extinct animals. Based on the frequency with which these lesions occur, we hypothesize that tyrannosaurids were commonly infected by a Trichomonas gallinae-like protozoan. For tyrannosaurid populations, the only non-avian dinosaur group that show trichomonosis-type lesions, it is likely that the disease became endemic and spread as a result of antagonistic intraspecific behavior, consumption of prey infected by a Trichomonas gallinae-like protozoan and possibly even cannibalism. The severity of trichomonosis-related lesions in specimens such as Tyrannosaurus rex FMNH PR2081 and Tyrannosaurus rex MOR 980, strongly suggests that these animals died as a direct result of this disease, mostly likely through starvation.     

Increased age of transformed mouse neural progenitor/stem cells recapitulates age‐dependent clinical features of human glioma malignancy

Increasing age is the most robust predictor of greater malignancy and treatment resistance in human gliomas. However, the adverse association of clinical course with aging is rarely considered in animal glioma models, impeding delineation of the relative importance of organismal versus progenitor cell aging in the genesis of glioma malignancy. To address this limitation, we implanted transformed neural stem/progenitor cells (NSPCs), the presumed cells of glioma origin, from 3‐ and 18‐month‐old mice into 3‐ and 20‐month host animals. Transplantation with progenitors from older animals resulted in significantly shorter (P ≤ 0.0001) median survival in both 3‐month (37.5 vs. 83 days) and 20‐month (38 vs. 67 days) hosts, indicating that age‐dependent changes intrinsic to NSPCs rather than host animal age accounted for greater malignancy. Subsequent analyses revealed that increased invasiveness, genomic instability, resistance to therapeutic agents, and tolerance to hypoxic stress accompanied aging in transformed NSPCs. Greater tolerance to hypoxia in older progenitor cells, as evidenced by elevated HIF‐1 promoter reporter activity and hypoxia response gene (HRG) expression, mirrors the upregulation of HRGs in cohorts of older vs. younger glioma patients revealed by analysis of gene expression databases, suggesting that differential response to hypoxic stress may underlie age‐dependent differences in invasion, genomic instability, and treatment resistance. Our study provides strong evidence that progenitor cell aging is responsible for promoting the hallmarks of age‐dependent glioma malignancy and that consideration of progenitor aging will facilitate development of physiologically and clinically relevant animal models of human gliomas.     

Crystal diversity and macropatterns in leaves of Oleaceae

Oleaceae leaves surveyed from herbarium specimens of 240 species from 23 genera were rehydrated, bleached, processed into xylol, mounted unstained, and viewed microscopically between crossed polarizers. Occurrence of five crystal types and two variants (tiny acicular crystals and sphaerites) within one family is unusual. Number of crystal types within a single species was one (108 spp.), two (53 spp.), three (51 spp.), four (15 spp.), and five (6 spp.). Seven species lacked crystals. The tiny acicular crystal variant was most common (167 spp.), followed by prisms (67 spp.), raphides (65 spp.), druses (61 spp.), sphaerites variant (50 spp.), styloids (36 spp.), and crystal sand (21 spp.). Epidermal crystals were common (155 spp.), with epidermal crystals clustering at base of trichomes in 21 species. Jasminum was exceptional in having mostly druses and almost no crystals around vascular bundles. Most Oleaceae crystals are tiny, usually about 5 μm in length, except for larger styloids and raphides.     

Effect of exercise and medium-chain fatty acids on postprandial lipemia.

The purpose of this study was to evaluate the effect of medium-chain triglycerides (MCT) with and without exercise on postprandial lipemia (PPL). Subjects were 25 young men and women. Each subject performed three trials: 1) control (fat meal only, 1.5 g fat/kg) 2) MCT (substitution of MCT oil, 30% of fat calories), and 3) MCT + Ex (exercise 12 h before the MCT meal). Before each trial, the subject underwent consistent dietary preparation. Blood was collected on 2 separate days for baseline measurements of postheparin lipases and, in each trial, at 0 h (premeal), at 2, 4, 6, and 8 h after the fat meal for triglycerides and cholesterol ester transfer protein (CETP), and at 8 h for postheparin lipoprotein lipase (LPL) and hepatic lipase activities (HL). ANOVA indicated that the partial substitution of MCT oil to the fat meal did not affect the PPL response. However, the PPL was significantly lower after the MCT + Ex trial vs. the other trials. LPL activity was significantly elevated after all trials compared with baseline, whereas HL was lower in the MCT + Ex trial only. CETP mass was significantly lower at 4 and 8 h than 0 h during all trials but relatively higher in the MCT + Ex trial vs. the nonexercise trials. These results suggest that MCT does not affect the TG response to a fat meal. LPL and CETP are affected by a fat meal with or without exercise, but HL is affected only when exercise is included.     

Contrasting roles for c-Myc and L-Myc in the regulation of cellular growth and differentiation in vivo.

Although myc family genes are differentially expressed during development, their expression frequently overlaps, suggesting that they may serve both distinct and common biological functions. In addition, alterations in their expression occur at major developmental transitions in many cell lineages. For example, during mouse lens maturation, the growth arrest and differentiation of epithelial cells into lens fiber cells is associated with a decrease in L- and c-myc expression and a reciprocal rise in N-myc levels. To determine whether the down-regulation of L- and c-myc are required for mitotic arrest and/or completion of differentiation and whether these genes have distinct or similar activities in the same cell type, we have studied the consequences of forced L- and c-myc expression in the lens fiber cell compartment using the alpha A-crystallin promoter in transgenic mice (alpha A/L-myc and alpha A/c-myc mice). With respect to morphological and molecular differentiation, alpha A/L-myc lenses were characterized by a severely disorganized lens fiber cell compartment and a significant decrease in the expression of a late-stage differentiation marker (MIP26); in contrast, differentiation appeared to be unaffected in alpha A/c-myc mice. Furthermore, an analysis of proliferation indicated that while alpha A/L-myc fiber cells withdrew properly from the cell cycle, inappropriate cell cycle progression occurred in the lens fiber cell compartment of alpha A/c-myc mice. These observations indicate that continued late-stage expression of L-myc affected differentiation processes directly, rather than indirectly through deregulated growth control, whereas constitutive c-myc expression inhibited proliferative arrest, but did not appear to disturb differentiation. As a direct corollary, our data indicate that L-Myc and c-Myc are involved in distinct physiological processes in the same cell type.     

The Bacterial Translocon SecYEG Opens upon Ribosome Binding

In co-translational translocation, the ribosome funnel and the channel of the protein translocation complex SecYEG are aligned. For the nascent chain to enter the channel immediately after synthesis, a yet unidentified signal triggers displacement of the SecYEG sealing plug from the pore. Here, we show that ribosome binding to the resting SecYEG channel triggers this conformational transition. The purified and reconstituted SecYEG channel opens to form a large ion-conducting channel, which has the conductivity of the plug deletion mutant. The number of ion-conducting channels inserted into the planar bilayer per fusion event roughly equals the number of SecYEG channels counted by fluorescence correlation spectroscopy in a single proteoliposome. Thus, the open probability of the channel must be close to unity. To prevent the otherwise lethal proton leak, a closed post-translational conformation of the SecYEG complex bound to a ribosome must exist.     

The effect of permeant buffers on initial ATP synthesis by chloroplasts using rapid mix-quench techniques

The chemiosmotic hypothesis predicts that buffers which permeate chloroplast membranes should delay the formation of the proton gradient at the onset of illumination. If valinomycin and KCl are present to collapse the electrical potential as well, this delay should result in a lag in initial ATP synthesis. Using rapid-mix, acid-quench techniques, we have found that in light-driven ATP synthesis the permeant buffer imidazole does not increase the initial lag caused by the valinomycin-KCl pair. Similar results are obtained under methyl viologen or phenazine methosulfate/ascorbate-mediated photophosphorylation and are independent of the internal volume of the chloroplasts. Furthermore, we have observed that chloroplasts can synthesize significant amounts of ATP in darkness following an illumination period as short as 100 ms. This capacity for ATP synthesis in darkness after short pre-illumination periods is decreased in the presence of imidazole, and this may account for the apparent lags reported in earlier studies which have used rapid flash photophosphorylation in the presence of permeant buffers. The results of the present study argue that in chloroplasts, initial ATP synthesis and post-illumination ATP synthesis are driven by distinct components of the proton motive potential.