Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus

The major histocompatibility complex (MHC) is a cluster of genes encoding products central to all major functions of the vertebrate immune system. Evidence for an MHC can be found in all vertebrate groups that have been examined except the jawless fishes. Expression of MHC class I and class II antigens early in ontogeny is critically important for development of T lymphocytes capable of discriminating self from nonself. Because of this essential role in T-cell development, the ontogeny of MHC expression in the South African clawed frog, Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis. We therefore examined the possible role of thyroid hormones (TH) in the induction of class I. By flow cytometry, a small amount of class I expression was detectable on splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis is associated with increased intensity of class I expression. Neither inhibition nor acceleration of metamorphosis altered the timing of onset of class I expression. However, inhibition of metamorphosis prevented the increase in class I expression characteristic of adult cell populations. Because expression was not accelerated in TH-treated frogs or delayed in metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that induce expression, although they seem to be required for the upregulation of class I expression occurring at metamorphosis. Differences in the pattern of expression in different subpopulations of cells suggest a complex pattern of regulation of expression of class I antigens during ontogeny

Involvement of Thyroid Hormones in the Expression of MHC class I Antigens During Ontogeny in Xenopus

The major histocompatibility complex (MHC) is a cluster of genes encoding products central to all major functions of the vertebrate immune system. Evidence for an MHC can be found in all vertebrate groups that have been examined except the jawless fishes. Expression of MHC class I and class II antigens early in ontogeny is critically important for development of T lymphocytes capable of discriminating self from nonself. Because of this essential role in T-cell development, the ontogeny of MHC expression in the South African clawed frog, Xenopus laevis, was studied. Previous studies of MHC class I expression in Xenopus laevis suggested that class I antigens are virtually absent from tadpole tissues until climax of metamorphosis. We therefore examined the possible role of thyroid hormones (TH) in the induction of class I. By flow cytometry, a small amount of class I expression was detectable on splenocytes and erythrocytes in untreated frogs at prometamorphic stages 55-58, and the amount increased significantly at the conclusion of metamorphic climax. Thus, metamorphosis is associated with increased intensity of class I expression. Neither inhibition nor acceleration of metamorphosis altered the timing of onset of class I expression. However, inhibition of metamorphosis prevented the increase in class I expression characteristic of adult cell populations. Because expression was not accelerated in TH-treated frogs or delayed in metamorphosis-inhibited frogs, it is unlikely that TH are the direct developmental cues that induce expression, although they seem to be required for the upregulation of class I expression occurring at metamorphosis. Differences in the pattern of expression in different subpopulations of cells suggest a complex pattern of regulation of expression of class I antigens during ontogeny

No news from old drawings? Stomach anatomy in muroid rodents in relation to body size and ecology

Muroid rodents mostly have a complex stomach: one part is lined with a cornified (nonglandular) epithelium, referred to as a “forestomach”, whereas the rest is lined with glandular epithelium. Numerous functions for the forestomach have been proposed. We collated a catalog of anatomical depictions of the stomach of 174 muroid species from which the respective nonglandular and glandular areas could be digitally measured, yielding a “stomach ratio” (nonglandular:glandular area) as a scale‐independent variable. Stomach ratios ranged from 0.13 to 20.15, and the coefficient of intraspecific variation if more than one picture was available for a species averaged at 29.7% (±21.5). We tested relationships of the ratio with body mass and various anatomical and ecological variables, including diet. There was a consistent phylogenetic signal, suggesting that closely related species share a similar anatomy. Apart from classifying stomachs into hemiglandular and discoglandular, no anatomical or ecological measure showed a consistent relationship to the stomach ratio. In particular, irrespective of statistical method or the source of dietary information, dietary proxies did not significantly correlate with the stomach ratio, except for a trend towards significance for invertivory (insectivory). Yet, even this relationship was not convincing: whereas highly insectivorous species had high but no low stomach ratios, herbivorous species had both low and high stomach ratios. Thus, the statistical effect is not due to a systematic increase in the relative forestomach size with invertivory. The most plausible hypotheses so far associate the muroid forestomach and its microbiome with a generic protective role against microbial or fungal toxins and diseases, without evident correlates of a peculiar need for this function under specific ecological conditions. Yet, this function remains to be confirmed. While providing a catalog of published depictions and hypotheses, this study highlights that the function of the muroid rodent forestomach remains enigmatic to date

Extended van Royen-Weisskopf formalism for lepton-antilepton meson decay widths within non-relativistic quark models

The classical van Royen-Weisskopf formula for the decay width of a meson into a lepton-antilepton pair is modified in order to include non-zero quark momentum contributions within the meson as well as relativistic effects. Besides, a phenomenological electromagnetic density for quarks is introduced. The meson wave functions are obtained from two different models: a chiral constituent quark model and a quark potential model including instanton effects. The modified van Royen-Weisskopf formula is found to improve systematically the results for the widths, giving an overall good description of all known decays.Comment: 22 pages, 3 figures, RevTex, epsfig. To be published in Nucl. Phys.

Dust and grit matter: abrasives of different size lead to opposing dental microwear textures in experimentally fed sheep (Ovis aries)

External abrasives ingested along with the herbivore diet are considered main contributors to dental wear, though how the different sizes and concentrations of these abrasives influence wear remains unclear. Dental microwear texture analysis (DMTA) is an establishedmethod for dietary reconstructionwhich describes a tooth’s surface topography on a micrometre scale. The method has yielded conflicting results as to the effect of external abrasives. In the present study, a feeding experiment was performed on sheep (Ovis aries) fed seven diets of different abrasiveness. Our aim was to discern the individual effects of size (4, 50 and 130 μm) and concentration (0%,4% and 8% of dry matter) of abrasives on dental wear, applying DMTA to four tooth positions. Microwear textures differed between individual teeth, but surprisingly, showed no gradient along the molar tooth row, and the strongest differentiation of experimental groups was achieved when combining data of all maxillary molars. Overall, a pattern of increasing height, volume and complexity of the tooth’s microscopic surface appeared with increasing size of dietary abrasives, and when compared with the control, the small abrasive diets showed a polishing effect. The results indicate that the size of dietary abrasives is more important for dental microwear texture traces than their concentration, and that different sizes can have opposing effects on the dietary signal. The latter finding possibly explains conflicting evidence from previous experimental DMTA applications. Further exploration is required to understand whether and how microscopic traces created by abrasives translate quantitatively to tissue loss

Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo.

BACKGROUND: The low-density lipoprotein (LDL) receptor gene family is a highly conserved group of membrane receptors with diverse functions in developmental processes, lipoprotein trafficking, and cell signaling. The low-density lipoprotein (LDL) receptor-related protein 1b (LRP1B) was reported to be deleted in several types of human malignancies, including non-small cell lung cancer. Our group has previously reported that a distal extracellular truncation of murine Lrp1b that is predicted to secrete the entire intact extracellular domain (ECD) is fully viable with no apparent phenotype. METHODS AND PRINCIPAL FINDINGS: Here, we have used a gene targeting approach to create two mouse lines carrying internally rearranged exons of Lrp1b that are predicted to truncate the protein closer to the N-terminus and to prevent normal trafficking through the secretary pathway. Both mutations result in early embryonic lethality, but, as expected from the restricted expression pattern of LRP1b in vivo, loss of Lrp1b does not cause cellular lethality as homozygous Lrp1b-deficient blastocysts can be propagated normally in culture. This is similar to findings for another LDL receptor family member, Lrp4. We provide in vitro evidence that Lrp4 undergoes regulated intramembraneous processing through metalloproteases and gamma-secretase cleavage. We further demonstrate negative regulation of the Wnt signaling pathway by the soluble extracellular domain. CONCLUSIONS AND SIGNIFICANCE: Our results underline a crucial role for Lrp1b in development. The expression in mice of truncated alleles of Lrp1b and Lrp4 with deletions of the transmembrane and intracellular domains leads to release of the extracellular domain into the extracellular space, which is sufficient to confer viability. In contrast, null mutations are embryonically (Lrp1b) or perinatally (Lrp4) lethal. These findings suggest that the extracellular domains of both proteins may function as a scavenger for signaling ligands or signal modulators in the extracellular space, thereby preserving signaling thresholds that are critical for embryonic development, as well as for the clear, but poorly understood role of LRP1b in cancer

Indications and practical approach to non-invasive ventilation in acute heart failure

In acute heart failure (AHF) syndromes significant respiratory failure (RF) is essentially seen in patients with acute cardiogenic pulmonary oedema (ACPE) or cardiogenic shock (CS). Non-invasive ventilation (NIV), the application of positive intrathoracic pressure through an interface, has shown to be useful in the treatment of moderate to severe RF in several scenarios. There are two main modalities of NIV: continuous positive airway pressure (CPAP) and pressure support ventilation (NIPSV) with positive end expiratory pressure. Appropriate equipment and experience is needed for NIPSV, whereas CPAP may be administered without a ventilator, not requiring special training. Both modalities have shown to be effective in ACPE, by a reduction of respiratory distress and the endotracheal intubation rate compared to conventional oxygen therapy, but the impact on mortality is less conclusive. Non-invasive ventilation is also indicated in patients with AHF associated to pulmonary disease and may be considered, after haemodynamic stabilization, in some patients with CS. There are no differences in the outcomes in the studies comparing both techniques, but CPAP is a simpler technique that may be preferred in low-equipped areas like the pre-hospital setting, while NIPSV may be preferable in patients with significant hypercapnia. The new modality 'high-flow nasal cannula' seems promising in cases of AHF with less severe RF. The correct selection of patients and interfaces, early application of the technique, the achievement of a good synchrony between patients and the ventilator avoiding excessive leakage, close monitoring, proactive management, and in some cases mild sedation, may warrant the success of the technique

Elemental Bioimaging of Sheep Bone and Articular Cartilage After Single Application of Gadolinium-Based Contrast Agents

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are applied to enhance magnetic resonance imaging. Gadolinium (Gd), a rare earth metal, is used in a chelated form when administered as GBCA to patients. There is an ongoing scientific debate about the clinical significance of Gd retention in tissues after administration of GBCAs. It is known that bone serves as Gd reservoir, but only sparse information on localization of Gd in bone is available. PURPOSE: The aim of this study was to compare Gd tissue concentration and spatial distribution in femoral epiphysis and diaphysis 10 weeks after single-dose injection of linear and macrocyclic GBCAs in a large animal model. MATERIALS AND METHODS: In this prospective animal study, Swiss-Alpine sheep (n = 36; age range, 4-10 years) received a single injection (0.1 mmol/kg) of macrocyclic (gadobutrol, gadoteridol, and gadoterate meglumine), linear (gadodiamide and gadobenate dimeglumine) GBCAs, or saline. Ten weeks after injection, sheep were killed, and femur heads and shafts were harvested. Gadolinium spatial distribution was determined in 1 sample of each treatment group by laser ablation-inductively coupled plasma-mass spectrometry. All bone specimens were analyzed histopathologically. RESULTS: Injection of GBCAs in female Swiss-Alpine sheep (n = 36) resulted in Gd localization at the endosteal and periosteal surface and in a subset of GBCAs additionally at the cement lines and the bone cartilage junction. No histopathological alterations were observed in the investigated tissue specimens. CONCLUSIONS: Ten weeks after single injection of a clinically relevant dose in adult sheep, both linear species of GBCA resulted in considerably higher accumulation than macrocyclic GBCAs. Gadolinium deposits were restricted to distinct bone and cartilage compartments, such as in bone linings, cement lines, and bone cartilage junctions. Tissue histology remained unaffected

Submesoscale Fronts in the Antarctic Marginal Ice Zone and Their Response to Wind Forcing

Submesoscale flows in the ocean are energetic motions, O(1–10 km), that influence stratification and the distributions of properties, such as heat and carbon. They are believed to play an important role in sea‐ice‐impacted oceans by modulating air‐sea‐ice fluxes and sea‐ice extent. The intensity of these flows and their response to wind forcing are unobserved in the sea‐ice regions of the Southern Ocean. We present the first submesoscale‐resolving observations in the Antarctic marginal ice zone (MIZ) collected by surface and underwater autonomous vehicles, for >3 months in austral summer. We observe salinity‐dominated lateral density fronts occurring at sub‐kilometer scales. Surface winds are shown to modify the magnitude of the mixed‐layer density fronts, revealing strongly coupled atmosphere‐ocean processes. We posture that these wind‐front interactions occur as a continuous interplay between front slumping and vertical mixing, which leads to the dispersion of submesoscale fronts. Such processes are expected to be ubiquitous in the Southern Ocean MIZ

Submesoscale Fronts in the Antarctic Marginal Ice Zone and Their Response to Wind Forcing

Submesoscale flows in the ocean are energetic motions, O(1–10 km), that influence stratification and the distributions of properties, such as heat and carbon. They are believed to play an important role in sea‐ice‐impacted oceans by modulating air‐sea‐ice fluxes and sea‐ice extent. The intensity of these flows and their response to wind forcing are unobserved in the sea‐ice regions of the Southern Ocean. We present the first submesoscale‐resolving observations in the Antarctic marginal ice zone (MIZ) collected by surface and underwater autonomous vehicles, for >3 months in austral summer. We observe salinity‐dominated lateral density fronts occurring at sub‐kilometer scales. Surface winds are shown to modify the magnitude of the mixed‐layer density fronts, revealing strongly coupled atmosphere‐ocean processes. We posture that these wind‐front interactions occur as a continuous interplay between front slumping and vertical mixing, which leads to the dispersion of submesoscale fronts. Such processes are expected to be ubiquitous in the Southern Ocean MIZ