DIAGNOSIS OF SCHIZOPHRENIA IN YOUNG CHILDREN

Schizophrenia can be discovered in pre-school children by observation of: Social indifference; uneven and intermittent motor or physical development; irregularity in speech development with tendency toward infantile speech; early fear of falling or rising, giving way to obsession with jumping and falling; excessive interest in spinning toys and circular motility; and preoccupation with body periphery—hands, feet and hair.When the physician observes these symptoms, or is consulted about them by the parents, clinical appraisal in consultation with a pediatric psychiatrist will usually suffice for diagnosis. Early treatment—before school age—is important for the child''s future development.     

Detection of mRNAs coding for translationally regulated heat-shock proteins in non-heat-shocked thymic lymphocytes

Heat shock induces 31 proteins in thymic lymphocytes in 1 h, 11 of which are not blocked by cordycepin, suggesting that their induction may be regulated at the level of translation (Maytin, E.V., Colbert, R.A., and Young, D.A. (1985) J. Biol. Chem. 260, 2384-2392). The possibility that mRNAs coding for these 11 cordycepin-insensitive heat-shock proteins would be found in non-heat-shocked thymus cells was investigated. Analysis of 1500 in vitro translation products separated by giant two-dimensional gel electrophoresis revealed that poly(A)+ RNA isolated from non-heat-shocked thymus cells coded for proteins corresponding to 10 of the 11 non-cordycepin-inhibitable heat-shock proteins. Comparison of the relative rates of synthesis of these 10 proteins in whole cells incubated at 37 and 42 degrees C, with their synthesis in vitro directed by poly(A)+ RNA isolated from cells incubated at 37 degrees C, suggests that mRNAs for 7 of them are present in sufficient amounts in non-heat-shocked cells to account for their increased synthesis during heat shock. These results indicate that part of the response of thymic lymphocytes to heat shock involves a rapid increase in the translation of a group of pre-existing mRNAs that are normally translated at very low rates or not at all.     

Bronchial vasodilation by histamine in sheep: characterization of receptor subtype.

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

HLA-B27 and Human β2-Microglobulin Affect the Gut Microbiota of Transgenic Rats

The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m), compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.     

Glycosylation Directs Targeting and Activation of Cystatin F from Intracellular and Extracellular Sources

Cystatin F is a cysteine protease inhibitor that is selectively expressed in immune cells and unlike other cystatin family members is targeted to a significant extent to intracellular compartments. Initially made as an inactive glycosylated disulfide-linked dimer, cystatin F is converted to an active monomer by proteolytic cleavage following transport to the endosomal/lysosomal system. This active form of cystatin F targets cathepsin C/DPPI and probably other cathepsins in immune cells. We show that efficient targeting of cystatin F to the endocytic pathway is dependent not on its unique dimeric conformation but rather on its oligosaccharide chains. We demonstrate the unusual addition of N -linked sugars to an Asn-X-Cys motif in cystatin F and provide evidence that the mannose 6-phosphate sorting machinery is used to divert cystatin F from the secretory pathway and to mediate its uptake from extracellular pools. These studies identify a function for the oligosaccharides on cystatin F and raise the possibility that cystatin F might regulate proteases in trans by secretion in an inactive form by one cell and subsequent internalization and activation by another cell.     

Low-resolution structural studies of human Stanniocalcin-1

Background  

Stanniocalcins (STCs) represent small glycoprotein hormones, found in all vertebrates, which have been functionally implicated in Calcium homeostasis. However, recent data from mammalian systems indicated that they may be also involved in embryogenesis, tumorigenesis and in the context of the latter especially in angiogenesis. Human STC1 is a 247 amino acids protein with a predicted molecular mass of 27 kDa, but preliminary data suggested its di- or multimerization. The latter in conjunction with alternative splicing and/or post-translational modification gives rise to forms described as STC₅₀ and "big STC", which molecular weights range from 56 to 135 kDa.     

Trabecular bone structure in the mandibular condyles of gouging and nongouging platyrrhine primates

The relationship between mandibular form and biomechanical function is a topic of significant interest to morphologists and paleontologists alike. Several previous studies have examined the morphology of the mandible in gouging and nongouging primates as a means of understanding the anatomical correlates of this feeding behavior. The goal of the current study was to quantify the trabecular bone structure of the mandibular condyle of gouging and nongouging primates to assess the functional morphology of the jaw in these animals. High‐resolution computed tomography scan data were collected from the mandibles of five adult common marmosets (Callithrix jacchus), saddle‐back tamarins (Saguinus fuscicollis), and squirrel monkeys (Saimiri sciureus), respectively, and various three‐dimensional morphometric parameters were measured from the condylar trabecular bone. No significant differences were found among the taxa for most trabecular bone structural features. Importantly, no mechanically significant parameters, such as bone volume fraction and degree of anisotropy, were found to vary significantly between gouging and nongouging primates. The lack of significant differences in mechanically relevant structural parameters among these three platyrrhine taxa may suggest that gouging as a habitual dietary behavior does not involve significantly higher loads on the mandibular condyle than other masticatory behaviors. Alternatively, the similarities in trabecular architecture across these three taxa may indicate that trabecular bone is relatively unimportant mechanically in the condyle of these primates and therefore is functionally uninformative. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.     

The histological structure of the calcified lung of the fossil coelacanth Axelrodichthys araripensis (Actinistia: Mawsoniidae)

Abstract: The palaeohistological study of the calcified internal organ of Axelrodichthys araripensis Maisey, 1986, a coelacanthiform from the Lower Cretaceous of Brazil (Crato (Aptian) and Santana (Albian) formations of the Araripe Basin), shows that the walls of this organ consist of osseous blades of variable thickness separated from each other by the matrix. This indicates that, in the living individuals, the walls were reinforced by ossified plates, probably separated by conjunctive tissue. This calcified sheath present in Axelrodichthys, as well as in other fossil coelacanths, lies in ventral position relative to the gut and its single anterior opening is located under the opercle, suggesting a direct connection with the pharynx or the oesophagus. The calcified organ of Axelrodichthys, like that of other fossil coelacanths, is here regarded as an ‘ossified lung’ and compared with the ‘fatty lung’ of the extant coelacanth Latimeria. The reinforcement of the pulmonary walls by the overlying osseous blades could be interpreted as a means of adapting volumetric changes in the manner of bellows, a necessary function for ventilation in pulmonary respiration. Other functional hypotheses such as hydrostatic and/or acoustic functions are also discussed.     

3D computational imaging of the petrosal of a new multituberculate mammal from the Late Cretaceous of China and its paleobiologic inferences

The derived middle and inner ears of mammals are the major features distinguishing them from non-mammalian vertebrates. Among them, multituberculate mammals represent an important transitional stage and a groundplan for further therian ear evolution. We present the reconstruction of petrosal features of a new multituberculate from the Late Cretaceous of Inner Mongolia (China) based on high resolution computed tomography and three-dimensional imaging analysis. Besides questioning some aspects of previous interpretations, this study reveals a combination of derived and primitive characters, such as a therian-like vascular and nervous pattern and internal acoustic meatus, and a monotreme-like inner ear, but with a derived semicircular canal planarity. The possible presence of a primary bony lamina for the basilar membrane could demonstrate that the first step in the elaboration of a coiled cochlea was already present in multituberculates. Auditory capabilities can be deduced for this animal, which was certainly terrestrial and possibly fossorial.