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PubMed1994

Regional expression of mRNA for proteoglycans and collagen in tendon.

Regions of tissue that ressemble cartilage develop at the point where tendon wraps under a bone and receives compressive forces in addition to tension. Northern blot analysis was used to assess expression of mRNA for several extracellular matrix constituents in cells immediately after their isolation from tensional and compressive regions of fetal, adult and old adult bovine deep flexor tendon. Messenger RNA for aggrecan and type II collagen, as well as for biglycan and decorin, was highly expressed in cells from the compressed region of adult tendon, indicating that this tissue contains cells with a chondrocytic phenotype. In contrast, only mRNA for decorin was highly expressed in cells from the tensional region of adult tendon. The major developmental changes in mRNA expression in the compressed region of tendon included a approximately 25-fold increase in aggrecan expression between fetal and adult tissue and an increase in type II collagen mRNA from undetectable in fetal tendon to expression in adult tendon that was nearly as high as the level expressed in cells from adult articular cartilage. Developmental changes in the tensional region consisted of a approximately 10-fold decrease in type I collagen expression and a 4-fold increase in decorin expression in cells from adult tissue, as compared to fetal tissue. These observations indicate that levels of gene expression for proteoglycans and collagen in tendon correlate with the mechanical environment in the tissue. The regional distinctions in mRNA expression were lost when cells were grown in monolayer culture for one week.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggrecans↗
PubMed2026

Deep DNA and protein level feature integration for robust clinical variant interpretation using probabilistic gradient boosting.

A major challenge in clinical genomics is to classify genetic variations correctly, since it directly affects disease diagnosis and personal care. The existing methods tend to be based on the combination of different factors, such as protein structure, population frequencies, phenotypic annotations, and sequence conservation. Nevertheless, these methods often cannot be used to achieve the necessary interpretability, quantify uncertainty, and address rare cases. This paper presents a probabilistic gradient boosting model on variant pathogenicity prediction. The suggested framework applies biological characteristics at both level of DNA and protein levels while also scaling the level of uncertainty in clinical decision making. Our machine learning aims to solve the issues of variant interpretation by managing the features and through probability-based pathogenicity prediction. The framework formulation is aimed at generalizing over various datasets and minimizing overfitting. At the same time, it can ensure reasonable performance to facilitate clinical experiments. The model has also been tested on three standard datasets and demonstrated to be more predictive of the pathogenic effect of variants, in comparison with a variety of existing tools. The probabilistic gradient boosting model proposed had ROC AUC values of 0.9293, 0.9610, and 0.9646 on ClinVar variants, GRCh37, and GRCh38 human genome respectively. Furthermore, the dataset was ensured to include both exonic and intronic variants, and Variants of Uncertain Significance were also taken into consideration for Performance Testing. Through this it also aims to provide better clinical significance which will lead to a good interpretable tool for priority of variants for a large variety of disease conditions.

ClinVar↗
PubMed1997

Scanning electron microscopy of the development of structured aerial mycelia and satellite colonies of phenotypically switched Candida albicans.

Candida albicans is an asexual diploid fungus that can express high frequency phenotypic switching. Switched variants can develop structured aerial mycelia (SAM) and cultures that have been grown for a protracted period exhibit satellite colonies. This study investigated the development of both SAM and satellite colonies by means of a freeze-drying technique and scanning electron microscopy. The results show that SAM may develop due to hyphae developing in the colony at the base of the structures. The development of satellite colonies is a result of cells that have grown deep into the agar re-emerging on to the agar/air surface and producing a new colony. Although both SAM and satellite colonies are often seen together on mature colonies, their cause and development are different.

Candida albicans↗
PubMed2000

Photoaging of the skin from phenotype to mechanisms.

The skin is increasingly exposed to ambient UV-irradiation thus increasing its risk for photooxidative damage with longterm detrimental effects like photoaging, which is characterized by wrinkles, loss of skin tone, and resilience. Photoaged skin displays prominent alterations in the cellular component and the extracellular matrix of the connective tissue with an accumulation of disorganized elastin and its microfibrillar component fibrillin in the deep dermis and a severe loss of interstitial collagens, the major structural proteins of the dermal connective tissue. The unifying pathogenic agents for these changes are UV-generated reactive oxygen species (ROS) that deplete and damage non-enzymatic and enzymatic antioxidant defense systems of the skin. As well as causing permanent genetic changes, ROS activate cytoplasmic signal transduction pathways in resident fibroblasts that are related to growth, differentiation, senescence, and connective tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photoaging. In addition, the relationship of photoaging to intrinsic aging of the skin will be discussed. A decrease in the overall ROS load by efficient sunscreens or other protective agents may represent promising strategies to prevent or at least minimize ROS induced photoaging.

Animals↗
PubMed1997

Mosaicism in trisomy 8: phenotype differences according to tissular repartition of normal and trisomic clones.

Three new observations of trisomy 8 mosaicism are presented. In two postnatal cases, both patients showed agenesis of corpus callosum associated with different clinical findings. In a third case, the prenatal diagnosis revealed trisomy 8 mosaicism exclusively in chorionic villi (CV) cells long term culture. Normal results were obtained in CV direct preparation and in cultured amniotic cells. In lymphocytes, the child showed low level trisomy 8 mosaicism. The only clinical findings were deep palmar and plantar furrows. The present cases as well as reports in the literature indicate that the variation in tissular repartition of normal and trisomic clones in trisomy 8 mosaicism is possibly responsible for the missing correlation between cytogenetic findings and clinical severity in this syndrome.

Child, Preschool↗
PubMed1998

Rhino-9J (hr(rh9J)): a new allele at the hairless locus.

A spontaneous mutation arose in the MRL/MpJ-Fas(lpr)/Fas(lpr) colony in which mice lost hair after completion of the first hair cycle. Hair loss was progressive from head to tail. As these mice aged, they developed wrinkled skin and long curved nails. Histologically, affected skin developed comedones (pilary cysts), deep dermal cysts, and dermal foreign body granulomas associated with rupture of the follicles. The alopecic epidermis was acanthotic. The mutation was autosomal recessive. Crosses with RHJ/Le +/hr(rhJ) (rhino-J) mutant mice yielded affected offspring with the same phenotype, verifying the presence of a new allele of rhino, a mutation at the hairless (hr) locus on mouse chromosome 14.

Alleles↗
PubMed2000

Focal denervation alters cellular phenotypes and survival in the rat olfactory bulb: a developmental analysis.

Our previous work (Couper Leo et al. [2000] J. Comp. Neurol. 417:325-336) introduced a technique for focally denervating the olfactory bulb soon after birth and described the pattern of changes incurred by this procedure by postnatal day (P) 30. The current study extends these findings with a developmental analysis of the effects of focal denervation in P10 and P20 rats. The results suggest that denervation begins to affect bulb architecture and cell survival soon after the procedure is performed, but that alterations within the bulb occur over an extended time period. For example, at P10, bulb and laminar sizes and mitral/tufted cell profile number had begun their decline, and nearly all measurements were significantly reduced by P20. Furthermore, a superficial-to-deep gradient of alterations in bulb architecture and a temporal separation of the effects on mitral/tufted cell dendrites vs. somata were observed. Immunohistochemical analyses of olfactory marker protein (OMP)-, calretinin- calbindin-, parvalbumin-, tyrosine hydroxylase-, and glutamic acid decarboxylase-stained sections indicated that: 1) denervation alters the interaction between olfactory axons and their targets in a developmentally significant manner; 2) the fine structure of denervated cells is altered; 3) cell phenotypes are differentially affected by loss of afferent contact, perhaps due to the age-dependent expression of their defining antigens; and 4) specific cell populations may be lost as a result of denervation.

Animals↗
PubMed1994

Production and Characterization of an Exopolysaccharide Excreted by a Deep-Sea Hydrothermal Vent Bacterium Isolated from the Polychaete Annelid Alvinella pompejana.

The heterotrophic and mesophilic marine bacterium HYD-1545 was isolated on a metal-amended medium from the dorsal integument of the hydrothermal vent polychaete Alvinella pompejana. This strain, which can be assigned to the genus Alteromonas on the basis of its G+C content and phenotypical features, produced large amounts of an acidic polysaccharide in batch cultures. The polysaccharide was excreted during the stationary phase of growth and contained glucose, galactose, glucuronic acid, galacturonic acid, and 4,6-O-(1-carboxyethilidene)-galactose as major components. This polysaccharide was a polyelectrolyte, and the viscosity of its solutions depended on the ionic strength. The decrease in viscosity with increasing NaCl concentrations and the effect of Ca in decreasing the viscosity at low Ca concentrations support a model in which the polysaccharide carries anionic groups. However, an unusual behavior was observed at higher concentrations and could be related to intermolecular interactions involving Ca ions.

Journal Article↗
PubMed2000

The phylogenetics of mycotoxin and sclerotium production in Aspergillus flavus and Aspergillus oryzae.

Aspergillus flavus is a common filamentous fungus that produces aflatoxins and presents a major threat to agriculture and human health. Previous phylogenetic studies of A. flavus have shown that it consists of two subgroups, called groups I and II, and morphological studies indicated that it consists of two morphological groups based on sclerotium size, called "S" and "L." The industrially important non-aflatoxin-producing fungus A. oryzae is nested within group I. Three different gene regions, including part of a gene involved in aflatoxin biosynthesis (omt12), were sequenced in 33 S and L strains of A. flavus collected from various regions around the world, along with three isolates of A. oryzae and two isolates of A. parasiticus that were used as outgroups. The production of B and G aflatoxins and cyclopiazonic acid was analyzed in the A. flavus isolates, and each isolate was identified as "S" or "L" based on sclerotium size. Phylogenetic analysis of all three genes confirmed the inference that group I and group II represent a deep divergence within A. flavus. Most group I strains produced B aflatoxins to some degree, and none produced G aflatoxins. Four of six group II strains produced both B and G aflatoxins. All group II isolates were of the "S" sclerotium phenotype, whereas group I strains consisted of both "S" and "L" isolates. Based on the omt12 gene region, phylogenetic structure in sclerotium phenotype and aflatoxin production was evident within group I. Some non-aflatoxin-producing isolates of group I had an omt12 allele that was identical to that found in isolates of A. oryzae.

Aflatoxins↗
PubMed2026

Temporal DIA-MS proteomics reveals coordinated metabolic reprogramming associated with oil accumulation in oil palm mesocarp.

Oil palm (Elaeis guineensis Jacq.) is the most productive oil-bearing crop globally, yet the molecular basis of mesocarp development and lipid accumulation remains poorly understood. Ultra-deep data-independent acquisition mass spectrometry (DIA-MS) was applied to characterize proteome dynamics in two contrasting genotypes, seedless (KS) and thin-shelled (TS), across five developmental stages (P1-P5) spanning fruit development to mature oil accumulation. Phenotypic analysis revealed higher mesocarp proportion and oil content in KS during late maturation. A total of 137,615 peptides corresponding to 12,163 protein groups were identified, providing a temporal proteomic landscape of mesocarp development. Multivariate analysis indicated that developmental progression was the primary contributor to proteomic variation, whereas genotype-associated differences increased during lipid accumulation. Differentially abundant proteins were mainly associated with carbohydrate metabolism, photosynthesis, proteolysis, antioxidant responses, and lipid biosynthesis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and KOG analyses suggested extensive remodeling of metabolic networks, including developmental changes in photosynthesis-associated proteins and increased representation of lipid-associated pathways during maturation. Weighted protein co-expression network analysis identified 17 modules associated with developmental progression and lipid accumulation, highlighting candidate proteins involved in carbon metabolism, energy production, and cellular protection. Genes encoding selected hub protein candidates were further examined by RT-qPCR. Biochemical analyses supported these proteomic patterns, showing increased acetyl-CoA availability, enhanced antioxidant enzyme activities (SOD, CAT, APX, and GR), improved GSH/GSSG balance, and reduced oxidative damage in KS. Together, these findings provide a temporal proteomic and biochemical framework for understanding genotype-associated differences in oil accumulation and identify candidate metabolic networks for functional studies.

Carbon metabolism↗
PubMed2000

Identification of a marine benthic P(3HB)-degrading bacterium isolate and characterization of its P(3HB) depolymerase.

A poly[(R)-3-hydroxybutyrate] (P(3HB))-degrading marine bacterium (strain NK-1, JCM10458) was isolated from the Pacific Ocean deep-sea floor (1165 m in depth) in Japan. The organism was a motile and Gram negative, aerobic, and rod-shaped bacterium, and its DNA had a guanine-plus-cytosine content of 57.7 mol%. On the basis of several phenotypic characters and a phylogenetic analysis of the gene coding for 16S rRNA, this strain was identified as Marinobacter sp. The strain required sodium salt for growth in the medium and secreted a P(3HB) depolymerase into the supernatant when it was cultivated on (S)-3-hydroxybutyric acid or P(3HB) as the sole carbon source. The P(3HB) depolymerase (PhaZMsp) was purified to homogeneity from the culture supernatant of Marinobacter sp. by hydrophobic and ion exchange column chromatography and showed a molecular mass of 70 kDa. PhaZMsp was stable at temperatures below 37 degrees C and at pH values of 7.5-10.0. The N-terminal amino acid sequences of both the purified enzyme and the truncated one shared high homologies to the N-terminal and internal sequences of Pseudomonas stutzeri depolymerase, respectively. High-performance liquid chromatography analysis revealed that the enzymatic products of P(3HB) yielded monomer, dimer, and trimer of 3-hydroxybutyric acid. PhaZMsp was capable of hydrolyzing P(3HB), poly(3-hydroxypropionate), and poly(4-hydroxybutyrate).

Amino Acid Sequence↗
PubMed2000

The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma.

Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13-15, whereas well differentiated liposarcomas (WDL) show supernumerary ring and giant marker chromosomes, known to contain amplified 12q sequences. The tight correlation between the presence of ring chromosomes and both amplification and overexpression of MDM2 and CDK4 genes suggests the exploration of the possibility that immunocytochemistry (ICC) might assist in the differential diagnosis of lipoma-like well differentiated liposarcomas (LL-WDL) and large deep-seated lipomas (LDSL). For this purpose, 21 cases of the former and 19 cases of the latter tumours were analysed by ICC and, according to the availability of material, by molecular and cytogenetic approaches. All lipomas displayed a null MDM2/CDK4 phenotype, whereas all LL-WDL showed MDM2/CDK4 or CDK4 phenotypes. Southern blot analysis performed on 16 suitable cases, complemented by fluorescence in situ hybridization and classical cytogenetic analysis in 11 cases, was consistent with, and further supported the immunophenotyping data. In conclusion, MDM2/CDK4 product-based immunophenotyping appears to represent a valuable method for the categorization of arguable LDSL.

Adult↗
PubMed2026

X-linked spondyloepiphyseal dysplasia tarda misdiagnosed as growth hormone deficiency: identification of a novel intronic TRAPPC2 variant by whole-genome sequencing.

BACKGROUND: X-linked spondyloepiphyseal dysplasia tarda (SEDT) is a rare skeletal dysplasia caused by pathogenic variants in TRAPPC2 and typically presents in late childhood or adolescence with short-trunk disproportion and vertebral dysplasia. CASE PRESENTATION: We describe a family series centered on an adolescent male initially diagnosed with GHD due to reduced height velocity and subnormal GH stimulation results, who received recombinant human GH (rhGH) therapy for three years with negligible improvement. During puberty, he developed progressive short-trunk disproportion and characteristic radiographic features, including platyspondyly and posterior hump-shaped vertebral endplates, suggestive of SEDT. Whole-exome sequencing (WES) was nondiagnostic, whereas whole-genome sequencing (WGS) identified a novel intronic TRAPPC2 variant, c.239-20_239-12delinsAATGAA, initially classified as a variant of uncertain significance (VUS). Segregation analysis across the family enabled reclassification of the variant to likely pathogenic, confirming X-linked SEDT. The proband's younger brother exhibited earlier radiologic abnormalities and, notably, a favorable response to rhGH, whereas the younger sister-an asymptomatic heterozygous carrier-showed normal spinal morphology, consistent with expected female carrier phenotypes. CONCLUSIONS: This family-based report underscores the generally limited therapeutic effect of rhGH in SEDT while highlighting potential interindividual variability, as evidenced by the younger male sibling's response. It further emphasizes the diagnostic utility of WGS for detecting deep intronic variants missed by WES and the importance of segregation analysis in resolving VUS in rare skeletal dysplasias.

Humans↗
PubMed2003

A Salmonella typhimurium rfaE mutant recovers invasiveness for human epithelial cells when complemented by wild type rfaE (controlling biosynthesis of ADP-L-glycero-D-mannoheptose-containing lipopolysaccharide).

Invasion of host cells is essential for the pathogenicity of Salmonella. The author's group has recently reported the cloning of the rfaE gene of Salmonella typhimurium, previously implicated in biosynthesis of the lipopolysaccharide (LPS)-inner core [Jin et al. (2001); Kim (2002)]. The product of the rfaE gene is involved in ADP-L-glycero-D-manno-heptose biosynthesis. rfaE mutants synthesize heptose-deficient LPS (Re-LPS) consisting only of lipid A and 3-deoxy-D-manno-octulosonic acid (KDO). Mutants that make incomplete LPS are rough mutants and "deep-rough" mutants affected in the heptose region of the inner core have reduced growth rate and increased sensitivity to high temperature. Complementation of S. typhimurium rfaE mutant strain SL1102 (rfaE543) with rfaE demonstrated conclusively that this gene restored the smooth phenotype, and the LPS produced by the complemented strain was indistinguishable from that of wild type smooth strains. In vitro infection experiments showed that complementation with rfaE permitted invasion of human Chang epithelial cells, larynx epidermal carcinoma HEp-2 cells and intestinal epithelial Henle-407 cells. These data imply that the structure of the LPS that is synthesized is critical for Salmonella invasiveness.

Bacterial Proteins↗
PubMed1996

[Autosomal chromosomes and anomalies of the oromaxillofacial area].

The study deals with genetic diseases due to anomalies in the number and structure of autosomal chromosomes associated with oro-facial malformations. Pertinent literature from 1980 and clinical cases for each defect were analyzed. By comparing clinical signs and symptoms with chromosome abnormalities it was possible to build an analytical diagram showing the prevalence of malformation exhibited by each anatomical oro-facial region (cranial, labial, palatal, nasal, ocular, dental, lingual region). A very high prevalence of malformation was assessed for lip-and-palate regions (78%). These region often shows "micro-signs" of cleft lip and/or palate (deep palatal vault, maxillary hypoplasia, congenitally missing upper central incisors) which may indicate the presence of a mildly expressed chromosome abnormality. The whole sample of autosomal chromosome abnormalities induce anomalies in structures lying along body and face mid-line. The phenotypic expression of such anomalies may be defective (cleft lip and/or palate), or excessive as well (excessive thickness of the lingual frenum, broadening of the nasal bridge).

Chromosome Aberrations↗
PubMed1984

Börjeson-Forssman-Lehmann syndrome: further delineation in five cases.

We have studied five males with Börjeson-Forssman-Lehmann syndrome (BFLS) from two unrelated families. They had a characteristic facial appearance with prominent supraorbital ridges, deep-set eyes, ptosis, and large ears, as well as obesity, severe mental retardation, hypotonia, and hypogonadism. Ophthalmologic, EEG, and skeletal abnormalities were also present. The findings in several presumed or possible heterozygous women were evaluated and suggested a wide range of phenotypic effects varying between apparent normality to mild or moderately evident BFLS manifestations. The observed pattern of occurrence of the BFLS in our two families provides strong support for X-linked inheritance. In clinically normal female relatives at risk for being carriers of BFLS, we have been unsuccessful in identifying a reliable screening test. The condition in our and previously reported patients was contrasted with other malformation syndromes and our findings support the conclusion that BFLS is a distinct and clinically identifiable disorder.

Abnormalities, Multiple↗
PubMed1997

B-cell deficiency does not abrogate development of cutaneous hyperplasia in mice inheriting the defective fibrillin-1 gene.

Tight-skin (TSK) mouse, the experimental model for scleroderma, develops cutaneous hyperplasia, cardiac hypertrophy, pulmonary emphysema and autoimmunity against scleroderma target autoantigens. The cutaneous hyperplasia is associated with the accumulation of microfibrils and elastic fibers in the middle and deep dermis. Fibrillin-1 (Fbn-1) is a major component of the 10-12 nm microfibrils found in the extracellular matrix. In this study we report the identification of a genetic marker in the Fbn-1 gene that can distinguish the mutant phenotype. TSK mice exhibit an unique polymorphism in the Fbn-1 gene. RNA analysis, PCR analysis and sequence determination of the mutant gene showed that the Fbn-1 gene polymorphism is due to intragenic duplication of a segment of the gene coding for 3.0 Kb of mRNA sequence (10 Kb of the genome). Histological analysis of skin samples from F1 progeny obtained by crossing TSK mice with JH-/-, RAG2-/- or vit/vit showed a significant correlation between the inheritance of the defective Fbn-1 gene and the development of cutaneous hyperplasia. Further, our results also show that in mice deficient in mature B cells inheriting the defective Fbn-1 gene, development of cutaneous hyperplasia is not abrogated. Thus, production of autoantibodies or the presence of mature B lymphocytes do not play an integral role in the pathogenesis of cutaneous hyperplasia.

Amino Acid Sequence↗