FAM20C is a gene coding for a protein kinase that targets S-X-E/pS motifs on different phosphoproteins belonging to diverse tissues. Pathogenic variants of FAM20C are responsible for Raine syndrome ...(RS), initially described as a lethal and congenital osteosclerotic dysplasia characterized by generalized atherosclerosis with periosteal bone formation, characteristic facial dysmorphisms and intracerebral calcifications. The aim of this review is to give an overview of targets and variants of FAM20C as well as RS aspects. We performed a wide phenotypic review focusing on clinical aspects and differences between all lethal (LRS) and non-lethal (NLRS) reported cases, besides the FAM20C pathogenic variant description for each. As new targets of FAM20C kinase have been identified, we reviewed FAM20C targets and their functions in bone and other tissues, with emphasis on novel targets not previously considered. We found the classic lethal and milder non-lethal phenotypes. The milder phenotype is defined by a large spectrum ranging from osteonecrosis to osteosclerosis with additional congenital defects or intellectual disability in some cases. We discuss our current understanding of FAM20C deficiency, its mechanism in RS through classic FAM20C targets in bone tissue and its potential biological relevance through novel targets in non-bone tissues.
The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of ...terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.
Three tiers of genome evolution in reptiles Organ, Chris L.; Moreno, Ricardo Godínez; Edwards, Scott V.
Integrative and comparative biology,
10/2008, Letnik:
48, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Characterization of reptilian genomes is essential for understanding the overall diversity and evolution of amniote genomes, because reptiles, which include birds, constitute a major fraction of the ...amniote evolutionary tree. To better understand the evolution and diversity of genomic characteristics in Reptilia, we conducted comparative analyses of online sequence data from Alligator mississippiensis (alligator) and Sphenodon punctatus (tuatara) as well as genome size and karyological data from a wide range of reptilian species. At the whole-genome and chromosomal tiers of organization, we find that reptilian genome size distribution is consistent with a model of continuous gradual evolution while genomic compartmentalization, as manifested in the number of microchromosomes and macrochromosomes, appears to have undergone early rapid change. At the sequence level, the third genomic tier, we find that exon size in Alligator is distributed in a pattern matching that of exons in Gallus (chicken), especially in the 101-200 bp size class. A small spike in the fraction of exons in the 301 bp-1 kb size class is also observed for Alligator, but more so for Sphenodon. For introns, we find that members of Reptilia have a larger fraction of introns within the 101 bp-2 kb size class and a lower fraction of introns within the 5-30 kb size class than do mammals. These findings suggest that the mode of reptilian genome evolution varies across three hierarchical levels of the genome, a pattern consistent with a mosaic model of genomic evolution.
Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: ...generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic
pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new
variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is expressed in most human cell types (example: Epithelial cells, fibroblasts and endothelial), it serves a key role in the control ...of cell survival, proliferation and motility. The abnormal expression of FAK has been associated with poor prognosis in cancer, including ovarian cancer. However, although FAK isoforms with specific molecular and functional properties have been characterized, there are a limited number of published studies that examine FAK isoforms in ovarian cancer. The aim of the present study was to analyze the expression level of FAK and its isoforms in ovarian cancer. The expression of FAK kinase and focal adhesion targeting (FAT) domains was determined with immunohistochemistry in healthy ovary, and serous and mucinous cystadenoma, borderline tumor and carcinoma samples. Additionally, the expression of FAK and its isoforms were investigated in three ovarian cancer-derived cell lines with western blotting and reverse transcription-semi-quantitative polymerase chain reaction. An increased expression of FAK kinase domain was determined in serous tumor samples and was associated with advancement of the lesion. FAK kinase domain expression was moderate-to-low in mucinous tumor samples. The expression of the FAK FAT domain in tumor samples was reduced, compared with healthy ovary samples; however, the FAT domain was localized to the cellular nucleus. Expression of alternative transcripts FAK°, FAK
and FAK
was determined in all three cell lines investigated. In conclusion, FAK kinase and FAT domains are differentially expressed among ovarian tumor types. These results indicated the presence of at least two isoforms of FAK (FAK and the putative FAK-related non-kinase) in tumor tissue, which is supported by the cells producing at least three FAK alternative transcripts. These results may support the use of FAK and its isoforms as biomarkers for ovarian cancer.
Water activity (aw) influences the growth of fungi as well as the biosynthesis of ochratoxin A (OTA). The objective of this study was to obtain the critical storage conditions at which coffee beans ...are not susceptible to deteriorative physical changes and quantification of OTA in dry cherries and green‐coffee beans after 60 days of storage at 35°C. aw significantly affected the color, texture, and morphology in dry cherries and in green‐coffee beans after storing. Three different genera of fungi were isolated from coffee samples, Aspergillus, Rhizopus, and Penicillium. The analyzed coffee beans showed a high concentration of OTA (15.49–65.22 μg·kg−1). The conditions at 35°C under which the physical changes and the highest concentration of OTA were found are the following: aw between 0.515 and 0.821. These results suggest that the control of aw during coffee bean storage can be useful to limit OTA formation, whereas the physical properties are maintained.
Novelty impact statement
Dry cherries showed higher OTA content than green‐coffee beans. In addition, water activity affects the OTA content, color, texture, and morphology in dry cherries and green‐coffee beans. Thus, the control of water activity during coffee bean storage can be useful to limit OTA formation.
Aim: We test a new species distribution modelling (SDM) framework, while comparing results to more common distribution modelling techniques. This framework allows for the combination of presence-only ...(PO) and presence-absence (PA) data and accounts for imperfect detection and spatial bias in presence data. The new framework tested here is based on a Poisson point process model, which allows for predictions of population size. We compared these estimates to those provided by experts on the species. Species and Location: Presence data on Baird's tapir (Tapirus bairdii) throughout its range from southern Mexico to northern Colombia were used in this research, primarily from the years 2000 to 2016. Methods: Four SDM frameworks are compared as follows: (1) Maxent, (2) a presenceonly (PO) SDM based on a Poisson point process model (PPM), (3) a presence-absence (PA) SDM also based on a PPM and (4) an Integrated framework which combines the previous two models. Model averaging was used to produce a single set of coefficient estimates and predictive maps for each model framework. A hotspot analysis (Gi*) was used to identify habitat cores from the predicted intensity of the Integrated model framework. Results: Important variables to model the distribution of Baird's tapir included land cover, human pressure and topography. Accounting for spatial bias in the presence data affected which variables were important in the model. Maxent and the Integrated model produced predictive maps with similar patterns and were considered to be more in agreement with expert knowledge compared to the PO and PA models. Main conclusions: Total abundance as predicted by the model was higher than expert opinion on the species, but local density estimates from our model were similar to available independent assessments. We suggest that these results warrant further validation and testing through collection of independent test data, development of more precise predictor layers and improvements to the model framework.
To determine whether gait and balance dysfunction are present in young urbanites exposed to fine particular matter PM2.5 ≥ annual USEPA standard, we tested gait and balance with Tinetti and Berg ...tests in 575 clinically healthy subjects, age 21.0 ± 5.7 y who were residents in Metropolitan Mexico City, Villahermosa and Reynosa. The Montreal Cognitive Assessment was also applied to an independent cohort n:76, age 23.3 ± 9.1 y. In the 575 cohort, 75.4% and 34.4% had abnormal total Tinetti and Berg scores and high risk of falls in 17.2% and 5.7% respectively. BMI impacted negatively Tinetti and Berg performance. Gait dysfunction worsen with age and males performed worse than females. Gait and balance dysfunction were associated with mild cognitive impairment MCI (19.73%) and dementia (55.26%) in 57/76 and 19 cognitively intact subjects had gait and balance dysfunction. Seventy-five percent of urbanites exposed to PM2.5 had gait and balance dysfunction. For MMC residents-with historical documented Alzheimer disease (AD) and CSF abnormalities, these findings suggest Alzheimer Continuum is in progress. Early development of a Motoric Cognitive Risk Syndrome ought to be considered in city dwellers with normal cognition and gait dysfunction. The AD research frame in PM2.5 exposed young urbanites should include gait and balance measurements. Multicity teens and young adult cohorts are warranted for quantitative gait and balance measurements and neuropsychological and brain imaging studies in high vs low PM2.5 exposures. Early identification of gait and balance impairment in young air pollution-exposed urbanites would facilitate multidisciplinary prevention efforts for modifying the course of AD.
•Exposure to air pollution is associated with gait and balance dysfunction.•Mexico City 575 urbanites 21.0 ± 5.7 y had abnormal Tinetti 75% and Berg 34%.•High risk of falls in 17% (Tinetti) and 5.7% (Berg) is of deep concern.•Gait and balance dysfunction are associated with MCI and dementia scores.•Gait and balance dysfunction suggest Alzheimer Continuum is in progress.
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