Differential Expression of Collagen Type V and XI α-1 in Human Ascending Thoracic Aortic Aneurysms

Background—The molecular mechanisms leading to ascending thoracic aortic aneurysms (ATAAs) remain unknown. We hypothesized that alterations in expression levels of specific fibrillar collagens occur during the aneurysmal process. Methods—Surgical samples from ascending aortas from patients with degenerative ATAAs were subdivided by aneurysm diameter: small, 5 to 6 cm; medium, 6 to 7 cm; and large, greater than 7 cm; and compared with nonaneurysmal aortas (mean diameter, 2.3 cm). Results—Histology, immunofluorescence, and electron microscopy demonstrated greater disorganization of extracellular matrix constituents in ATAAs as compared with control with an increase in collagen α1(XI) within regions of cystic medial degenerative lesions. Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed collagens type V and α1(XI) were significantly and linearly increased in ATAAs as compared with control (p \u3c 0.001). There was no change in the messenger ribonucleic acid (mRNA) expression levels of collagens type I and III. Western blot analysis showed collagens type I and III were significantly decreased and collagens α1(XI) and V were significantly increased and were linearly correlated with the size of the aneurysm (p \u3c 0.001 for both). Conclusions—These results demonstrate that increased collagen α1(XI) and collagen V mRNA and protein levels are linearly correlated with the size of the aneurysm and provide a potential mechanism for the generation and progression of aneurysmal enlargement

Extracellular Matrix in Development and Disease

The extracellular matrix in development and disease deals with the molecular and cellular aspects of development and disease. Cells exist in three-dimensional scaffolding called the extracellular matrix. The matrix holds together the millions of cells that make up our blood vessels, organs, skin, and all tissues of the body. The matrix serves as a reservoir of signaling molecules as well. In bacterial cultures, biofilms form as an extracellular matrix and play essential roles in disease and drug resistance. Topics such as matrix structure and function, cell attachment and cell surface proteins mediating cell-matrix interactions, synthesis, regulation, composition, structure, assembly, remodeling, and function of the matrix are included. A common thread uniting the topics is the essential nature that the matrix plays in normal development and pathophysiology. Providing new knowledge will lead us to improved diagnostics, the preventions of disease progression, and therapeutic strategies for the repair and regeneration of tissues. Topics such as the extracellular matrix in hereditary diseases, reproduction, cancer, muscle, and tissue engineering applications, and diverse roles for integrins, are included in this collection

Autism as the Early Closure of a Neuroplastic Critical Period Normally Seen in Adolescence

The most severe cases of autism are diagnosed by extreme social dysfunction and other behavioral abnormalities. A number of genetic studies have been conducted to correlate behavioral phenotypes to genetic dysfunctions, but no “autism gene” has yet been discovered. In addition, environmental factors have been found to influence the development of autistic traits with high probability. This review will examine the role of a shortened period of neuroplasticity as a unifying feature of the autistic phenotype. The neuroplastic period of interest normally extends into adolescence, allowing for neural integration and the development of language and social skills. Early closure of this period may result in a shortened period of development, forcing the brain to rely on underdeveloped structures

A Lipid-Rich Gestational Diet Predisposes Offspring to Nonalcoholic Fatty Liver Disease: A Potential Sequence of Events

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It affects 20%–30% of the US population, and it is increasing worldwide. Recently, the role of lipid-rich maternal gestational nutrition in spurring the development of NAFLD among offspring has been indicated. Fetal predisposition to NAFLD involves numerous physiological reroutings that are initiated by increased delivery of nonesterified fatty acids to the fetal liver. Hampered ß-oxidation, uncontrolled oxidative stress, increased triacylglycerol synthesis, and the endoplasmic reticulum unfolded protein response are all implicated in sculpting a hepatic phenotype with a propensity to develop NAFLD in the postnatal state. This review suggests a mechanism that integrates outcomes reported by a variety of studies conducted in an analysis of fetal hepatic metabolic capacity amid the maternal consumption of a high-fat diet. Potential preventive measures and therapies for use both as part of prenatal nutrition and for those at risk for the development of NAFLD are also discussed

Application of palaeoecology for peatland conservation at Mossdale Moor, UK

In a recent discussion of research priorities for palaeoecology, it was suggested that palaeoecological data can be applied and used to inform nature conservation practice. The present study exemplifies this approach and was conducted on a degraded blanket mire in Yorkshire, UK, in collaboration with a field-based moorland restoration agency. High-resolution, multiproxy palaeoecological analyses on a peat core from Mossdale Moor reconstructed mid to late-Holocene vegetation changes. Humification, pollen, plant macrofossil and charcoal analyses carried out throughout the peat profile show marked changes in species composition and indicate their potential causes. Results suggest that human clearance in the Mesolithic–Neolithic transition may have initiated peat growth at Mossdale Moor, making this landscape ‘semi-natural’ in its origin. Further human-induced changes are identified at 1300 cal years BP, most likely clearance by fire, and between 20 and 0 cm depth where a substantial charcoal increase is interpreted as recent (<400 years) management practices using burning to encourage browse on the moor. The long-term ecological history of the moor, derived using palaeoecological techniques, will be used to inform conservation practice and to help set feasible targets for restoration and conservation at Mossdale Moo

Ascertaining the nature and timing of mire degradation : using palaeoecology to assist future conservation management in Northern England

This study was initiated under contract VT0419 from English Nature (Natural England) to CECQR. In 2015, additional funding was provided by the Yorkshire Peat Partnership, for 210Pb dating, to refine age–depth estimates. We thank the following for fieldwork co-ordination, logistics or field assistance: Miriam Baynes, Mike Sutcliffe, Martin Furness, Gez Marshall, Paul Duncan, Tim Page, Andrew Windrum, Craig Sandham and Jackie Smith. We thank the Editor and two anonymous reviewers for suggestions for improvements.Peer reviewedPublisher PD

DICER1 Syndrome: \u3cem\u3eDICER1\u3c/em\u3e Mutations in Rare Cancers

DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions for future research are discussed

Advances in Cartilage Tissue Engineering Using Bioinks with Decellularized Cartilage and Three-Dimensional Printing

Osteoarthritis, a chronic, debilitating, and painful disease, is one of the leading causes of disability and socioeconomic burden, with an estimated 250 million people affected worldwide. Currently, there is no cure for osteoarthritis and treatments for joint disease require improvements. To address the challenge of improving cartilage repair and regeneration, three-dimensional (3D) printing for tissue engineering purposes has been developed. In this review, emerging technologies are presented with an overview of bioprinting, cartilage structure, current treatment options, decellularization, bioinks, and recent progress in the field of decellularized extracellular matrix (dECM)–bioink composites is discussed. The optimization of tissue engineering approaches using 3D-bioprinted biological scaffolds with dECM incorporated to create novel bioinks is an innovative strategy to promote cartilage repair and regeneration. Challenges and future directions that may lead to innovative improvements to currently available treatments for cartilage regeneration are presented

Doxorubicin-Induced Modulation of TGF-β Signaling Cascade in Mouse Fibroblasts: Insights into Cardiotoxicity Mechanisms

Doxorubicin (DOX)-induced cardiotoxicity has been widely observed, yet the specific impact on cardiac fibroblasts is not fully understood. Additionally, the modulation of the transforming growth factor beta (TGF-β) signaling pathway by DOX remains to be fully elucidated. This study investigated DOX’s ability to modulate the expression of genes and proteins involved in the TGF-β signaling cascade in mouse fibroblasts from two sources by assessing the impact of DOX treatment on TGF-β inducible expression of pivotal genes and proteins within fibroblasts. Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX in the presence of TGF-β1 to assess changes in protein levels by western blot and changes in mRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our results revealed a dose-dependent reduction in cellular communication network factor 2 (CCN2) protein levels upon DOX treatment in both NIH3T3 and CFs, suggesting an antifibrotic activity by DOX in these fibroblasts. However, DOX only inhibited the TGF-β1 induced expression of COL1 in NIH3T3 cells but not in CFs. In addition, we observed that DOX treatment reduced the expression of BMP1 in NIH3T3 but not primary cardiac fibroblasts. No significant changes in SMAD2 protein expression and phosphorylation in either cells were observed after DOX treatment. Finally, DOX inhibited the expression of Atf4 gene and increased the expression of Cdkn1a, Id1, Id2, Runx1, Tgfb1, Inhba, Thbs1, Bmp1, and Stat1 genes in NIH3T3 cells but not CFs, indicating the potential for cell-specific responses to DOX and its modulation of the TGF-β signaling pathway