Fibronectin isoforms promote postnatal skeletal development.

Fibronectin (FN) is a ubiquitous extracellular matrix glycoprotein essential for the development of various tissues. Mutations in FN cause a unique form of spondylometaphyseal dysplasia, emphasizing its importance in cartilage and bone development. However, the relevance and functional role of FN during skeletal development has remained elusive.

Reduced frontocingulate theta connectivity during emotion regulation in major depressive disorder.

Background: Cognitive reappraisal is an essential emotion regulation skill for social life and psychological health. However, individuals with major depressive disorder (MDD) cannot use this skill effectively. Successful cognitive reappraisal in healthy controls (HC) has been shown to be associated with theta activity in a frontal and subcortical network.

The Late Effects of Hematopoietic Stem Cell Transplants in Pediatric Patients: A 25-Year Review.

Context: A rare, large, single-center study covering all long-term health outcomes of pediatric allogeneic hemopoietic stem cell transplant (HSCT) survivors, to provide comprehensive local data and identify gaps and future directions for improved care.

Objective: To document endocrine sequelae and other late effects of all HSCT recipients.

Design: Retrospective review.

Umbilical Cord Blood Cell Clearance Post-Infusion in Immune-Competent Children with Cerebral Palsy.

Umbilical cord blood cells have therapeutic potential for neurological disorders, through a paracrine mechanism of action. A greater understanding of the safety and immunological effects of allogeneic donor cord blood cells in the context of a healthy recipient immune system, such as in cerebral palsy, is needed. This study aimed to determine how quickly donor cord blood cells were cleared from the circulation in children with cerebral palsy who received a single intravenous infusion of 12/12 human leucocyte antigen (HLA)-matched sibling cord blood cells.

Male Marfan mice are predisposed to high-fat diet-induced obesity, diabetes, and fatty liver.

Gene mutations in the extracellular matrix protein fibrillin-1 cause connective tissue disorders including Marfan syndrome (MFS) with clinical symptoms in the cardiovascular, skeletal, and ocular systems. Patients with MFS also exhibit alterations in adipose tissues, which in some individuals leads to lipodystrophy, whereas in others to obesity. We have recently demonstrated that fibrillin-1 regulates adipose tissue homeostasis.

Platelets and osteoblasts: secretome connections.

Megakaryocyte hyperplasia associated with myeloproliferative neoplasms commonly leads to abnormal bone tissue deposition in the bone marrow, known as osteosclerosis. In this study, we aimed to synthesize the known proteomics literature describing factors released by megakaryocytes and platelets and to examine if any of the secreted factors have a known ability to stimulate the bone-forming cells, osteoblasts. Using a systematic search of Medline, we identified 77 articles reporting on factors secreted by platelets and megakaryocytes.

Fibrillin-1-regulated miR-122 has a critical role in thoracic aortic aneurysm formation.

Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1) revealed a spectrum of differentially regulated miRNAs.

The Role of the Nucleotides in the Insertion of the bis-Molybdopterin Guanine Dinucleotide Cofactor into apo-Molybdoenzymes.

The role of the GMP nucleotides of the bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor of the DMSO reductase family has long been a subject of discussion. The recent characterization of the bis-molybdopterin (bis-Mo-MPT) cofactor present in the YdhV protein, which differs from bis-MGD solely by the absence of the nucleotides, now enables studying the role of the nucleotides of bis-MGD and bis-MPT cofactors in Moco insertion and the activity of molybdoenzymes in direct comparison. Using the well-known TMAO reductase TorA as a model enzyme for cofactor insertion, we were able to show that the GMP nucleotides of bis-MGD are crucial for the insertion of the bis-MGD cofactor into apo-TorA.

Electrochemical Trimethylamine -Oxide Biosensor with Enzyme-Based Oxygen-Scavenging Membrane for Long-Term Operation under Ambient Air.

An amperometric trimethylamine -oxide (TMAO) biosensor is reported, where TMAO reductase (TorA) and glucose oxidase (GOD) and catalase (Cat) were immobilized on the electrode surface, enabling measurements of mediated enzymatic TMAO reduction at low potential under ambient air conditions. The oxygen anti-interference membrane composed of GOD, Cat and polyvinyl alcohol (PVA) hydrogel, together with glucose concentration, was optimized until the O reduction current of a Clark-type electrode was completely suppressed for at least 3 h. For the preparation of the TMAO biosensor, TorA was purified under anaerobic conditions and immobilized on the surface of a carbon electrode and covered by the optimized O scavenging membrane.

Active hematopoiesis triggers exosomal release of PRDX2 that promotes osteoclast formation.

Hematopoietic disorders, particularly hemolytic anemias, commonly lead to bone loss. We have previously reported that actively proliferating cancer cells stimulate osteoclastogenesis from late precursors in a RANKL-independent manner. We theorized that cancer cells exploit the physiological role of bone resorption to support expanding hematopoietic bone marrow and examined if hematopoietic cells can trigger osteoclastogenesis.

Role of Altered Metabolic Microenvironment in Osteolytic Metastasis.

Metastatic bone disease is generally incurable and leads to pathological fractures, pain, hypercalcemia, spinal cord compression and decreased mobility. The skeleton is the major site of bone metastases from solid cancers, including breast and prostate carcinoma. Bone metastasis is facilitated by activation of bone-resorbing osteoclasts, terminally differentiated multinucleated cells formed by fusion from monocytic precursors.

Spontaneous pregnancies in female survivors of childhood allogeneic haemopoietic stem cell transplant for haematological malignancies.

Objective: Spontaneous pregnancies and live births are rarely reported after haematopoietic stem cell transplant (HSCT). We report spontaneous pregnancy outcomes of sexually active female survivors of childhood allogeneic HSCT, to provide more data for future counselling.

Design, Patients And Measurements: Retrospective review of all female survivors of childhood haematological malignancies who had allogeneic HSCT at the Royal Children Hospital between 1985 and 2011.

Exosomal Release of L-Plastin by Breast Cancer Cells Facilitates Metastatic Bone Osteolysis.

Bone metastasis from breast and prostate carcinomas is facilitated by activation of bone-resorbing osteoclasts. Using proteomics approaches, we have identified peroxiredoxin-4 (PRDX4) as a cancer-secreted mediator of osteoclastogenesis. We now report characterization of L-plastin in the conditioned media (CM) of MDA-MB-231 human breast cancer cells using immunoblotting and mass spectrometry.

Regulation of Osteoclast Growth and Fusion by mTOR/raptor and mTOR/rictor/Akt.

Osteoclasts are giant bone cells formed by fusion from monocytes and uniquely capable of a complete destruction of mineralized tissues. Previously, we have demonstrated that in energy-rich environment not only osteoclast fusion index (the number of nuclei each osteoclast contains), but also cytoplasm volume per single nucleus was increased. The goal of this study was to investigate the regulation of metabolic sensor mTOR during osteoclast differentiation in energy-rich environment simulated by addition of pyruvate.

Fibulin-5 Regulates Angiopoietin-1/Tie-2 Receptor Signaling in Endothelial Cells.

Background: Fibulin-5 is an extracellular matrix glycoprotein that plays critical roles in vasculogenesis and embryonic development. Deletion of Fibulin-5 in mice results in enhanced skin vascularization and upregulation of the angiogenesis factor angiopoietin-1 (Ang-1), suggesting that Fibulin-5 functions as an angiogenesis inhibitor. In this study, we investigate the inhibitory effects of Fibulin-5 on Ang-1/TIE-2 receptor pathway signaling and cell survival in human endothelial cells.

Peroxiredoxin 4: a novel secreted mediator of cancer induced osteoclastogenesis.

Bone is a common site of metastasis from breast and prostate carcinoma, where activation of bone resorbing osteoclasts is important for cancer progression. A large body of evidence indicates that soluble factors produced by the cancer cells act to promote osteoclast formation. Using mass spectrometry, we identified peroxiredoxin (PRDX) as a secreted mediator of cancer-induced osteoclastogenesis.

Effects of low frequency cyclic mechanical stretching on osteoclastogenesis.

Bone cells are continuously exposed to mechanical deformations originating from movement. Mechanical stimulation at fundamental frequencies associated with most frequent normal locomotion (0.167-10Hz) has been reported to suppress differentiation of osteoclasts.

Effects of unilateral acoustic trauma on tinnitus-related spontaneous activity in the inferior colliculus.

This study describes the long-term effects of sound-induced cochlear trauma on spontaneous discharge rates in the central nucleus of the inferior colliculus (ICC). As in previous studies, single-unit recordings in Sprague-Dawley rats revealed pervasive increases in spontaneous discharge rates. Based on differences in their sources of input, it was hypothesized that physiologically defined neural populations of the auditory midbrain would reveal the brainstem sources that dictate ICC hyperactivity.

Autocrine signaling is a key regulatory element during osteoclastogenesis.

Osteoclasts are responsible for bone destruction in degenerative, inflammatory and metastatic bone disorders. Although osteoclastogenesis has been well-characterized in mouse models, many questions remain regarding the regulation of osteoclast formation in human diseases. We examined the regulation of human precursors induced to differentiate and fuse into multinucleated osteoclasts by receptor activator of nuclear factor kappa-B ligand (RANKL).

A new class of bioactive glasses: calcium-magnesium sulfophosphates.

Low-melting ionic sulfophosphate glasses from the system P2O5-SO4-MO-Na2O (M = Zn(2+), Ca(2+) or Mg(2+)) have been previously shown by us to allow tuneable aqueous dissolution and also enable processing temperatures well below 400°C. Sulfate ions are extremely safe for use in the body as decades of use of calcium sulfate bone grafts testifies and there is no known limit on their adult oral toxicity. This glass system therefore offers great potential for use as biomaterials, especially in organic-inorganic hybrid systems such as glass-polymer composites for tissue engineering or drug encapsulation and delivery applications.

Fibrillin-1 directly regulates osteoclast formation and function by a dual mechanism.

Mutations in the fibrillin-1 gene give rise to a number of heritable disorders, which are all characterized by various malformations of bone as well as manifestations in other tissues. However, the role of fibrillin-1 in the development and homeostasis of bone is not well understood. Here, we examined the role of fibrillin-1 in regulating osteoclast differentiation from primary bone-marrow-derived precursors and monocytic RAW 264.

Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: a report from the Australian and New Zealand Children's Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry.

We report a retrospective analysis of 53 haematopoietic stem cell transplants for inherited metabolic disorders performed at ANZCHOG transplant centres between 1992 and 2008. Indications for transplant included Hurler syndrome, ALD, and MLD. The majority of transplants utilized unrelated donor stem cells (66%) with 65% of those being unrelated cord blood.