Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy

Modes of Aβ toxicity in Alzheimer’s disease

Alzheimer’s disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide

Accelerating Uplift in the North Atlantic Region as an Indicator of Ice Loss

Vertical motions of the rocky margins of Greenland and Antarctica respond to mass changes of their respective ice sheets1, 2. However, these motions can be obscured by episodes of glacial advance or retreat that occurred hundreds to thousands of years ago3, 4, 5, 6, which trigger a delayed response because of viscous flow in the underlying mantle. Here we present high-precision global positioning system (GPS) data that describe the vertical motion of the rocky margins of Greenland, Iceland and Svalbard. We focus on vertical accelerations rather than velocities to avoid the confounding effects of past events. Our data show an acceleration of uplift over the past decade that represents an essentially instantaneous, elastic response to the recent accelerated melting of ice throughout the North Atlantic region. Our comparison of the GPS data to models for glacial isostatic adjustment suggests that some parts of western coastal Greenland were experiencing accelerated melting of coastal ice by the late 1990s. Using a simple elastic model, we estimate that western Greenland’s ice loss is accelerating at an average rate of 8.7±3.5 Gt yr−2, whereas the rate for southeastern Greenland—based on limited data—falls at 12.5±5.5 Gt yr−2

Adaptações neuromusculares de flexores dorsais e plantares a duas semanas de imobilização após entorse de tornozelo Dorsiflexor and plantarflexor neuromuscular adaptations at two-week immobilization after ankle sprain

INTRODUÇÃO: A entorse de tornozelo é uma lesão de alta incidência comumente tratada com períodos de imobilização, levando a adaptações estruturais e funcionais dos músculos atuantes nesta articulação. OBJETIVO: Identificar as adaptações dos músculos flexores dorsais e flexores plantares após duas semanas de imobilização em sujeitos que sofreram entorse de tornozelo. MÉTODOS: Onze indivíduos (seis mulheres e cinco homens) acometidos por entorse de tornozelo grau II foram submetidos a 14 dias de imobilização por tala gessada. Após a retirada da imobilização, foram realizadas avaliações bilaterais de (1) perimetria da perna, (2) amplitude de movimento (ADM) do tornozelo, (3) torque isométrico máximo de flexores dorsais e flexores plantares em sete ângulos do tornozelo e (4) ativação eletromiográfica dos músculos tibial anterior (TA), sóleo (SO) e gastrocnêmio medial (GM). Os resultados obtidos no segmento imobilizado foram comparados com os do segmento saudável contralateral através de um teste t de Student pareado (p < 0,05). RESULTADOS: O segmento imobilizado apresentou redução (1) da circunferência nas regiões proximais da perna, (2) da ADM de flexão dorsal e plantar, (3) do torque isométrico máximo de flexores dorsais e plantares e (4) do sinal eletromiográfico do TA em todos os ângulos articulares e do SO nos maiores comprimentos musculares. Não houve diferença no sinal eletromiográfico do músculo GM. CONCLUSÃO: Um período relativamente curto de imobilização (duas semanas) prejudica a funcionalidade dos músculos flexores dorsais e flexores plantares do tornozelo.<br>INTRODUCTION: Ankle sprains are a kind of injury with high incidence that is usually treated with an immobilization period, leading to structural and functional adaptation in the muscles around this joint. PURPOSE: To identify the dorsiflexor and plantarflexor muscles adaptations after two weeks of immobilization in subjects who suffered ankle sprain. METHODS: Eleven subjects (six women and five men) who suffered a second degree ankle sprain underwent 14 days of ankle joint immobilization with a plaster cast. After removal of the plaster cast, the following bilaterally evaluations were obtained: (1) leg circumference; (2) ankle joint range of motion (ROM); (3) maximal isometric torque of plantar and dorsiflexors obtained in seven different angles; and (4) electromyographic signals of the tibialis anterior (TA), gastrocnemius medialis (GM) and soleus (SO) muscles. Results obtained in the immobilized side were compared to the contralateral healthy side with a paired Student's t-test (p<0.05). RESULTS: Immobilized side presents decrease (1) at the proximal leg circumference, (2) in dorsiflexor and plantarflexor ROM, (3) in dorsiflexor and plantarflexor maximal isometric torque and (4) in electromyographic signal of the TA at all joint angles and at the longest muscle lengths in SO. There was no alteration in the electromyographic signal of the GM muscle. CONCLUSION: A relatively short immobilization period (two weeks) impairs the functionality of ankle dorsiflexor and plantarflexor muscles

A DNA vaccine candidate for B. anthracis immunization, pcDNA3.1+PA plasmid, induce Th1/Th2 mixed responses and protection in mice

The protective antigen (PA) of Bacillus anthracis (B. anthracis) is a potent immunogen and a candidate subunit vaccine. To address the question whether antibodies raised against PA following injection of pcDNA3.1+PA plasmid, encoding PA, can protect against virulent B. anthracis two different regimens of PA based vaccines (DNA and live spore) were used. The groups of BALB/c mice that received live spores of the Sterne strain, naked pcDNA3.1 and naked pcDNA3.1+PA were compared to control groups. All groups were injected three times with 30-day intervals. Two weeks after the last immunization, all mice were subjected to challenge with a pathogenic strain of B. anthracis (C2). Blood samples were taken before each injection and challenge. Evaluation of the sera by ELISA method showed that DNA immunization using pcDNA3.1+PA plasmid resulted in an antibody profile representative of a mixed Th1 and Th2 response, with a skewing to a Th1 response. The group which received the naked pcDNA3.1+PA had a survival rate of >80%. This challenge assay revealed that antibodies raised following DNA vaccination against PA can confer strong protection, and resistance against virulent species of B. anthracis