Defective hematopoietic differentiation of immune aplastic anemia patient-derived iPSCs

In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation.Subject terms: Anaemia, Induced pluripotent stem cells     

Fire ants: What do rural and urban areas show us about occurrence, diversity,and ancestral state reconstruction?

In South America, Solenopsis saevissima and S. invicta are the most common fire ants. Nests are founded in areas under anthropic interference like urban or rural areas, but S. invicta is found preferentially in those with the greatest anthropic interference. However, we do not know the rates at which they exist in anthropized areas next to high density of native vegetation. Areas with 60 to 90% of native Atlantic Forest were selected to verify the occurrence of both species in rural and urban areas. We investigated the molecular diversity and applied the reconstruction of the ancestral state analysis for each species. A total of 186 nests were analyzed and we found that the two species had the same proportion in the urban area. However, S. saevissima had a higher rate of prevalence in the rural area, in addition to having a greater number of haplotypes and ancestry associated with this type of habitat for the region. S. invicta had the same number of haplotypes in both rural and urban regions, and less haplotypic diversity. We conclude that S. saevissima is a species typically associated with rural areas and S. invicta, although present, is not dominant in urban areas. Keywords: Biodiversity, haplotype diversity, DNA barcoding, mtDNA     

A mechanistic model for internal bone remodeling exhibits different dynamic responses in disuse and overload

Bone is a dynamic tissue which, through the process of bone remodeling in the mature skeleton, renews itself during normal function and adapts to mechanical loads. It is, therefore, important to understand the effect of remodeling on the mechanical function of bone, as well as the effect of the inherent time lag in the remodeling process. In this study, we develop a constitutive model for bone remodeling which includes a number of relevant mechanical and biological processes and use this model to address differences in the remodeling behavior as a volume element of bone is placed in disuse or overload. The remodeling parameters exhibited damped oscillatory behavior as the element was placed in disuse, with the amplitude of the oscillations increasing as the severity of disuse increased. In overload situations, the remodeling parameters exhibited critically sensitive behavior for loads beyond a threshold value. These results bear some correspondence to experimental findings, suggesting that the model may be useful when examining the importance of transient responses for bone in disuse, and for investigating the role fatigue damage removal plays in preventing or causing stress fractures. In addition, the constitutive algorithm is currently being employed in finite element simulations of bone adaptation to predict important features of the internal structure of the normal femur, as well as to study bone diseases and their treatment.     

Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. Implications for its physiological role

Studies on the localization of paraoxonases (PON's) are of interest because of its involvement in both the detoxication of activated organophosphorus pesticides and in the prevention of peroxidative damage to phospholipids and cholesteryl-esters in LDL and HDL particles and cell membranes during the atherogenic process. In the present study, we have investigated the cellular localization of PON1 by immunohistochemistry in different rat tissues. The protein was mainly detected in the endothelial lining of every tissue studied (liver, kidney, lung and brain). Besides, it was found in hepatocytes from the centrolobular region of the liver, in the glomeruli and basal pole of the proximal convoluted tubule of the kidney, in cells from bronchiolar epithelium and type I pneumocytes of the lung, and in leptomeningeal cells, ependymal cells and ventricular side of choroid plexus cells of the brain. However, neurons and glia lacked immunostaining. After 3-methylcholanthrene induction an increase in the intensity of immunostaining was observed in the same areas, as well as an additional staining in midzonal hepatocytes. On the basis of the tissue distribution observed for PON1, it is proposed that this enzyme might have a function related to the inactivation of oxidative stress by-products (either at a cellular level or blood-vessel wall) and other environmental chemicals. At present it has not yet been established whether the paraoxonase detected in the various tissues is truly a product of the PON1 gene or could represent products of the PON2 or PON3 genes.     

Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection

To understand the high variability of the asymptomatic interval between primary human immunodeficiency virus type 1 (HIV-1) infection and the development of AIDS, we studied the evolution of the C2-V5 region of the HIV-1 env gene and of T-cell subsets in nine men with a moderate or slow rate of disease progression. They were monitored from the time of seroconversion for a period of 6 to 12 years until the development of advanced disease in seven men. Based on the analysis of viral divergence from the founder strain, viral population diversity within sequential time points, and the outgrowth of viruses capable of utilizing the CXCR4 receptor (X4 viruses), the existence of three distinct phases within the asymptomatic interval is suggested: an early phase of variable duration during which linear increases ( approximately 1% per year) in both divergence and diversity were observed; an intermediate phase lasting an average of 1.8 years, characterized by a continued increase in divergence but with stabilization or decline in diversity; and a late phase characterized by a slowdown or stabilization of divergence and continued stability or decline in diversity. X4 variants emerged around the time of the early- to intermediate-phase transition and then achieved peak representation and began a decline around the transition between the intermediate and late phases. The late-phase transition was also associated with failure of T-cell homeostasis (defined by a downward inflection in CD3(+) T cells) and decline of CD4(+) T cells to 相似文献   

Pollinarium morphology and floral rewards in Brazilian Maxillariinae (Orchidaceae)

BACKGROUND AND AIMS: There is strong support for the monophyly of the orchid subtribe Maxillariinae s.l., yet generic boundaries within it are unsatisfactory and need re-evaluation. In an effort to assemble sets of morphological characters to distinguish major clades within this subtribe, the pollinarium morphology and floral rewards of representative Brazilian species of this subtribe were studied. METHODS: The study was based on fresh material from 60 species and seven genera obtained from cultivated specimens. Variation of pollinarium structure and floral rewards was assessed using a stereomicroscope and by SEM analysis. KEY RESULTS: Four morphological types of pollinaria are described. Type 1 appears to be the most widespread and is characterized by a well-developed tegula. Type 2 lacks a stipe and the pollinia are attached directly to the viscidium. Type 3 also lacks a stipe, and the viscidium is rigid and dark. In Type 4, the stipe consists of the whole median rostelar portion and, so far, is known only from Maxillaria uncata. Nectar, trichomes, wax-like and resin-like secretions are described as flower rewards for different groups of species within the genus Maxillaria. Data on the biomechanics and pollination biology are also discussed and illustrated. In Maxillariinae flowers with arcuate viscidia, the pollinaria are deposited on the scuttellum of their Hymenopteran pollinators. In contrast, some flowers with rounded to rectangular, pad-like viscidia fix their pollinaria on the face of their pollinators. CONCLUSIONS: Pollinarium morphology and floral features related to pollination in Brazilian Maxillariinae are more diverse than previously suggested. It is hoped that the data presented herein, together with other data sources such as vegetative traits and molecular tools, will be helpful in redefining and diagnosing clades within the subtribe Maxillariinae.     

Effect of photon flux density and temperature on the production of halogenated monoterpenes by Plocamium cartilagineum (Plocamiaceae, Rhodophyta)

The effect of different photon flux densities (PFD) and temperatures on the relative growth rate (RGR) and the concentration of three halogenated monoterpenes in samples of Plocamium cartilagineum L.( Dixon), a marine alga (Rhodophyceae), were studied. The highest RGR (22.8 +/- 0.04 d(-1)) was obtained at 15 degreebC and 41 ,mol m(-2) s)(-1) of PFD and the lowest (18.0 +/- 0.12 d(-1)) was obtained at 18 degrees C and 120 micromol m(-2) s(-1). The different temperatures and light used in assays did not affect significantly the production of organic compounds. The production of mertensene and violacene was not affected significantly. However, compound 1 reached the highest concentration at 15 degrees C and 65 micromol m(-2) s(-1)). The relationship between growth and production of monoterpenes of P. cartilagineum and the effect of temperature and the PFD were analyzed.     

Dynamic formation of optically trapped microstructure arrays for biosensor applications

We explore the dynamic properties of multiple-beam optical traps to manipulate arrays of microstructures for biosensor applications. Multiple optical traps are generated by a virtually loss-less transformation of input phase patterns into high-intensity trapping-beams. A direct image projection of the phase patterns enables an adjustable number of optical traps in addition to instantaneous control of the position, size, shape and intensity of each trapping-beam. We present experimental results showing various colloidal formations through dynamic optical manipulation of polystyrene microspheres and yeast cells in aqueous media. The experimental configurations are geared towards the use of multiple-beam optical traps for biosensor applications.