Increased expression of HLA DR2 in acquired aplastic anemia and its impact on response to immunosuppressive therapy

Objective: To study the frequency of HLA DR2 status of patients with aplastic anemia and their response to immunosuppressive therapy at a tertiary care hospital. Methods: Thirty eight consecutive patients of acquired aplastic anemia were evaluated with respect to demographic features, severity of HLA DR2 status and response outcome to immunosuppressive therapy. Results: The mean age of the patients was 24.6 years + 16.4 with a male to female ratio of 2.8:1. Positivity of HLA DR2 was markedly high in acquired aplastic anemia patients. Twenty four (65%) out of 38 patients as compared to 45 (15%) of 300 healthy controls (p\u3c0.0001) were positive for HLA DR2. Response to immunosuppressive therapy, which included antilymphocyte globulin, cyclosporin and methylprednisolone, was available in sixteen HLA DR2 positive patients and was found satisfactory in 12/16 (75%) patients. Conclusion: HLA DR2 was significantly higher in patients with acquired aplastic anemia and favourable response to immunosuppressive therapy was also associated with HLA DR2 positivity (JPMA 54:251;2004)

Four-dimensional cardiac imaging in living embryos via postacquisition synchronization of nongated slice sequences

Being able to acquire, visualize, and analyze 3D time series (4D data) from living embryos makes it possible to understand complex dynamic movements at early stages of embryonic development. Despite recent technological breakthroughs in 2D dynamic imaging, confocal microscopes remain quite slow at capturing optical sections at successive depths. However, when the studied motion is periodic— such as for a beating heart—a way to circumvent this problem is to acquire, successively, sets of 2D+time slice sequences at increasing depths over at least one time period and later rearrange them to recover a 3D+time sequence. In other imaging modalities at macroscopic scales, external gating signals, e.g., an electro-cardiogram, have been used to achieve proper synchronization. Since gating signals are either unavailable or cumbersome to acquire in microscopic organisms, we have developed a procedure to reconstruct volumes based solely on the information contained in the image sequences. The central part of the algorithm is a least-squares minimization of an objective criterion that depends on the similarity between the data from neighboring depths. Owing to a wavelet-based multiresolution approach, our method is robust to common confocal microscopy artifacts. We validate the procedure on both simulated data and in vivo measurements from living zebrafish embryos

Nonuniform temporal alignment of slice sequences for four-dimensional imaging of cyclically deforming embryonic structures

The temporal alignment of nongated slice-sequences acquired at different axial positions in the living embryonic zebrafish heart permits the reconstruction of dynamic, three-dimensional data. This approach overcomes the current acquisition- speed limitation of confocal microscopes for real-time three-dimensional imaging of fast processes. Current synchronization methods align and uniformly scale the data in time, but do not compensate for slight variations in the heart rhythm that occur within a heartbeat. Therefore, they impose constraints on the admissible data quality. Here, we derive a nonuniform registration procedure based on the minimization of the absolute value of the intensity difference between adjacent slice-sequence pairs. The method compensates for temporal intra-sample variations and allows the processing of a wider range of data to build functional, dynamic models of the beating embryonic heart. We show reconstructions from data acquired in living, fluorescent zebrafish embryos

Quantitative mapping of intracardiac blood flow in embryonic zebrafish

Using real-time in vivo imaging and digital particle image velocimetry (DPIV) we quantitatively described the intracardiac flow environment of early zebrafish (Danio rerio) embryos. Gross cardiac dynamics were defined for two embryonic stages: 4.5 days post fertilization (dpf) and 37 hours post fertilization (hpf) using high-speed transmitted light microscopy with valve dynamics visualized through high-speed laser-scanning microscopy on transgenic embryos expressing GFP

A moral panic over cats

Some conservationists believe that free-ranging cats pose an enormous risk to biodiversity and public health and therefore should be eliminated from the landscape by any means necessary. They further claim that those who question the science or ethics behind their arguments are science deniers (merchants of doubt) seeking to mislead the public. As much as we share a commitment to conservation of biodiversity and wild nature, we believe these ideas are wrong and fuel an unwarranted moral panic over cats. Those who question the ecological or epidemiological status of cats are not science deniers, and it is a false analogy to compare them with corporate and right-wing special interests that perpetrate disinformation campaigns over issues, such as smoking and climate change. There are good conservation and public-health reasons and evidence to be skeptical that free-ranging cats constitute a disaster for biodiversity and human health in all circumstances. Further, there are significant and largely unaddressed ethical and policy issues (e.g., the ethics and efficacy of lethal management) relative to how people ought to value and coexist with cats and native wildlife. Society is better served by a collaborative approach to produce better scientific and ethical knowledge about free-ranging cats

Soybean aphid biotype 1 genome: Insights into the invasive biology and adaptive evolution of a major agricultural pest

The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae) is a serious pest of the soybean plant, Glycine max, a major world-wide agricultural crop. We assembled a de novo genome sequence of Ap. glycines Biotype 1, from a culture established shortly after this species invaded North America. 20.4% of the Ap. glycines proteome is duplicated. These in-paralogs are enriched with Gene Ontology (GO) categories mostly related to apoptosis, a possible adaptation to plant chemistry and other environmental stressors. Approximately one-third of these genes show parallel duplication in other aphids. But Ap. gossypii, its closest related species, has the lowest number of these duplicated genes. An Illumina GoldenGate assay of 2380 SNPs was used to determine the world-wide population structure of Ap. Glycines. China and South Korean aphids are the closest to those in North America. China is the likely origin of other Asian aphid populations. The most distantly related aphids to those in North America are from Australia. The diversity of Ap. glycines in North America has decreased over time since its arrival. The genetic diversity of Ap. glycines North American population sampled shortly after its first detection in 2001 up to 2012 does not appear to correlate with geography. However, aphids collected on soybean Rag experimental varieties in Minnesota (MN), Iowa (IA), and Wisconsin (WI), closer to high density Rhamnus cathartica stands, appear to have higher capacity to colonize resistant soybean plants than aphids sampled in Ohio (OH), North Dakota (ND), and South Dakota (SD). Samples from the former states have SNP alleles with high FST values and frequencies, that overlap with genes involved in iron metabolism, a crucial metabolic pathway that may be affected by the Rag-associated soybean plant response. The Ap. glycines Biotype 1 genome will provide needed information for future analyses of mechanisms of aphid virulence and pesticide resistance as well as facilitate comparative analyses between aphids with differing natural history and host plant range

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis