Langerhans cell hyperplasia in the tumor stage of mycosis fungoides: a mimic of Langerhans cell histiocytosis

AbstractMycosis fungoides is a form of cutaneous T-cell lymphoma (CTCL). Malignant CD4+ T cells have been found to adopt the T-regulatory (Treg) cell phenotype and function. We present the case of a 66-year-old man diagnosed with mycosis fungoides that was progressing from the plaque to the tumor stage. The histopathological examinations showed that the Langerhans cell (LC) infiltration in the skin lesion of the tumor stage was greater than that in the patch/plaque stage; the tumor stage lesions resembled LC histiocytosis pathologically. The associations among LCs, apoptotic tumor cells, Treg CTCL cells, and relevant cytokines are complex. Treg CTCL cells produce the immunosuppressive cytokines interleukin-10 and transforming growth factor beta, which facilitate continuous recruitment of LCs and maintenance of long-term dendritic cell immaturity, thereby explaining the remarkable LC infiltration in the tumor stage samples from our patient. This phenomenon indicates that LCs accompanied by Treg CTCL cells may play an important synergistic role in the tumor progression. The development of immunotherapy directed against Treg CTCL cells and LCs overproduction and other immunosuppressive cytokines may be a potent useful adjuvant and worthy of further investigation

AMP-Activated Protein Kinase Activation during Cardioplegia-Induced Hypoxia/Reoxygenation Injury Attenuates Cardiomyocytic Apoptosis via Reduction of Endoplasmic Reticulum Stress

Cardioplegic-induced H/R injury results in cardiomyocytic apoptosis. AMPK has been shown to reduce ER stress and the unfolded protein response (UPR). Whether AMPK activation can attenuate cardiomyocytic apoptosis after cardioplegia-induced H/R injury is unknown. Cardiomyocytes were exposed to simulated ischemia by incubation in a hypoxic chamber with intermittent cold cardioplegia solution infusion at 20-minute intervals and subsequently reoxygenated in a normoxic environment. Various doses of AMPK activators (AICAR or metformin) were given 2 days before H/R injury. The cardiomyocytes were harvested after reoxygenation for subsequent examination. With both AMPK activators, the antiapoptotic genes of ER stress and UPR, the subsequent production of proapoptotic proteins was attenuated, and the antiapoptotic proteins were elevated. The activity of the apoptotic effectors of ER stress was also reduced with AMPK activation. Moreover, TUNEL staining showed that AMPK activation significantly reduced the percentage of apoptotic cardiomyocytes after cardioplegia-induced H/R injury. Our results revealed that AMPK activation during cardioplegia-induced H/R injury attenuates cardiomyocytic apoptosis, via enhancement of antiapoptotic and reduction of proapoptotic responses, resulting from lessening ER stress and the UPR. AMPK activation may serve as a future pharmacological target to reduce H/R injury in the clinical setting

磷肥濃度對迷你型聖誕紅生長之影響

以聖誕紅 ‘Freedom’ 及營養系 ‘FO 90-3’ 之單節扦插苗經栽培於密閉式養液栽培系統。養液為Hoagland養液，但其含磷量調整半量、全量、1.5倍及2倍量。栽培於含半量磷肥之Hoagland養液中其株高、枝幹直徑、樹冠直徑、節間長度或莖、葉或苞葉的乾鮮重皆小於培養於Hoagland養液者，培養於1.5或2倍磷量者其植株性狀與培養於Hoagland養液者無差異。養液中磷提高至2倍植株之含氮量會提高，但植株之含鐵量則會隨養液中磷含量增加而降低。In this study one-node cutting of poinsettia ‘freedom' and ‘FO 90-3' were cultured in closed hydroponic system. The hydroponic solution was Hoagland solution with half strength of phosphorus, respectively. When the plant grown in a solution with double strength of phosphorus, the growth was similar to those grown in Hoagland solution. However, the nitrogen content in plant increased but iron content decreased, when the phosphorus strength were doubled

Image operator learning coupled with CNN classification and its application to staff line removal

Many image transformations can be modeled by image operators that are characterized by pixel-wise local functions defined on a finite support window. In image operator learning, these functions are estimated from training data using machine learning techniques. Input size is usually a critical issue when using learning algorithms, and it limits the size of practicable windows. We propose the use of convolutional neural networks (CNNs) to overcome this limitation. The problem of removing staff-lines in music score images is chosen to evaluate the effects of window and convolutional mask sizes on the learned image operator performance. Results show that the CNN based solution outperforms previous ones obtained using conventional learning algorithms or heuristic algorithms, indicating the potential of CNNs as base classifiers in image operator learning. The implementations will be made available on the TRIOSlib project site.Comment: To appear in ICDAR 201

Development of a Transgenic Flammulina velutipes Oral Vaccine for Hepatitis B

Oralna primjena cjepiva dobivenih iz gljiva obećavajuća je za prevenciju zaraznih bolesti. Jestive gljive smatraju se prikladnim domaćinom za proizvodnju cjepiva zbog malih troškova proizvodnje i malog rizika kontaminacije gena. Međutim, zbog slabe ekspresije antitijela gljive imaju limitirani potencijal za razvoj oralnih cjepiva. Niska razina ekspresije gena vjerojatno je posljedica nečistoće transgenih micelija, budući da se za transformaciju uglavnom koriste miceliji dikariona. U radu je transformacijom gena iz gljive Flammulina velutipes pomoću bakterije Agrobacterium dobiven stabilni antigen hepatitisa B (HBsAg). Zatim je uslijedilo formiranje plodišta i klijanje bazidiospora. Metodom Western blot potvrđeno je formiranje HBsAg. Razine ekspresije HBsAg u plodištima gljive F. velutipes bile su: (129,3±15,1), (1 10,9±1,7) i (161,1±8,5) ng po gramu ukupnog topljivog proteina. Međutim, te vrijednosti mogu biti i veće, jer u radu nije postignuta potpuna ekstrakcija proteina. Dvije od četiri svinje u pokusnoj skupini imale su IgG protutijela na HBsAg nakon hranidbe plodištima transgene gljive F. velutipes tijekom 20 tjedana. U uzorcima krvi svinja u kontrolnoj skupini nisu opažena protutijela na HBsAg. Jedna od dviju pozitivnih svinja imala je vrijednosti titra protutijela na HBsAg od 5,36 miliinternacionalnih jedinica po mililitri (mlJ/mL) u desetom tjednu i 14,9 mlJ/mL u četrnaestom tjednu ispitivanja, nakon čega su se te vrijednosti smanjivale. Druga je svinja imala vrijednosti titra od 9,75 mlJ/mL u četrnaestom tjednu, 17,86 mlJ/mL u osamnaestom tjednu i 39,87 mlJ/mL u dvadesetom tjednu ispitivanja. Imunogenost svinja hranjenih plodištima transgene gljive F. velutipes potvrđuje mogućnost primjene ove gljive kao oralnog cjepiva.Orally administered fungal vaccines show promise for the prevention of infectious diseases. Edible mushrooms are deemed appropriate hosts to produce oral vaccines due to their low production cost and low risk of gene contamination. However, their low expression level of antigens has limited the potential development of oral vaccines using mushrooms. The low expression level might result from impurity of the transgenic mycelia since dikaryotic mycelia are commonly used as transformation materials. In this study, stable transgenic hepatitis B virus surface antigen (HBsAg) in Flammulina velutipes transformants was obtained by Agrobacterium-mediated transformation, followed by fruiting and basidiospore mating. The formation of HBsAg was detected by western blot analysis. The expression levels of HBsAg in transgenic F. velutipes fruiting bodies were (129.3±15.1), (110.9±1.7) and (161.1±8.5) ng/g total soluble protein. However, the values may be underestimated due to incomplete protein extraction. Two of the four pigs in the experimental group produced positive anti-HBsAg-specific IgG after being fed the HBsAg transgenic F. velutipes fruiting bodies for 20 weeks, while no anti-HBsAg antibody was detected in the control group. One of the positive pigs had HBsAg titres of 5.36 and 14.9 mIU/mL in weeks 10 and 14, respectively, but expression faded thereafter. The other positive pig displayed HBsAg titres of 9.75, 17.86 and 39.87 mIU/mL in weeks 14, 18 and 20, respectively. The successful immunogenicity in pigs fed transgenic F. velutipes fruiting bodies demonstrated the potential of using the fungus as an oral vaccine

Borders of Cis-Regulatory DNA Sequences Preferentially Harbor the Divergent Transcription Factor Binding Motifs in the Human Genome

Changes in cis-regulatory DNA sequences and transcription factor (TF) repertoires provide major sources of phenotypic diversity that shape the evolution of gene regulation in eukaryotes. The DNA-binding specificities of TFs may be diversified or produce new variants in different eukaryotic species. However, it is currently unclear how various levels of divergence in TF DNA-binding specificities or motifs became introduced into the cis-regulatory DNA regions of the genome over evolutionary time. Here, we first estimated the evolutionary divergence levels of TF binding motifs and quantified their occurrence at DNase I-hypersensitive sites. Results from our in silico motif scan and experimentally derived chromatin immunoprecipitation (TF-ChIP) show that the divergent motifs tend to be introduced in the edges of cis-regulatory regions, which is probably accompanied by the expansion of the accessible core of promoter-associated regulatory elements during evolution. We also find that the genes neighboring the expanded cis-regulatory regions with the most divergent motifs are associated with functions like development and morphogenesis. Accordingly, we propose that the accumulation of divergent motifs in the edges of cis-regulatory regions provides a functional mechanism for the evolution of divergent regulatory circuits

Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h.</p> <p>Results</p> <p>In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05).</p> <p>Conclusion</p> <p>MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.</p