Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Cathepsin V Protease Participates in Production of Enkephalin and NPY Neuropeptide Neurotransmitters*

Background: Proteases are required to generate peptide neurotransmitters. Results: Human cathepsin V participates in the production of enkephalin and NPY peptide neurotransmitters illustrated by gene expression and silencing. Conclusion: Human cathepsin V participates in producing enkephalin and NPY neurotransmitters in secretory vesicles. Significance: Elucidation of human-specific proteases participating in peptide neurotransmitter production is essential for understanding human health and disease. Proteases are required for processing precursors into active neuropeptides that function as neurotransmitters for cell-cell communication. This study demonstrates the novel function of human cathepsin V protease for producing the neuropeptides enkephalin and neuropeptide Y (NPY). Cathepsin V is a human-specific cysteine protease gene. Findings here show that expression of cathepsin V in neuroendocrine PC12 cells and human neuronal SK-N-MC cells results in production of (Met)enkephalin from proenkephalin. Gene silencing of cathepsin V by siRNA in human SK-N-MC cells results in reduction of (Met)enkephalin by more than 80%, illustrating the prominent role of cathepsin V for neuropeptide production. In vitro processing of proenkephalin by cathepsin V occurs at dibasic residue sites to generate enkephalin-containing peptides and an ∼24-kDa intermediate present in human brain. Cathepsin V is present in human brain cortex and hippocampus where enkephalin and NPY are produced and is present in purified human neuropeptide secretory vesicles. Colocalization of cathepsin V with enkephalin and NPY in secretory vesicles of human neuroblastoma cells was illustrated by confocal microscopy. Furthermore, expression of cathepsin V with proNPY results in NPY production. These findings indicate the unique function of human cathepsin V for producing enkephalin and NPY neuropeptides required for neurotransmission in health and neurological diseases.
Chronic Oral Amiodarone but not Dronedarone Therapy Increases Ventricular Defibrillation Threshold During Acute Myocardial Ischemia in a Closed-Chest Animal Model

Abstract: Dronedarone, a recently approved antiarrhythmic drug, has been shown to have fewer side effects than amiodarone, particularly with regard to thyroid and neurologic events. Since the effects of either drug on ventricular defibrillation threshold during ischemia are unknown, the aim of this study was to compare the effects of dronedarone and amiodarone on defibrillation efficacy during ischemia in a closed-chest animal model. Dronedarone (30 mg·kg−1·d−1) and amiodarone (20 mg·kg−1·d−1) were administered orally for 3 weeks to 19 and 21 pigs, respectively. A control group (no treatment) comprised 19 pigs. A 2-lead endovascular defibrillation system was used. Each biphasic shock was delivered after 8 seconds of ventricular fibrillation. A step-up/step-down protocol was used to calculate mean defibrillation threshold before and 10 minutes after coronary artery occlusion using an angioplasty balloon in the left descending artery. At basal state, defibrillation threshold did not differ between the control (20.8 ± 4.8 J), amiodarone (21.2 ± 2 J), and dronedarone (19.5 ± 3 J) groups. After ischemia, the amiodarone group had a significantly higher defibrillation threshold than the control group (29.6 ± 3 J vs. 21.8 ± 5 J, respectively; P = 0.015), but the dronedarone (22.8 ± 4 J) and control groups had similar defibrillation threshold values. These data indicate that oral dronedarone treatment, unlike oral amiodarone, does not affect defibrillation threshold during ischemia in pigs.
Nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents – a comprehensive review of biology, clinical course and treatment options

Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is a unique variant of Hodgkin lymphoma with an overall good prognosis. It is conspicuously different from classical Hodgkin lymphoma (cHL) and is now recognized as distinctive form of B cell lymphoma. Although it has an indolent clinical course, it has a propensity for multiple and often late relapses. Although the majority of children present with early stage disease and without B symptoms, treatment strategy has, until recently, been identical to that used for cHL. This approach is excessively toxic as it predisposes these children and adolescents to serious late effects including end organ damage to heart, gonads, lungs, thyroid and second malignant neoplasms. The aim of this article is to review the published literature on the treatment outcomes of nLPHL in affected children and adolescents, and discuss the options for treatment including surgery, chemotherapy, radiotherapy and targeted anti‐CD 20 antibody therapy.
Acquisition settings for PET of 124I administered simultaneously with therapeutic amounts of 131I.

UNLABELLED Radiation dosimetry of thyroid cancer therapy with 131I can be performed by coadministration of 124I followed by longitudinal PET scans over several days. The photons emitted by 131I may affect PET image quality. The aim of this study was to assess the influence of large amounts of 131I on PET image quality and accuracy with various acquisition settings. METHODS Noise equivalent count (NEC) rates of 124I only were measured with a standard clinical PET scanner. Apart from the standard 350- to 650-keV energy window, 425- to 650-keV and 460- to 562-keV windows were used and data were acquired both with (2-dimensional) and without (3-dimensional [3D]) septa. A phantom containing 6 hot spheres, filled with a combination of 131I and 124I and with a sphere-to-background ratio of 18:1, was scanned repeatedly with energy window settings as indicated and emission and transmission scan durations of 7 and 3 min, respectively. NEC rates were calculated and compared with those measured with the phantom filled with only 124I. Sphere-to-background ratios in the reconstructed images were determined. One patient with known metastatic thyroid cancer was scanned using energy window settings and scan times as indicated 3 and 6 d after administration of 5.5 GBq of 131I and 75 MBq of 124I. RESULTS The highest 124I-only NEC rates were obtained using a 425- to 650-keV energy window in 3D mode. In the presence of (131)I, the settings giving the highest NEC rate and contrast were 425-650 keV and 460-562 keV in 3D mode, with the clinical scans giving the highest quality images with the same settings. CONCLUSION Acquisition in 3D mode with a 425- to 650-keV or 460- to 562-keV window leads to the highest image quality and contrast when imaging 124I in the presence of large amounts of 131I using a standard clinical PET scanner.
Regulation of cytoplasmic proline levels in Salmonella typhimurium: effect of osmotic stress on synthesis, degradation, and cellular retention of proline

I investigated the effects of osmotic stress on the synthesis and catabolism of proline in Salmonella typhimurium by measuring the intracellular and extracellular proline levels in various strains. In the wild-type strain, exposure to 0.8 M NaCl did not cause a significant change in the intracellular proline level; however, it brought about a 6.5-fold increase in the intracellular glutamate pool size. These results indicate that gamma-glutamyl kinase is inhibited by proline in wild-type cells in media of normal or elevated osmolarity. I also tested whether proline is subject to turnover in cells wild type with respect to the enzymes of the proline degradation pathway. In strains that were wild type for proline biosynthesis, the loss of the proline catabolic enzymes, due to putA mutations, did not result in a statistically significant increase in the intracellular proline levels. Therefore, in the wild-type strain, proline turnover does not seem to be important for control of the intracellular proline levels. However, in a proline-overproducing mutant, a putA lesion caused a threefold increase in the intracellular proline level and a 6.5-fold increase in the extracellular proline level, indicating that proline is subject to turnover in the overproducing mutant. The proline-overproducing mutants excreted large quantities of the proline into the culture medium; osmotic stress altered the partitioning of proline such that the ratio of intracellular to extracellular levels of proline increased with increased osmotic stress. The increased cellular retention of proline in media of high osmolarity is probably due to the functioning of the ProP and ProU proline transport systems, which are stimulated under conditions of osmotic stress.
Enhancement by asbestos of oncogenesis by moloney murine sarcoma virus in CBA mice

Five μg of finely ground crocidolite asbestos (UICC standard sample) were Injected intraper‐ itoneally into 3‐week‐old CBA mice, together with 105 FFU of Moloney murine sarcoma virus. Altogether 44 out of 61 mice (72.1%) so treated developed palpable intraperitoneal tumours, and half of these died of such tumours within 100 days. The same amount of quartr and carbon similarly administered gave lower tumour incidences, namely, 19.4% (3.2% fatal) and 11.9% (1.5% fatal) respectively. Only 1 out of 59 mice inoculated with the virus alone developed a palpable intraperitoneal tumour, and this regressed spontaneously within 10 days of its first appearance. No tumours were encountered in mice treated with either asbestos, quartz or carbon alone. All the neoplasms had the appearance, under the light microscope, of anaplastic sarcomas. Most of them were confined to the serosal surface of the abdominal cavity, although invasion of underlying tissues was observed in some of the animals that died. Electron microscopical examination of tumours revealed the presence of C‐type particles budding off from cellular surface. Some neoplastic cells showed characteristic features of mesothelial lining cells. The role of milky spots (taches laiteuses) in oncogenesis by asbestos and virus, especially in the induction of mesothelioma, is discussed.
The impact of age and gender on biology, clinical features and treatment outcome of non‐Hodgkin lymphoma in childhood and adolescence

We analysed the impact of age and gender on biology and outcome of 2084 patients diagnosed with non‐Hodgkin lymphoma (NHL) between October 1986 and December 2002 and treated according to the Berlin‐Frankfurt‐Münster (BFM) multicentre protocols NHL‐BFM‐86, ‐90 and ‐95. Median age at diagnosis was 8·0 years for 97 precursor B‐lymphoblastic lymphoma (pB‐LBL) patients, 8·8 years for 335 T‐lymphoblastic lymphoma (T‐LBL) patients, 8·4 years for 1004 Burkitt's lymphoma/leukaemia (BL/B‐AL) patients, 11·4 years for 173 diffuse large B‐cell lymphoma (centroblastic subtype) (DLBCL‐CB) patients, 13·2 years for 40 primary mediastinal large B‐cell lymphoma (PMLBL) patients and 10·8 years for 215 anaplastic large‐cell lymphoma (ALCL) patients (P < 0·00001). The male:female ratio was 0·9:1 for pB‐LBL and PMLBL, 1·7:1 for DLBCL‐CB, 1·8:1 for ALCL, 2·5:1 for T‐LBL and 4·5:1 for BL/B‐AL (P < 0·00001). The probability of event‐free survival at 5 years (5‐year pEFS) was 85 ± 1% for all 2084 patients [median follow‐up 5·7 (0·1–15·9) years], and was significantly superior for male T‐LBL and DLBCL‐CB patients. Comparing age‐groups 0–4, 5–9, 10–14 and 15–18 years, pEFS was inferior for the youngest patients only in the pB‐LBL‐ and ALCL‐groups. T‐LBL and DLBCL‐CB adolescent females had worse outcome than younger girls while age had no impact on pEFS for boys. We conclude that the distribution of age and gender differed between NHL‐subtypes. The impact of gender on outcome differed between NHL subgroups. The prognostic impact of age differed not only by NHL‐subtype but also according to gender in some subtypes.
Wild-Type MIC Distribution and Epidemiological Cutoff Values for Aspergillus fumigatus and Three Triazoles as Determined by the Clinical and Laboratory Standards Institute Broth Microdilution Methods

ABSTRACT Antifungal susceptibility testing of Aspergillus species has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recent studies suggest the emergence of strains of Aspergillus fumigatus with acquired resistance to azoles. The mechanisms of resistance involve mutations in the cyp51A (sterol demethylase) gene, and patterns of azole cross-resistance have been linked to specific mutations. Studies using the EUCAST broth microdilution (BMD) method have defined wild-type (WT) MIC distributions, epidemiological cutoff values (ECVs), and cross-resistance among the azoles. We tested a collection of 637 clinical isolates of A. fumigatus for which itraconazole MICs were ≤2 μg/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of ≤1 μg/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of ≤0.25 μg/ml was established for posaconazole. Our results demonstrate that the WT distribution and ECVs for A. fumigatus and the mold-active triazoles were the same when determined by the CLSI or the EUCAST BMD method. A collection of 43 isolates for which itraconazole MICs fell outside of the ECV were used to assess cross-resistance. Cross-resistance between itraconazole and posaconazole was seen for 53.5% of the isolates, whereas cross-resistance between itraconazole and voriconazole was apparent in only 7% of the isolates. The establishment of the WT MIC distribution and ECVs for the azoles and A. fumigatus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.
Identification and characterization of spdR mutations that bypass the BsgA protease‐dependent regulation of developmental gene expression in Myxococcus xanthus

The BsgA protease of Myxococcus xanthus is an intracellular protease closely related to the Lon protease of Escherichia coli. BsgA is required for normal levels of developmentally induced gene expression. In this report, we describe the identification of mutations that suppress the developmental defect of bsgA mutants. These mutations localized to the spdR gene (suppressor protease deficiency regulator) that appears to play a role in the regulation of early developmental gene expression. Mutations in spdR fully restored the ability of a bsgA mutant to form fruiting bodies and spores and, with one exception, restored the expression of several development‐specific lacZ fusions. spdR mutants exhibited characteristic phenotypic properties including increased expression of the development‐specific tps gene during vegetative growth, formation of fruiting bodies and spores on semi‐rich nutrient medium and completion of starvation‐induced development in a shorter time period than wild‐type strains. The spdR locus was cloned and sequenced and found to encode a member of the NtrC family of two‐component transcriptional regulators. One interpretation of these data is that SpdR acts, directly or otherwise, to regulate developmental gene expression negatively and that the BsgA protease is required to relieve this inhibitory effect at the onset of development. However, Western immunoblot analysis indicated that SpdR is present at a relatively constant level during growth and early development in both wild‐type and BsgA protease‐deficient cells. This finding suggests that BsgA does not function to degrade SpdR at the onset of development.
Her-2/neu over-expression correlates with more advanced disease in Iranian colorectal cancer patients.

BACKGROUND Her-2/neu protein is a member of the epidermal growth factor family of receptors which, upon activation, contributes positively to the growth and dissemination of neoplasia. Over-expression of this protein has been reported in different human tumors and shown to be a valuable prognostic factor especially in breast cancer. A limited number of studies have also shown positive correlation between Her-2/neu over-expression and advanced tumor progression in colorectal cancer. Here we studied the prevalence of Her-2/neu over-expression in Iranian colorectal cancer patients and assessed its correlation with the disease's progression. MATERIAL/METHODS Fifty-five colorectal cancer patients in different stages of disease were studied. The pathology specimens were immunohistochemically stained using monoclonal antibody against Her-2/neu protein. Correlation of the degree of staining with clinicopathological parameters was investigated. RESULTS It was shown that in an Iranian population of colorectal cancer patients, the Her-2/neu oncogene is over-expressed in a significant number of cases and positively correlates with tumor stage and grade, being more frequent in the advanced and less differentiated samples. CONCLUSIONS These data can be applied in designating new chemotherapeutic regimens using drugs that block the function of Her-2/neu in colorectal cancer patients in Iran.
Molecular consequences of dominant Bethlem myopathy collagen VI mutations

Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown.
"Microthrix parvicella": a new approach for kinetic and physiological characterization.

Two strains of "Microthrix parvicella" (RN1 and 4B strains) have been physiologically and kinetically characterized by utilizing a new technique particularly suitable for slow growing bacteria. The proposed method is based on the Total Extended Filament Length (TEFL) measure on filaments grown on agar surfaces. This allows us to study more easily and rapidly slow growing bacteria under many different conditions without altering the growth environment during the test. "Microthrix parvicella" appears to have versatile physiological capabilities allowing effective competition against other bacteria in the complex biocenosis of activated sludge. Main peculiarities of this organism are its storage capabilities under an aerobic/anoxic/anaerobic reaction environment, the resistance to long periods of anoxic/anaerobic conditions, the possibility of growing with appreciable kinetics at very low temperatures. In the kinetic characterization low Ks values have been observed; this finding supports the assumption that "Microthrix parvicella" is a "Ks- strategist" with high substrate affinity. Kinetics tests performed in a mixed population of activated sludge bacteria and on pure culture of filaments isolated from the same sludge sample showed that no beneficial effect on the growth rates of "Microthrix parvicella" seems attributable to the presence of activated sludge. This last result confirms the validity of pure culture studies for this microorganism and the reliability of physiological and kinetic data so evaluated in describing real systems.
Cholera toxin B subunit acts as a potent systemic adjuvant for HIV-1 DNA vaccination intramuscularly in mice

Cholera toxin B subunit (CTB) was investigated as a classical mucosal adjuvant that can increase vaccine immunogenicity. In this study, we found out the in vitro efficacy of cholera toxin B subunit (CTB) in activating mice bone marrow-derived dendritic cells (BMDCs) through Toll-like receptor signaling pathways. In vitro RNA and transcriptional level profiling arrays revealed that CTB guides high levels of Th1 and Th2 type cytokines, inflammatory cytokines, and chemokines. Based on the robustness of these profiling results, we examined the induction of HIV Env-specific immunity by CTB co-inoculated with HIV Env DNA vaccine intramuscularly in vivo. CTB enhanced HIV-Env specific cellular immune responses in Env-specific IFN-γ ELISPOT, compared with DNA vaccine alone. Moreover, CTB induced high levels of Env specific humoral response and promoted antibody maturation after the third round of vaccination. This combination immunization strategy induced a Th2-type bias response which is indicative of a high ratio of IgG1/IgG2a. This study reports that CTB as a classical mucosal adjuvant could enhance HIV-1 DNA-based vaccine immunogenicity intramuscularly; therefore, these findings suggest that CTB could serve as an effective candidate adjuvant for DNA vaccination.
HDR image compression with optimized JPEG coding

This paper presents an efficient compression system adapted to High Dynamic Range (HDR) images. First a Tone Mapping Operator (TMO) generates the Low Dynamic Range (LDR) version of the HDR content together with its extra information. The obtained LDR image is encoded using an optimized JPEG coding scheme, whereas the extra information is encoded as side data. Specifically, the optimized JPEG based algorithm constructs near-optimal rate-distortion quantization tables using DCT coefficient distribution statistics and Lagrangian optimization approach. To ensure accurate HDR reconstruction, the extra information is compressed with conventional JPEG encoder using the highest quality level. The aim of the proposed HDR coding system is twofold. First, it performs a bit allocation mechanism, to achieve near-optimal rate control. Second, it maintains the backward compatibility with the conventional JPEG. Experiments show that the compression performance of the proposed HDR coder outperforms that of the reference method.
Relationship between output from MIDI-keyboard playing and hand function assessments on affected hand after stroke.

BACKGROUND While a number of studies have tested the therapeutic effectiveness of playing musical instruments, such as the electronic keyboard using Musical Instrument Digital Interface (MIDI), it is still unclear whether outcomes of electronic keyboard playing are related to hand function tests. OBJECTIVE The purpose of this study was to investigate the correlation between MIDI-keyboard playing and hand function tests, including grip strength, Box and Block test (BBT), and Jensen-Taylor Hand Function Test (JTHF). METHODS A total of 66 stroke patients were recruited from medical centers and were classified into acute (n = 21), subacute (n = 28), and chronic (n = 17) recovery stages. The participants' mean age was 60.5 years. The MIDI-keyboard playing protocol based on sequential key pressing was implemented. All hand function tests were performed by certified occupational therapists. RESULTS MIDI scores from participants at all three recovery stages were significantly correlated with BBT and grip strength. Overall, MIDI-keyboard playing scores demonstrated moderate to high correlations with hand function tests except for participants at the chronic stage and the JTHF, which showed no correlation. CONCLUSIONS These findings suggest that MIDI-keyboard playing has great potential as an assessment tool of hand function, especially hand dexterity in acute and subacute stroke patients. Further studies are needed to refine the specific keyboard playing tasks that increase responsiveness to traditional hand function tests.