Growth inhibition of human promonocytic leukaemic U937 cells by interferon gamma is irreversible and not cell cycle phase-specific.

Growth of human promonocytic leukaemic U937 cells was found arrested within 24 h upon exposure to interferon gamma (IFN-gamma). Removal of the interferon did not result in the resumption of growth, as is evident from the absence of doubling of viable cell count and(3)H-thymidine incorporation. 5-Bromo-2'-deoxyuridine-based flow cytometric analysis of the growth-arrested cells, 24 h subsequent to the removal of IFN-gamma, showed absence of DNA synthesis, confirming the irreversible nature of the growth inhibition. Propidium iodide-based flow cytometric analysis of the growth-arrested cells showed a distribution which is typical of a growth inhibition without resulting in the accumulation of cells in any specific phase of the cell cycle. These results indicated that IFN-gamma arrested growth of U937 cells in an irreversible and cell cycle phase-independent manner. These observations were in contrast to our earlier report on the reversible and cell cycle phase-specific growth inhibition of human amniotic (fetal epithelial) WISH cells by the interferon.     

Competition of PTB with TIA proteins for binding to a U-rich cis-element determines tissue-specific splicing of the myosin phosphatase targeting subunit 1

A considerable amount of smooth muscle phenotypic diversity is generated by tissue-specific and developmentally regulated splicing of alternative exons. The control mechanisms are unknown. We are using a myosin phosphatase targeting subunit-1 (MYPT1) alternative exon as a model to investigate this question. In the present study, we show that the RNA binding proteins TIA and PTB function as antagonistic enhancers and suppressors of splicing of the alternative exon, respectively. Each functions through a single U-rich element, containing two UCUU motifs, just downstream of the alternative exon 5' splice site. Tissue-specific down-regulation of TIA protein in the perinatal period allows PTB to bind to the U-rich element and suppress splicing of the alternative exon as the visceral smooth muscle acquires the fast-phasic smooth muscle contractile phenotype. This provides a novel role for PTB in the tissue-specific regulation of splicing of alternative exons during the generation of smooth muscle phenotypic diversity.     

Bioisosteric phentolamine analogs as potent alpha-adrenergic antagonists

The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat alpha1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human alpha1- and alpha2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the alpha2- versus the alpha1-ARs, affinities being the least at the alpha1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six alpha-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human alpha1A- and alpha2A-AR subtypes indicate that a basic functional group is important for optimum binding to the alpha1- and alpha2A-adrenergic receptors.     

Light‐Induced Degradation of Perovskite Solar Cells: The Influence of 4‐Tert‐Butyl Pyridine and Gold

Stability is one of the key challenges for industrial scale commercialization of perovskite solar cells. In this work, a degradation mechanism that depends on materials and bias conditions of the device during light‐soaking is proposed. The observed degradation is linked to the additive 4‐tert‐butyl pyridine (tBP), crucial to the hole transport layer of most perovskite solar cells, and gold. This conclusion is reached through the statistical analysis of multiple compositional profiles of light‐soaked and nonlight‐soaked devices and by selective replacement of material layers of the device. Moreover, the rate of the light‐induced degradation is enhanced by operation at forward bias, which is required for power generation. Thus, this work stresses the need for the development of transport layers that do not require tBP, and to replace gold to produce high‐performing devices that are also stable under operating conditions.     

Effect of daytime aeration on the growth of Indian carp fingerlings

The effect of artificial daytime aeration on the growth of Indian major carp fingerlings ( Labeo rohtta, Catla catla, Cirrhinus mrigala ) was tested in production tanks using 5, 2.5 and 0 hours of dail aeration with a stocking density of 60,000 ha^- each and 5 hours of daily aeration at 100,000 ha^-1. Under similar stocking conditions, the total fish yields at the end of a seven months growth period in the tanks with 2.5 (2.93 kg) and 5 (1.92 kg) hours of aeration were more than 85 and 21 % higher than that of the control system (1.58 kg), respectively. This was attributable to the higher rates of net primary productivity of phytoplankton, lowered ammonium and nitrite values as well as low N/P ratio in the 2.5 hour aeration treatment compared with the rest of the treatment.

Zusammenfassung

Die Auswirkungen der Belüftung zur Tageszeit auf das Wachrtum von Jungfiscben indischer Karpfen
Die Wirkung täglicher Belüftung auf das Wachstum der Jungfische der wichtigsten indischen Karpfen ( Labeo rohita, Catla catla, Cirrhinus mrigala ) wurde in Produktionsbecken getestet, die nichr, 2,5 Stunden und 5 Stunden täglich belüftet wurden (Besatzdichte = 60.000 Stück ha^-1). In einem weiteren Experiment betrug die Besatzdichte 100.000 Stück pro ha bei 5 Stunden täglicher Belüftungsdauer. Bei vergleichbarer Besatzdichte waren die Fischerträge am Ende der sieben Monate dauernden Wachstumsperiode in den Becken mir 2,5 Stunden (2,93 kg) und 5 Stunden (1,92 k) Belüftung über 85%, bzw. 21 % höher als im Kontrollsystem (1,58 kg). Dies wurde in dem 2,5 Stunien Belüftungsexperiment der erhohten Netro-Primärproduktion des Phytoplanktons in den belüfteten Systemen zugeschrieben sowie den resultierenden geringeren Ammonium- und Nitritwerten und dem niedrigen N/P-Verhältnis.     

Season-Induced Changes in the Liver Cells and Ovarian Tissues During Growth,Maturation, Spawning and Post-spawning Phases in Spiny Eel <Emphasis Type="Italic">Mastacembelus</Emphasis> <Emphasis Type="Italic">armatus</Emphasis> (Lacepède, 1800)

Cytological status of hepatocytes in respect to seasons influencing ovarian activities has been studied in Mastacembelusarmatus (Hamilton). Histologically, the hepatocyte of female liver was provided with distinct nucleus and basophilic cytoplasmic granules. In M. armatus different germ line cells were recognized on the basis of size and histoarchitecture of the cells. By examining seasonal changes in relation to hepatocytes and ovary, it was found that during growth and maturation phases the density of cytoplasmic granules of hepatocytes was increased in number as well as the nucleus become hypertrophied. These features were well correlated with the occurrence of cortical alveolus and yolk granule stage in the ovary. During spawning phase the cytoplasmic granules were sparse in the hypertrophied hepatic cells. This was due to the dynamic cytological activities like vitellogenesis and occurrence of mature oocytes in the ovary. However, no significant alterations were noticed in the hepatocytes during post spawning phase due to the appearance of new germ line cells in the ovary. Cytological changes in the hepatocytes were correlated with the reproductive phases in female M. armatus.     

Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation,MGMT Promoter Methylation,and TERT Mutation Status: Experience from a Tertiary Care Center in India

This study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs.Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations.     

Simultaneous fingerprint and high‐wavenumber fiber‐optic Raman spectroscopy enhances real‐time in vivo diagnosis of adenomatous polyps during colonoscopy

Colorectal cancer can be prevented if detected early (e.g., precancerous polyps‐adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber‐optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real‐time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber‐optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800–1800 cm^–1) and HW (i.e., 2800–3600 cm^–1) Raman spectra from colorectal tissue subsurface (<200 µm) for real‐time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra were acquired from 50 patients with 17 colorectal polyps during clinical colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be attributed to changes in inter‐ and intra‐cellular proteins, lipids, DNA and water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy technique has the potential to be a clinically powerful tool for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination.