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Astroblastoma is a rare tumor of glial origin with characteristics of both astrocytoma and ependymoma. It is usually seen in children and young adults, and is peripherally located, well circumscribed, of solid-cystic composition and with heterogeneous contrast enhancement. Histopathology reveals perivascular pseudorosette formation and thick hyalinised vessels. Hemorrhage in astroblastoma is unusual and rarely described in literature. We report two patients with astroblastoma who presented with hemorrhage and discuss the natural history, radiological findings, pathophysiology of hemorrhage and histopathological characteristics. We emphasize the importance of early suspicion in peripherally located lesions with bleeding. [ABSTRACT FROM AUTHOR]

Summary Multiple strategies evolved by Mycobacterium tuberculosis ( M. tb ) have contributed to its successful prevalence. We previously identified specific genes in the cysteine protease and calcium-calmodulin pathways that regulated immune responses from dendritic cells (DCs). In this study we have characterized the role of neddylation in regulating various defense responses from DCs during mycobacterial infection. Neddylation is a process that is similar to ubiquitination. It however has its own enzyme machinery. It is coupled to ubiquitination and is important for maintaining cellular homeostasis. Here we show that stimulation of DCs with M. tb antigens Rv2463 and Rv3416 as well as infection with live M. tb modulates the expression levels of key proteins in the neddylation pathway. Further, stimulation with the two antigens promoted the association of NEDD8 with its target Cullin-1. The modulation in the expression levels of NEDD8 and SENtrin specific Protein 8 (SENP8) by the two antigens was in a calcium, MAPK and TLR dependent mechanism. Further, knockdown of specific genes of neddylation promoted the generation of oxidative burst, promoted phagolysosome fusion in mycobacteria infected DCs and induced higher expression of autophagy and apoptosis associated proteins in DCs. These results point toward a unique strategy employed by mycobacteria and its antigens towards immune suppression via modulating neddylation in DCs. [ABSTRACT FROM AUTHOR]

Abstract: The equilibrium structures and bonding features of [NeHHe]+, [ArHHe]+, and [ArHNe]+ are investigated using correlated ab initio methods and a large number of basis sets. For all the three systems, linear structures with the hydrogen atom in the middle have been found to be the most stable. The bond lengths of argon atoms with hydrogen are shorter than the HeH and NeH bond lengths in [ArHHe]+ and [ArHNe]+, respectively. This leads to the dissociation energies being very large for breaking the heavier rare gas-hydrogen atom bond. In [NeHHe]+, the NeH bond length is larger than HeH length. In addition to the global minima, two other local minima are also located for each of the systems with either of the rare gases in the middle. All the stable geometries are characterized by frequency calculations. [Copyright &y& Elsevier]

Abstract: Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling. [Copyright &y& Elsevier]

Abstract: Overexpression of procathepsin D (pCD) is reported to occur in numerous types of cancer and is associated with increased growth and metastasis. It has been established that pCD affects multiple stages of tumor progression including proliferation, angiogenesis and metastasis. Previously, we showed that the mitogenic effect of pCD on cancer cells is mediated by interaction of its activation peptide (AP) with yet unidentified cell surface receptor. In this investigation, gene expression profiles were compared between AP-treated and control human breast cancer ZR-75-1 cells to elucidate the mechanism of AP mitogenicity. Several differentially expressed genes involved in signal transduction, regulation of cell cycle, apoptosis, tumor invasion and metastasis were identified using microarray technology. These findings, including overexpression of NF-κB2, were confirmed in breast cancer cell lines by reverse-transcriptase PCR (RT-PCR). Understanding the mechanism of pCDs effect on breast cancer cells could extend possibilities of breast cancer treatment in the future. [Copyright &y& Elsevier]

Abstract: Napins belong to the family of 2S albumin seed storage proteins and are shown to possess antifungal activity. Napins, in general, consist of two subunits (derived from single precursor) linked by disulphide bridges. Usually, reducing environment of the E. coli cytosol is not conducive for proper folding of heterodimeric proteins containing disulphide bridges. Present investigation reports for the first time expression of napin-like protein of Momordica charantia (rMcnapin) in E. coli and its in vitro refolding to produce biologically active protein. Full-length cDNA encoding napin-like protein (2S albumin) was isolated from M. charantia seeds by immunoscreening a cDNA expression library. The cDNA consisted of an open reading frame encoding a protein of 140 amino acid residues. The 36 amino acids at the N-terminus represent the signal and propeptide. The region encoding small and large chains of the M. charantia napin is separated by a linker of 8 amino acid residues. The region encoding napin (along with the linker) was PCR amplified, cloned into pQE-30 expression vector and expressed in E. coli. rMcnapin expressed as inclusion bodies was solubilized and purified by Ni2+-NTA affinity chromatography. The denatured and reduced rMcnapin was refolded by rapid dilution in an alkaline buffer containing glycerol and redox couple (GSH and GSSG). Refolded His-rMcnapin displayed similar spectroscopic properties as that of mature napin-like protein of M. charantia with 48.7% α-helical content. In addition, it also exhibited antifungal activity against T. hamatum with IC50 of 3 μg/ml. Refolded His-rMcnapin exhibited ∼90% antifungal activity when compared with that of mature napin-like protein of M. charantia. Thus, a heterologous expression system and in vitro refolding conditions to obtain biologically active napin-like protein of M. charantia were established. [Copyright &y& Elsevier]

The nucleolus serves as a principal site of ribosome biogenesis but is also implicated in various non-ribosomal functions, including negative regulation of the pro-apoptotic transcription factor p53. Although disruption of the nucleolus may trigger the p53-dependent neuronal death, neurotoxic consequences of a selective impairment of ribosome production are unclear. Here, we report that in rat forebrain neuronal maturation is associated with a remarkable expansion of ribosomes despite postnatal down-regulation of ribosomal biogenesis. In cultured rat hippocampal neurons, inhibition of the latter process by knockdowns of ribosomal proteins S6, S14, or L4 reduced ribosome content without disrupting nucleolar integrity, cell survival, and signaling responses to the neurotrophin brain-derived neurotrophic factor. Moreover, reduced general protein synthesis and/or formation of RNA stress granules suggested diminished ribosome recruitment to at least some mRNAs. Such a translational insufficiency was accompanied by impairment of brain-derived neurotrophic factor-mediated dendritic growth. Finally, RNAstress granules and smaller dendritic trees were also observed when ribosomal proteins were depleted from neurons with established dendrites. Thus, a robust ribosomal apparatus is required to carry out protein synthesis that supports dendritic growth and maintenance. Consequently, deficits of ribosomal biogenesis may disturb neurodevelopment by reducing neuronal connectivity. Finally, as stress granule formationanddendritic loss occur early in neurodegenerative diseases, disrupted homeostasis of ribosomes may initiate and/or amplify neurodegeneration-associated disconnection of neuronal circuitries. [ABSTRACT FROM AUTHOR]

Six teaching courses with focus on 3D IGABT for cervical cancer were conducted in India between 2017 & 2023, as collaborative effort of AROI and ESTRO. The purpose is to report impact of teaching courses, as observed from pre-course surveys and a recent master survey of all course participants. Pre-course surveys were conducted before each of the six courses, where in information related to pre-course BT practice of each participating team (physician and physicist) was collected. Recently, a detailed online master survey was conducted to understand impact of courses on BT approach and practice. A total of 456 participants (344 physicians and 112 physicists) who were responsible for treating cervical cancer patients attended the courses. As per pre-course surveys, BT planning was frequently done using X rays, CT and MRI by 25%, 75% and 10% of participants respectively. Hybrid IC+IS and 3D dose prescription (to high-risk CTV) were commonly used by 31% and 35% participants. Among 456 participants, 104 teams (one team per institute was allowed to respond) from 104 centres responded (83 physicians and 21 physicists). Of these, 101 (97.1%) continued to practice cervical cancer brachytherapy at the time of the survey. Percentage-wise implementation/utilisation of various critical processes/resources in cervical cancer brachytherapy workflow at the time of master survey are presented in Figure 1 (upper panel).Teaching course empowered participants in implementing/ improvising critical processes, like examination under anaesthesia (14%), clinical drawings (55%), ultrasound guidance (23%), IC+IS (32%), target volume delineation (46%) & volume-based prescription (39%); however, these processes could be sustained in 8%, 32%, 17%, 25%, 41% and 33% centres, respectively,. (FIgure1 lower panel). Frequent reasons cited for inability to implement and sustain these critical processes include heavy patient load, lack of availability of infrastructure (dedicated ultrasonography, compatible applicators, access to MRI etc), suboptimal human resources (Anesthesiologists, Radiologists, Radiation Oncologists) etc.Among the participants, 94% and 87% felt that their knowledge and practice of BT improved substantially after the course, respectively. About 94% of the participants expressed interest in collaborative prospective research related to IGABT for cervical cancer. Survey results suggest that the teaching courses substantially improved clinical workflow, use of ultrasonography for guidance, utilisation of pre-BT MR/MR/CT-TRUS based BT, advanced BT applications (IC + IS), target volume delineation and volumetric dose prescription. Majority of centres appear to be interested in exploring prospective research related to IGABT. [ABSTRACT FROM AUTHOR]