Cosmological models with bulk viscosity in presence of adiabatic matter creation and with G, c and Lambda variables

Some properties of cosmological models with a time variable bulk viscous coefficient in presence of adiabatic mater creation and G, c, Lambda variables are investigated in the framework of flat FRW line element. We trivially find a set of solutions through Dimensional Analysis. In all the studied cases it is found that the behaviour of these constants is inversely prportional to the cosmic time.Comment: 12 pages. We have been rewriting and completing the bibliography of this paper. Submitted to General Relativity and Gravitatio

Quality assurance guidelines for interstitial hyperthermia

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40–44 \ub0C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle

A source of resistance against yellow mosaic disease in soybeans correlates with a novel mutation in a resistance gene

Yellow mosaic disease (YMD) is one of the major devastating constraints to soybean production in Pakistan. In the present study, we report the identification of resistant soybean germplasm and a novel mutation linked with disease susceptibility. Diverse soybean germplasm were screened to identify YMD-resistant lines under natural field conditions during 2016-2020. The severity of YMD was recorded based on symptoms and was grouped according to the disease rating scale, which ranges from 0 to 5, and named as highly resistant (HR), moderately resistant (MR), resistant (R), susceptible (S), moderately susceptible (MS), and highly susceptible (HS), respectively. A HR plant named “NBG-SG Soybean” was identified, which showed stable resistance for 5 years (2016-2020) at the experimental field of the National Institute for Biotechnology and Genetic Engineering (NIBGE), Faisalabad, Pakistan, a location that is a hot spot area for virus infection. HS soybean germplasm were also identified as NBG-47 (PI628963), NBG-117 (PI548655), SPS-C1 (PI553045), SPS-C9 (PI639187), and cv. NARC-2021. The YMD adversely affected the yield and a significant difference was found in the potential yield of NBG-SG-soybean (3.46 ± 0.13a t/ha) with HS soybean germplasm NARC-2021 (0.44 ± 0.01c t/ha) and NBG-117 (1.12 ± 0.01d t/ha), respectively. The YMD incidence was also measured each year (2016-2020) and data showed a significant difference in the percent disease incidence in the year 2016 and 2018 and a decrease after 2019 when resistant lines were planted. The resistance in NBG-SG soybean was further confirmed by testing for an already known mutation (SNP at 149th position) for YMD in the Glyma.18G025100 gene of soybean. The susceptible soybean germplasm in the field was found positive for the said mutation. Moreover, an ortholog of the CYR-1 viral resistance gene from black gram was identified in soybean as Glyma.13G194500, which has a novel deletion (28bp/90bp) in the 5`UTR of susceptible germplasm. The characterized soybean lines from this study will assist in starting soybean breeding programs for YMD resistance. This is the first study regarding screening and molecular analysis of soybean germplasm for YMD resistance

Tissue transglutaminase (TG2) enables survival of human malignant pleural mesothelioma cells in hypoxia

Malignant pleural mesothelioma (MPM) is an aggressive tumor linked to environmental/occupational exposure to asbestos, characterized by the presence of significant areas of hypoxia. In this study, we firstly explored the expression and the role of transglutaminase 2 (TG2) in MPM cell adaptation to hypoxia. We demonstrated that cells derived from biphasic MPM express the full-length TG2 variant at higher levels than cells derived from epithelioid MPM and normal mesothelium. We observed a significant induction of TG2 expression and activity when cells from biphasic MPM were grown as a monolayer in chronic hypoxia or packed in spheroids, where the presence of a hypoxic core was demonstrated. We described that the hypoxic induction of TG2 was HIF-2 dependent. Importantly, TGM2-v1 silencing caused a marked and significant reduction of MPM cell viability in hypoxic conditions when compared with normoxia. Notably, a TG2-selective irreversible inhibitor that reacts with the intracellular active form of TG2, but not a non-cell-permeable inhibitor, significantly compromised cell viability in MPM spheroids. Understanding the expression and function of TG2 in the adaptation to the hypoxic environment may provide useful information for novel promising therapeutic options for MPM treatment

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity

The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD – human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117–1202 µM). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD – hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD – hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

<p>Abstract</p> <p>Background</p> <p>Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between <it>nm23-H1</it>, <it>Rb, EGFR </it>and <it>p53 </it>in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).</p> <p>Methods</p> <p><it>nm23-H1</it>, <it>Rb, EGFR and p53 </it>expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.</p> <p>Results</p> <p>Overexpression of <it>EGFR </it>and <it>p53 </it>proteins was detected in 66.1% and 35.6%; respectively. Loss of <it>nm23-H1</it>and <it>Rb </it>proteins was detected in 42.4% and 57.6%; respectively. Increased <it>EGFR and </it>loss of <it>nm23-H1 </it>RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between <it>p53 </it>and <it>EGFR </it>overexpression (<it>p </it>< 0.0001), <it>nm23 </it>loss (protein and RNA), lymph node status (<it>p </it>< 0.0001); between the incidence of local recurrence and <it>EGFR </it>RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered <it>Rb </it>expression (<it>p </it>= 0.026), <it>p53 </it>overexpression (<it>p </it>< 0.0001) and mutation (<it>p </it>= 0.04). Advanced disease stage correlated significantly with increased <it>EGFR </it>(protein and RNA) (<it>p </it>= 0.003 & 0.01), reduced <it>nm23-H1 </it>RNA (<it>p </it>= 0.02), altered <it>Rb </it>(<it>p </it>= 0.023), and <it>p53 </it>overexpression (<it>p </it>= 0.004). OS rates correlated significantly, in univariate analysis, with <it>p53 </it>overexpression (<it>p </it>= 0.011), increased <it>EGFR </it>(protein and RNA, <it>p </it>= 0.034&0.031), <it>nm23-H1 RNA </it>loss (<it>p </it>= 0.021) and aberrations of ≥ 2 genes. However, multivariate analysis showed that only high <it>EGFR </it>overexpression, metastatic recurrence, high tumor grade and the combination of ≥ 2 affected markers were independent prognostic factors.</p> <p>Conclusion</p> <p><it>nm23-H1, EGFR </it>and <it>p53 </it>could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≥ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.</p

Povezanost između polimorfizama XRCC1 ARG399GLN i P53 ARG72PRO s rizikom od raka želuca i debeloga crijeva u turskoj populaciji

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall fi ve-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence. As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.Rak želuca najčešći je oblik karcinoma probavnoga sustava, a ukupno mu je preživljenje i dalje 15 % do 20 %, budući da se većinom dijagnosticira u poodmakloj fazi razvoja. S druge pak strane, premda rak debeloga crijeva ima prilično dobru prognozu, smrtnost je i dalje 50 %. Vjeruje se da je nastanak karcinoma povezan s reaktivnim radikalima koji uzrokuju stvaranje DNA-adukata, onemogućavaju popravak DNA te slabe supresiju tumora. Stoga bi bilo korisno razumjeti ulogu polimorfi zama gena za enzim XRCC1 koji sudjeluje u popravku isjecanjem nukleotida i tumor-supresorskoga gena p53 u nastanku raka želuca i debeloga crijeva. Naše je ispitivanje obuhvatilo 94 bolesnika s rakom želuca, 96 bolesnika s rakom debeloga crijeva te 108 kontrolnhih ispitanika (koji nisu oboljeli od bilo kojeg oblika raka) s ciljem da se utvrdi povezanost između polimorfi zama XRCC1 Arg399Gln i p53 Arg72Pro i sklonosti nastanku raka. DNA je dobiven iz stanica periferne krvi, a genotip utvrđen s pomoću metode lančane reakcije polimerazom - polimorfi zma restrikcijskih fragmenata na osnovi dužine (PCRRLFP). Polimorfi zam p53 Arg72Pro nije se pokazao povezanim s povećanim rizikom od raka želuca ili debeloga crijeva niti je XRCC1 Arg399Gln bio povezan s povećanim rizikom od raka debeloga crijeva, ali je zato rizik od raka želuca u homozigotnih nositelja ovoga polimorfi zma bio 2,54 puta veći