High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay in Human Cervical Cancer: Recent Evidence and Future Directions

Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical.Qatar University: QUHICMED-19/20-1, GCC # 2017-002 QU/KU, and QUST-1-CMED2020-2

Electricity generation by microorganisms in the sediment-water interface of an extreme acidic microcosm

The attachment of microorganisms to electrodes is of great interest for electricity generation in microbial fuel cells (MFC) or other applications in bioelectrochemical systems (BES). In this work, a microcosm of the acidic ecosystem of Río Tinto was built and graphite electrodes were introduced at different points. This allowed the study of electricity generation in the sediment/water interface and the involvement of acidophilic microorganisms as biocatalysts of the anodic and cathodic reactions in a fuel-cell configuration. Current densities and power outputs of up to 3.5 A/m2 and 0.3 W/m2, respectively, were measured at pH 3. Microbial analyses of the electrode surfaces showed that Acidiphilium spp., which uses organic compounds as electron donors, were the predominant biocatalysts of the anodic reactions, whereas the aerobic iron oxidizers Acidithiobacillus ferrooxidans and Leptospirillum spp. were detected mainly on the cathode surface.&nbsp

E-Cigarette Liquid Provokes Significant Embryotoxicity and Inhibits Angiogenesis.

E-cigarette smoking (ECS) is a new method of tobacco smoking that is gaining popularity as it is thought to be a "healthy method" of tobacco consumption. The adverse outcomes of ECS on the respiratory and cardiovascular systems in humans have been recently demonstrated. Nevertheless, the effect of e-cigarette liquid (ECL) on the early stage of embryogenesis and angiogenesis has not been explored yet. Chicken embryo at 3 days of incubation and its chorioallantoic membrane (CAM) of 5 days were used to explore the outcome of ECL on the embryo. Real-time PCR was also employed to study the regulation of a set of key controller genes of embryogenesis as well as angiogenesis. Our study revealed that ECL exposure is associated with a high rate of mortality in embryos as around 70% of treated embryos, at 3 days of incubation, die after 5 days of exposure. Additionally, ECL inhibits angiogenesis of the CAM of 5 days of incubation by more than 30%. These effects could be explained by the upregulation of , and as well as the downregulation of and genes, which are important key controller genes of embryogenesis as well as angiogenesis. Our data suggest clearly that ECS can have dramatic toxic outcomes on the early stage of embryogenesis as well as angiogenesis. Accordingly, we believe that further studies to assess the effects of ECS on human health are essential.A-E-A.M’s lab is supported by grants from the Qatar University: QUHI-CMED-19/20-1, GCC # 2017- 002 QU/KU, and QUST-1-CMED-2020-2

The responses of an anaerobic microorganism, Yersinia intermedia MASE-LG-1 to individual and combined simulated Martian stresses

The limits of life of aerobic microorganisms are well understood, but the responses of anaerobic microorganisms to individual and combined extreme stressors are less well known. Motivated by an interest in understanding the survivability of anaerobic microorganisms under Martian conditions, we investigated the responses of a new isolate, Yersinia intermedia MASE-LG-1 to individual and combined stresses associated with the Martian surface. This organism belongs to an adaptable and persistent genus of anaerobic microorganisms found in many environments worldwide. The effects of desiccation, low pressure, ionizing radiation, varying temperature, osmotic pressure, and oxidizing chemical compounds were investigated. The strain showed a high tolerance to desiccation, with a decline of survivability by four orders of magnitude during a storage time of 85 days. Exposure to X-rays resulted in dose-dependent inactivation for exposure up to 600 Gy while applied doses above 750 Gy led to complete inactivation. The effects of the combination of desiccation and irradiation were additive and the survivability was influenced by the order in which they were imposed. Ionizing irradiation and subsequent desiccation was more deleterious than vice versa. By contrast, the presence of perchlorates was not found to significantly affect the survival of the Yersinia strain after ionizing radiation. These data show that the organism has the capacity to survive and grow in physical and chemical stresses, imposed individually or in combination that are associated with Martian environment. Eventually it lost its viability showing that many of the most adaptable anaerobic organisms on Earth would be killed on Mars today

Acidithiobacillus ferrooxidans y su papel en la geomicrobiología del ciclo del hierro en el río Tinto

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura 21-11-2003The main objective of the work has been to study the role of a chemolithotrophic bacteria, Acidithiobaciflus ferrooxidans, in the iron cycle in the Tinto River, an extreme acidic environment. Different strains of strict iron oxidizing bacteria have been isolated from water samples from the river. One of the At, ferrooxidans isolates, isolate FRMMO2, has been tested for its ability to oxidize iron in aerobic conditions and to reduce it in the anaerobio conditions. A sampling station from the river, the dam 3.2, has been selected for a futher geomicrobiology characterization. A gradient of pH, redox potential, conductivity and ferric/ferrous iron have been detected in the water column and associated with the oxygen concentration and the microbial distribution of chemolithotrophic bacteria using fluorescence in situ hybridization and DGGE analysis. Different microcosmos have been constructed using different energy conditions after the addition of the main chemolithotrophic bacteria detected in the natural 3.2 system. The temporal and spatial evolution of the physico-chemical properties and chemolithotrophic microorganisms correlate very well with the observed properties of the natural system. The results atlowed to develop a model for the iron cycle in the dam 3.2 and to extrapolate them to a general performance of the geomicrobiology of the Tinto system

In-Flight Estimation of Center of Gravity Position Using All-Accelerometers

Changing the position of the Center of Gravity (CoG) for an aerial vehicle is a challenging part in navigation, and control of such vehicles. In this paper, an all-accelerometers-based inertial measurement unit is presented, with a proposed method for on-line estimation of the position of the CoG. The accelerometers’ readings are used to find and correct the vehicle’s angular velocity and acceleration using an Extended Kalman Filter. Next, the accelerometers’ readings along with the estimated angular velocity and acceleration are used in an identification scheme to estimate the position of the CoG and the vehicle’s linear acceleration. The estimated position of the CoG and motion measurements can then be used to update the control rules to achieve better trim conditions for the air vehicle

DNA Damage/Repair Management in Cancers

DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention. In this review we will discuss the relationship between DNA damage/repair mechanisms and cancer, and how we can target these pathways.</jats:p

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements.

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients

Preferential Use of an Anode as an Electron Acceptor by an Acidophilic Bacterium in the Presence of Oxygen▿

Several anaerobic metal-reducing bacteria have been shown to be able to donate electrons directly to an electrode. This property is of great interest for microbial fuel cell development. To date, microbial fuel cell design requires avoiding O2 diffusion from the cathodic compartment to the sensitive anodic compartment. Here, we show that Acidiphilium sp. strain 3.2 Sup 5 cells that were isolated from an extreme acidic environment are able to colonize graphite felt electrodes. These bacterial electrodes were able to produce high-density electrocatalytic currents, up to 3 A/m2 at a poised potential of +0.15 V (compared to the value for the reference standard calomel electrode) in the absence of redox mediators, by oxidizing glucose even at saturating air concentrations and very low pHs

Co-Incidence of Human Papillomaviruses and Epstein-Barr Virus is Associated with Advanced Tumor Stage: A Tissue Microarray Study of Head and Neck Cancers

Background: Human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), are known oncoviruses and can be co-present and hence cooperate in the development of human carcinomas, including head and neck. Methods: We herein explore for the first time the co-prevalence of high-risk HPVs and EBV in 98 head and neck (HN) squamous cell carcinoma (SCC) tissues from Bosnian patients using polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis, as well as tissue microarray methodology. Results: The majority of these cancer tissue cases were from the oral cavity (68%). We found that high-risk HPVs and EBV are co-present in 34.7% of SCC samples; with a significant correlation between various high-risk HPV types and EBV co-incidence (p=0.03). Our data showed that 30.8% of oral SCCs are positive for E6 oncoproteins of high-risk HPVs and 44.6% are positive for LMP1 of EBV. The most commonly expressed HPVs in our HNSCC samples include HPV types 16, 18, 45 and 58. More importantly, 37.5% of oral SCCs are positive for both HPVs and EBV, with statistically significant association between high-risk HPV types and EBV (p<0.05). More significantly, we report that the co-presence of HPV and EBV is highly correlated with advanced tumor stage (p=0.035). Conclusion: In conclusion, HPV and EBV oncoviruses are co-present in HNSCC, particularly in oral cancer, where they can cooperate in the initiation and/or progression of this cancer. Thus, further studies are necessary to elucidate the mechanism of high-risk HPVs and EBV cooperation in human carcinoma