Zinc Status Impacts the Epidermal Growth Factor Receptor and Downstream Protein Expression in A549 Cells

Zinc has been suggested to play a role in carcinogenesis and tumor progression. Serum zinc levels of lung cancer patients are for example lower than in healthy individuals. The activation and expression of the epidermal growth factor receptor (EGFR), which plays a role in tumor biology, are presumably influenced by zinc. EGFR activation influences cell adhesion and immune escape. This study provides insights into the impacts of zinc on the EGFR activation and expression of downstream proteins such as E-cadherin and PD-L1 in the alveolar carcinoma cell line A549. To model chronic changes in zinc homeostasis, A549 cells were cultured in media with different zinc contents. EGFR surface expression of unstimulated and stimulated A549 cells was determined by flow cytometry. EGFR phosphorylation as well as the protein expression of E-cadherin and PD-L1 were analyzed by Western blot. In our hands, chronic zinc deficiency led to increased EGFR surface expression, decreased E-cadherin protein expression and increased PD-L1 protein expression. Zinc supplementation decreased EGFR surface expression and PD-L1 protein expression. In summary, zinc-deficient A549 cells may display a more malignant phenotype. Thus, future clinical research should further focus on the possible benefits of restoring disturbed zinc homeostasis, especially in lung cancer patients.     

Utilizing Genomically Targeted Molecular Data to Improve Patient-Specific Outcomes in Autism Spectrum Disorder

Molecular biology combined with genomics can be a powerful tool for developing potential intervention strategies for improving outcomes in children with autism spectrum disorders (ASD). Monogenic etiologies rarely cause autism. Instead, ASD is more frequently due to many polygenic contributing factors interacting with each other, combined with the epigenetic effects of diet, lifestyle, and environment. One limitation of genomics has been identifying ways of responding to each identified gene variant to translate the information to something clinically useful. This paper will illustrate how understanding the function of a gene and the effects of a reported variant on a molecular level can be used to develop actionable and targeted potential interventions for a gene variant or combinations of variants. For illustrative purposes, this communication highlights a specific genomic variant, SHANK3. The steps involved in developing molecularly genomically targeted actionable interventions will be demonstrated. Cases will be shared to support the efficacy of this strategy and to show how clinicians utilized these targeted interventions to improve ASD-related symptoms significantly. The presented approach demonstrates the utility of genomics as a part of clinical decision-making.     

Premarin Reduces Neurodegeneration and Promotes Improvement of Function in an Animal Model of Spinal Cord Injury

Spinal cord injury (SCI) causes significant mortality and morbidity. Currently, no FDA-approved pharmacotherapy is available for treating SCI. Previously, low doses of estrogen (17β-estradiol, E2) were shown to improve the post-injury outcome in a rat SCI model. However, the range of associated side effects makes advocating its therapeutic use difficult. Therefore, this study aimed at investigating the therapeutic efficacy of Premarin (PRM) in SCI. PRM is an FDA-approved E2 (10%) formulation, which is used for hormone replacement therapy with minimal risk of serious side effects. The effects of PRM on SCI were examined by magnetic resonance imaging, immunofluorescent staining, and western blot analysis in a rat model. SCI animals treated with vehicle alone, PRM, E2 receptor antagonist (ICI), or PRM + ICI were graded in a blinded way for locomotor function by using the Basso–Beattie–Bresnahan (BBB) locomotor scale. PRM treatment for 7 days decreased post-SCI lesion volume and attenuated neuronal cell death, inflammation, and axonal damage. PRM also altered the balance of pro- and anti-apoptotic proteins in favor of cell survival and improved angiogenesis and microvascular growth. Increased expression of estrogen receptors (ERs) ERα and ERβ following PRM treatment and their inhibition by ER inhibitor indicated that the neuroprotection associated with PRM treatment might be E2-receptor mediated. The attenuation of glial activation with decreased inflammation and cell death, and increased angiogenesis by PRM led to improved functional outcome as determined by the BBB locomotor scale. These results suggest that PRM treatment has significant therapeutic implications for the improvement of post-SCI outcome.     

Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways

Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.     

Isolation and identification of phosphate‐solubilizing microorganisms and distribution of orthophosphate in different seasons from sewage‐fed East Kolkata Wetland

This study focused on isolation and identification of possible phosphate‐solubilizing bacteria (PSB ) from the sewage‐fed East Kolkata Wetland (EKWL ), a prospective water resource for pisciculture. In addition, different limnological parameters have been correlated with orthophosphate and seasonal variations. PSB have been isolated in Pikovskaya medium and identified morphologically and biochemically and finally analysed by 16S rDNA gene sequence. Limnological studies involving temperature (potentiometric), pH (potentiometric), dissolved oxygen (iodometric), ammonia‐nitrogen (spectrophotometric) and orthophosphate (spectrophotometric) concentrations were conducted. The results of this study established the presence of Bacillus megaterium , a potential PSB in EKWL . The activity of B. megaterium is also supported by the seasonal orthophosphate variations. The changes in concentration of other limnological parameters were also prominent. The water quality parameters of temperature (r  = 0.886), dissolved oxygen (r  = 0.729) and ammonia‐nitrogen (r  = 0.396) concentrations exhibited a positive correlation with orthophosphate and a negative correlation with pH (r  = ?0.699). The B. megaterium obtained in this study, exhibited a significant alteration in regard to orthophosphate content and relationships with other factors. Further experiment on the soluble phosphorus solubilization potential of B. megaterium revealed the biological availability of phosphorus was increased by threefold after 120 hr of incubation, with the decreasing pH value, although the phytase activity was 0.419 U/ml. PSB have a vital function in plant nutrition in supplying phosphate, essential nutrients and its uptake results in appropriate functioning and metabolism of different aquatic plants and organisms. PSB are competent biofertilizer to amplify aquaculture production for sustainable development.     

From daily movements to population distributions: weather affects competitive ability in a guild of soaring birds

The ability of many animals to access and exploit food is dependent on the ability to move. In the case of scavenging birds, which use soaring flight to locate and exploit ephemeral resources, the cost and speed of movement vary with meteorological factors. These factors are likely to modify the nature of interspecific interactions, as well as individual movement capacity, although the former are less well understood. We used aeronautical models to examine how soaring performance varies with weather within a guild of scavenging birds and the consequences this has for access to a common resource. Birds could be divided broadly into those with low wing loading that are more competitive in conditions with weak updraughts and low winds (black vultures and caracaras), and those with high wing loading that are well adapted for soaring in strong updraughts and moderate to high winds (Andean condors). Spatial trends in meteorological factors seem to confine scavengers with high wing loading to the mountains where they out-compete other birds; a trend that is borne out in worldwide distributions of the largest species. However, model predictions and carcass observations suggest that the competitive ability of these and other birds varies with meteorological conditions in areas where distributions overlap. This challenges the view that scavenging guilds are structured by fixed patterns of dominance and suggests that competitive ability varies across spatial and temporal scales, which may ultimately be a mechanism promoting diversity among aerial scavengers.     

Moving toward more perfect unions: Daily and long-term consequences of approach and avoidance goals in romantic relationships.

In 2 daily experience studies and a laboratory study, the authors test predictions from approach-avoidance motivational theory to understand how dating couples can maintain feelings of relationship satisfaction in their daily lives and over the course of time. Approach goals were associated with increased relationship satisfaction on a daily basis and over time, particularly when both partners were high in approach goals. Avoidance goals were associated with decreases in relationship satisfaction over time, and people were particularly dissatisfied when they were involved with a partner with high avoidance goals. People high in approach goals and their partners were rated as relatively more satisfied and responsive to a partner's needs by outside observers in the lab, whereas people with high avoidance goals and their partners were rated as less satisfied and responsive. Positive emotions mediated the link between approach goals and daily satisfaction in both studies, and responsiveness to the partner's needs was an additional behavioral mechanism in Study 2. Implications of these findings for approach-avoidance motivational theory and for the maintenance of satisfying relationships over time are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sustainability of Groundwater Resources in the North-Eastern Region of Bangladesh

Water is essential for economic, social, and environmental development. Global water resources are vulnerable due to increasing demand related to population growth, pollution potential, and climate change. Competition for water between different sectors is increasing. To meet the increasing demand, the use of groundwater is increasing worldwide. In this paper, the water-table dynamics of the north-eastern region of Bangladesh were studied using the MEKESENS software. This study reveals that the depth to water-table (WT) of almost all the wells is declining slowly. In many cases, the depth will approximately double by the year 2040, and almost all will double by 2060, if the present trend continues. If the decline of the water-table is allowed to continue in the long run, the result could be a serious threat to the ecology and to the sustainability of food production, which is vital for the nation’s food security. Therefore, necessary measures should be taken to sustain water resources and thereby agricultural production. Demand-side management of water and the development of alternative surface water sources seem to be viable strategies for the area. These strategies could be employed to reduce pressure on groundwater and thus maintain the sustainability of the resource.     

Reliability-Based Design Optimization for Durability of Ground Vehicle Suspension System Components

The effect of materials processing- and component manufacturing-induced uncertainties in material properties and component shape and size on the reliability of component performance is investigated. Specifically, reliability of a suspension system component from a high-mobility multipurpose wheeled vehicle which typically can fail under low-cycle strain-based fatigue conditions is analyzed. Toward that end, the most advanced reliability-based design optimization methods available in the literature were combined with the present understanding of low-cycle fatigue durability and applied to the component in question. This entailed intricate integration of several computational tools such as multibody vehicle dynamics, finite-element simulations, and fatigue strain-life assessment/prediction techniques. The results obtained clearly revealed the importance of consideration of material property uncertainties in attaining vehicle performance of critical structural components in complex systems (e.g., a vehicle).