Design principles of nuclear receptor signaling: how complex networking improves signal transduction

Nuclear receptors often function in the cytoplasm.A triple conveyor belt pumps ligand (signal) into the nucleus and onto the DNA.The active export of importins enhances signaling to the nucleus.Sharing a single nuclear pore may reduce rather than increase crosstalk

Advice from a systems-biology model of the corona epidemics

Using standard systems biology methodologies a 14-compartment dynamic model was developed for the Corona virus epidemic. The model predicts that: (i) it will be impossible to limit lockdown intensity such that sufficient herd immunity develops for this epidemic to die down, (ii) the death toll from the SARS-CoV-2 virus decreases very strongly with increasing intensity of the lockdown, but (iii) the duration of the epidemic increases at first with that intensity and then decreases again, such that (iv) it may be best to begin with selecting a lockdown intensity beyond the intensity that leads to the maximum duration, (v) an intermittent lockdown strategy should also work and might be more acceptable socially and economically, (vi) an initially intensive but adaptive lockdown strategy should be most efficient, both in terms of its low number of casualties and shorter duration, (vii) such an adaptive lockdown strategy offers the advantage of being robust to unexpected imports of the virus, e.g. due to international travel, (viii) the eradication strategy may still be superior as it leads to even fewer deaths and a shorter period of economic downturn, but should have the adaptive strategy as backup in case of unexpected infection imports, (ix) earlier detection of infections is the most effective way in which the epidemic can be controlled, whilst waiting for vaccines

Effects of the Addition of Various Protectants on the Stability of Freeze-dried Lactobacillus rhamnosus Strain during Storage

Accelerated storaged testing is a rapid method used for the prediction of storage stability and quality, and for the estimation of shelf-life. It also could be used to predict a model for the stability of bacteria and the temperatures-dependence. In this research, NFDMS(non-fat dry milk solids, NFDMS)+sorbitol, NFDMS+inositol, NFDMS+fructose, NFDMS+trehalose, and NFDMS were used as protectants for Lactobacillus rhamnosus in freeze-drying and the ability of these materials to stabilize the bacteria in the accelerated storaged testing was studied. Results showed that NFDMS+sorbitol and NFDMS+inositol were the most effective protectants for Lactobacillus rhamnosus in freeze-drying, and the residual survival rates were 62.51 %and 60.27% respecitively. The worst one was NFDMS, and the residual survival rate was 3.94%. By means of the Arrhenius relationship, the stability of L. rhamnosus with different protectants during storage could be predicted. From the k vaules obtained, NFDMS+sorbitol were found to be the most effective material because of the lowest k vaules (day-1), 0.000116 (5℃) and 0.015 (25℃). The effect of different protentants were NFDMS+sorbitol>NFDMS+inositol>NFDMS+fructose>NFDMS+trehalose>NFDMS. Results coincided with the actual storage test.加速貯藏試驗是藉由預測樣品貯存穩定性來快速評估產品保存期限(shelf-life)的重要方法，它亦可用來做為溫度與微生物存活率間變化的預估模式。本研究透過加速貯藏試驗來預估保護劑脫脂奶粉、脫脂奶粉合併肌醇、果糖、海藻糖及山梨醇的使用對菌株Lactobacillus rhamnosus冷凍乾燥的保護效益，結果顯示以脫脂奶粉合併山梨醇及果糖的使用對菌株冷凍乾燥的保護效果最佳，其存活率分別為62.51%及60.27%，而單一使用脫脂奶粉時保護效果最差，菌株存活率只有3.94%。透過阿瑞尼士方程式來探討不同保護劑對L. rhamnosus冷凍乾燥菌體於貯藏期間安定性的影響，實驗結果發現脫脂奶粉合併山梨醇組所得之5及25℃預估k值(day-1)為0.000116及0.015為最小，表示其保護效果最好，而不同保護劑對L. rhamnosus貯藏安定性的保護效果由高到低為：脫脂奶粉+山梨醇>脫脂奶粉+肌醇>脫脂奶粉+果糖>脫脂奶粉+海藻糖>脫脂奶粉，其加速貯藏試驗結果與實際貯藏試驗結果相同。中文摘要(i) 英文摘要(ii) 壹、前言(1) 貳、文獻整理(3) 一、 加速貯藏試驗(accelerated storage test)(3) (一) 加速貯藏試驗的意義(3) (二) 阿瑞尼士方程式(Arrhenius equation)於加速貯藏試之 應用(4) (三) 加速貯藏試驗於冷凍乾燥菌株安定性評估之應用(5) (四) 加速貯藏試驗於食品中之應用實例(7) 二、乳酸菌之簡介(10) (一) 乳酸菌之定義(10) (二) 乳酸菌之分類(11) (三) 乳酸菌之代謝(12) (四) 乳酸菌與人體健康保健(13) (五) 鼠李糖乳酸桿菌(Lactobacillus rhamnosus)(16) 三、冷凍乾燥技術(freeze-drying)(20) (一) 冷凍乾燥之原理(20) (二) 冷凍乾燥裝置(23) (三) 冷凍乾燥之特性(25) (四) 冷凍乾燥改善技術(28) 四、冷凍乾燥對乳酸菌之影響(29) 五、影響冷凍乾燥菌酛穩定性的因子(30) (一) 菌株種類(31) (二) 菌株培養條件(31) (三) 保護劑之添加(33) (四) 冷凍乾燥條件(34) (五) 菌體回溶之條件(36) 六、冷凍保護劑(cryoprotectant)之保護機制(37) (一) 脫脂奶粉(non-fat dry milk solids)(37) (二) 醣類(carbohydrates)(38) 參、研究目的(46) 肆、材料與方法(47) 一、試驗材料與儀器(47) (一) 試驗材料(47) (二) 儀器(48) 二、實驗方法(49) (一) 實驗菌株之製備(49) (二) 濃厚菌體懸浮液之備製(49) (三) 菌體懸浮液菌數之計算(50) (四) 凍結實驗(50) (五) 冷凍乾燥試驗(51) (六) 乾燥菌體存活率測定(51) (七) 加速貯藏試驗(52) (八) 實際貯藏試驗(52) (九) 半乳糖苷酶(β-galactosidase)活性測定(54) (十) 實驗設計流程(54) (十一) 統計分析(54) 伍、結果與討論(58) 一、冷凍及冷凍乾燥對菌數之影響(58) (一) L. rhamnosus 經冷凍及冷凍乾燥之存活率(58) (二) 不同保護劑對L. rhamnosus 於冷凍及冷凍乾燥保護之 比較(59) 二、加速貯藏試驗結果(62) (一) 不同貯藏溫度對活菌數變化之影響(62) (二) 熱致死速率常數(k) (63) (三) 加速貯藏試驗之預測結果 (71) 三、冷凍乾燥L. rhamnosus之貯藏安定性(78) (一) 實際貯藏安定性(80) (二) 實際貯藏與加速貯藏試驗結果之比較(87) 四、β-galactosidase 酵素活性之測定(89) 陸、結論(93) 柒、參考文獻(94

Network analysis for systems biology

Network analysis is an essential component of systems biology approaches toward understanding the molecular and cellular interactions underlying biological systems functionalities and their perturbations in disease. Regulatory and signalling pathways, which involve DNA, RNA proteins and metabolites as key elements, coordinate most aspects of cellular functioning. Cellular processes, which are dependent on the structure and dynamics of gene regulatory networks, can be studied by employing a network representation of molecular interactions. In this chapter we describe several types of networks and how combination of different analytic approaches can be used to study diseases. We provide a list of selected tools for visualization and network analysis. We introduce protein-protein interaction networks, gene regulatory networks, signalling networks and metabolic networks. We then define concepts underlying network representation of cellular processes and molecular interactions. We finally discuss how the level of accuracy in inferring functional relationships influences the choice of methods applied for the analysis of a particular network type

Systems biology towards life in silico: mathematics of the control of living cells.

Systems Biology is the science that aims to understand how biological function absent from macromolecules in isolation, arises when they are components of their system. Dedicated to the memory of Reinhart Heinrich, this paper discusses the origin and evolution of the new part of systems biology that relates to metabolic and signal-transduction pathways and extends mathematical biology so as to address postgenomic experimental reality. Various approaches to modeling the dynamics generated by metabolic and signal-transduction pathways are compared. The silicon cell approach aims to describe the intracellular network of interest precisely, by numerically integrating the precise rate equations that characterize the ways macromolecules' interact with each other. The non-equilibrium thermodynamic or 'lin-log' approach approximates the enzyme rate equations in terms of linear functions of the logarithms of the concentrations. Biochemical Systems Analysis approximates in terms of power laws. Importantly all these approaches link system behavior to molecular interaction properties. The latter two do this less precisely but enable analytical solutions. By limiting the questions asked, to optimal flux patterns, or to control of fluxes and concentrations around the (patho)physiological state, Flux Balance Analysis and Metabolic/Hierarchical Control Analysis again enable analytical solutions. Both the silicon cell approach and Metabolic/Hierarchical Control Analysis are able to highlight where and how system function derives from molecular interactions. The latter approach has also discovered a set of fundamental principles underlying the control of biological systems. The new law that relates concentration control to control by time is illustrated for an important signal transduction pathway, i.e. nuclear hormone receptor signaling such as relevant to bone formation. It is envisaged that there is much more Mathematical Biology to be discovered in the area between molecules and Life

ROS networks:designs, aging, Parkinson’s disease and precision therapies

How the network around ROS protects against oxidative stress and Parkinson's disease (PD), and how processes at the minutes timescale cause disease and aging after decades, remains enigmatic. Challenging whether the ROS network is as complex as it seems, we built a fairly comprehensive version thereof which we disentangled into a hierarchy of only five simpler subnetworks each delivering one type of robustness. The comprehensive dynamic model described in vitro data sets from two independent laboratories. Notwithstanding its five-fold robustness, it exhibited a relatively sudden breakdown, after some 80 years of virtually steady performance: it predicted aging. PD-related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the collapse, while antioxidants or caffeine retarded it. Introducing a new concept (aging-time-control coefficient), we found that as many as 25 out of 57 molecular processes controlled aging. We identified new targets for "life-extending interventions": mitochondrial synthesis, KEAP1 degradation, and p62 metabolism

Cross-Cultural Perspectives on the Role of Empathy during COVID-19's First Wave

The COVID-19 pandemic has spread throughout the world, and concerns about psychological, social, and economic consequences are growing rapidly. Individuals' empathy-based reactions towards others may be an important resilience factor in the face of COVID-19. Self-report data from 15,375 participants across 23 countries were collected from May to August 2020 during the early phases of the COVID-19 pandemic. In particular, this study examined different facets of empathy-Perspective-Taking, Empathic Concern, and Personal Distress, and their association with cross-cultural ratings on Individualism, Power Distance, The Human Development Index, Social Support Ranking, and the Infectious Disease Vulnerability Index, as well as the currently confirmed number of cases of COVID-19 at the time of data collection. The highest ratings on Perspective-Taking were obtained for USA, Brazil, Italy, Croatia, and Armenia (from maximum to minimum); on Empathetic Concern, for the USA, Brazil, Hungary, Italy, and Indonesia; and on Personal Distress, from Brazil, Turkey, Italy, Armenia, Indonesia. Results also present associations between demographic factors and empathy across countries. Limitations and future directions are presented