Biophysics Reports

2020 Vol. 6, No. 2-3

Cover Story

The gallbladder is an important component of the hepatobiliary system whose primary function is to aid in digestion of foodstuffs, excretion of drugs and facilitate removal of waste products from the body. The gall bladder is principally a storage organ for bile, chemically modified salts and acids of cholesterol which are synthesized in the liver and which function as surfactants to solubilize fatty substances of limited aqueous solubility. Any disruption in the amount or activity of bile surfactant can lead to an accumulation of insoluble molecular clumps (e.g., gallstones) that deposit in and obstruct fluid movement within the gallbladder, and which can lead to pathological congestion and tissue damage. The natural host defense response to any event that causes tissue damage is to stimulate inflammation, which non-specifically but aggressively reacts to the stimuli so to remove the cause and repair damaged tissues. The C-reactive protein (CRP) is a primarily hepatically produced serum protein whose blood levels increase within 6–10 h of any tissue-damaging event. The extent with which it increases cor-relates with the level of tissue damage and associated inflammation. CRP levels are reported to be of value in diagnosing acute cholecystitis severity, in predicting the outcome and prognosis of cancer-associated gallbladder resection, and in helping identify cystic structures during emergency laparo-scopic cholecystectomies. As an understanding of distinctive CRP structural isoforms is evolving, its role not only as a biomarker but as regulator of both physiologic and pathophysiologic processes of inflammation may be relevant in the understanding of and treatment approaches for gallbladder-associated disease.

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Epigenetic regulation and mechanobiology

Shitian Li, Dingyi Yang, Li Gao, Yingxiao Wang, Qin Peng

2020, 6(2-3): 33-48. doi: 10.1007/s41048-020-00106-x

Abstract(406)

PDF(148)

Abstract:
Mechanical force regulates a variety of cellular functions through inducing modulations in nuclear chromatin structures and epigenetic landscapes (outside in). The epigenetic modifications, in turn, regulate gene expressions and affect phenotypic outcomes, including cytoskeletal organization and cell-cell/cell-ECM interactions (inside out). While there have been significant advances in the understanding of mechanotransduction in the nucleus, there is still a lack of knowledge on the potential mechanisms through which mechanical cues affect epigenetic and chromatin regulations to determine genetic outcomes. This review firstly focuses on the current understanding of epigenetic regulations and then summarizes how mechanotransduction and epigenetic modification couple together to regulate molecular and cellular functions, eventually causing functional phenotype changes e.g., diseases. Lastly, we introduce related technologies for mechanistic studies, particularly fluorescence resonance energy transfer (FRET) biosensors for the visualization of dynamic epigenetic regulations in single living cells, as well as the applications of FRET biosensors to visualize mechanotransduction events occurring in the nucleus. These studies could provide new insights into epigenetics in regulating the physiological and pathological processes in living cells under different mechanical environments.

C-reactive protein in gallbladder diseases: diagnostic and therapeutic insights

Ibraheem M. Rajab, Daniel Majerczyk, Margaret E. Olson, Jenna M. B. Addams, Mihee L. Choe, Matthew S. Nelson, Lawrence A. Potempa

2020, 6(2-3): 49-67. doi: 10.1007/s41048-020-00108-9

Abstract(1910)

PDF(80)

Abstract:
The gallbladder is an important component of the hepatobiliary system whose primary function is to aid in digestion of foodstuffs, excretion of drugs and facilitate removal of waste products from the body. The gall bladder is principally a storage organ for bile, chemically modified salts and acids of cholesterol which are synthesized in the liver and which function as surfactants to solubilize fatty substances of limited aqueous solubility. Any disruption in the amount or activity of bile surfactant can lead to an accumulation of insoluble molecular clumps (e.g., gallstones) that deposit in and obstruct fluid movement within the gallbladder, and which can lead to pathological congestion and tissue damage. The natural host defense response to any event that causes tissue damage is to stimulate inflammation, which non-specifically but aggressively reacts to the stimuli so to remove the cause and repair damaged tissues. The C-reactive protein (CRP) is a primarily hepatically produced serum protein whose blood levels increase within 6-10 h of any tissue-damaging event. The extent with which it increases correlates with the level of tissue damage and associated inflammation. CRP levels are reported to be of value in diagnosing acute cholecystitis severity, in predicting the outcome and prognosis of cancerassociated gallbladder resection, and in helping identify cystic structures during emergency laparoscopic cholecystectomies. As an understanding of distinctive CRP structural isoforms is evolving, its role not only as a biomarker but as regulator of both physiologic and pathophysiologic processes of inflammation may be relevant in the understanding of and treatment approaches for gallbladderassociated disease.

Type II toxin-antitoxin system in bacteria: activation, function, and mode of action

Si-Ping Zhang, Qian Wang, Shuo-Wei Quan, Xiao-Quan Yu, Yong Wang, Ding-Ding Guo, Liang Peng, Hu-Yuan Feng, Yong-Xing He

2020, 6(2-3): 68-79. doi: 10.1007/s41048-020-00109-8

Abstract(444)

PDF(72)

Abstract:
The toxin-antitoxin (TA) system is composed of a stable toxin and an unstable antitoxin that neutralizes the toxin. Being perhaps the most studied among the different TA types, type II TA systems are widely distributed and often exist in multiple copies within chromosomes of eubacteria and archaea. Exhibiting diverse molecular activities such as RNases, kinases, and acetyltransferases, type II TA systems have been confirmed to be involved in diverse biological processes including plasmid maintenance, phage inhibition, persistence, stress response, and biofilm formation. In this review, we summarize the current state of the research in the type II TA field, emphasizing the activation mechanism, structure-function relationship, and biological functions of type II TA systems.

Performance of CHARMM36m with modified water model in simulating intrinsically disordered proteins: a case study

Laura I. Gil Pineda, Laurie N. Milko, Yi He

2020, 6(2-3): 80-87. doi: 10.1007/s41048-020-00107-w

Abstract(589)

PDF(55)

Abstract:
Molecular dynamics simulations can be a powerful tool to complement experiments in the study of the structures and dynamics of intrinsically disordered proteins. Though the accuracy of the physics-based all-atom force fields has improved significantly in simulating structured proteins over the past twenty years, most of these force fields face a big challenge to simulate flexible proteins. Recently, CHARMM36m with modified TIP3P model was proposed as a possible solution to simulate intrinsically disordered proteins. Here, we tested the proposed solution using an extensively studied protein, namely NCBD, to explore the performance of CHARMM36m plus modified TIP3P water. Our results suggest that the modified TIP3P water model does enhance the sampling of conformational space compared to the standard TIP3P water model. However, the new CHARMM36m force field still leads to over-compact structures and over-stabilized helices.