Progressive Kidney Degeneration in Mice Lacking Tensin

Tensin is a focal adhesion phosphoprotein that binds to F-actin and contains a functional Src homology 2 domain. To explore the biological functions of tensin, we cloned the mouse tensin gene, determined its program of expression, and used gene targeting to generate mice lacking tensin. Even though tensin is expressed in many different tissues during embryogenesis, tensin null mice developed normally and appeared healthy postnatally for at least several months. Over time, −/− mice became frail because of abnormalities in their kidneys, an organ that expresses high levels of tensin. Mice with overt signs of weakness exhibited signs of renal failure and possessed multiple large cysts in the proximal kidney tubules, but even in tensin null mice with normal blood analysis, cysts were prevalent. Ultrastructurally, noncystic areas showed typical cell– matrix junctions that readily labeled with antibodies against other focal adhesion molecules. In abnormal regions, cell–matrix junctions were disrupted and tubule cells lacked polarity. Taken together, our data imply that, in the kidney, loss of tensin leads to a weakening, rather than a severing, of focal adhesion. All other tissues appeared normal, suggesting that, in most cases, tensin's diverse functions are redundant and may be compensated for by other focal adhesion proteins.     

The role of SIRT2 in vascular-related and heart-related diseases: A review

At present, cardiovascular disease is one of the important factors of human death, and there are many kinds of proteins involved. Sirtuins family proteins are involved in various physiological and pathological activities of the human body. Among them, there are more and more studies on the relationship between sirtuin2 (SIRT2) protein and cardiovascular diseases. SIRT2 can effectively inhibit pathological cardiac hypertrophy. The effect of SIRT2 on ischaemia-reperfusion injury has different effects under different conditions. SIRT2 can reduce the level of reactive oxygen species (ROS), which may help to reduce the severity of diabetic cardiomyopathy. SIRT2 can affect a variety of cardiovascular diseases, energy metabolism and the ageing of cardiomyocytes, thereby affecting heart failure. SIRT2 also plays an important role in vascular disease. For endothelial cell damage used by oxidative stress, the role of SIRT2 is bidirectional, which is related to the degree of oxidative stress stimulation. When the degree of stimulation is small, SIRT2 plays a protective role, and when the degree of stimulation increases to a certain level, SIRT2 plays a negative role. In addition, SIRT2 is also involved in the remodelling of blood vessels and the repair of skin damage.     

Genome Sequence of a Nicotine-Degrading Strain of Arthrobacter

We announce a 4.63-Mb genome assembly of an isolated bacterium that is the first sequenced nicotine-degrading Arthrobacter strain. Nicotine catabolism genes of the nicotine-degrading plasmid pAO1 were predicted, but plasmid function genes were not found. These results will help to better illustrate the molecular mechanism of nicotine degradation by Arthrobacter.     

Cardiolipin interacts with beta‐2‐glycoprotein I and forms an open conformation–Mechanisms analyzed using hydrogen/deuterium exchange

Beta‐2‐glycoprotein I (β₂GPI) is the major antigen for the antiphospholipid antibodies in the antiphospholipid syndrome. The exposed epitope in domain I of β₂GPI can be recognized by the anti‐β₂GPI antibody. Here, we prepared the anionic di‐oleoyl‐phosphatidylserine (DOPS) and cardiolipin (CL) liposomes to interact with the β₂GPI. The conformational changes of β₂GPI upon binding with the liposomes were analyzed using hydrogen/deuterium exchange mass spectrometry. The exchange level of sequences 21–27 significantly increased after β₂GPI had interacted with DOPS. This change indicated a reduced interaction between domain I and domain V, inferring to a protrusion of the sequences 21–27 from the ring conformation. After β₂GPI had interacted with CL for 30 min, the exchange levels in 4 of the 5 domains increased significantly. The deuteration levels of sequences 1–20, 21–27, 196–205, 273–279 and 297–306 increased, suggesting that these regions had become more exposed, and the domain I was no longer in contact with domain V. The increasing deuteration levels in sequences 70–86, 153–162, 191–198, 196–205 and 273–279 indicated β₂GPI undergoing conformational changes to expose these inner regions, suggesting a structural transition. Overall, DOPS and CL induced minor conformational changes of β₂GPI at sequences 21–27 and forms an intermediate conformation after 10 min of interaction. After a complete protein–lipid interaction, high negatively charged CL membrane induced a major conformation transition of β₂GPI.     

The Neural Mechanisms Underlying the Acute Effect of Cigarette Smoking on Chronic Smokers

Although previous research had related structural changes and impaired cognition to chronic cigarette smoking, recent neuroimaging studies have associated nicotine, which is a main chemical substance in cigarettes, with improvements in cognitive functions (e.g. improved attention performance). However, information about the alterations of whole-brain functional connectivity after acute cigarette smoking is limited. In this study, 22 smokers underwent resting-state functional magnetic resonance imaging (rs-fMRI) after abstaining from smoking for 12 hours (state of abstinence, SOA). Subsequently, the smokers were allowed to smoke two cigarettes (state of satisfaction, SOS) before they underwent a second rs-fMRI. Twenty non-smokers were also recruited to undergo rs-fMRI. In addition, high-resolution 3D T1-weighted images were acquired using the same magnetic resonance imaging(fMRI)scanner for all participants. The results showed that smokers had structural changes in insula, thalamus, medial frontal cortex and several regions of the default mode network (DMN) compared with non-smokers. Voxel-wise group comparisons of newly developed global brain connectivity (GBC) showed that smokers in the SOA condition had higher GBC in the insula and superior frontal gyrus compared with non-smokers. However, smokers in the SOS condition demonstrated significantly lower GBC in several regions of the DMN, as compared with smokers in the SOA condition. These results suggest that structural integrity combined with dysfunction of the DMN might be involved in relapses after a short period of time among smokers.     

Dynamics of a Cytokine Storm

Six volunteers experienced severe inflammatory response during the Phase I clinical trial of a monoclonal antibody that was designed to stimulate a regulatory T cell response. Soon after the trial began, each volunteer experienced a “cytokine storm”, a dramatic increase in cytokine concentrations. The monoclonal antibody, TGN1412, raised serum concentrations of both pro- and anti-inflammatory cytokines το very hiγh values during the first day, while lymphocyte and monocyte concentrations plummeted. Because the subjects were healthy and had no prior indications of immune deficiency, this event provided an unusual opportunity to study the dynamic interactions of cytokines and other measured parameters. Here, the response histories of nine cytokines have been modeled by a set of linear ordinary differential equations. A general search procedure identifies parameters of the model, whose response fits the data well during the five-day measurement period. The eighteenth-order model reveals plausible cause-and-effect relationships among the cytokines, showing how each cytokine induces or inhibits other cytokines. It suggests that perturbations in IL2, IL8, and IL10 have the most significant inductive effect, while IFN-γ and IL12 have the greatest inhibiting effect on other cytokine concentrations. Although TNF-α is a major pro-inflammatory factor, IFN-γ and three other cytokines have faster initial and median response to TGN1412 infusion. Principal-component analysis of the data reveals three clusters of similar cytokine responses: [TNF-α, IL1, IL10], [IFN-γ, IL2, IL4, IL8, and IL12], and [IL6]. IL1, IL6, IL10, and TNF-α have the highest degree of variability in response to uncertain initial conditions, exogenous effects, and parameter estimates. This study illuminates details of a cytokine storm event, and it demonstrates the value of linear modeling for interpreting complex, coupled biological system dynamics from empirical data.     

A mechanism coordinating root elongation,endodermal differentiation,redox homeostasis and stress response

Root growth relies on both cell division and cell elongation, which occur in the meristem and elongation zones, respectively. SCARECROW (SCR) and SHORT-ROOT (SHR) are GRAS family genes essential for root growth and radial patterning in the Arabidopsis root. Previous studies showed that SCR and SHR promote root growth by suppressing cytokinin response in the meristem, but there is evidence that SCR expressed beyond the meristem is also required for root growth. Here we report a previously unknown role for SCR in promoting cell elongation. Consistent with this, we found that the scr mutant accumulated a higher level of reactive oxygen species (ROS) in the elongation zone, which is probably due to decreased expression of peroxidase gene 3, which consumes hydrogen peroxide in a reaction leading to Casparian strip formation. When the oxidative stress response was blocked in the scr mutant by mutation in ABSCISIC ACID 2 (ABA2) or when the redox status was ameliorated by the upbeat 1 (upb1) mutant, the root became significantly longer, with longer cells and a larger and more mitotically active meristem. Remarkably, however, the stem cell and radial patterning defects in the double mutants still persisted. Since ROS and peroxidases are essential for endodermal differentiation, these results suggest that SCR plays a role in coordinating cell elongation, endodermal differentiation, redox homeostasis and oxidative stress response in the root. We also provide evidence that this role of SCR is independent of SHR, even though they function similarly in other aspects of root growth and development.     

基于低相干光干涉的眼睛光学生物参数测量研究

目的 眼睛的光学生物参数中的眼轴长度（AL）和角膜曲率半径（CR）可以作为预防和监测眼球近视的两个重要参数。为了提高测量眼轴长度的速度与精度和同步实现角膜曲率高精度动态测量，本文提出一种基于低相干光干涉技术眼睛光学生物参数测量的系统。方法 该系统使用旋转光学延迟线快速改变参考光的光程，利用曲率半径为8 mm的标准件标定人眼角膜顶点到靶环之间的距离，利用角膜的干涉信号对相机和数据采集卡进行触发实现同步采集，从而实现眼轴长度的快速测量和精准定位靶环到角膜顶点之间的距离，同时保证成像系统的放大倍率恒定和数据的实时采集。结果 实验结果表明，这种低相干光干涉测量系统，可以实时测量眼轴长度和角膜曲率半径，眼轴长度误差低于40 μm，人眼角膜曲率半径方差为2.082 36×10^-2 μm。结论 该系统能够快速、精准地测量AL和CR，可在近视的预防和监测中发挥重要作用。