Evolution of herbs: key to the conundrum might be tolerance not avoidance

草本植物的进化：解决难题的关键在于忍耐而非逃避 木本植物延续了其祖先被子植物的生长形态,而草本植物则不断地从中进化演变。虽然关于驱动草本植物习性进化的因素已有许多假设,但是通过舍弃地上生物质从而避免冬季冻害的能力常常被认为是促使其进化的主要力量。然而,鉴于草本植物在反复干扰中依旧能够轻松存活,我们提出了不可预测的干扰可能比季节性霜冻更为重要的假设。我们通过比较草本植物和木本植物应对3种模拟干扰(容易预测的冬季冰冻、不易预测的春季冰冻和食草作用)的能力来验证这一假设。通过比较20种不同植物在同质园实验中的表现,我们评估了这些干扰对植物死亡和再生方面的影响。研究结果表明,在冬季冰冻条件下,比起木本植物,草本植物在存活率上并没有优势。在不易预测的春季冰冻条件下,草本植物比木本植物的存活率更高。而在模拟食草作用的条件下,草本植物的这种生存优势更大。在不可预测的条件下,草本植物相较于木本植物的生存优势表明,草本植物的生长形式可能是对不可预测的干扰的适应,这种逆境忍耐通过其损失地上生物质也能够生存的能力得以实现。因此,哺乳动物的食草行为或火灾等原因或许最有可能是木本植物向草本植物过渡的因素。     

SARS-CoV-2 tropism,entry, replication,and propagation: Considerations for drug discovery and development

Since the initial report of the novel Coronavirus Disease 2019 (COVID-19) emanating from Wuhan, China, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally. While the effects of SARS-CoV-2 infection are not completely understood, there appears to be a wide spectrum of disease ranging from mild symptoms to severe respiratory distress, hospitalization, and mortality. There are no Food and Drug Administration (FDA)-approved treatments for COVID-19 aside from remdesivir; early efforts to identify efficacious therapeutics for COVID-19 have mainly focused on drug repurposing screens to identify compounds with antiviral activity against SARS-CoV-2 in cellular infection systems. These screens have yielded intriguing hits, but the use of nonhuman immortalized cell lines derived from non-pulmonary or gastrointestinal origins poses any number of questions in predicting the physiological and pathological relevance of these potential interventions. While our knowledge of this novel virus continues to evolve, our current understanding of the key molecular and cellular interactions involved in SARS-CoV-2 infection is discussed in order to provide a framework for developing the most appropriate in vitro toolbox to support current and future drug discovery efforts.     

Implementation and validation of thoracic side impact injury prediction metrics in a human body model

This study's purpose was to implement injury metrics into the Total Human Model for Safety (THUMS) mirroring the spinal accelerometers, rib accelerometers and chest band instrumentation from two lateral post-mortem human subject sled test configurations. In both sled configurations, THUMS contacted a flat rigid surface (either a wall or beam) at 6.7 m/s. Sled A maximum simulated wall forces for the thorax, abdomen and pelvis were 7.1, 5.0 and 10.0 kN versus 5.7 ± 0.8, 3.4 ± 1.2 and 6.2 ± 2.7 kN experimentally. Sled B maximum simulated beam forces for the torso and pelvis were 8.0 and 7.6 kN versus 8.5 ± 0.2 and 7.9 ± 2.5 kN experimentally. Quantitatively, force magnitude contributed more to variation between simulated and experimental forces than phase shift. Acceleration-based injury metrics were within one standard deviation of experimental means except for the lower spine in the rigid wall sled test. These validated metrics will be useful for quantifying occupant loading conditions and calculating injury risks in various loading configurations.     

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

SUMMARY

Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae, group A and B streptococci, Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo. This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.     

PURIFICATION AND CHARACTERIZATION OF A PROTEINASE FROM THE PROBIOTIC Lactobacillus rhamnosus OXY

A proteinase produced by the human gastrointestinal isolate Lactobacillus rhamnosus strain OXY was identified and characterized. The prtR2 gene coding for proteinase activity was detected in the examined strain. The PCR primers used were constructed on the basis of the sequence of the prtR2 proteinase gene from Lactobacillus rhamnosus GG. The enzyme was purified by fast protein liquid chromatography (FPLC) using CM-Sepharose Fast Flow and Sephacryl S-300 columns. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that the enzyme had a relatively low molecular mass of 60 kD. Protease activity was observed at a pH range from 6.5 to 7.5 with optimum k _cat/K _m values at pH 7.0 and 40°C. Maximum proteolytic activity (59 U mL^?1) was achieved after 48 hr of cultivation. The activity of the enzyme was inhibited only by irreversible inhibitors specific for serine proteinases (PMSF and 3,4-dichloro-isocumarine), suggesting that the enzyme was a serine proteinase. Proteinase activity was increased by Ca²⁺ and Mg²⁺, and inhibited by Cu²⁺, Zn²⁺, Cd²⁺, and Fe^2+.     

Aging aggravates ischemic stroke‐induced brain damage in mice with chronic peripheral infection

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1‐polarized chronic systemic infection was induced in 18–22 month and 4‐month‐old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin‐17α and tumor necrosis factor‐α levels. Neither age nor infection status alone or in combination altered the ischemia‐induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.