Interactions of sugars with membranes

Water profoundly affects the stability of biological membranes, and its removal leads to destructive events including fusion and liquid crystalline to gel phase transitions. In heterogeneous mixtures such as those found in biological membranes the phase transitions can lead to increases in permeability and lateral phase separations that often are irreparable. Certain sugars are capable of preventing these deleterious events by inhibiting fusion during drying and by maintaining the lipid in a fluid state in the absence of water. As a result, the increased permeability and lateral phase separations that accompany dehydration are absent. The weight of the evidence suggests strongly that there is a direct interaction between the sugars and lipids in the dry state. Although the evidence is less clear about whether these sugars can interact directly with hydrated bilayers, there are strong suggestions in the literature that sugars free in solution or covalently linked to membrane constituents can also affect the physical properties and presumably the stability of bilayers. Finally, we have far less evidence concerning the mechanism by which they do so, but the same sugars are also capable of preserving the structure and function of both membrane-bound and soluble proteins in the absence of water. We believe these effects may be important in the survival of intact cells and organisms such as seeds in the absence of water. Furthermore, in view of the practical importance of preserving biological structures we suspect that the results described here will ultimately have important applications in biology and medicine.     

Degradation and inhibition of epigenetic regulatory protein BRD4 exacerbate Alzheimer’s disease-related neuropathology in cell models

Epigenetic regulation plays substantial roles in human pathophysiology, which provides opportunities for intervention in human disorders through the targeting of epigenetic pathways. Recently, emerging evidence from preclinical studies suggested the potential in developing therapeutics of Alzheimer’s disease (AD) by targeting bromodomain containing protein 4 (BRD4), an epigenetic regulatory protein. However, further characterization of AD-related pathological events is urgently required. Here, we investigated the effects of pharmacological degradation or inhibition of BRD4 on AD cell models. Interestingly, we found that both degradation and inhibition of BRD4 by ARV-825 and JQ1, respectively, robustly increased the levels of amyloid-beta (Aβ), which has been associated with the neuropathology of AD. Subsequently, we characterized the mechanisms by which downregulation of BRD4 increases Aβ levels. We found that both degradation and inhibition of BRD4 increased the levels of BACE1, the enzyme responsible for cleavage of the amyloid-beta protein precursor (APP) to generate Aβ. Consistent with Aβ increase, we also found that downregulation of BRD4 increased AD-related phosphorylated Tau (pTau) protein in our 3D-AD human neural cell culture model. Therefore, our results suggest that downregulation of BRD4 would not be a viable strategy for AD intervention. Collectively, our study not only shows that BRD4 is a novel epigenetic component that regulates BACE1 and Aβ levels, but also provides novel and translational insights into the targeting of BRD4 for potential clinical applications.     

Pro-sequence assisted folding and disulfide bond formation of human nerve growth factor

Nerve growth factor (NGF) is a member of the neurotrophin family. These growth factors support neuronal survival and differentiation. Neurotrophins are synthesized as pre-pro-proteins. Whereas the pre-sequences mediate secretion, the function of the pro-peptides is largely unknown. To test the role of the pro-sequence as a folding enhancer, recombinant human pro-NGF (rh-pro-NGF) was produced in Escherichia coli. The oxidative refolding of rh-pro-NGF and rh-NGF was studied using electrospray mass spectrometry (ESIMS) time-course analysis. This analysis permitted both the identification and quantification of intermediates present during the process. The disulfide bonds formed at different times of the refolding processes were characterized by proteolytic digestion followed by matrix assisted laser desorption ionization mass spectrometry (MALDIMS) analysis. Folding yields and kinetics of rh-pro-NGF were significantly enhanced when compared to the in vitro refolding of mature rh-NGF. These results suggest that the pro-sequence of NGF promotes folding of the mature part.     

秦渭玫瑰精油研究

采用ISO9842和GB11538-89对在陕西渭南栽培的大马士革玫瑰“卡赞勒克”精油(工业化蒸馏法提取产品)进行了分析,结果表明,精油产品各项指标均符合ISO 9842和保加利亚БДС653标准要求。证明引种国际香型(纯甜型)玫瑰品种在陕西渭南栽培是成功的,所用精油提取工艺是合理的。     

PARP inhibitors trap PARP2 and alter the mode of recruitment of PARP2 at DNA damage sites

Dual-inhibitors of PARP1 and PARP2 are promising anti-cancer drugs. In addition to blocking PARP1&2 enzymatic activity, PARP inhibitors also extend the lifetime of DNA damage-induced PARP1&2 foci, termed trapping. Trapping is important for the therapeutic effects of PARP inhibitors. Using live-cell imaging, we found that PARP inhibitors cause persistent PARP2 foci by switching the mode of PARP2 recruitment from a predominantly PARP1- and PAR-dependent rapid exchange to a WGR domain-mediated stalling of PARP2 on DNA. Specifically, PARP1-deletion markedly reduces but does not abolish PARP2 foci. The residual PARP2 foci in PARP1-deficient cells are DNA-dependent and abrogated by the R140A mutation in the WGR domain. Yet, PARP2-R140A forms normal foci in PARP1-proficient cells. In PARP1-deficient cells, PARP inhibitors - niraparib, talazoparib, and, to a lesser extent, olaparib - enhance PARP2 foci by preventing PARP2 exchange. This trapping of PARP2 is independent of auto-PARylation and is abolished by the R140A mutation in the WGR domain and the H415A mutation in the catalytic domain. Taken together, we found that PARP inhibitors trap PARP2 by physically stalling PARP2 on DNA via the WGR-DNA interaction while suppressing the PARP1- and PAR-dependent rapid exchange of PARP2.     

Tree and bird functional groups as indicators of recovery of regenerating subtropical coastal dune forests

Functional diversity indicators are increasingly used to monitor forest function recovery because they connect biodiversity to ecosystem functions. However, identifying which functions deviate from a reference forest has not received much attention, despite its potential to inform restoration interventions. In this study, we used functional groups to assess the recovery of ecosystem functions in regenerating coastal dune forests. We surveyed birds and trees in forest of different ages and a reference old‐growth forest in KwaZulu‐Natal, South Africa. We classified species into functional groups for each taxa based on functional traits or a priori defined categories (i.e. guilds) and quantified the number of species within functional groups as a proxy of function stability. Bird species density followed an asymptotic trajectory, reaching old‐growth forest values after 25 years. Insectivores and granivores showed saturating trajectories, whereas small frugivores and generalists increased linearly. With the exception of large frugivores, relative abundances of bird functional groups progressed towards old‐growth forest values as the forest aged. Tree species density increased linearly with forest age. In contrast to old‐growth forests, large‐canopy trees and understory shrubs were under‐represented, while mid‐canopy trees dominated regenerating forests. Our result suggests that most bird, but not tree, functions may have been restored. The trend in large frugivore numbers may warrant further investigation, as their low numbers may have hampered the recovery of tree functions. We conclude that functional group trajectories can track functions that deviate from a benchmark, and may therefore direct adaptive actions to recover the stability of regenerating forest.     

Pan‐Arctic sea ice‐algal chl a biomass and suitable habitat are largely underestimated for multiyear ice

There is mounting evidence that multiyear ice (MYI) is a unique component of the Arctic Ocean and may play a more important ecological role than previously assumed. This study improves our understanding of the potential of MYI as a suitable habitat for sea ice algae on a pan‐Arctic scale. We sampled sea ice cores from MYI and first‐year sea ice (FYI) within the Lincoln Sea during four consecutive spring seasons. This included four MYI hummocks with a mean chl a biomass of 2.0 mg/m², a value significantly higher than FYI and MYI refrozen ponds. Our results support the hypothesis that MYI hummocks can host substantial ice‐algal biomass and represent a reliable ice‐algal habitat due to the (quasi‐) permanent low‐snow surface of these features. We identified an ice‐algal habitat threshold value for calculated light transmittance of 0.014%. Ice classes and coverage of suitable ice‐algal habitat were determined from snow and ice surveys. These ice classes and associated coverage of suitable habitat were applied to pan‐Arctic CryoSat‐2 snow and ice thickness data products. This habitat classification accounted for the variability of the snow and ice properties and showed an areal coverage of suitable ice‐algal habitat within the MYI‐covered region of 0.54 million km² (8.5% of total ice area). This is 27 times greater than the areal coverage of 0.02 million km² (0.3% of total ice area) determined using the conventional block‐model classification, which assigns single‐parameter values to each grid cell and does not account for subgrid cell variability. This emphasizes the importance of accounting for variable snow and ice conditions in all sea ice studies. Furthermore, our results indicate the loss of MYI will also mean the loss of reliable ice‐algal habitat during spring when food is sparse and many organisms depend on ice‐algae.     

A quorum sensing‐defective mutant of Pectobacterium carotovorum ssp. brasiliense 1692 is attenuated in virulence and unable to occlude xylem tissue of susceptible potato plant stems

Pectobacterium carotovorum ssp. brasiliense 1692 (Pcb1692) is an important emerging pathogen of potatoes causing blackleg in the field and soft rot during post‐harvest storage. Blackleg diseases involve the bacterial colonization of vascular tissue and the formation of aggregates, also known as biofilms. To understand the role of quorum sensing in vascular colonization by Pcb1692, we generated a Pcb1692ΔexpI mutant strain. Inactivation of expI led to the reduced production of plant cell wall‐degrading enzymes (PCWDEs), the inability to produce acyl homoserine lactone (AHL) and reduced virulence in potato tubers and stems. Complementation of the mutant strain with the wild‐type expI gene in trans successfully restored AHL and PCWDE production as well as virulence. Transmission electron microscopy and in vitro motility assays demonstrated hyperpiliation and loss of flagella and swimming motility in the mutant strain compared with the wild‐type Pcb1692. Furthermore, we noted that, in the early stages of infection, Pcb1692 wild‐type cells had intact flagella which were shed at the later stages of infection. Confocal laser microscopy of PcbΔexpI‐inoculated plants showed that the mutant strain tended to aggregate in intercellular spaces, but was unable to transit to xylem tissue. On the contrary, the wild‐type strain was often observed forming aggregates within xylem tissue of potato stems. Gene expression analyses confirmed that flagella are part of the quorum sensing regulon, whereas fimbriae and pili appear to be negatively regulated by quorum sensing. The relative expression levels of other important putative virulence genes, such as those encoding different groups of PCWDEs, were down‐regulated in the mutant compared with the wild‐type strain.     

草地贪夜蛾对不同品种玉米的适应性比较研究

为了解不同玉米品种对草地贪夜蛾生长发育的影响,本文通过比较草地贪夜蛾Spodoptera frugiperda取食2种糯质型玉米(明玉1203和苏玉糯5号)与3种普通玉米(苏玉29、苏玉30和郑单958)后的发育历期、死亡率、蛹重、成虫畸形率、繁殖力与幼虫取食选择率等生物学参数,分析了草地贪夜蛾对不同品种玉米的适应性差...