The C-terminal sequence from common bugle leaf galactan:galactan galactosyltransferase is a non-sequence-specific vacuolar sorting determinant

The Ajuga reptans L. galactan:galactan galactosyltransferase (ArGGT) is a vacuolar enzyme that synthesizes long-chain raffinose family oligosaccharides (RFOs), the major storage carbohydrates of this plant. ArGGT is structurally and functionally related to acid plant alpha-galactosidases (alpha-Gals) of the glycosylhydrolase family 27, present in the apoplast or the vacuole. Sequence comparison of acid alpha-Gals with ArGGT revealed that they all contain an N-terminal signal sequence and a highly similar core sequence. Additionally, ArGGT and some acid alpha-Gals contain C-terminal extensions with low sequence similarities to each other. Here, we show that the C-terminal pentapeptide, SLQMS, is a non-sequence-specific vacuolar sorting determinant. Analogously, we demonstrate that the C-terminal extensions of selected acid alpha-Gals from Arabidopsis, barley, and rice, are also non-sequence-specific vacuolar sorting determinants, suggesting the presence of at least one vacuolar form of acid alpha-Gal in every plant species.     

A serine involved in actin-dependent subcellular localization of a stress-induced tobacco BY-2 hydroxymethylglutaryl-CoA reductase isoform

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is unique in the first part of the cytoplasmic isoprenoid pathway, as it contains a membrane domain that includes ER-specific retention motifs. When fused to GFP, this domain targets two tobacco BY-2 HMGR isoforms differentially. While the first isoform is ER-localized, a second stress-induced one forms globular structures connected by tubular structures. A serine positioned upstream of the ER retention motif seems to be implicated in this specific subcellular localization. Surprisingly, these structures are closely connected to F-actin, and their intactness is dependent upon the integrity of the filaments or the action of a calmodulin antagonist.     

How to correct relative voxel scale factors for calculations of vector-difference Fourier maps in cryo-EM

The atomic coordinates derived from cryo-electron microscopy (cryo-EM) maps can be inaccurate when the voxel scaling factors are not properly calibrated. Here, we describe a method for correcting relative voxel scaling factors between pairs of cryo-EM maps for the same or similar structures that are expanded or contracted relative to each other. We find that the correction of scaling factors reduces the amplitude differences of Fourier-inverted structure factors from voxel-rescaled maps by up to 20–30%, as shown by two cryo-EM maps of the SARS-CoV-2 spike protein measured at pH 4.0 and pH 8.0. This allows for the calculation of the difference map after properly scaling, revealing differences between the two structures for individual amino acid residues. Unexpectedly, the analysis uncovers two previously overlooked differences of amino acid residues in structures and their local structural changes. Furthermore, we demonstrate the method as applied to two cryo-EM maps of monomeric apo-photosystem II from the cyanobacteria Synechocystis sp. PCC 6803 and Thermosynechococcus elongatus. The resulting difference maps reveal many changes in the peripheral transmembrane PsbX subunit between the two species.     

α-bisabolol β-D-fucopyranoside as a potential modulator of β-amyloid peptide induced neurotoxicity: An in vitro & in silico study

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder affecting the elderly people. For the AD treatment, there is inefficiency in the existing medication, as these drugs reduce only the symptoms of the disease. Since multiple pathological proteins are involved in the development of AD, searching for a single molecule targeting multiple AD proteins will be a new strategy for the management of AD. In view of this, the present study was designed to synthesize and evaluate the multifunctional neuroprotective ability of the sesquiterpene glycoside α-bisabolol β-D-fucopyranoside (ABFP) against multiple targets like acetylcholinesterase, oxidative stress and β-amyloid peptide aggregation induced cytotoxicity. In silico computational docking and simulation studies of ABFP with acetylcholinesterase (AChE) showed that it can interact with Asp74 and Thr75 residues of the enzyme. The in vitro studies showed that the compound possess significant ability to inhibit the AChE enzyme apart from exhibiting antioxidant, anti-aggregation and disaggregation properties. In addition, molecular dynamics simulation studies proved that the interacting residue between Aβ peptide and ABFP was found to be involved in Leu34 and Ile31. Furthermore, the compound was able to protect the Neuro2 a cells against Aβ_25-35 peptide induced toxicity. Overall, the present study evidently proved ABFP as a neuroprotective agent, which might act as a multi-target compound for the treatment of Alzheimer’s disease.     

基于SIFT特征和近似最近邻算法的医学CT图像检索

针对医学X线计算机断层（Computed Tomography,CT）图像,提出了一种基于尺度不变特征变换（Scale InvariantFeature Transform,SIFT）特征和近似最近邻算法的检索方法。首先通过SIFT算法得到图像的特征点和相应的特征向量,再采用近似最近邻算法进行SIFT特征向量的匹配搜索,得到数据库中与参考图像最相似的图像序列。实验结果表明,该法能检索到与目标图像细节相符的结果,大大提高了检索速度。与传统的基于纹理的检索方法相比,查准率和检索结果与目标图像的相似程度方面更佳,符合医学CT图像检索的要求。     

A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates

The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel “magnet probe test”. Three excipients, microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually blended with 0.5% magnesium stearate, as a lubricant, and 2.5% tetracycline HCl, as a fluorescent marker, and were compressed using a Carver press. Tablets were coated with a solution consisting of 7% hydroxypropyl methylcellulose (HPMC) phthalate (HP-55), and 0.5% cetyl alcohl in acetone and isopropanol (11:9). The nature of polymer interaction with the tablets and coating was evaluated using CLSM and a designed magnet probe test. CLSM images clearly showed coating efficiency, thickness, and uniformity of film formation, and the extent of drug migration into the film at the coating interfaces of tablets. Among the excipients, MCC demonstrated the best interface for both film formation and uniformity in thickness relative to lactose monohydrate and dibasic calcium phosphate dihydrate. The detachment force of the coating layers from the tablet surfaces, as measured with the developed magnet probe test, was in the order of MCC>lactose monohydrate>dibasic calcium phosphate dihydrate. It was also shown that the designed magnet probe test provides reliable and reproducible results when used for measurement of film adhesion and bonding strength.     

Volumetric and spectroscopic characterizations of glucose-hexokinase association

The binding of D-glucose to hexokinase PII at 25 degrees C and pH 8.7 has been investigated by a combination of ultrasonic velocimetry, high precision densimetry, and fluorescence spectroscopy. The binding of glucose to the enzyme results in significant dehydration of the two interacting molecules, while the intrinsic coefficient of adiabatic compressibility of hexokinase slightly decreases. Glucose-hexokinase association is an entropy-driven process. The favorable change in entropy results from compensation between two large contributions. The binding-induced increase in hydrational entropy slightly prevails over the decrease in the configurational entropy of the enzyme. Taken together, our results emphasize the crucial role of water in modulating the energetics of protein recognition.     

Contextualizing Images in Dreams and Daydreams

A contextualizing image (CI) is a powerful central image of a dream which appears to contextualize (provide a picture-context for) the dreamer's emotion. For instance, dreamers who have experienced any serious traumatic event sometimes dream, I was overwhelmed by a tidal wave. This appears to picture their feeling of terror and/or vulnerability.A scoring system for CIs is examined here and is applied to dreams and daydreams supplied by 40 students. Two raters scoring dreams on a blind basis showed good inter-rater reliability. Recent dreams were shown to have more as well as more intense CIs than recent daydreams; likewise, dreams that stand out had more intense CIs than daydreams that stand out. Students with thin boundaries had more and more intense CIs than students with thick boundaries in their recent dreams and nightmare, but not so clearly in dreams and nightmares that stand out. The emotions judged as contextualized by the powerful images tended towards fear/terror and helplessness/vulnerability in dreams (especially in dreams that stand out) whereas emotions contextualized by images in daydreams showed a wide range with no clusters.     

Description of a new marine species of Askenasia Blochmann, 1895 (Ciliophora,Haptoria), with notes on its ecology

A marine planktonic ciliate, belonging to the genus Askenasia Blochmann, 1895, is described with notes on its distribution and ecology. Specimens of this new species were collected from four coastal sites across the northern hemisphere. Samples were collected between March and December, from depths of 1-20 m. Relatively low (< 1 ml(-1)) densities were recorded from Atlantic and Pacific Oceans and North Sea coastal sites, whereas samples from the English Channel suggested that this species has the ability to form blooms. Specimens were protargol-stained, revealing the key features of the genus, including the diagnostic sub-equatorial kinety belt consisting of three unciliated monokinetids. However, the species is larger than other Askenasia with a single distinctive, rope-like, scalloped macronucleus. This species also appears to have an extra somatic kinety belt, which may be present but has not been observed in other Askenasia species. Based on size, kinety structure, kinety number, and macronuclear shape a new species has been established.