Computational biomechanics of human brain with and without the inclusion of the body under different blast orientation

Three different human head models in a free space are exposed to blast waves coming from four different directions. The four head–neck–body models composed of model a, with the neck free in space; model b, with neck fixed at the bottom; and model c, with the neck attached to the body. The results show that the effect of the body can be ignored for the first milliseconds of the head–blast wave interactions. Also one can see that although most biomechanical responses of the brain have similar patterns in all models, the shear stresses are heavily increased after a few milliseconds in model b in which the head motion is obstructed by the fixed-neck boundary conditions. The free-floating head model results are closer to the attached-body model.     

无创颅内压监测在创伤性急性弥漫性脑肿胀治疗中的临床应用研究

目的:探讨无创颅内压监测(Intracranial pressure,ICP)监测对救治创伤性急性弥漫性脑肿胀(Posttraumatic acute diffuse brains welling,PADBS)患者的辅助作用,为无创ICP检测的临床应用提供参考依据。方法:收集2011年1月至2016年1月我院神经外科收治的114例PADBS患者的临床资料进行回顾性分析,依据纳入与排除标准共取得病例组53例,对照组61例,分别给予采用无创颅内压监测和有创颅内压监测,根据患者资料进行组间比较及生存分析。结果:病例组与对照组不同分型颅内压检测值比较无统计学差异(P0.05);患者48h内进行大骨瓣开颅手术时间的生存分析,病例组中位手术时间为35.6个月,对照组中位DFS为33.5个月,两组患者检测进行手术时间的生存曲线无统计学差异(P0.05);有创ICP检测患者继发性出血率为3.2%,脑脊液感染病况为7.9%;两组患者预后情况差异并无统计学意义(P0.05)。无创ICP检测患者住院天数短于有创ICP检测患者(P0.05)。结论:无创ICP应用于PADBS治疗的临床价值与有创ICP相当,但无创ICP更便捷、创伤小,有利于对患者进行持续性检测。     

Manganese,copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis

The concentrations of manganese, copper, and zinc in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and patients with no known neurological disease (control group) were measured. Manganese and copper levels were determined by two different analytical methods: atomic absorption spectrometry (AAS) and high-resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS), whereas zinc levels were determined by HR-ICP-MS only. Manganese levels (mean±SEM) were significantly decreased in the CSF of MS patients (1.07±0.13 μg/L, ICP-MS; 1.08±0.11 μg/L, AAS) compared to the levels in the control group (1.78±0.26 μg/L, ICP-MS; 1.51±0.17 μg/L, AAS). Copper levels were significantly elevated in the CSF of MS patients (10.90±1.11 μg/L; ICP-MS, 11.53±0.83 μg/L, AAS) compared to the levels in the control group (8.67±0.49 μg/L, ICP-MS; 9.10±0.62 μg/L, AAS). There were no significant differences between the CSF zinc levels of MS and control patients. The physiological basis for the differences in manganese and copper concentrations between MS patients and controls is unknown, but could be related to alterations in the manganese-containing enzyme glutamine synthetase and the copper-containing enzyme cytochrome oxidase.     

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that typically develops as a result of acute liver failure or chronic liver disease. Brain edema is a common feature associated with HE. In acute liver failure, brain edema contributes to an increase in intracranial pressure, which can fatally lead to brain stem herniation. In chronic liver disease, intracranial hypertension is rarely observed, even though brain edema may be present. This discrepancy in the development of intracranial hypertension in acute liver failure versus chronic liver disease suggests that brain edema plays a different role in relation to the onset of HE. Furthermore, the pathophysiological mechanisms involved in the development of brain edema in acute liver failure and chronic liver disease are dissimilar. This review explores the types of brain edema, the cells, and pathogenic factors involved in its development, while emphasizing the differences in acute liver failure versus chronic liver disease. The implications of brain edema developing as a neuropathological consequence of HE, or as a cause of HE, are also discussed.     

Study of early events during herpes simplex virus type 1 infection by confocal microscopy

Laser scanning confocal microscopy is a powerful technique that can be applied to study the localisation and behaviour of proteins and nucleic acids in many experimental situations. It is a particularly useful technique for the study of virus infections because of the changes that occur in the distribution and amounts of both viral and cellular proteins as infection develops. These changes reflect key stages and important regulatory events that govern the efficiency of infection. Using herpes simplex virus type 1 infected cells as an experimental model, this article provides guidance for users new to confocal microscopy on basic principles and techniques. The emphasis is on recognising, diagnosing and avoiding potential artifacts, and the workflow of the production of high quality, technically correct images.     

Alignment of two-dimensional electrophoresis gels

Two-dimensional electrophoresis is a major separating technique for proteins in proteomics. Alignment of gel images is critical for intra-laboratory or even more difficult inter-laboratory gel comparisons. In the paper, we propose a novel iterative closest point (ICP) method for 2D-gel electrophoresis image alignment. The paper seeks to introduce an information theoretic measure as one part of distance metric to gel image alignment. We combine intensity information of spots with geometric information of landmarks by applying information potential idea. The proposed method has been applied to both synthetic and real gel images accessible in public 2D-electrophoresis gel protein databases. The high accuracy and robustness of the algorithm indicate that it is promising for gel image alignment.     

Dynamic 3D scanning as a markerless method to calculate multi-segment foot kinematics during stance phase: Methodology and first application

Multi-segmental foot kinematics have been analyzed by means of optical marker-sets or by means of inertial sensors, but never by markerless dynamic 3D scanning (D3DScanning). The use of D3DScans implies a radically different approach for the construction of the multi-segment foot model: the foot anatomy is identified via the surface shape instead of distinct landmark points. We propose a 4-segment foot model consisting of the shank (Sha), calcaneus (Cal), metatarsus (Met) and hallux (Hal). These segments are manually selected on a static scan. To track the segments in the dynamic scan, the segments of the static scan are matched on each frame of the dynamic scan using the iterative closest point (ICP) fitting algorithm. Joint rotations are calculated between Sha–Cal, Cal–Met, and Met–Hal. Due to the lower quality scans at heel strike and toe off, the first and last 10% of the stance phase is excluded. The application of the method to 5 healthy subjects, 6 trials each, shows a good repeatability (intra-subject standard deviations between 1° and 2.5°) for Sha–Cal and Cal–Met joints, and inferior results for the Met–Hal joint (>3°). The repeatability seems to be subject-dependent. For the validation, a qualitative comparison with joint kinematics from a corresponding established marker-based multi-segment foot model is made. This shows very consistent patterns of rotation. The ease of subject preparation and also the effective and easy to interpret visual output, make the present technique very attractive for functional analysis of the foot, enhancing usability in clinical practice.     

Mapping the Interactions between the Alzheimer’s Aβ-Peptide and Human Serum Albumin beyond Domain Resolution

Human serum albumin (HSA) is a potent inhibitor of Aβ self-association and this novel, to our knowledge, function of HSA is of potential therapeutic interest for the treatment of Alzheimer’s disease. It is known that HSA interacts with Aβ oligomers through binding sites evenly partitioned across the three albumin domains and with comparable affinities. However, as of this writing, no information is available on the HSA-Aβ interactions beyond domain resolution. Here, we map the HSA-Aβ interactions at subdomain and peptide resolution. We show that each separate subdomain of HSA domain 3 inhibits Aβ self-association. We also show that fatty acids (FAs) compete with Aβ oligomers for binding to domain 3, but the determinant of the HSA/Aβ oligomer interactions are markedly distinct from those of FAs. Although salt bridges with the FA carboxylate determine the FA binding affinities, hydrophobic contacts are pivotal for Aβ oligomer recognition. Specifically, we identified a site of Aβ oligomer recognition that spans the HSA (494–515) region and aligns with the central hydrophobic core of Aβ. The HSA (495–515) segment includes residues affected by FA binding and this segment is prone to self-associate into β-amyloids, suggesting that sites involved in fibrilization may provide a lead to develop inhibitors of Aβ self-association.     

Human platelet 12-lipoxygenase, new findings about its activity, membrane binding and low-resolution structure

Human platelet 12-lipoxygenase (hp-12LOX, 662 residues + iron nonheme cofactor) and its major metabolite 12S-hydroxyeicosatetraenoic acid have been implicated in cardiovascular and renal diseases, many types of cancer and inflammatory responses. However, drug development is slow due to a lack of structural information. The major hurdle in obtaining a high-resolution X-ray structure is growing crystals, a process that requires the preparation of highly homogenous, reproducible and stable protein samples. To understand the properties of hp-12LOX, we have expressed and studied the behavior, function and low-resolution structure of the hp-12LOX His-tagged recombinant enzyme and its mutants in solution. We have found that it is a dimer easily converted into bigger aggregates, which are soluble/covalent-noncovalent/reversible. The heavier oligomers show a higher activity at pH 8, in contrast to dimers with lower activity showing two maxima at pH 7 and pH 8, indicating the existence of two different conformers. In the seven-point C → S mutant, aggregation is diminished, activity has one broad peak at pH 8 and there is no change in specificity. Truncation of the N_t-β-barrel domain (PLAT, residues 1-116) reduces activity to ∼ 20% of that shown by the whole enzyme, does not affect regio- or stereospecificity and lowers membrane binding by a factor of ∼ 2. “NoPLAT” mutants show strong aggregation into oligomers containing six or more catalytic domains regardless of the status of the seven cysteine residues tested. Time-of-flight mass spectrometry suggests two arachidonic acid molecules bound to one molecule of enzyme. Small angle X-ray scattering studies (16 Å resolution, χ∼ 1) suggest that two hp-12LOX monomers are joined by the catalytic domains, with the PLAT domains floating on the flexible linkers away from the main body of the dimer.