The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient''s propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum.A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI.These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.     

A qualitative difference in the interleukin 2 (IL-2) requirement of helper and cytotoxic T lymphocytes

A qualitative difference in the requirement of mouse helper and cytotoxic T lymphocytes for interleukin 2 (IL-2) was revealed by offering such cells IL-2 synthesized in Xenopus laevis oocytes that had been microinjected with messenger RNA (mRNA) encoding human IL-2. While both helper and cytotoxic mouse T-cell lines proliferate in response to the IL-2 present in medium conditioned by stimulated human lymphocytes, only helper-T-cell lines respond to human IL-2 secreted from oocytes. This result demonstrates a difference between helper and cytotoxic T lymphocytes in their response to IL-2. The growth response of murine cells shows that IL-2 secreted from human cells has properties not found in the IL-2 secreted from oocytes, even though a monoclonal antibody directed against the human IL-2 receptor blocks the activity of both types of IL-2. Quite possibly, this difference results from a post-translational modification.     

AAA-ATPase p97/Cdc48p, a Cytosolic Chaperone Required for Endoplasmic Reticulum-Associated Protein Degradation

Endoplasmic reticulum-associated degradation (ERAD) disposes of aberrant proteins in the secretory pathway. Protein substrates of ERAD are dislocated via the Sec61p translocon from the endoplasmic reticulum to the cytosol, where they are ubiquitinated and degraded by the proteasome. Since the Sec61p channel is also responsible for import of nascent proteins, this bidirectional passage should be coordinated, probably by molecular chaperones. Here we implicate the cytosolic chaperone AAA-ATPase p97/Cdc48p in ERAD. We show the association of mammalian p97 and its yeast homologue Cdc48p in complexes with two respective ERAD substrates, secretory immunoglobulin M in B lymphocytes and 6myc-Hmg2p in yeast. The membrane 6myc-Hmg2p as well as soluble lumenal CPY*, two short-lived ERAD substrates, are markedly stabilized in conditional cdc48 yeast mutants. The involvement of Cdc48p in dislocation is underscored by the accumulation of ERAD substrates in the endoplasmic reticulum when Cdc48p fails to function, as monitored by activation of the unfolded protein response. We propose that the role of p97/Cdc48p in ERAD, provided by its potential unfoldase activity and multiubiquitin binding capacity, is to act at the cytosolic face of the endoplasmic reticulum and to chaperone dislocation of ERAD substrates and present them to the proteasome.     

Human ecology and the albedo effect in an arid environment

The results of a comparison of agricultural settlement and land-use and local precipitation patterns in the arid region of the Arava in Israel indicated that as the number of settlements and the area of cultivated land has increased since the 1950s, the albedo effect in the region has decreased, and the amounts of precipitation at the first October rains have increased. It is suggested that the albedo effect in desert areas is influenced by extended agricultural land-use.     

Differential climatic conditions drive growth of Acacia tortilis tree in its range edges in Africa and Asia

Premise

Tree growth is a fundamental biological process that is essential to ecosystem functioning and water and element cycling. Climate exerts a major impact on tree growth, with tree species often requiring a unique set of conditions to initiate and maintain growth throughout the growing season. Still, little is known about the specific climatic factors that enable tree growth in savannah and desert tree species. Among the global tree species, Acacia tortilis occupies one of the largest distribution ranges (crossing 6500 km and 54 latitudes), spanning large parts of Africa and into the Middle East and Asia.

Methods

Here we collected climate data and monitored Acacia tortilis tree growth (continuous measurements of stem circumference) in its southern and northern range edges in South Africa (SA) and Israel (IL), respectively, to elucidate whether the growth–climate interactions were similar in both edges.

Results

Growth occurred during the summer (between December and March) in SA and in IL during early summer and autumn (April–June and October–November, respectively). Surprisingly, annual growth was 40% higher in IL than in SA. Within the wide distribution range of Acacia tortilis, our statistical model showed that climatic drivers of tree growth differed between the two sites.

Conclusions

High temperatures facilitated growth at the hot and arid IL site, while high humidity permitted growth at the more humid SA site. Our results confer an additional understanding of tree growth adaptation to extreme conditions in Acacia's world range edges, a major point of interest with ongoing climate change.     

β-Cell Expansion for Therapeutic Compensation of Insulin Resistance in Type 2 Diabetes

Insulin resistance is the primary cause of type 2 diabetes. However, if compensated by increased insulin production, insulin resistance by itself does not lead to overt disease. Type 2 diabetes develops when this compensation is insufficient, due to defects in β-cell function and in regulation of the β-cell mass. β-Cell transplantation, as well as approaches that replenish or preserve the endogenous β-cell mass, may facilitate the treatment of type 2 diabetes in patients requiring exogenous insulin.     

The effect of pollen source on seed traits and dispersability in the heterocarpic annual Crepis sancta

不同花粉来源对一年生植物种子性状和扩散能力的影响 与扩散有关的性状进化和表达与其他生活史功能交织在一起，并在各种生理约束条件下表现出 来。这种关系可以在近交水平和扩散性之间得到预测，而且在解剖学和个体发育上联系在一起，从而使 某个选择压力可能影响另外的一个。虽然近交对生殖成功和扩散策略的影响都引起了广泛关注，但只有 少数研究同时考虑了这两者。此外，此类研究通常依赖于繁殖和扩散的表示：使用自交与异源杂交表示繁殖水平，使用扩散比表示扩散策略。本研究利用菊科Crepis sancta的授粉实验，以两种不同的方式扩展 繁殖和扩散的二分表示法。首先，我们使用授粉处理来表示一种统一连续体，即从亲缘授粉的自交到距离较远的邻居授粉。其次，我们不仅测量了繁殖成功率和扩散比，还测量了一整套连续的与形态和扩散相关的性状。研究结果显示，头状花序的比例，以及扩散的和非扩散的瘦果在自花传粉处理中都显著低于异源杂交处理。尽管自花授粉的植物很少产生不扩散的种子，但花粉来源对扩散比的影响统计上不显著。瘦果的生物量随亲本植物之间的距离增加而增加，但冠毛宽度没有增加，从而导致授粉对下落速度的影响不显着。总之，花粉来源主要影响与生殖产量有关的性状，但对主要与扩散有关的性状没有显著影响。繁殖和扩散性状对花粉来源变化响应的这种差异表明，与扩散有关的选择可能很弱和/或被其他因素所掩盖。