Endocannabinoid transport revisited.

Endocannabinoids are arachidonic acid-derived endogenous lipids that activate the endocannabinoid system which plays a major role in health and disease. The primary endocannabinoids are anandamide (AEA, N-arachidonoylethanolamine) and 2-arachidonoyl glycerol. While their biosynthesis and metabolism have been studied in detail, it remains unclear how endocannabinoids are transported across the cell membrane. In this review, we critically discuss the different models of endocannabinoid trafficking, focusing on AEA cellular uptake which is best studied. The evolution of the current knowledge obtained with different AEA transport inhibitors is reviewed and the confusions caused by the lack of their specificity discussed. A comparative summary of the most important AEA uptake inhibitors and the studies involving their use is provided. Based on a comprehensive literature analysis, we propose a model of facilitated AEA membrane transport followed by intracellular shuttling and sequestration. We conclude that novel and more specific probes will be essential to identify the missing targets involved in endocannabinoid membrane transport.

Heavy Metals in Crop Plants: Transport and Redistribution Processes on the Whole Plant Level

Copper, zinc, manganese, iron, nickel and molybdenum are essential micronutrients for plants. However, when present in excess they may damage the plant or decrease the quality of harvested plant products. Some other heavy metals such as cadmium, lead or mercury are not needed by plants and represent pollutants. The uptake into the roots, the loading into the xylem, the acropetal transport to the shoot with the transpiration stream and the further redistribution in the phloem are crucial for the distribution in aerial plant parts. This review is focused on long-distance transport of heavy metals via xylem and phloem and on interactions between the two transport systems. Phloem transport is the basis for the redistribution within the shoot and for the accumulation in fruits and seeds. Solutes may be transferred from the xylem to the phloem (e.g., in the small bundles in stems of cereals, in minor leaf veins). Nickel is highly phloem-mobile and directed to expanding plant parts. Zinc and to a lesser degree also cadmium are also mobile in the phloem and accumulate in meristems (root tips, shoot apex, axillary buds). Iron and manganese are characterized by poor phloem mobility and are retained in older leaves.

Annexins sense changes in intracellular pH during hypoxia

The pH(i) (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pH(i). Sensors of pH(i) include ion transport systems which control intracellular Ca2+ gradients and link changes in pH(i) to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca(2+)-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2-S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pH(i) on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2-S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2-S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2-S100A10 might have consequences for their functions as membrane organizers and channel modulators.

The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction

The central nervous system (CNS) is tightly sealed from the changeable milieu of blood by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB). While the BBB is considered to be localized at the level of the endothelial cells within CNS microvessels, the BCSFB is established by choroid plexus epithelial cells. The BBB inhibits the free paracellular diffusion of water-soluble molecules by an elaborate network of complex tight junctions (TJs) that interconnects the endothelial cells. Combined with the absence of fenestrae and an extremely low pinocytotic activity, which inhibit transcellular passage of molecules across the barrier, these morphological peculiarities establish the physical permeability barrier of the BBB. In addition, a functional BBB is manifested by a number of permanently active transport mechanisms, specifically expressed by brain capillary endothelial cells that ensure the transport of nutrients into the CNS and exclusion of blood-borne molecules that could be detrimental to the milieu required for neural transmission. Finally, while the endothelial cells constitute the physical and metabolic barrier per se, interactions with adjacent cellular and acellular layers are prerequisites for barrier function. The fully differentiated BBB consists of a complex system comprising the highly specialized endothelial cells and their underlying basement membrane in which a large number of pericytes are embedded, perivascular antigen-presenting cells, and an ensheathment of astrocytic endfeet and associated parenchymal basement membrane. Endothelial cell morphology, biochemistry, and function thus make these brain microvascular endothelial cells unique and distinguishable from all other endothelial cells in the body. Similar to the endothelial barrier, the morphological correlate of the BCSFB is found at the level of unique apical tight junctions between the choroid plexus epithelial cells inhibiting paracellular diffusion of water-soluble molecules across this barrier. Besides its barrier function, choroid plexus epithelial cells have a secretory function and produce the CSF. The barrier and secretory function of the choroid plexus epithelial cells are maintained by the expression of numerous transport systems allowing the directed transport of ions and nutrients into the CSF and the removal of toxic agents out of the CSF. In the event of CNS pathology, barrier characteristics of the blood-CNS barriers are altered, leading to edema formation and recruitment of inflammatory cells into the CNS. In this review we will describe current knowledge on the cellular and molecular basis of the functional and dysfunctional blood-CNS barriers with focus on CNS autoimmune inflammation.

Riding the Escalator: How Dangerous is it Really?

INTRODUCTION About 10,000 escalator-related injuries per year result in emergency department treatment in the United States. Since the 1990s, a steady increase has been reported, but few statistics on escalator-related injuries have been published worldwide. We have therefore analyzed escalator accident statistics in admissions to our hospital in Switzerland since 2000. METHODS Using retrospective electronic patient chart analysis, we included in our study patients >16 years treated over an 11-year period. We categorized patients in terms of gender, age and associated risk factors, and classified accidents according to day, time, location and cause. Resulting trauma was categorized according to type and location. We divided post-admission treatment into surgical and conservative, and into treatment as an outpatient, in a short-stay unit, or as a hospital admission. Women and men were compared using Fisher's exact test. RESULTS We identified 173 patients with 285 discrete injuries. Of these, 87 patients (50%) were women. Fifty-three (61%) of the women and 38 (44%) of the men were >60 years old (P = 0.033). Fifty percent of the men (43/86) of the men, but only 7% (6/87) of the women showed signs of alcohol intoxication (P < 0.0001). Accidents in women occurred predominantly on Tuesdays (19/87; 22%) between 12pm and 6pm (35/87; 40%), and in men on Saturdays (16/86; 19%) between 6pm and 12am (29/86; 34%; P = 0.0097). Sixty-two percent (44/71) of the accidents were in public transport facilities and 30% (21/71) in shopping centers. The majority of injuries in women were to the lower extremities (49/87; 56%), while most accidents in men were to the head and neck (51/86; 59%; P = 0.0052). About half (90; 52%) of the patients were treated conservatively. Almost half of all patients (76, 44%) required hospital admission. Of those, 45% left the hospital within 24 hours of admission (short stay unit) and 55% stayed longer than 24 hours. CONCLUSION Escalator accidents can result in severe trauma. Significant gender differences in escalator accidents have been observed. Alcohol intoxication and age are significant risk factors in escalator-related accidents and might be possible targets for preventive measures.

High affinity amino acid transporters specifically expressed in xylem parenchyma and developing seeds of Arabidopsis

Arabidopsis amino acid transporters (AAPs) show individual temporal and spatial expression patterns. A new amino acid transporter, AAP8 was isolated by reverse transcription-PCR. Growth and transport assays in comparison to AAP1-5 characterize AAP8 and AAP6 as high affinity amino acid transport systems from Arabidopsis. Histochemical promoter-beta-glucuronidase (GUS) studies identified AAP6 expression in xylem parenchyma, cells requiring high affinity transport due to the low amino acid concentration in xylem sap. AAP6 may thus function in uptake of amino acids from xylem. Histochemical analysis of AAP8 revealed stage-dependent expression in siliques and developing seeds. Thus AAP8 is probably responsible for import of organic nitrogen into developing seeds. The only missing transporter of the family AAP7 was nonfunctional in yeast with respect to amino acid transport, and expression was not detectable. Therefore, AAP6 and -8 are the only members of the family able to transport aspartate with physiologically relevant affinity. AAP1, -6 and -8 are the closest AAP paralogs. Although AAP1 and AAP8 originate from a duplicated region on chromosome I, biochemical properties and expression pattern diverged. Overlapping substrate specificities paired with individual properties and expression patterns point to specific functions of each of the AAP genes in nitrogen distribution rather than to mere redundancy.

Strengthening the Reporting of Observational Studies in Epidemiology for respondent-driven sampling studies: "STROBE-RDS" statement.

OBJECTIVES Respondent-driven sampling (RDS) is a new data collection methodology used to estimate characteristics of hard-to-reach groups, such as the HIV prevalence in drug users. Many national public health systems and international organizations rely on RDS data. However, RDS reporting quality and available reporting guidelines are inadequate. We carried out a systematic review of RDS studies and present Strengthening the Reporting of Observational Studies in Epidemiology for RDS Studies (STROBE-RDS), a checklist of essential items to present in RDS publications, justified by an explanation and elaboration document. STUDY DESIGN AND SETTING We searched the MEDLINE (1970-2013), EMBASE (1974-2013), and Global Health (1910-2013) databases to assess the number and geographical distribution of published RDS studies. STROBE-RDS was developed based on STROBE guidelines, following Guidance for Developers of Health Research Reporting Guidelines. RESULTS RDS has been used in over 460 studies from 69 countries, including the USA (151 studies), China (70), and India (32). STROBE-RDS includes modifications to 12 of the 22 items on the STROBE checklist. The two key areas that required modification concerned the selection of participants and statistical analysis of the sample. CONCLUSION STROBE-RDS seeks to enhance the transparency and utility of research using RDS. If widely adopted, STROBE-RDS should improve global infectious diseases public health decision making.

Real-time simulation of nonequilibrium transport of magnetization in large open quantum spin systems driven by dissipation

Using quantum Monte Carlo, we study the nonequilibrium transport of magnetization in large open strongly correlated quantum spin-12 systems driven by purely dissipative processes that conserve the uniform or staggered magnetization, disregarding unitary Hamiltonian dynamics. We prepare both a low-temperature Heisenberg ferromagnet and an antiferromagnet in two parts of the system that are initially isolated from each other. We then bring the two subsystems in contact and study their real-time dissipative dynamics for different geometries. The flow of the uniform or staggered magnetization from one part of the system to the other is described by a diffusion equation that can be derived analytically.