Cerebrospinal fluid may mediate CNS ischemic injury

BACKGROUND: The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. METHODS: Lumbar spinal cord ischemia was induced in rabbits by cross-clamping the descending abdominal aorta for 1 h, 2 h or 3 h followed by 7 d of reperfusion. Prior to ischemia, rabbits were subjected to the following procedures; 1) CSF depletion, 2) CSF replenishment at 0 mmHg intracranial pressure (ICP), and 3) replacement of CSF with 8% albumin- or 1% gelatin-modified artificial CSF, respectively. Motor function of the hind limbs and histopathological changes of the spinal cord were scored. Post-ischemic microcirculation of the spinal cord was visualized by fluorescein isothiocyanate (FITC) albumin. RESULTS: The severity of histopathological damage paralleled the neurological deficit scores. Paraplegia and associated histopathological changes were accompanied by a clear post-ischemic deficit in blood perfusion. Spinal cord ischemia for 1 h resulted in permanent paraplegia in the control group. Depletion of the CSF significantly prevented paraplegia. CSF replenishment with the ICP reduced to 0 mmHg, did not prevent paraplegia. Replacement of CSF with albumin- or gelatin-modified artificial CSF prevented paraplegia in rabbits even when the ICP was maintained at 10–15 mmHg. CONCLUSION: We conclude that the presence of normal CSF may contribute to the vulnerability of the spinal cord to ischemic injury. Depletion of the CSF or replacement of the CSF with an albumin- or gelatin-modified artificial CSF can be neuroprotective

Experiments of Interfacial Roughening in Hele-Shaw Flows with Weak Quenched Disorder

We have studied the kinetic roughening of an oil--air interface in a forced imbibition experiment in a horizontal Hele--Shaw cell with quenched disorder. Different disorder configurations, characterized by their persistence length in the direction of growth, have been explored by varying the average interface velocity v and the gap spacing b. Through the analysis of the rms width as a function of time, we have measured a growth exponent beta ~= 0.5 that is almost independent of the experimental parameters. The analysis of the roughness exponent alpha through the power spectrum have shown different behaviors at short (alpha_1) and long (alpha_2) length scales, separated by a crossover wavenumber q_c. The values of the measured roughness exponents depend on experimental parameters, but at large velocities we obtain alpha_1 ~= 1.3 independently of the disorder configuration. The dependence of the crossover wavenumber with the experimental parameters has also been investigated, measuring q_c ~ v^{0.47} for the shortest persistence length, in agreement with theoretical predictions.Comment: 20 pages, 22 figure

Electrogenicity accompanies photoreduction of the iron-sulfur clusters FA and FB in photosystem I

AbstractPhotovoltage responses accompanying electron transfer on the acceptor side of photosystem I (PS I) were investigated in proteoliposomes containing PS I complexes from the cyanobacterium Synechococcus sp. PCC 6301 using a direct electrometrical technique. The relative contributions of the FX→FB and the FX→FA electron transfer reactions to the overall electrogenicity were elucidated by comparing the sodium dithionite-induced decrease in the magnitude of the total photoelectric responses in control and in FB-less (HgCl2-treated) PS I complexes. The results obtained suggest that the electrogenesis on the acceptor side of PS I is related to electron transfers between both FX and FA and FA and FB. Based on the electrogenic nature of the latter reaction in PS I complexes, we conclude that FA rather than FB is the acceptor proximal to FX

Tspan5 is an independent favourable prognostic factor and suppresses tumour growth in gastric cancer

Tetraspanins are believed to interact with specific partner proteins forming tetraspanin-enriched microdomains and regulate some aspects of partner protein functions. However, the role of Tspan5 during pathological processes, particularly in cancer biology, remains unknown. Here we report that Tspan5 is significantly downregulated in gastric cancer (GC) and closely associated with clinicopathological features including tumour size and TNM stage. The expression of Tspan5 is inversely correlated with patient overall survival and is an independent prognostic factor in GC. Upregulation of Tspan5 in tumour cells results in inhibition of cell proliferation and colony formation in vitro and suppression of xenograft growth of GC by reducing tumour cell proliferation in vivo. Thus, Tspan5 functions as a tumour suppressor in stomach to control the tumour growth. Mechanistically, Tspan5 inhibits the cell cycle transition from G1-S phase by increasing the expression of p27 and p15 and decreasing the expression of cyclin D1, CDK4, pRB and E2F1. The correlation of Tspan5 expression with the expression of p27, p15, cyclin D1, CDK4, pRB and E2F1 in vivo are also revealed in xenografted tumours. Reconstitution of either cyclin D1 or CDK4 in Tspan5-overexpressing GC cells rescues the inhibitory phenotype produced by Tspan5, suggesting that cyclin D1/CDK4 play a dominant role in mediating the suppression of tumour growth by Tspan5 in GC. Our results suggest that Tspan5 may serve as a prognostic biomarker for predicting outcome of GC patients and provide new insights into the pathogenesis of GC and rational for the development of clinical intervention strategies against GC

2-Amino-6-methyl­pyridinium 4-nitro­benzoate

In the crystal structure of the title salt, C6H9N2 +·C7H4NO4 −, the cations and anions are linked by N—H⋯O hydrogen bonds, forming chains running parallel to the b axis

Edar is a downstream target of beta-catenin and drives collagen accumulation in the mouse prostate

Beta-catenin (CTNNB1) directs ectodermal appendage spacing by activating ectodysplasin A receptor (EDAR) transcription, but whether CTNNB1 acts by a similar mechanism in the prostate, an endoderm-derived tissue, is unclear. Here we examined the expression, function, and CTNNB1 dependence of the EDAR pathway during prostate development. In situ hybridization studies reveal EDAR pathway components including Wnt10b in the developing prostate and localize these factors to prostatic bud epithelium where CTNNB1 target genes are co-expressed. We used a genetic approach to ectopically activate CTNNB1 in developing mouse prostate and observed focal increases in Edar and Wnt10b mRNAs. We also used a genetic approach to test the prostatic consequences of activating or inhibiting Edar expression. Edar overexpression does not visibly alter prostatic bud formation or branching morphogenesis, and Edar expression is not necessary for either of these events. However, Edar overexpression is associated with an abnormally thick and collagen-rich stroma in adult mouse prostates. These results support CTNNB1 as a transcriptional activator of Edar and Wnt10b in the developing prostate and demonstrate Edar is not only important for ectodermal appendage patterning but also influences collagen organization in adult prostates. This article has an associated First Person interview with the first author of the paper

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

Preventing undesirable structure flexibility in pyromellitate metal organic frameworks

This project has received funding from: the European Union's Horizon 2020 research and innovation program under grant agreement No 685727; the Engineering & Physical Sciences Research Council (EPSRC) under awards EP/K005499/1 and EP/K039210/1; and the University of St Andrews School of Chemistry.Removal of coordinated water molecules from the porous Zn‐pyromellitate metal organic framework Zn5(OH)2(PMA)2(H2O)4 · x H2O (PMA = pyromellitic acid or 1,2,4,5‐benzene tetracarboxylic acid) should generate coordinatively unsaturated metal sites suitable for gas adsorption. However, reports of instability towards dehydration have restricted the study and utility of this MOF. Here we examine in more detail the nature of the structural transformation that occurs upon dehydration. This study reveals that a fully reversible crystalline‐crystalline transformation from a porous to a non‐porous homologue takes place, proceeding through a partially dehydrated intermediate. We show that doping the structure with Ni2+ ions at greater than 30 % prevents structural rearrangement, thereby maintaining porosity, and rendering the material effective for gas (nitric oxide) adsorption applications. These results indicate that doping can be an effective means to increase the utility of otherwise unserviceable structures.Publisher PDFPeer reviewe