Prevention of liver ischemia reperfusion injury by a combined thyroid hormone and fish oil protocol

Several preconditioning strategies are used to prevent ischemia–reperfusion (IR) liver injury, a deleterious condition associated with tissue resection, transplantation or trauma. Although thyroid hormone (T₃) administration exerts significant protection against liver IR injury in the rat, its clinical application is controversial due to possible adverse effects. Considering that prevention of liver IR injury has also been achieved by n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation to rats, we studied the effect of n-3 PUFA dietary supplementation plus a lower dose of T₃ against IR injury. Male Sprague-Dawley rats receiving fish oil (300 mg/kg) for 3 days followed by a single intraperitoneal dose of 0.05 mg T₃/kg were subjected to 1 h of ischemia followed by 20 h of reperfusion. Parameters of liver injury (serum transaminases, histology) and oxidative stress (liver contents of GSH and oxidized proteins) were correlated with fatty acid composition, NF-κB activity, and tumor necrosis factor-α (TNF-α) and haptoglobin expression. IR significantly modified liver histology; enhanced serum transaminases, TNF-α response or liver oxidative stress; and decreased liver NF-κB activity and haptoglobin expression. Although IR injury was not prevented by either n-3 PUFA supplementation or T₃ administration, substantial decrease in liver injury and oxidative stress was achieved by the combined protocol, which also led to increased liver n-3 PUFA content and decreased n-6/n-3 PUFA ratios, with recovery of NF-κB activity and TNF-α and haptoglobin expression. Prevention of liver IR injury achieved by a combined protocol of T₃ and n-3 PUFA supplementation may represent a novel noninvasive preconditioning strategy with potential clinical application.     

Identification of a 4-microRNA signature for clear cell renal cell carcinoma metastasis and prognosis

Renal cell carcinoma (RCC) metastasis portends a poor prognosis and cannot be reliably predicted. Early determination of the metastatic potential of RCC may help guide proper treatment. We analyzed microRNA (miRNA) expression in clear cell RCC (ccRCC) for the purpose of developing a miRNA expression signature to determine the risk of metastasis and prognosis. We used the microarray technology to profile miRNA expression of 78 benign kidney and ccRCC samples. Using 28 localized and metastatic ccRCC specimens as the training cohort and the univariate logistic regression and risk score methods, we developed a miRNA signature model in which the expression levels of miR-10b, miR-139-5p, miR-130b and miR-199b-5p were used to determine the status of ccRCC metastasis. We validated the signature in an independent 40-sample testing cohort of different stages of primary ccRCCs using the microarray data. Within the testing cohort patients who had at least 5 years follow-up if no metastasis developed, the signature showed a high sensitivity and specificity. The risk status was proven to be associated with the cancer-specific survival. Using the most stably expressed miRNA among benign and tumorous kidney tissue as the internal reference for normalization, we successfully converted his signature to be a quantitative PCR (qPCR)-based assay, which showed the same high sensitivity and specificity. The 4-miRNA is associated with ccRCC metastasis and prognosis. The signature is ready for and will benefit from further large clinical cohort validation and has the potential for clinical application.     

Gating charge immobilization in Kv4.2 channels: the basis of closed-state inactivation

Kv4 channels mediate the somatodendritic A-type K+ current (I(SA)) in neurons. The availability of functional Kv4 channels is dynamically regulated by the membrane potential such that subthreshold depolarizations render Kv4 channels unavailable. The underlying process involves inactivation from closed states along the main activation pathway. Although classical inactivation mechanisms such as N- and P/C-type inactivation have been excluded, a clear understanding of closed-state inactivation in Kv4 channels has remained elusive. This is in part due to the lack of crucial information about the interactions between gating charge (Q) movement, activation, and inactivation. To overcome this limitation, we engineered a charybdotoxin (CTX)-sensitive Kv4.2 channel, which enabled us to obtain the first measurements of Kv4.2 gating currents after blocking K+ conduction with CTX (Dougherty and Covarrubias. 2006J. Gen. Physiol. 128:745-753). Here, we exploited this approach further to investigate the mechanism that links closed-state inactivation to slow Q-immobilization in Kv4 channels. The main observations revealed profound Q-immobilization at steady-state over a range of hyperpolarized voltages (-110 to -75 mV). Depolarization in this range moves <5% of the observable Q associated with activation and is insufficient to open the channels significantly. The kinetics and voltage dependence of Q-immobilization and ionic current inactivation between -153 and -47 mV are similar and independent of the channel's proximal N-terminal region (residues 2-40). A coupled state diagram of closed-state inactivation with a quasi-absorbing inactivated state explained the results from ionic and gating current experiments globally. We conclude that Q-immobilization and closed-state inactivation at hyperpolarized voltages are two manifestations of the same process in Kv4.2 channels, and propose that inactivation in the absence of N- and P/C-type mechanisms involves desensitization to voltage resulting from a slow conformational change of the voltage sensors, which renders the channel's main activation gate reluctant to open.     

On the identity of Festuca jubata Lowe (Poaceae) and the description of a new Festuca species in the Azores Islands

The majority of authors consider Festuca jubata Lowe as an endemic species common to Madeira and the Azores. Saint-Yves proposed that F. jubata was an Azorean endemic and described a geovicarious taxon in Madeira: F. filiformis C. Sm. ex Link in Buch ssp. mandonii St.-Yves. We undertook a complete bibliographical revision of the taxonomy, nomenclature, and chorology of F. jubata s.l. , and contrasted it with morphological and anatomical studies performed on samples from the Azores and Madeira. Azorean plants usually identified as F. jubata had a character combination distinct from that of those with a Madeiran provenance. Saint-Yves' proposal of two independent taxa was correct, but he erroneously considered F. jubata as an Azorean endemic because the name F. jubata was based on Madeiran plants. Consequently, F. jubata auct. pl. from the Azores belongs to a new species.  © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society , 2008, 157 , 493–499.     

DESCRIPTION OF THE SENSORY CHARACTERISTICS OF SPANISH UNIFLORAL HONEYS BY FREE CHOICE PROFILING

Different Spanish unifloral honeys (eucalyptus, sunflower, rosemary, thyme, lavender, citrus, anise, quercus, and lemon blossom) and one multifloral honey were studied by Free-Choice Profiling (FCP) analysis. Generalized Procrustes Analysis (GPA) applied to the FCP data allowed discrimination between samples and provided information on the attributes responsible for the differences observed. The honeys had significantly different sensory characteristics. Textural attributes were the predominant factor in discriminating between samples, and appearance (color included) was also correlated with GPA dimensions to a lesser extent.     

Reproductive ecology of Rhododendron ponticum (Ericaceae) in relict Mediterranean populations

In the southern Iberian Peninsula, Rhododendron ponticum occurs in restricted and vulnerable populations as a Tertiary relict. Population structure and the main phases of the reproductive process were examined in order to shed light on recruitment patterns and limitations. Rhododendron ponticum flowers are self-compatible and attract a diverse array of insects, which are responsible for a considerable number of seeds set in the populations. Nevertheless, only adults form populations, whilst seedlings are scarce and saplings virtually absent (only two juveniles out of 2489 adults sampled). Non-specialized vegetative multiplication by layering was observed. Recruitment failure seems to depend on the scarcity of safe microsites, which are free from drought, for seedling establishment. The observations contrast with R. ponticum 's reputation as an aggressive invader in temperate Atlantic areas. It is proposed that the species shows a variable balance between sexual reproduction and vegetative multiplication depending on environmental conditions. At present, only the latter seems to be prevailing in relict populations in the Iberian Peninsula. This flexible reproductive strategy is also discussed as a mechanism allowing persistence during geological climatic oscillations.  © The Linnean Society of London, Botanical Journal of the Linnean Society , 2002, 140 , 297–311.