Intestinal Lymph-Borne Factors Induce Lung Release of Inflammatory Mediators and Expression of Adhesion Molecules After an Intestinal Ischemic Insult

Background. Intestinal ischemia and reperfusion (I/R) is a documented cause of acute lung injury (ALI) and systemic inflammation. We previously reported that obstruction of thoracic lymphatic flow during intestinal I/R blunts pulmonary neutrophil recruitment and microvascular injury and decreases the systemic levels of tumor necrosis factor. Here, we consider the existence of a gut-lung axis promoting the induction of systemic inflammation, whereby drained intestinal lymph stimulates lung expression of adhesion molecules and matrix components and generation of inflammatory mediators. Material and Methods. Upon administration of anesthesia, male Wistar rats were subjected to occlusion of the superior mesenteric artery for 45 min, followed by 2 h of intestinal reperfusion (I/R); groups of rats were subjected to I/R with or without thoracic lymphatic duct ligation immediately before the procedure. The non-manipulated rats were used to investigate basal parameters. Results. Obstruction of thoracic lymphatic flow before intestinal I/R decreased the ability of cultured lung tissue explants to release IL-1 beta, IL-10, and VEGF. In contrast, lymphatic obstruction normalized the elevated lung expression of PECAM-1 caused by intestinal I/R. On the other hand, lung E-selectin expression was significantly reduced, whereas fibronectin expression and collagen synthesis were not affected. Lymph levels of LTB4 and TXB2 were found to be significantly increased. Conclusions. These data suggest that lymph factors drained from the intestine during ischemic trauma stimulate the lung to generate inflammatory mediators and alter the expression of adhesion molecules. Disturbances in lung homeostasis mediated by lymph might contribute to the spread of inflammatory processes, thereby accounting for the systemic inflammation induced by intestinal I/R. (C) 2012 Elsevier Inc. All rights reserved.

A familial case with interstitial 2q36 deletion: Variable phenotypic expression in full and mosaic state

Submicroscopic chromosomal anomalies play an important role in the etiology of craniofacial malformations, including midline facial defects with hypertelorism (MFDH). MFDH is a common feature combination in several conditions, of which Frontonasal Dysplasia is the most frequently encountered manifestation; in most cases the etiology remains unknown. We identified a parent to child transmission of a 6.2 Mb interstitial deletion of chromosome region 2q36.1q36.3 by array-CGH and confirmed by FISH and microsatellite analysis. The patient and her mother both presented an MFDH phenotype although the phenotype in the mother was much milder than her daughter. Inspection of haplotype segregation within the family of 2q36.1 region suggests that the deletion arose on a chromosome derived from the maternal grandfather. Evidences based on FISH, microsatellite and array-CGH analysis point to a high frequency mosaicism for presence of a deleted region 2q36 occurring in blood of the mother. The frequency of mosaicism in other tissues could not be determined. We here suggest that the milder phenotype observed in the proband's mother can be explained by the mosaic state of the deletion. This most likely arose by an early embryonic deletion in the maternal embryo resulting in both gonadal and somatic mosaicism of two cell lines, with and without the deleted chromosome. The occurrence of gonadal mosaicism increases the recurrence risk significantly and is often either underestimated or not even taken into account in genetic counseling where new mutation is suspected. (C) 2012 Elsevier Masson SAS. All rights reserved.

Intrauterine food restriction alters the expression of uncoupling proteins in brown adipose tissue of rat newborns

A previous study from our laboratory showed that maternal food restriction (MFR) delays thermoregulation in newborn rats. In neonates brown adipose tissue (BAT) is essential for thermogenesis due to the presence of uncoupling proteins (UCPs). The aim of this study was to evaluate the influence of MFR on the UCPs mRNA and protein expression in BAT and skeletal muscle (SM) of the newborn rat. Female Wistar EPM-1 control rats (CON) received chow ad libitum during pregnancy, whereas food-restricted dams (RES) received 50% of the amount ingested by CON. Fifteen hours after birth, the litters were weighed and sacrificed. Blood was collected for hormonal analysis. BAT and SM were used for determination of UCPs mRNA and protein expression, and Ca2+-ATPase sarcoplasmic reticulum (SERCA1). RES pups showed a significant reduction in body weight and fat content at birth. MFR caused a significant increase in the expression of UCP1 and UCP2 in BAT, without changes in UCP3 and SERCA1 expression in BAT and SM. No differences between groups were found for leptin, T4 and glucose levels. RES pups showed increased insulin and decreased T3 levels. The delay in development of thermoregulation previously described in RES animals appears not to result from impairment in thermogenesis, but from an increase in heat loss, since MFR caused low birth weight in pups, leading to greater surface/volume ratio. The higher expression of UCP1 and UCP2 in BAT suggests a compensatory mechanism to increased thermogenesis. (C) 2011 Elsevier Ltd. All rights reserved.

GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation

Some organ-transplanted patients achieve a state of "operational tolerance" (01) in which graft function is maintained after the complete withdrawal of immunosuppressive drugs. We used a gene panel of regulatory/inflammatory molecules (FOXP3, GATA3, 100, TGFB1, TGFBR1/TBX21, TNF and IFNG) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI). OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups. This predominant REG gene expression profile displayed stability over time. The significant GATA3 gene and protein expressions in OT individuals suggest that a Th2 deviation may be a relevant pathway to OT. Moreover, the capacity of the REG/INFLAMMA gene panel to discriminate OT by peripheral blood analysis indicates that this state has systemic repercussions. (C) 2011 Elsevier Inc. All rights reserved.

Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women. Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n=17), estrogen or estrogen plus progestagen (HT, n=34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT+AT, n=36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan (R) PCR. APOE epsilon 2/epsilon 3/epsilon 4 genotyping was performed using PCR-RFLP. Total cholesterol (TC). LDL-c and apoB were reduced after each treatment (p<0.001). Triglycerides, VLDL-c and apoAl were reduced only after atorvastatin (p<0.05), whereas triglycerides and VLDL-c were increased after HT (p=0.01). HT women had lower reduction on TC, LDL-c and apoB than AT and HT+AT groups (p<0.05). APOE mRNA expression was reduced after atorvastatin treatment (p=0.03). Although LXRA gene expression was not modified by atorvastatin, it was correlated with APOE mRNA before and after treatments. Basal APOE mRNA expression was not influenced by gene polymorphisms, however the reduction on APOE expression was more pronounced in epsilon 3 epsilon 3 than in epsilon 3 epsilon 4 carriers. Atorvastatin down-regulates APOE mRNA expression and it is modified by APOE genotypes in PBMC from postmenopausal women. (C) 2011 Elsevier Ltd. All rights reserved.

Recombinant expression, localization and in vitro inhibition of midgut cysteine peptidase (Sl-CathL) from sugarcane weevil, Sphenophorus levis

A cDNA coding for a digestive cathepsin L, denominated Sl-CathL, was isolated from a cDNA library of Sphenophorus levis larvae, representing the most abundant EST (10.49%) responsible for proteolysis in the midgut. The open reading frame of 972 bp encodes a preproenzyme similar to midgut cathepsin L-like enzymes in other coleopterans. Recombinant Sl-CathL was expressed in Pichia pastoris, with molecular mass of about 42 kDa. The recombinant protein was catalytically activated at low pH and the mature enzyme of 39 kDa displayed thermal instability and maximal activity at 37 degrees C and pH 6.0. Immunocytochemical analysis revealed Sl-CathL production in the midgut epithelium and secretion from vesicles containing the enzyme into the gut lumen, confirming an important role for this enzyme in the digestion of the insect larvae. The expression profile identified by RT-PCR through the biological cycle indicates that Sl-CathL is mainly produced in larval stages, with peak expression in 30-day-old larvae. At this stage, the enzyme is 1250-fold more expressed than in the pupal fase, in which the lowest expression level is detected. This enzyme is also produced in the adult stage, albeit in lesser abundance, assuming the presence of a different array of enzymes in the digestive system of adults. Tissue-specific analysis revealed that Sl-CathL mRNA synthesis occurs fundamentally in the larval midgut, thereby confirming its function as a digestive enzyme, as detected in immunolocalization assays. The catalytic efficiency of the purified recombinant enzyme was calculated using different substrates (Z-Leu-Arg-AMC, Z-Arg-Arg-AMC and Z-Phe-Arg-AMC) and rSl-CathL exhibited hydrolysis preference for Z-Leu-Arg-AMC (k(cat)/K-m = 37.53 mM S-1), which is similar to other insect cathepsin L-like enzymes. rSl-CathL activity inhibition assays were performed using four recombinant sugarcane cystatins. rSl-CathL was strongly inhibited by recombinant cystatin CaneCPI-4 (K-i = 0.196 nM), indicating that this protease is a potential target for pest control. (C) 2011 Elsevier Ltd. All rights reserved.

Expression of laminin-5 and integrins in actinic cheilitis and superficially invasive squamous cell carcinomas of the lip

The progression of carcinogenesis entails the detachment of cells, invasion and migration of neoplastic cells. Alterations in epithelial adhesion and basement membrane proteins might mediate the early stages of carcinogenesis. This study investigated the expression of adhesion molecules and the basement membrane protein laminin-5 in actinic cheilitis (AC) and incipient squamous cell carcinoma of the lower lip to understand early photocarcinogenesis. Ln-5 gamma 2 chain as well as alpha 3, beta 1 subunits of alpha 3 beta 1 heterodimer and beta 4 subunit of integrin alpha 6 beta 4 were evaluated by immunohistochemistry in 16 cases of AC and 16 cases of superficially invasive squamous cell carcinoma (SISCC). Most AC cases showed reduced expression of beta 1, beta 4 and alpha 3 integrins, and SISCCs lacked beta 1, beta 4 and alpha 3 integrins in the invasive front. AC cases were negative for the Ln-5 gamma 2 chain. Five cases of SISCC (31%) showed heterogeneous Ln-5 gamma 2 chain expression in the invasive front of the tumor. Integrin beta 1, beta 4 and alpha 3 expression is lost during the early stages of lip carcinogenesis. Expression of Ln-5 gamma 2 in the invasive front in cases and its correlation with tumor progression suggest that it mediates the acquisition of the migrating and invading epithelial cell phenotype. (C) 2012 Elsevier GmbH. All rights reserved.

Practical Dynamic Grammars for Dynamic Languages

Grammars for programming languages are traditionally specified statically. They are hard to compose and reuse due to ambiguities that inevitably arise. PetitParser combines ideas from scannerless parsing, parser combinators, parsing expression grammars and packrat parsers to model grammars and parsers as objects that can be reconfigured dynamically. Through examples and benchmarks we demonstrate that dynamic grammars are not only flexible but highly practical.

Cortical control of facial expression.

The present topical review deals with the motor control of facial expressions in humans. Facial expressions are a central part of human communication. Emotional face expressions have a crucial role in human non-verbal behavior, allowing a rapid transfer of information between individuals. Facial expressions can be both voluntarily or emotionally controlled. Recent studies in non-human primates and humans revealed that the motor control of facial expressions has a distributed neural representation. At least 5 cortical regions on the medial and lateral aspects of each hemisphere are involved: the primary motor cortex, the ventral lateral premotor cortex, the supplementary motor area on the medial wall, and, finally, the rostral and caudal cingulate cortex. The results of studies in humans and non-human primates suggest that the innervation of the face is bilaterally controlled for the upper part, and mainly contralaterally controlled for the lower part. Furthermore, the primary motor cortex, the ventral lateral premotor cortex, and the supplementary motor area are essential for the voluntary control of facial expressions. In contrast, the cingulate cortical areas are important for emotional expression, since they receive input from different structures of the limbic system. This article is protected by copyright. All rights reserved.

Human rights and international trade

Economic globalization and respect for human rights are both highly topical issues. In theory, more trade should increase economic welfare and protection of human rights should ensure individual dignity. Both fields of law protect certain freedoms: economic development should lead to higher human rights standards, and UN embargoes are used to secure compliance with human rights agreements. However the interaction between trade liberalisation and human rights protection is complex, and recently, tension has arisen between these two areas. Do WTO obligations covering intellectual property prevent governments from implementing their human rights obligations, including rights to food or health? Is it fair to accord the benefits of trade subject to a clean human rights record? This book first examines the theoretical framework of the interaction between the disciplines of international trade law and human rights. It builds upon the well-known debate between Professor Ernst-Ulrich Petersmann, who construes trade obligations as human rights, and Professor Philip Alston, who warns of a merger and acquisition of human rights by trade law. From this starting point, further chapters explore the differing legal matrices of the two fields and examine how cooperation between them might be improved, both in international law-making and institutions,in dispute settlement. The interaction between trade and human rights is then explored through seven case studies:freedom of expression and competition law; IP protection and health; agricultural trade and the right to food; trade restrictions on conflict WHO convention on tobacco control; and, finally, human rights conditionalities in preferential trade schemes.

Evaluating knowledge-based approaches to the multilingual extension of a temporal expression normalizer

The extension to new languages is a well known bottleneck for rule-based systems. Considerable human effort, which typically consists in re-writing from scratch huge amounts of rules, is in fact required to transfer the knowledge available to the system from one language to a new one. Provided sufficient annotated data, machine learning algorithms allow to minimize the costs of such knowledge transfer but, up to date, proved to be ineffective for some specific tasks. Among these, the recognition and normalization of temporal expressions still remains out of their reach. Focusing on this task, and still adhering to the rule-based framework, this paper presents a bunch of experiments on the automatic porting to Italian of a system originally developed for Spanish. Different automatic rule translation strategies are evaluated and discussed, providing a comprehensive overview of the challenge.

Multilingual extension of a temporal expression normalizer using annotated corpora

This paper presents the automatic extension to other languages of TERSEO, a knowledge-based system for the recognition and normalization of temporal expressions originally developed for Spanish. TERSEO was first extended to English through the automatic translation of the temporal expressions. Then, an improved porting process was applied to Italian, where the automatic translation of the temporal expressions from English and from Spanish was combined with the extraction of new expressions from an Italian annotated corpus. Experimental results demonstrate how, while still adhering to the rule-based paradigm, the development of automatic rule translation procedures allowed us to minimize the effort required for porting to new languages. Relying on such procedures, and without any manual effort or previous knowledge of the target language, TERSEO recognizes and normalizes temporal expressions in Italian with good results (72% precision and 83% recall for recognition).

The future of human rights protection in the new Libya: prospects and challenges. Jean Monnet Occasional Paper No. 6/2014

There is no doubt that demand for the respect of human rights was one of the factors behind the Arab Spring and Libya is no exception. Four decades of absolute dictatorship headed by Muammar Gaddafi had been further tainted with gross violations of human rights of Libyan citizens and restrictions on their basic freedoms. Before the revolution, Libya was a country where no political parties were allowed. Freedom of expression and the press were extremely restricted. Reports about the country’s human rights violations published by a number of international organizations documented large scale human rights abuses at the hands of the Gaddafi regime. The 17 February 2011 revolution in Libya led to a turning point in the country’s history. The regime of Muammar Gaddafi which had dominated the country since 1969 eventually collapsed, leading to the beginning of the painful task of reconciliation and state building. Nonetheless it is estimated that more than 7000 prisoners are held captive by various militias and armed groups without due process. This in addition to thousands of internally displaced persons. State building involves the consolidation of a democratic state based on a democratic constitution. In 2011, a constitutional declaration was adopted to replace the one that had been in effect since 1969. This was intended as a stop-gap solution to allow the new political forces unleashed in the country time to write a new democratic constitution. To help consolidate the democratic state, three elements are required: that human rights be placed at its core; that these rights are truly implemented and applied; and lastly that the independence of the judiciary is safeguarded. For all this to happen it is also essential to strengthen education on human rights by encouraging non-governmental organizations to take a stronger role in promoting human rights. Libyan citizens can only avail themselves of these rights and strengthen their implementation if they know what they are and how they can benefit from their implementation

Did Egypt's Parliamentary Election just trump citizens’ rights? Arab Citizenship Review No. 12, 19 November 2015

Since the Muslim Brotherhood rule was toppled in July 2013, the regime of President Abd al-Fattah al-Sisi has strived to consolidate his one-man rule; he painted the political opposition and civil society as traitors and foreign agents and exploited the fight against terrorism to suppress freedom of expression, justify a crackdown on the press, eclipse justice in courtrooms, throw thousands in prison, and tighten his grip on police forces. The regime has postponed parliamentary elections for some time, while it marginalised and weakened the non-Islamist political parties that helped Sisi take power. He did so by promoting electoral lists with candidates who are loyal to the president, to ensure control over the new assembly and by obstructing any political alliance that could form an opposition. At the same time, the security apparatus has been given free rein to control the public sphere and engineer the electoral process. This may ultimately lead to a parliament that includes no advocates for rights and liberties, which is particularly significant since the incoming assembly will review the huge amount of legislation that President Sisi has issued in the absence of a parliament. In addition, shortly before elections, President Sisi raised questions about the constitution, calling for it to be amended to reduce the powers of the parliament and increase those of the president. It is thus clear that Sisi seeks not only to consolidate his regime, without political opposition, but to free his rule of any effective oversight from society or parliament.

The primitive Aryans of America; origin of the Aztecs and kindred tribes, showing their relationship to the Indo-Iranians and the place of the Nauatl or Mexican in the Aryan group of languages,

"Authorities consulted": p. 171-181.