Rate of gene sequence evolution and species diversification in flowering plants: a re-evaluation

Barraclough and co-workers (in a paper published in 1996) observed that there was a significant positive correlation between the rate of evolution of the rbcL chloroplast gene within families of flowering plants and the number of species in those families. We tested three additional data sets of our own (based on both plastid and nuclear genes) and used methods designed specifically for the comparison of sister families (based on random speciation and extinction). We show that, over all sister groups, the correlation between the rate of gene evolution and an increased diversity is not always present. Despite tending towards a positive association, the observation of individual probabilities presents a U-shaped distribution of association (i.e. it can be either significantly positive or negative). We discuss the influence of both phylogenetic sampling and applied taxonomies on the results.

Anti-Nogo-A Antibody Treatment Promotes Recovery of Manual Dexterity after Unilateral Cervical Lesion in Adult Primates--re-examination and Extension of Behavioral Data.

In rodents and nonhuman primates subjected to spinal cord lesion, neutralizing the neurite growth inhibitor Nogo-A has been shown to promote regenerative axonal sprouting and functional recovery. The goal of the present report was to re-examine the data on the recovery of the primate manual dexterity using refined behavioral analyses and further statistical assessments, representing secondary outcome measures from the same manual dexterity test. Thirteen adult monkeys were studied; seven received an anti-Nogo-A antibody whereas a control antibody was infused into the other monkeys. Monkeys were trained to perform the modified Brinkman board task requiring opposition of index finger and thumb to grasp food pellets placed in vertically and horizontally oriented slots. Two parameters were quantified before and following spinal cord injury: (i) the standard 'score' as defined by the number of pellets retrieved within 30 s from the two types of slots; (ii) the newly introduced 'contact time' as defined by the duration of digit contact with the food pellet before successful retrieval. After lesion the hand was severely impaired in all monkeys; this was followed by progressive functional recovery. Remarkably, anti-Nogo-A antibody-treated monkeys recovered faster and significantly better than control antibody-treated monkeys, considering both the score for vertical and horizontal slots (Mann-Whitney test: P = 0.05 and 0.035, respectively) and the contact time (P = 0.008 and 0.005, respectively). Detailed analysis of the lesions excluded the possibility that this conclusion may have been caused by differences in lesion properties between the two groups of monkeys.

Epidemiological characterization of Plasmodium falciparum in the Republic of Cabo Verde: implications for potential large-scale re-emergence of malaria

Background: Malaria has come near eradication at archipelago of Cabo Verde in 1970. Infections are now only observed in Santiago, where outbreaks occur. In these islands, malaria is considered by the international community as being of limited risk and, therefore, no prophylaxis is recommended. Since the understanding of factors that determine malaria outbreaks are crucial for controlling the disease, the present study aimed to investigate if the malaria infections observed in Santiago Island are maintained in isolated foci and in asymptomatic individuals.

(Re-) Shaping hatred: Anti-Semitic attitudes in Germany, 1890-2006

In this paper, we assess the determinants of long-run persistence of localculture, and examine the success of policy interventions designed to change attitudes.We analyze anti-Semitic attitudes drawing on individual-level survey results fromGermany s social value survey in 1996 and 2006. On average, we find that historicalvoting patterns for anti-Semitic parties between 1890 and 1933 are powerfulpredictors of anti-Jewish attitudes today. There is evidence that transmission takesplace both vertically (parent to child) and horizontally (among peers). Policy modifiedGerman views on Jews in important ways: The cohort that grew up under the Naziregime shows significantly higher levels of anti-Semitism. After 1945, the victoriousAllies implemented denazification programs in their zones of occupation. We usedifferences in these policies between the occupying powers as a source of identifyingvariation. The US and French zones today still show high anti-Semitism, reflecting anambitious botched attempt at denazification. In contrast, the British and Soviet zones,register much lower levels of Jew-hatred.

Swiss consensus statement: Recommendations for optimising re-treatment with MabThera (rituximab) in rheumatoid arthritis.

Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.

Role of the REST/RE-1 system in beta-cell life, function and differentiation

SUMMARYDiabetes is characterized by insulin deficiency that results from the destruction of insulin-secreting pancreatic beta-cells (Type 1), or in part from beta-cell death and insulin secretion defects (Type 2). Therefore, understanding the mechanisms of beta cell neogenesis (to generate unlimited supply of beta cells for T1D transplantation] or identifying the specific genes that favors insulin secretion or beta-cell survival is of great importance for the management of diabetes. The transcriptional repressor RE-1 Silencing Transcription Factor (REST) restricts the expression of a large number of genes containing its binding element, called Repressor Element-1 (RE-1), to neurons and beta cells. To do so, REST is ubiquitously expressed but in neurons and beta cells. To identify these essential genes and their functional significance in beta cells, we have generated transgenic mice that express REST specifically in beta cells under the control of the rat insulin promoter (RIP-REST mice). This resulted in the repression of the RE-1- containing genes in beta cells, and we analyzed the consequences.We first showed that RIP-REST mice were glucose-intolerant because of a defective insulin secretion. To explain this defect, we identified that a subset of the REST target genes were necessary for insulin exocytosis, such as Snap25, Synaptotagmin (Syt) IX, Complexin II, and Ica512, and we further demonstrated that among the identified REST targets, Syt IV and VII were also involved in insulin release. We next analyzed a novel RIP-REST mouse line that featured diabetes and we showed that this defect was due to a major loss of beta-cell mass. To explain this phenotype, we identified REST target genes that were involved in beta-cell survival, such as Ibl, Irs2, Ica512 and Connexin36, and revealed that another REST target, Cdk5r2 is also involved in beta-cell protection. In a third part, we finally suggest that REST may be important for pancreatic endocrine differentiation, since transgenic mice expressing constitutive REST in pancreatic multipotent progenitors show impaired formation of Ngn3-expressing endocrine- committed precursors, and impaired formation of differentiated endocrine cells. Mapping the pattern of REST expression in wild type animals indicates that it is expressed in multipotent progenitors to become then excluded from endocrine cells. Preliminary results suggest that a downregulation of REST would result in relieved expression of at least the Mytl target, favoring subsequent acquisition of the endocrine competence by endocrine precursor cells.Thus, we propose that the REST/RE-1 system is an important feature for beta-cell neogenesis, function and survivalRESUMELe diabète se caractérise par une déficience en insuline qui résulte d'une destruction des cellules bêta (β) pancréatiques sécrétant l'insuline [Type 1], ou à un défaut de sécrétion d'insuline qui peut être associé à la mort des cellules β (Type 2). La compréhension des mécanismes de néogenèse des cellules β, ainsi que l'identification de gènes impliqués dans leur survie et dans le contrôle de la sécrétion d'insuline est donc importante pour le traitement du diabète. Le facteur de transcription de type répresseur, RE-1 Silencing Transcription Factor [REST], contribue à la spécificité d'expression dans les neurones et les cellules β, d'un grand nombre de gènes portant son motif de fixation, le Repressor Element-1 (RE-1). Pour cela, REST est exprimé dans toutes les cellules, sauf dans les neurones et les cellules β. Afin d'identifier les gènes cibles de REST ainsi que leur fonction au sein de la cellule β, nous avons généré des souris transgéniques qui expriment REST spécifiquement dans ces cellules, sous la dépendance du promoteur de l'insuline (souris RIP-REST]. Cette expression ectopique de REST a permis de diminuer l'expression des gènes contrôlés par REST, et d'en analyser les conséquences. Nous avons montré que les souris RIP-REST étaient intolérantes au glucose et que ceci était du à un défaut de sécrétion d'insuline. Pour expliquer ce phénotype, nous avons mis en évidence le fait que des gènes cibles de REST codent pour des protéines importantes pour l'exocytose de l'insuline, comme SNAP25, Synaptotagmin (Syt) IX, Complexin II ou ICA512. De plus, nous avons découvert deux nouvelles cibles de REST impliquées dans la sécrétion d'insuline, Syt IV et Syt VII. Par la suite, nous avons démontré qu'une nouvelle lignée de souris RIP-REST étaient atteintes d'un diabète sévère à cause d'une perte massive des cellules β. La disparition de ces cellules a été expliquée par l'identification de gènes cibles de REST impliqués dans la survie des cellules β, comme Ibl, Irs2, Ica512 ou la Connexine36. De plus, nous avons découvert qu'une nouvelle cible, Cdk5r2, était aussi impliquée dans la survie des cellules β. Dans une dernière partie, nous suggérons, grâce à l'analyse de nouvelles souris transgéniques exprimant constitutivement REST dans les cellules progénitrices du pancréas embryonnaire, que REST empêche la formation des précurseurs de cellules endocrines ainsi que la différenciation de ces cellules. L'analyse de l'expression de REST au cours du développement embryonnaire du pancréas indique que la diminution de l'expression de REST conduit en partie, à l'induction d'un de ses gènes cible Mytl, qui favorise la formation de précurseurs endocrines. Nous proposons donc que le système REST/RE-1 est important pour la génération, la fonction et la survie des cellules β.

Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers.

BACKGROUND: Dysregulation of voltage-gated sodium channels (Na(v)s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Na(v)s under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Na(v)s mRNA levels in mouse dorsal root ganglia (DRG) were studied in the spared nerve injury (SNI) and spinal nerve ligation (SNL) models of neuropathic pain. In the SNI model, injured and non-injured neurons were intermingled in lumbar DRG, which were pooled to increase the tissue available for experiments. RESULTS: A strong downregulation was observed for every Na(v)s isoform expressed except for Na(v)1.2; even Na(v)1.3, known to be upregulated in rat neuropathic pain models, was lower in the SNI mouse model. This suggests differences between these two species. In the SNL model, where the cell bodies of injured and non-injured fibers are anatomically separated between different DRG, most Na(v)s were observed to be downregulated in the L5 DRG receiving axotomized fibers. Transcription was then investigated independently in the L3, L4 and L5 DRG in the SNI model, and an important downregulation of many Na(v)s isoforms was observed in the L3 DRG, suggesting the presence of numerous injured neurons there after SNI. Consequently, the proportion of axotomized neurons in the L3, L4 and L5 DRG after SNI was characterized by studying the expression of activating transcription factor 3 (ATF3). Using this marker of nerve injury confirmed that most injured fibers find their cell bodies in the L3 and L4 DRG after SNI in C57BL/6 J mice; this contrasts with their L4 and L5 DRG localization in rats. The spared sural nerve, through which pain hypersensitivity is measured in behavioral studies, mostly projects into the L4 and L5 DRG. CONCLUSIONS: The complex regulation of Na(v)s, together with the anatomical rostral shift of the DRG harboring injured fibers in C57BL/6 J mice, emphasize that caution is necessary and preliminary anatomical experiments should be carried out for gene and protein expression studies after SNI in mouse strains.

Cardiac re-synchronization therapy in a patient with isolated ventricular non-compaction: a case report.

Isolated ventricular non-compaction (IVNC) is a rare, congenital, unclassified cardiomyopathy characterized by prominent trabecular meshwork and deep recesses. Major clinical manifestations of IVNC are heart failure, atrial and ventricular arrhythmias, and thrombo-embolic events. We describe a case of a 69-year-old woman in whom the diagnosis of IVNC was discovered late, whereas former echocardiographic examinations were considered normal. She was known for systolic left ventricular dysfunction for 3 years and then became symptomatic (NYHA III). In the past, she suffered from multiple episodes of deep vein thrombosis and pulmonary embolism. Electrocardiogram revealed a wide QRS complex, and transthoracic echocardiography showed typical apical thickening of the left and right ventricular myocardial wall with two distinct layers. The ratio of non-compacted to compacted myocardium was >2:1. Cardiac MRI confirmed the echocardiographic images. Cerebral MRI revealed multiple ischaemic sequellae. In view of the persistent refractory, heart failure in medical treatment of patients with classical criteria for cardiac re-synchronization therapy, as well as the ventricular arrhythmias, a biventricular automatic intracardiac defibrillator (biventricular ICD) was implanted. The 2-year follow-up period was characterized by improvement of NYHA functional class from III to I and increasing in left ventricular function. We hereby present a case of IVNC with favourable outcome after biventricular ICD implantation. Cardiac re-synchronization therapy could be considered in the management of this pathology.