Effect of mTOR inhibitors during CMV disease in kidney transplant recipients: Results of a pilot retrospective study

mTOR inhibitors exert a preventive effect on cytomegalovirus (CMV) disease in CMV seropositive (R+) kidney transplant recipients, but their impact during the curative treatment of CMV disease in high-risk kidney transplant recipients has not been investigated. We aimed to evaluate the efficacy and tolerance of mTOR inhibitors compared with mycophenolic acid in 63 consecutive kidney transplant recipients (80% of D+R−) suffering from CMV disease with a persistent or a recurrent CMV DNAemia. In this monocentric retrospective study, 16 had their treatment converted to mTOR inhibitors and 47 did not. The Kaplan–Meier curves did not show any significant differences in CMV DNAemia eradication (77% vs. 88% respectively; hazard ratio (HR), 1.648 [95% confidence interval (CI), 0.913–2.973]; log-rank test, P = .132), DNAemia recurrence (36% vs. 47%; HR, 1.517 [95% CI, 0.574–4.007]; log-rank test, P = .448) and CMV clinical recurrence (17% vs. 27%; HR, 1.375 [95% CI, 0.340–5.552]; log-rank test, P = .677) between patients who received mTOR inhibitors and those who did not. These results were confirmed in uni- and multivariate time-dependent Cox regressions. In summary, conversion from mycophenolic acid to mTOR inhibitors seems inadequate for improving CMV clearance or in better preventing CMV recurrences during severe or persistent CMV disease.     

Obesity and triple‐negative‐breast‐cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple‐negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high‐fat diet in TNBC tumour‐bearing mice significantly increased tumour growth. By showing no effect of high‐fat diet in obesity‐resistant mice, we demonstrated the necessity to develop obesity‐related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity‐related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.     

Clust&See: A Cytoscape plugin for the identification,visualization and manipulation of network clusters

Background and scope

Large networks, such as protein interaction networks, are extremely difficult to analyze as a whole. We developed Clust&See, a Cytoscape plugin dedicated to the identification, visualization and analysis of clusters extracted from such networks.

Implementation and performance

Clust&See provides the ability to apply three different, recently developed graph clustering algorithms to networks and to visualize: (i) the obtained partition as a quotient graph in which nodes correspond to clusters and (ii) the obtained clusters as their corresponding subnetworks. Importantly, tools for investigating the relationships between clusters and vertices as well as their organization within the whole graph are supplied.     

From limb to fin: an Eocene protocetid forelimb from Senegal sheds new light on the early locomotor evolution of cetaceans

Cetaceans constitute a textbook example of the secondary adaptation of tetrapods to aquatic life. This major event in the evolutionary history of mammals is often linked in the literature to the limb-to-fin transition. Paradoxically, limb bones are scarce in the fossil record of early cetaceans, and the transition from a limb-adapted morphology for an amphibious life in shallow water to a fin-adapted morphology for a pelagic lifestyle remains poorly documented. Here, we describe new protocetid remains from the upper Lutetian of Senegal, including a nearly complete articulated forelimb. A cladistic analysis including 24 taxa and 137 morphological characters recovers the new African specimen close to Carolinacetus. It also confirms that cetacean dispersal to the New World was not the result of a single colonization event. A 3D model of the forelimb was reconstructed. Anatomical comparisons suggest that it is unlikely that the Senegalese forelimb was used as a rigid pectoral flipper for steering as in basilosaurids and modern cetaceans. Instead, we suggest that the hand was actively used during swimming. This challenges previous reconstructions of protocetids as mainly foot-powered swimmers, and suggests that swimming specializations of early cetaceans were probably more diverse than previously considered.     

The role of obesity in inflammatory bowel disease

In just over a generation overweight and obesity has become a worldwide health concern. The ramifications for this on future health care costs and longevity are consequent, whilst increased adiposity is a harbinger for diabetes, kidney and bone failure, and cancer. An area of intense interest where the role of adiposity is avidly discussed is in inflammatory bowel disease (IBD), which presents mainly as Crohn's disease (CD) and ulcerative colitis (UC). Studies in patients associating IBD with a western diet are divergent. Nevertheless, elegant studies have found gene polymorphisms in humans that in murine models parallel the inflammatory and gut microbiome changes seen in IBD patients. However, an area not to be ignored are the alterations in adipocyte function with ensuing adiposity, in particular and a focus of this review, the dysregulation of the levels of adipocytokines such as leptin and adiponectin. Herein, we present and discuss the known influences of a western diet on IBD in patients and rodent models and how adipocytokines could influence the IBD disease process.     

The heritability of fertility makes world population stabilization unlikely in the foreseeable future

The forecasting of the future growth of world population is of critical importance to anticipate and address a wide range of global challenges. The United Nations produces forecasts of fertility and world population every two years. As part of these forecasts, they model fertility levels in post-demographic transition countries as tending toward a long-term mean, leading to forecasts of flat or declining population in these countries. We substitute this assumption of constant long-term fertility with a dynamic model, theoretically founded in evolutionary biology, with heritable fertility. Rather than stabilizing around a long-term level for post-demographic transition countries, fertility tends to increase as children from larger families represent a larger share of the population and partly share their parents' trait of having more offspring. Our results suggest that world population will grow larger in the future than currently anticipated.     

In situ laser manipulation of root tissues in transparent soil

Plant and Soil - Laser micromanipulation such as dissection or optical trapping enables remote physical modification of the activity of tissues, cells and organelles. To date, applications of laser...