University of Lausanne

About: University of Lausanne is a education organization based out in Lausanne, Switzerland. It is known for research contribution in the topics: Population & Medicine. The organization has 20508 authors who have published 46458 publications receiving 1996655 citations. The organization is also known as: Université de Lausanne & UNIL.

Therapeutic Targeting of the Tumor Microenvironment

Abstract: Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due to the critical roles of the TME in regulating tumor progression and modulating response to standard-of-care therapies Here, we summarize the current knowledge regarding the most advanced TME-directed therapies, which have either been clinically approved or are currently being evaluated in trials, including immunotherapies, antiangiogenic drugs, and treatments directed against cancer-associated fibroblasts and the extracellular matrix We also discuss some of the challenges associated with TME therapies, and future perspectives in this evolving field SIGNIFICANCE: This review provides a comprehensive analysis of the current therapies targeting the TME, combining a discussion of the underlying basic biology with clinical evaluation of different therapeutic approaches, and highlighting the challenges and future perspectives

NMR structures of biomolecules using field oriented media and residual dipolar couplings.

Abstract: 2. Theoretical treatment of dipolar interactions 376 2.1 Anisotropic interactions as probes of macromolecular structure and dynamics 376 2.1.1 The dipolar interaction 376 2.1.2 Averaging in the solution state 377 2.2 Ordering of a rigid body 377 2.2.1 The Saupe order tensor 378 2.2.2 Orientational probability distribution function 380 2.2.3 The generalized degree of order 380 2.3 Molecular structure and internal dynamics 381

Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: A quantitative approach

Abstract: The epithelial amiloride-sensitive sodium channel (ENaC) controls transepithelial Na+ movement in Na(+)-transporting epithelia and is associated with Liddle syndrome, an autosomal dominant form of salt-sensitive hypertension. Detailed analysis of ENaC channel properties and the functional consequences of mutations causing Liddle syndrome has been, so far, limited by lack of a method allowing specific and quantitative detection of cell-surface-expressed ENaC. We have developed a quantitative assay based on the binding of 125I-labeled M2 anti-FLAG monoclonal antibody (M2Ab*) directed against a FLAG reporter epitope introduced in the extracellular loop of each of the alpha, beta, and gamma ENaC subunits. Insertion of the FLAG epitope into ENaC sequences did not change its functional and pharmacological properties. The binding specificity and affinity (Kd = 3 nM) allowed us to correlate in individual Xenopus oocytes the macroscopic amiloride-sensitive sodium current (INa) with the number of ENaC wild-type and mutant subunits expressed at the cell surface. These experiments demonstrate that: (i) only heteromultimeric channels made of alpha, beta, and gamma ENaC subunits are maximally and efficiently expressed at the cell surface; (ii) the overall ENaC open probability is one order of magnitude lower than previously observed in single-channel recordings; (iii) the mutation causing Liddle syndrome (beta R564stop) enhances channel activity by two mechanisms, i.e., by increasing ENaC cell surface expression and by changing channel open probability. This quantitative approach provides new insights on the molecular mechanisms underlying one form of salt-sensitive hypertension.

Astrocyte function from information processing to cognition and cognitive impairment

Abstract: Astrocytes serve important roles that affect recruitment and function of neurons at the local and network levels. Here we review the contributions of astrocyte signaling to synaptic plasticity, neuronal network oscillations, and memory function. The roles played by astrocytes are not fully understood, but astrocytes seem to contribute to memory consolidation and seem to mediate the effects of vigilance and arousal on memory performance. Understanding the role of astrocytes in cognitive processes may also advance our understanding of how these processes go awry in pathological conditions. Indeed, abnormal astrocytic signaling can cause or contribute to synaptic and network imbalances, leading to cognitive impairment. We discuss evidence for this from animal models of Alzheimer's disease and multiple sclerosis and from animal studies of sleep deprivation and drug abuse and addiction. Understanding the emerging roles of astrocytes in cognitive function and dysfunction will open up a large array of new therapeutic opportunities.

A method for assessing "scientific" and "additional values" of geomorphosites

Abstract: . Over the last two decades, several methods have been developed to reduce subjectivity of geomorphosite selection through use of transparent assessment criteria. Most of these methods propose criteria such as integrity, rarity, representativeness and palaeogeographical importance for the evaluation of the «scientific value» of sites. For the assessment of their global quality, «additional values» of ecological, cultural, aesthetic and economic nature have, at times, been taken into consideration. This paper proposes a new assessment method that integrates both sets of values into the evaluation of geomorphosites. The method is described and its implementation in two different cases presented: compilation of an inventory of geomorphosites in the National Park of Adula (Ticino, Switzerland) and evaluation of the geocultural heritage of the Trient area (Valais, Switzerland).