Paris Descartes University

About: Paris Descartes University is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Transplantation. The organization has 20987 authors who have published 37456 publications receiving 1206222 citations. The organization is also known as: Université Paris V-Descartes & Université de Paris V.

Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels

Abstract: Dehydrated hereditary stomatocytosis is a genetic condition with defective red blood cell membrane properties that causes an imbalance in intracellular cation concentrations. Recently, two missense mutations in the mechanically activated PIEZO1 (FAM38A) ion channel were associated with dehydrated hereditary stomatocytosis. However, it is not known how these mutations affect PIEZO1 function. Here, by combining linkage analysis and whole-exome sequencing in a large pedigree and Sanger sequencing in two additional kindreds and 11 unrelated dehydrated hereditary stomatocytosis cases, we identify three novel missense mutations and one recurrent duplication in PIEZO1, demonstrating that it is the major gene for dehydrated hereditary stomatocytosis. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of PIEZO1. Remarkably, we find that all PIEZO1 mutations give rise to mechanically activated currents that inactivate more slowly than wild-type currents. This gain-of-function PIEZO1 phenotype provides insight that helps to explain the increased permeability of cations in red blood cells of dehydrated hereditary stomatocytosis patients. Our findings also suggest a new role for mechanotransduction in red blood cell biology and pathophysiology.

The Sex Ratio Transition in Asia

Abstract: This article adopts a comparative perspective to review the recent increase in the sex ratio at birth (SRB) across Asia. It first describes and compares the most recent birth statistics in Asia in order to identify commonalities in the gradual rise of SRBs observed from Armenia to South Korea. This comparison provides the basis for identifying specific transition patterns in the changes in SRBs. Their recent rise is then interpreted in a social and historical framework borrowed from fertility decline and based on three preconditions: access to sex-selection technology, preference for male births, and pressure from low fertility. On a broader plane, the process of growing imbalances in the sex composition of the population gives rise to a tragedy of the commons. This article indicates the factors that appear most likely to trigger a turnaround in this transitional demographic situation and to facilitate a return to biologically normal sex ratios in the future.

Trial watch: IDO inhibitors in cancer therapy

Abstract: Indoleamine 2,3-dioxigenase 1 (IDO1) is the main enzyme that catalyzes the first, rate-limiting step of the so-called “kynurenine pathway”, i.e., the metabolic cascade that converts the essential amino acid L-tryptophan (Trp) into L-kynurenine (Kyn). IDO1, which is expressed constitutively by some tissues and in an inducible manner by specific subsets of antigen-presenting cells, has been shown to play a role in the establishment and maintenance of peripheral tolerance. At least in part, this reflects the capacity of IDO1 to restrict the microenvironmental availability of Trp and to favor the accumulation of Kyn and some of its derivatives. Also, several neoplastic lesions express IDO1, providing them with a means to evade anticancer immunosurveillance. This consideration has driven the development of several IDO1 inhibitors, some of which (including 1-methyltryptophan) have nowadays entered clinical evaluation. In animal tumor models, the inhibition of IDO1 by chemical or genetic interventions is indeed associated with the (re)activation of therapeutically relevant anticancer immune responses. This said, several immunotherapeutic regimens exert robust clinical activity in spite of their ability to promote the expression of IDO1. Moreover, 1-methyltryptophan has recently been shown to exert IDO1-independent immunostimulatory effects. Here, we summarize the preclinical and clinical studies testing the antineoplastic activity of IDO1-targeting interventions.

Relationship Between Arterial Stiffness and Cognitive Function in Elderly Subjects With Complaints of Memory Loss

Abstract: Background and Purpose—To evaluate the relationship between arterial stiffness and cognitive function in a population of elderly subjects reporting memory loss. Methods—We studied the association between cognitive function and arterial stiffness in 308 consecutive elderly subjects attending a geriatric outpatient clinic reporting memory impairment. Subjects were classified into 4 categories according to neuropsychological evaluation: normal cognitive function, mild cognitive impairment (MCI), Alzheimer disease (AD), or vascular dementia (VaD). Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) measurement using Complior. Results—In this population, 788 years of age (women 64%), AD was present in 41%, VaD in 6%, MCI in 27%, and 26% of subjects had normal cognitive function. After adjustment for age, gender, systolic blood pressure, education level, cardiovascular diseases, and antihypertensive therapy, a significant association was observed between PWV and cognitive status (P0.0001). PWV appears significantly higher in subjects with VaD (15.23.9 m/s) or AD (13.32.9 m/s) than in those without cognitive impairment (11.52.0 m/s; P0.001). Moreover, PWV was higher in subjects with MCI (12.62.6 m/s) than in those without cognitive impairment (11.52.0 m/s; P0.01). For each 2 m/s increment in PWV, the adjusted odds ratio (95% CI) was 1.73 (1.27 to 2.47) for AD and 3.52 (1.87 to 8.05) for VaD. Conclusion—Our results showed a relationship between arterial stiffness and cognitive impairment, suggesting that functional changes of the arterial system could be involved in the onset of dementia (VaD or AD types). (Stroke. 2005; 36:2193-2197.)