Simple barcode system based on ionogels for real time pH-sweat monitoring

This paper presents the fabrication, characterization and the performance of a wearable, robust, flexible and disposable barcode system based on novel ionic liquid polymer gels (ionogels) for monitoring in real time mode the pH of the sweat generated during an exercise period. Up to now sweat analysis has been carried out using awkward methods of collecting sweat followed by laboratory analysis. The approach presented here can provide immediate feedback regarding sweat composition. The great advantage of sweat analysis is the fact that it is a completely non-invasive means of analyzing the wearer's physiological state and ensuring their health and well-being

Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids

This work presents the fabrication, characterisation and the performance of a wearable, robust, flexible and disposable chemical barcode device based on a micro-fluidic platform that incorporates ionic liquid polymer gels (ionogels). The device has been applied to the monitoring of the pH of sweat in real time during an exercise period. The device is an ideal wearable sensor for measuring the pH of sweat since it does not contents any electronic part for fluidic handle or pH detection and because it can be directly incorporated into clothing, head- or wristbands, which are in continuous contact with the skin. In addition, due to the micro-fluidic structure, fresh sweat is continuously passing through the sensing area providing the capability to perform continuous real time analysis. The approach presented here ensures immediate feedback regarding sweat composition. Sweat analysis is attractive for monitoring purposes as it can provide physiological information directly relevant to the health and performance of the wearer without the need for an invasive sampling approac

Archaebiotics Proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease

International audienceTrimethylamine (TMA) is produced by gut bacteria from dietary ingredients. In individuals with a hereditary defect in flavin-containing monooxygenase 3, bacterial TMA production is believed to contribute to the symptoms of trimethylaminuria (TMAU; fish-odor syndrome). Intestinal microbiota TMA metabolism may also modulate atherosclerosis risk by affecting trimethylamine oxide (TMAO) production levels. We propose that reducing TMA formation in the gut by converting it to an inert molecule could be used to prevent or limit these human diseases, while avoiding the major drawbacks of other clinical interventions. Reducing TMA levels by microbiological interventions could also be helpful in some vaginoses. Particular members of a recently discovered group of methanogens, that are variably present in the human gut, are unusual in being apparently restricted to utilizing only methyl compounds including TMA as substrates. We confirmed experimentally that one of these strains tested, Methanomassiliicoccus luminyensis B10, is able to deplete TMA, by reducing it with H2 for methanogenesis. We therefore suggest that members of this archaeal lineage could be used as treatments for metabolic disorders

A SINE Insertion in ATP1B2

Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified an ∼10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole-genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the β2 subunit of the Na+/K+-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry suggested a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knockout mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2-affected Malinois puppies may serve as a naturally occurring animal model for this disorder

Tumor inherent interferon regulators as biomarkers of long-term chemotherapeutic response in TNBC

Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients with TNBC is difficult, yet enhanced infiltration of tumor infiltrating lymphocytes (TILs) has been associated with therapeutic response and reduced risk of metastatic relapse. Immune biomarkers that predict the immune state of a tumor and risk of metastatic relapse pre- or mid-neoadjuvant chemotherapy are urgently needed to allow earlier implementation of alternate therapies that may reduce TNBC patient mortality. Utilizing a neoadjuvant chemotherapy trial where TNBC patients had sequential biopsies taken, we demonstrate that measurement of T-cell subsets and effector function, specifically CD45RO expression, throughout chemotherapy predicts risk of metastatic relapse. Furthermore, we identified the tumor inherent interferon regulatory factor IRF9 as a marker of active intratumoral type I and II interferon (IFN) signaling and reduced risk of distant relapse. Functional implications of tumor intrinsic IFN signaling were demonstrated using an immunocompetent mouse model of TNBC, where enhanced type I IFN signaling increased anti-tumor immunity and metastasis-free survival post-chemotherapy. Using two independent adjuvant cohorts we were able to validate loss of IRF9 as a poor prognostic biomarker pre-chemotherapy. Thus, IRF9 expression may offer early insight into TNBC patient prognosis and tumor heat, allowing for identification of patients that are unlikely to respond to chemotherapy alone and could benefit from further immune-based therapeutic intervention

Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling

Item does not contain fulltextNephronophthisis-related ciliopathies (NPHP-RC) are degenerative recessive diseases that affect kidney, retina, and brain. Genetic defects in NPHP gene products that localize to cilia and centrosomes defined them as "ciliopathies." However, disease mechanisms remain poorly understood. Here, we identify by whole-exome resequencing, mutations of MRE11, ZNF423, and CEP164 as causing NPHP-RC. All three genes function within the DNA damage response (DDR) pathway. We demonstrate that, upon induced DNA damage, the NPHP-RC proteins ZNF423, CEP164, and NPHP10 colocalize to nuclear foci positive for TIP60, known to activate ATM at sites of DNA damage. We show that knockdown of CEP164 or ZNF423 causes sensitivity to DNA damaging agents and that cep164 knockdown in zebrafish results in dysregulated DDR and an NPHP-RC phenotype. Our findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR

Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions

Integrins in focal adhesions (FAs) mediate adhesion and force transmission to extracellular matrices crucial for cell motility, proliferation and differentiation1,2. Different αβ-integrins binding to fibronectin (FN) perform distinct functions3-5 and are simultaneously present in FAs. Although the static nanoscale organization of FAs was described6, explaining how individual dynamics of specific integrins control biochemical and biomechanical events in FAs is still elusive. Combining single protein tracking and super-resolution imaging we show that β3- and β1-integrins act as distinct adhesion units displaying specific dynamics and nano-organizations within FAs. Integrins reside in FAs through free-diffusion and immobilization cycles, thus integrins are not constantly active inside FAs. Integrin activation promotes immobilization, stabilized in FAs by simultaneous FN and actin binding proteins (ABPs) connections. The integrin activator talin7, is recruited in FAs from the cytosol without membrane free-diffusion, spatially restricting integrin immobilization to FAs. Talin immobilization zones are concentrated and mainly stationary in FA, consistent with the formation of stable β-integrin/talin connections. β3-integrin immobilizations are concentrated and stationary within FAs, whereas β1-integrins are sparse displaying eventually rearward movements. Thus, differential transmission of F-actin motion to FN occurs through specific integrins within FAs. This dynamic nano-partitioning of β-integrins within FAs could control local forces and signaling necessary for distinct cellular functions such as migration and extracellular matrices remodeling