Search results for "Tertiary"

Protein denaturation caused by heat inactivation detrimentally affects biomolecular corona formation and cellular uptake

2018

Adsorption of blood proteins to the surface of nanocarriers is known to be the critical factor influencing cellular interactions and eventually determining the successful application of nanocarriers as drug carriers in vivo. There is an increasing number of reports summarizing large data sets of all identified corona proteins. However, to date our knowledge about the multiple mechanisms mediating interactions between proteins and nanocarriers is still limited. In this study, we investigate the influence of protein structure on the adsorption process and focus on the effect of heat inactivation of serum and plasma, which is a common cell culture procedure used to inactivate the complement sy…

Actin Filaments Are Involved in the Coupling of V0-V1 Domains of Vacuolar H+-ATPase at the Golgi Complex*

2016

We previously reported that actin-depolymerizing agents promote the alkalization of the Golgi stack and the trans-Golgi network. The main determinant of acidic pH at the Golgi is the vacuolar-type H+-translocating ATPase (V-ATPase), whose V1 domain subunits B and C bind actin. We have generated a GFP-tagged subunit B2 construct (GFP-B2) that is incorporated into the V1 domain, which in turn is coupled to the V0 sector. GFP-B2 subunit is enriched at distal Golgi compartments in HeLa cells. Subcellular fractionation, immunoprecipitation, and inversal FRAP experiments show that the actin depolymerization promotes the dissociation of V1-V0 domains, which entails subunit B2 translocation from Go…

A possible desensitized state conformation of the human α7 nicotinic receptor: A molecular dynamics study

2017

International audience; The determination of the conformational states corresponding to diverse functional roles of ligand gated ion channels is subject of intense investigation with various techniques, from X-rays structure determination to electrophysiology and computational modeling. Even with a certain number of structures becoming recently available, only few major structural features distinguishing conductive open channel from the non conductive resting protein have been highlighted, while high-resolution details are still missing. The characterization of the desensitized conformation(s) is even more complex, and only few specific characteristics have been identified. Furthermore, exp…

Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein

2019

JBC papers in press xx, 16604-16619 (2019). doi:10.1074/jbc.RA119.009845

Antigen specificity and clinical significance of IgG and IgA autoantibodies produced in situby tumor-infiltrating b cells in breast cancer

2018

An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ. The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyze…

Detection of two simultaneous outbreaks of Klebsiella pneumoniae coproducing OXA-48 and NDM-1 carbapenemases in a tertiary-care hospital in Valencia,…

2020

Klebsiella pneumoniae is one of the most common hospital-acquired Gram-negative pathogens. During the last decade, the emergence of strains with reduced susceptibility or resistance to carbapenems is becoming a therapeutic challenge. This study takes place after the isolation of 14 strains of carbapenem-resistant K. pneumoniae with similar susceptibility patterns and carriage of OXA-48 and NDM-1 carbapenemases genes. Fourteen patients were found to be colonized (faecal carriage) and/or infected by two different clones of carbapenemase-coproducing K. pneumoniae during a 1-year period of time. Some of the patients had shared a hospital ward and continued to be colonized several months after t…

Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates

2018

A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and ev…

2017

Introduction Mental disorders are characterised by a high likelihood of symptom recurrence or chronicity. Thus, in the vulnerable post-discharge phase, aftercare and follow-up aim at stabilising treatment effects, promoting functionality and preventing relapse or readmission. Internet- and mobile-based interventions may represent low threshold and effective extensions to aftercare in tertiary prevention of mental disorders. Objectives The planned systematic review and meta-analysis aims to synthesise and analyse existing evidence on the effectiveness of psychological internet- and mobile-based aftercare or follow-up in maintaining treatment effects and/or preventing recurrence in adults wit…

Études scientifiques et marché du travail : éléments de réflexion sur la crise des formations en sciences

2007

Student disaffection towards sciences, most evident in pure science undergraduates, is causing increasing concern for the future of scientific training in France. If access to employment deteriorates more for science graduates than for graduates in other disciplines, science graduates will have a distinct advantage in terms of earnings and employment status, when the economic situation becomes less favourable. Within sciences, graduates of pure sciences have a more difficult transition from education to employment than those from applied sciences. Yet graduates from both disciplines compete for the same job in the private sector with pure science graduates receiving lower wages. The “crisis…

Lower ST-elevation myocardial infarction incidence during COVID-19 epidemic in Northern Europe

2020

We compared the ST elevation myocardial infarction (STEMI) incidence during COVID-19 pandemic (March 2020) to January-February 2020 and to same time period in earlier years 2017-2019 in five Nordic-Baltic tertiary centers. During 2017-2019, there were no marked differences in STEMI incidence between January, February and March. During 2020, there was an average drop of 32% in STEMI incidence in March. The isolation measures may decrease the risk for respiratory virus infection and contribute to the lower STEMI incidence and that we might benefit from firmer suggestions on hand hygiene and social distancing during flu season at least among high-risk individuals.