In-cell NMR reveals potential precursor of toxic species from SOD1 fALS mutants

Mutations in the superoxide dismutase 1 (SOD1) gene are related to familial cases of amyotrophic lateral sclerosis (fALS). Here we exploit in-cell NMR to characterize the protein folding and maturation of a series of fALS-linked SOD1 mutants in human cells and to obtain insight into their behaviour in the cellular context, at the molecular level. The effect of various mutations on SOD1 maturation are investigated by changing the availability of metal ions in the cells, and by coexpressing the copper chaperone for SOD1, hCCS. We observe for most of the mutants the occurrence of an unstructured SOD1 species, unable to bind zinc. This species may be a common precursor of potentially toxic oligomeric species, that are associated with fALS. Coexpression of hCCS in the presence of copper restores the correct maturation of the SOD1 mutants and prevents the formation of the unstructured species, confirming that hCCS also acts as a molecular chaperone

A Janus Molecule for Screen-Printable Conductive Carbon Ink for Composites with Superior Stretchability

Inspired by decades of research in the compatibilization of fillers into elastomeric composites for high-performance materials, a novel polyurethane-based stretchable carbon ink is created by taking advantage of a Janus molecule, 2-(2,5-dimethyl-1H-pyrrol-1-yl)propane-1,3-diol (serinol pyrrole, SP). SP is used to functionalize the carbon and comonomer in the polymer phase. The use of SPs in both the organic and inorganic phases results in an improved interaction between the two phases. When printed, the functionalized material has a factor 1.5 lower resistance-strain dependence when compared to its unfunctionalized analogue. This behavior is superior to commercially available carbon inks. To demonstrate the suitability of ink in an industrial application, an all-printed, elastomer-based force sensor is fabricated. This “pyrrole methodology” is scalable and broadly applicable, laying the foundation for the realization of printed functionalities with improved electromechanical performance.</p

Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS).

Copper chaperone for superoxide dismutase 1 (SOD1), CCS, is the physiological partner for the complex mechanism of SOD1 maturation. We report an in vitro model for human CCS-dependent SOD1 maturation based on the study of the interactions of human SOD1 (hSOD1) with full-length WT human CCS (hCCS), as well as with hCCS mutants and various truncated constructs comprising one or two of the protein’s three domains. The synergy between electrospray ionization mass spectrometry (ESI-MS) and NMR is fully exploited. This is an in vitro study of this process at the molecular level. Domain 1 of hCCS is necessary to load hSOD1 with Cu(I), requiring the heterodimeric complex formation with hSOD1 fostered by the interaction with domain 2. Domain 3 is responsible for the catalytic formation of the hSOD1 Cys-57–Cys-146 disulfide bond, which involves both hCCS Cys-244 and Cys-246 via disulfide transfer

CCD-based imaging and 3D space--time mapping of terahertz fields via Kerr frequency conversion

We investigate the spatially and temporally resolved four-wave mixing of terahertz (THz) fields and optical pulses in large-bandgap dielectrics, such as diamond. We show that it is possible to perform beam profiling and space–time resolved mapping of THz fields by encoding the spatial information into an optical signal, which can then be recorded by a standard CCD camera

Probable disseminated Mycobacterium abscessus subspecies bolletii infection in a patient with idiopathic CD4+ T lymphocytopenia: a case report.

INTRODUCTION: Rapidly growing mycobacteria are opportunistic pathogens in patients with underlying riskfactors. Mycobacterium abscessus subsp. bolletii is a newly recognized member of rapidlygrowing mycobacteria, isolated from respiratory tract and cutaneous infections. CASE PRESENTATION: We describe a case of chronic disseminated infection caused by M. abscessus subsp. bolletiiin a 38-year-old Sri Lankan man with idiopathic CD4+ T lymphocytopenia. Idiopathic CD4+T lymphocytopenia is a rare cause of immunodysfunction that, similar to humanimmunodeficiency virus infection. M. abscessus subsp. bolletii infection was diagnosed byculture isolation from two sputum samples. CONCLUSIONS: To the best of our knowledge this is the first report of M. abscessus subsp. bolletiidisseminated infection in a patient affected by idiopathic CD4+ T lymphocytopenia. Incontrast to previous reports, the isolate of M. abscessus subsp. bolletii presented intermediateresistance to clarithromycin and was susceptible to cefoxitin and imipenem

Functionalization of graphene related materials with biosourced C-3 and C-6 building blocks. From synthesis to applications

The functionalization of sp2 carbon allotropes is one of the hot research topics in advanced research on materials. Nowadays, carbon nanotubes and graphene related materials are extensively studied due to their exceptional mechanical and electrical properties. They are capable of substantially improving the properties of polymeric materials. Their functionalization is a crucial step, for allowing an even dispersion in the matrix. In this research, the functionalization of graphene related materials was performed with biosourced C-3 and C-6 molecules. They were glycerol and galactaric acid derivatives: pyrrole compounds (PyC) and 2-pyrones. The reactions for their synthesis and for the carbon allotrope functionalization were green and characterized by high atom efficiency, with a yield up to 96%. Indeed, the reactions were carried out in the absence of solvents and catalysts and adducts were obtained by simply mixing, with the help of either thermal or mechanical energy. The developed functionalization methods were successful for: carbon black, carbon nanotubes, few layers graphene. The bulk structure of the carbon substrate was left substantially unaltered: functionalization occurred in peripheral positions, at the edges of the graphene layers. Functional groups of defined chemical structure were covalently bound to the carbon material and stable adducts, up to very high temperature, were formed. Reliable hypotheses for the functionalization mechanisms were elaborated. In Figure 1b the supposed domino reaction based on the pyrrole compound, with the Diels Alder cycloaddition as the last step is represented. Such functionalization technique was developed as a pervasive technology, which allowed to pursue a variety of applications: (i) decoration with metals to obtain catalysts for the selective deuteration of pharmaceutical molecules as well as antibacterial ingredients (ii) rubber compounds for dynamic-mechanical applications (tires) (iii) conductive inks

Counterpropagating frequency mixing with terahertz waves in diamond

Frequency conversion by means of Kerr-nonlinearity is one of the most common and exploited nonlinear optical processes in the UV, visible, IR and Mid-IR spectral regions. Here we show that wave mixing of an optical field and a Terahertz wave can be achieved in diamond, resulting in the frequency conversion of the THz radiation either by sum- or difference-frequency generation. In the latter case, we show that this process is phase-matched and most efficient in a counter-propagating geometry

MIS-C and co-infection with P. vivax and P. falciparum in a child: a clinical conundrum

Background The ongoing Coronavirus Disease 2019 (COVID-19) epidemic represents an unprecedented global health challenge. Many COVID-19 symptoms are similar to symptoms that can occur in other infections. Malaria should always be considered in patients with SARS-CoV-2 infection returning from endemic areas. Case presentation We present the first case of multisystem inflammatory syndrome (MIS-C) and Plasmodium vivax-falciparum and SARS-CoV2 coinfection in children. Despite clearance of parassitaemia and a negative COVID-19 nasopharyngeal PCR, the patient's clinical conditions worsened. The World Health Organization (WHO) criteria were used to make the diagnosis of MIS-C. Treatment with intravenous immunoglobulins and methylprednisolone was effective. Conclusions This case emphasizes the importance of considering malaria diagnosis in patients returning from endemic areas, even in the COVID 19 era. Malaria and SARS-CoV2 co-infection may increase the risk of MIS-C, for which early detection is critical for proper management