Charge Transfer and Chemisorption of Fullerene Molecules on Metal Surfaces: Application to Dynamics of Nanocars

It is widely believed that the dynamics of surface-bound fullerene molecules is not fully understood because current theoretical analyses do not include charge-transfer phenomena. A new theoretical approach to describe charge transfer and chemisorption processes for fullerenes on gold surfaces has been developed. The method is based on extensive semiempirical calculations that provide a consistent description of charge transfer and adsorption phenomena. Our theoretical approach is applied for analyzing complex dynamics of fullerene-based molecular machines, known as nanocars. It is found that the charge transfer makes the rolling of nanocars' wheels a preferable mode for translational motion because of the complex interactions with the metal surfaces. The physical-chemical aspects of the rolling mechanism are discussed

Additional file 1 of Caregivers’ experience of sleep management in Smith–Magenis syndrome: a mixed-methods study

Additional file 1: Paper version of Caregiver Survey. Understanding caregiver experiences of sleep management difficulties in individuals with Smith–Magenis syndrome (SMS)

Additional file 1: of Testing of therapies in a novel nebulin nemaline myopathy model demonstrate a lack of efficacy

Supplementary data for Testing of therapies in a novel nebulin nemaline myopathy model demonstrates and lack of efficacy. Figure S1: Characterisation of Tg(neb-/-; Lifeact-eGFP) fish. Figure S2-S4: Toxicity analyses for treatment of wildtype zebrafish with taurine, L-carnitine and creatine. Figure S5-S6: Quantification of distance travelled and average speed at 6 dpf. Figure S7: Quantification of the phenotypic severity at 6 dpf. Figure S8: Characterisation of facial muscles at 6 dpf. (PDF 7847 kb

Additional file 1 of Making visible the cost of informal caregivers’ time in Latin America: a case study for major cardiovascular, cancer and respiratory diseases in eight countries

Additional file 1: SM. Search strategies in the literature review. Table S1. Inputs used to estimate the hours per day of informal care by events. Table S2. Hourly wage used to proxy of the market value of informal care time, rate exchange and GDP by country, 2020 USD. Table S3. Total number of cases per health events and country in a year. Table S4. Medical direct costs per health event and country, million 2020 USD. Table S5. Average cost per day of informal care by health condition and country, in 2020 dollars

Metformin rescues muscle function in BAG3 myofibrillar myopathy models

Dominant de novo mutations in the co-chaperone BAG3 cause a severe form of myofibrillar myopathy, exhibiting progressive muscle weakness, muscle structural failure, and protein aggregation. To elucidate the mechanism of disease in, and identify therapies for, BAG3 myofibrillar myopathy, we generated two zebrafish models, one conditionally expressing BAG3P209L and one with a nonsense mutation in bag3. While transgenic BAG3P209L-expressing fish display protein aggregation, modeling the early phase of the disease, bag3-/- fish exhibit exercise dependent fiber disintegration, and reduced swimming activity, consistent with later stages of the disease. Detailed characterization of the bag3-/- fish, revealed an impairment in macroautophagic/autophagic activity, a defect we confirmed in BAG3 patient samples. Taken together, our data highlights that while BAG3P209L expression is sufficient to promote protein aggregation, it is the loss of BAG3 due to its sequestration within aggregates, which results in impaired autophagic activity, and subsequent muscle weakness. We therefore screened autophagy-promoting compounds for their effectiveness at removing protein aggregates, identifying nine including metformin. Further evaluation demonstrated metformin is not only able to bring about the removal of protein aggregates in zebrafish and human myoblasts but is also able to rescue the fiber disintegration and swimming deficit observed in the bag3−/- fish. Therefore, repurposing metformin provides a promising therapy for BAG3 myopathy. Abbreviations:ACTN: actinin, alpha; BAG3: BAG cochaperone 3; CRYAB: crystallin alpha B; DES: desmin; DMSO: dimethyl sulfoxide; DNAJB6: DnaJ heat shock protein family (Hsp40) member B6; dpf: days post fertilization; eGFP: enhanced green fluorescent protein; FDA: Food and Drug Administration; FHL1: four and a half LIM domains 1; FLNC: filamin C; hpf: hours post-fertilization; HSPB8: heat shock protein family B [small] member 8; LDB3/ZASP: LIM domain binding 3; MYOT: myotilin; TTN: titin; WT: wild-type.</p