20 research outputs found
Hand Rehabilitation and Telemonitoring through Smart Toys
We describe here a platform for autonomous hand rehabilitation and telemonitoring of young patients. A toy embedding the electronics required to sense fingers pressure in different grasping modalities is the core element of this platform. The system has been realized following the user-centered design methodology taking into account stakeholder needs from start: clinicians require reliable measurements and the ability to get a picture remotely on rehabilitation progression; children have asked to interact with a pleasant and comfortable object that is easy to use, safe, and rewarding. These requirements are not antithetic, and considering both since the design phase has allowed the realization of a platform reliable to clinicians and keen to be used by young children
The interactions of Cobalt(II) with mitochondria from rat liver
The interactions of Co2+ with mitochondria have been investigated. The results indicate that Co2+ inhibits ATP synthesis. Further investigations into ATP synthesis mechanisms indicated that inhibition is due to the opening of a transmembrane pore. The opening of this pore causes the collapse of the high-energy intermediate where, under a pH and a potential gradient, the energy is stored and subsequently utilized to form ATP from ADP
Bidirectional fluxes of spermine across the mitochondrial membrane.
The polyamine spermine is transported into the
mitochondrial matrix by an electrophoretic mechanism
having as driving force the negative electrical membrane
potential (DW). The presence of phosphate increases
spermine uptake by reducingDpH and enhancingDW. The
transport system is a specific uniporter constituted by a
protein channel exhibiting two asymmetric energy barriers
with the spermine binding site located in the energy well
between the two barriers. Although spermine transport is
electrophoretic in origin, its accumulation does not follow
the Nernst equation for the presence of an efflux pathway.
Spermine efflux may be induced by different agents, such as
FCCP, antimycin A and mersalyl, able to completely or
partially reduce theDWvalue and, consequently, suppress
or weaken the force necessary to maintain spermine in the
matrix. However this efflux may also take place in normal
conditions when the electrophoretic accumulation of the
polycationic polyamine induces a sufficient drop inDWable
to trigger the efflux pathway. The release of the polyamine
is most probably electroneutral in origin and can take place
in exchange with protons or in symport with phosphate
anion. The activity of both the uptake and efflux pathways
induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and
outer compartment. Thus, this event has a significant role on
mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
Lyn-mediated mitochondrial tyrosine phosphorylation is required to preserve mitochondrial integrity in early liver regeneration
Functional alterations in mitochondria such as overproduction of ROS (reactive oxygen species) and overloading of calcium, with subsequent change in the membrane potential, are traditionally regarded as pro-apoptotic conditions. Although such events occur in the early phases of LR (liver regeneration) after two-thirds PH (partial hepatectomy), hepatocytes do not undergo apoptosis but continue to proliferate until the mass of the liver is restored. The aim of the present study was to establish whether tyrosine phosphorylation, an emerging mechanism of regulation of mitochondrial function, participates in the response to liver injury following PH and is involved in contrasting mitochondrial pro-apoptotic signalling. Mitochondrial tyrosine phosphorylation, negligible in the quiescent liver, was detected in the early phases of LR with a trend similar to the events heralding mitochondrial apoptosis and was attributed to the tyrosine kinase Lyn, a member of the Src family. Lyn was shown to accumulate in an active form in the mitochondrial intermembrane space, where it was found to be associated with a multiprotein complex. Our results highlight a role for tyrosine phosphorylation in accompanying, and ultimately counteracting, mitochondrial events otherwise leading to apoptosis, hence conveying information required to preserve the mitochondrial integrity during LR
Human cardiac stem cells are involved in pathological processes
It has been proposed the use of resident stem cells (SCs) for the repair of cardiac injuries. However, several in vivo studies suggested a possible involvement of human cardiac SCs in ageing and disease states, such as heart failure. Therefore, the purpose of our study was to verify whether the population of pluripotent mesenchymal stem cells(PMSC), that we have recently identified as resident in the human heart, changes its properties in pathological states.
Methods and Results Small cells (<30mcm) were isolated from left atria of explanted human hearts affected by ischemic cardiomyopathy (Recipient Heart, RH, n=8), and from fragments of donor derived atrial tissue (Donor Heart, DH, n=7). Cells were grown in a medium selective for multipotent cells. Cell lines were obtained from every isolated adult human atrium, but the cloning efficiency was significantly higher in DH with respect to RH (p<0.001). RH and DH cells shared a similar mesenchymal immunophenotype (CD45-/CD34-/CD38-/CD117-/CD133-/HLA-DR-/CD29lo/KDRlo/CD90hi/CD13hi/CD49ahi/CD49bhi) (n=15), and expressed, at protein level, the pluripotent state-specific transcription factors OCT-4 and Nanog. As evaluated by FACS and RT-PCR, only a small fraction of PMSCs (<10%) continue to express the cardiac-specific transcription factors GATA-4, Nkx2.5 and Myocardin. Moreover, when exposed to appropriate differentiation inducing conditions RH and DH PMSCs (n=5), were able to differentiate along an adipogenic, osteogenic, endothelial, myogenic, epithelial and neurogenic fate, as confirmed by immunofluorescence and RT-PCR analyses. Importantly, when cloned at a single cell level, cardiac derived cells retained all these characteristics. Although RH- and DH- derived cell lines possessed telomerase activity (n=15), the average telomeric length, as evaluated by FLOW-FISH, was significantly higher in DH. In conclusion: Cells with a wide differentiation potential can be isolated and grown from atria of DHs and RHs. Although these cells share many important SC features (immunophenotype, pluripotency, clonogenicity, telomerase activity), they differ in terms of telomeric length and growth kinetics, suggesting that pathological processes can impair the resident cardiac SC reservoir