396 research outputs found
Long-Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections
Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm2. Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full-thickness burns as well as postburn scar contractures
Myosin and tropomyosin stabilize the conformation of formin-nucleated actin filaments
The conformational elasticity of the actin cytoskeleton is
essential for its versatile biological functions. Increasing
evidence supports that the interplay between the structural and
functional properties of actin filaments is finely regulated by
actin-binding proteins, however, the underlying mechanisms and
biological consequences are not completely understood. Previous
studies showed that the binding of formins to the barbed end
induces conformational transitions in actin filaments by making
them more flexible through long-range allosteric interactions.
These conformational changes are accompanied by altered
functional properties of the filaments. To get insight into the
conformational regulation of formin-nucleated actin structures,
in the present work we investigated in detail how binding
partners of formin-generated actin structures, myosin and
tropomyosin, affect the conformation of the formin-nucleated
actin filaments, using fluorescence spectroscopic approaches.
Time-dependent fluorescence anisotropy and temperature-dependent
Forster-type resonance energy transfer measurements revealed
that heavy meromyosin, similarly to tropomyosin, restores the
formin-induced effects and stabilizes the conformation of actin
filaments. The stabilizing effect of heavy meromyosin is
cooperative. The kinetic analysis revealed that despite the
qualitatively similar effects of heavy meromyosin and
tropomyosin on the conformational dynamics of actin filaments,
the mechanisms of the conformational transition is different for
the two proteins. Heavy meromyosin stabilizes the formin-
nucleated actin filaments in an apparently single-step reaction
upon binding, while the stabilization by tropomyosin occurs
after complex formation. These observations support the idea
that actin-binding proteins are key elements of the molecular
mechanisms that regulate the conformational and functional
diversity of actin filaments in living cells
Klüver-Bucy syndrome associated with a recessive variant in HGSNAT in two siblings with Mucopolysaccharidosis type IIIC (Sanfilippo C)
Kluver-Bucy syndrome (KBS) comprises a set of neurobehavioral symptoms with psychic blindness, hypersexuality, disinhibition, hyperorality, and hypermetamorphosis that were originally observed after bilateral lobectomy in Rhesus monkeys. We investigated two siblings with KBS from a consanguineous family by whole-exome sequencing and autozygosity mapping. We detected a homozygous variant in the heparan-alpha-glucosaminidase-N-acetyltransferase gene (HGSNAT; c.518G>A, p.(G173D), NCBI ClinVar RCV000239404.1), which segregated with the phenotype. Disease-causing variants in this gene are known to be associated with autosomal recessive Mucopolysaccharidosis type IIIC (MPSIIIC, Sanfilippo C). This lysosomal storage disease is due to deficiency of the acetyl-CoA:alpha-glucosaminidase-N-acetyltransferase, which was shown to be reduced in patient fibroblasts. Our report extends the phenotype associated with MPSIIIC. Besides MPSIIIA and MPSIIIB, due to variants in SGSH and NAGLU, this is the third subtype of Sanfilippo disease to be associated with KBS. MPSIII should be included in the differential diagnosis of young patients with KBS
Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis
Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2-4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl-protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1/CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, or b) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease
The Schroedinger Problem, Levy Processes Noise in Relativistic Quantum Mechanics
The main purpose of the paper is an essentially probabilistic analysis of
relativistic quantum mechanics. It is based on the assumption that whenever
probability distributions arise, there exists a stochastic process that is
either responsible for temporal evolution of a given measure or preserves the
measure in the stationary case. Our departure point is the so-called
Schr\"{o}dinger problem of probabilistic evolution, which provides for a unique
Markov stochastic interpolation between any given pair of boundary probability
densities for a process covering a fixed, finite duration of time, provided we
have decided a priori what kind of primordial dynamical semigroup transition
mechanism is involved. In the nonrelativistic theory, including quantum
mechanics, Feyman-Kac-like kernels are the building blocks for suitable
transition probability densities of the process. In the standard "free" case
(Feynman-Kac potential equal to zero) the familiar Wiener noise is recovered.
In the framework of the Schr\"{o}dinger problem, the "free noise" can also be
extended to any infinitely divisible probability law, as covered by the
L\'{e}vy-Khintchine formula. Since the relativistic Hamiltonians
and are known to generate such laws, we focus on
them for the analysis of probabilistic phenomena, which are shown to be
associated with the relativistic wave (D'Alembert) and matter-wave
(Klein-Gordon) equations, respectively. We show that such stochastic processes
exist and are spatial jump processes. In general, in the presence of external
potentials, they do not share the Markov property, except for stationary
situations. A concrete example of the pseudodifferential Cauchy-Schr\"{o}dinger
evolution is analyzed in detail. The relativistic covariance of related waveComment: Latex fil
Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden
We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD
A Novel Inactivated Intranasal Respiratory Syncytial Virus Vaccine Promotes Viral Clearance without Th2 Associated Vaccine-Enhanced Disease
Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in young children worldwide, and no vaccine is currently available. Inactivated RSV vaccines tested in the 1960's led to vaccine-enhanced disease upon viral challenge, which has undermined RSV vaccine development. RSV infection is increasingly being recognized as an important pathogen in the elderly, as well as other individuals with compromised pulmonary immunity. A safe and effective inactivated RSV vaccine would be of tremendous therapeutic benefit to many of these populations.In these preclinical studies, a mouse model was utilized to assess the efficacy of a novel, nanoemulsion-adjuvanted, inactivated mucosal RSV vaccine. Our results demonstrate that NE-RSV immunization induced durable, RSV-specific humoral responses, both systemically and in the lungs. Vaccinated mice exhibited increased protection against subsequent live viral challenge, which was associated with an enhanced Th1/Th17 response. In these studies, NE-RSV vaccinated mice displayed no evidence of Th2 mediated immunopotentiation, as has been previously described for other inactivated RSV vaccines.These studies indicate that nanoemulsion-based inactivated RSV vaccination can augment viral-specific immunity, decrease mucus production and increase viral clearance, without evidence of Th2 immune mediated pathology
TRY plant trait database - enhanced coverage and open access
Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
Downregulation of MIP-1α/CCL3 with praziquantel treatment in Schistosoma haematobium and HIV-1 co-infected individuals in a rural community in Zimbabwe
The results of our study show that the MIP-1alpha/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1alpha/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1alpha/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1alpha/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1alpha/CCL3
Characterization of magnesium requirement of human 5'-tyrosyl DNA phosphodiesterase mediated reaction
<p>Abstract</p> <p>Background</p> <p>Topo-poisons can produce an enzyme-DNA complex linked by a 3'- or 5'-phosphotyrosyl covalent bond. 3'-phosphotyrosyl bonds can be repaired by tyrosyl DNA phosphodiesterase-1 (TDP1), an enzyme known for years, but a complementary human enzyme 5'-tyrosyl DNA phosphodiesterase (hTDP2) that cleaves 5'-phosphotyrosyl bonds has been reported only recently. Although hTDP2 possesses both 3'- and 5'- tyrosyl DNA phosphodiesterase activity, the role of Mg<sup>2+ </sup>in its activity was not studied in sufficient details.</p> <p>Results</p> <p>In this study we showed that purified hTDP2 does not exhibit any 5'-phosphotyrosyl phosphodiesterase activity in the absence of Mg<sup>2+</sup>/Mn<sup>2+</sup>, and that neither Zn<sup>2+ </sup>or nor Ca<sup>2+ </sup>can activate hTDP2. Mg<sup>2+ </sup>also controls 3'-phosphotyrosyl activity of TDP2. In MCF-7 cell extracts and de-yolked zebrafish embryo extracts, Mg<sup>2+ </sup>controlled 5'-phosphotyrosyl activity. This study also showed that there is an optimal Mg<sup>2+ </sup>concentration above which it is inhibitory for hTDP2 activity.</p> <p>Conclusion</p> <p>These results altogether reveal the optimal Mg<sup>2+ </sup>requirement in hTDP2 mediated reaction.</p
- …