Miracle-dz/UniFAR-FTUs huggingface dataset:
Time Controlled Protein Release from Layer‐by‐Layer Assembled Multilayer Functionalized Agarose Hydrogels

Axons of the adult central nervous system exhibit an extremely limited ability to regenerate after spinal cord injury. Experimentally generated patterns of axon growth are typically disorganized and randomly oriented. Support of linear axonal growth into spinal cord lesion sites has been demonstrated using arrays of uniaxial channels, templated with agarose hydrogel, and containing genetically engineered cells that secrete brain‐derived neurotrophic factor (BDNF). However, immobilizing neurotrophic factors secreting cells within a scaffold is relatively cumbersome, and alternative strategies are needed to provide sustained release of BDNF from templated agarose scaffolds. Existing methods of loading the drug or protein into hydrogels cannot provide sustained release from templated agarose hydrogels. Alternatively, here it is shown that pH‐responsive H‐bonded poly(ethylene glycol)(PEG)/poly(acrylic acid)(PAA)/protein hybrid layer‐by‐layer (LbL) thin films, when prepared over agarose, provided sustained release of protein under physiological conditions for more than four weeks. Lysozyme, a protein similar in size and isoelectric point to BDNF, is released from the multilayers on the agarose and is biologically active during the earlier time points, with decreasing activity at later time points. This is the first demonstration of month‐long sustained protein release from an agarose hydrogel, whereby the drug/protein is loaded separately from the agarose hydrogel fabrication process.
What determines transitions to sick leave

The paper discusses some of the possible determinants of sick leave. The underlying medical health of workers is of course important, but other factors also determine if they manage to function at work. For example the degree to which workers are willing to endure discomfort at work and the demands for efficiency at work can be important. Also of importance is the ease with which workers can change jobs and whether increases in employment bring in marginal, less healthy, workers. Finally, one must take into consideration the ability of firms to accommodate workers with health problems, the age of the work force and the situation workers face at home. As an illustration, we discuss how these factors have influenced married women in ages 35 to 44 using a multinomial model. The main finding is that changes in wages has had a very strong effect on transitions to sick leave in the 90’s. In our estimation they explain almost all the change in the group.
Iron Oxide‐Labeled Collagen Scaffolds for Non‐Invasive MR Imaging in Tissue Engineering

Non‐invasive imaging holds significant potential for implementation in tissue engineering. It can be used to monitor the localization and function of tissue‐engineered implants, as well as their resorption and remodelling. Thus far, however, the vast majority of effort in this area of research have focused on the use of ultrasmall super‐paramagnetic iron oxide (USPIO) nanoparticle‐labeled cells, colonizing the scaffolds, to indirectly image the implant material. Reasoning that directly labeling scaffold materials might be more beneficial (enabling imaging also in the case of non‐cellularized implants), more informative (enabling the non‐invasive visualization and quantification of scaffold degradation), and easier to translate into the clinic (cell‐free materials are less complex from a regulatory point‐of‐view), three different types of USPIO nanoparticles are prepared and incorporated both passively and actively (via chemical conjugation; during collagen crosslinking) into collagen‐based scaffold materials. The amount of USPIO incorporated into the scaffolds is optimized, and correlated with MR signal intensity, showing that the labeled scaffolds are highly biocompatible, and that scaffold degradation can be visualized using MRI. This provides an initial proof‐of‐principle for the in vivo visualization of the scaffolds. Consequently, USPIO‐labeled scaffold materials seem to be highly suitable for image‐guided tissue engineering applications.
Dissimilar mispair‐recognition spectra of Arabidopsis DNA‐mismatch‐repair proteins MSH2·MSH6 (MutSα) and MSH2·MSH7 (MutSγ)

Besides orthologs of other eukaryotic mismatch-repair (MMR) proteins, plants encode MSH7, a paralog of MSH6. The Arabidopsis thaliana recognition heterodimers AtMSH2·MSH6 (AtMutSα) and AtMSH2·MSH3 (AtMutSβ) were previously found to bind the same subsets of mismatches as their counterparts in other eukaryotes—respectively, base–base mismatches and single extra nucleotides, loopouts of extra nucleotides (one or more) only—but AtMSH2·MSH7 (AtMutSγ) bound well only to a G/T mismatch. To test hypotheses that MSH7 might be specialized for G/T, or for base mismatches in 5-methylcytosine contexts, we compared binding of AtMutSα and AtMutSγ to a series of mismatched DNA oligoduplexes, relative to their (roughly similar) binding to G/T DNA. AtMutSγ bound G/G, G/A, A/A and especially C/A mispairs as well or better than G/T, in contrast to MutSα, for which G/T was clearly the best base mismatch. The presence of 5-methylcytosine adjacent to or in a mispair generally lowered binding by both heterodimers, with no systematic difference between the two. Alignment of protein sequences reveals the absence in MSH7 of the clamp domains that in bacterial MutS proteins—and by inference MSH6 proteins—non-specifically bind the backbone of mismatched DNA, raising new questions as to how clamp domains enhance mismatch recogni tion. Plants must rigorously suppress mutation during mitotic division of meristematic cells that eventually give rise to gametes and may also use MMR proteins to antagonize homeologous recombination. The MSH6 versus MSH7 divergence may reflect specializations for particular mismatches and/or sequence contexts, so as to increase both DNA-replication and meiotic-recombination fidelity, or dedication of MSH6 to the former and MSH7 to the latter, consistent with genetic evidence from wheat.
Facile One‐Step Micropatterning Using Photodegradable Gelatin Hydrogels for Improved Cardiomyocyte Organization and Alignment

Hydrogels are often employed as temporary platforms for cell proliferation and tissue organization in vitro. Researchers have incorporated photodegradable (PD) moieties into synthetic polymeric hydrogels as a means of achieving spatiotemporal control over material properties. In this study protein‐based PD hydrogels composed of methacrylated gelatin and a crosslinker containing o‐nitrobenzyl ester groups are developed. The hydrogels are able to degrade rapidly and specifically in response to UV light and can be photopatterned to a variety of shapes and dimensions in a one‐step process. Micropatterned PD hydrogels are shown to improve cell distribution, alignment, and beating regularity of cultured neonatal rat cardiomyocytes. Overall this work introduces a new class of PD hydrogel based on natural and biofunctional polymers as cell culture substrates for improving cellular organization and function.
Dissociated and Reconstituted Cartilage Microparticles in Densified Collagen Induce Local hMSC Differentiation

Current use of decellularized articular cartilage as a regenerative platform suffers from limited implant diffusion characteristics and cellular infiltration. Attempts to address this concern using decellularized cartilage microparticles allow for customized implant shape, tailored porosity, and improved cell infiltration. However, these developments utilize severe crosslinking agents that adversely affect cell differentiation, and fail to attain clinically relevant mechanical properties required for the implant survival. These issues have been overcome through the formation of a composite approach, combining the advantages of mature, decellularized tissue with tunable features of a reconstituted collagen hydrogel system. Through the application of a plastic compression regime, cellularized composite structures are formed that exceeded the percolation threshold of the cartilage microparticles and exhibited clinically relevant mechanical properties. Chemical reduction and mechanical reconstitution methods to investigate the contributions of glycosaminoglycan and collagenous components to chondrogenic induction and matrix properties have been utilized. With the inclusion of human mesenchymal stem cells into the composite system, microenvironment‐dependent cell morphology and phenotype when in contact with cartilage microparticles are shown. This work demonstrates a cartilage microparticle composite matrix with clinically relevant mechanical properties, and chondrogenic differentiation of human mesenchymal stem that infiltrate both native and chemically reduced cartilage microparticles.
Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs

Bioprinting is the most convenient microfabrication method to create biomimetic three‐dimensional (3D) cardiac tissue constructs, that can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, a gold nanorod (GNR)‐incorporated gelatin methacryloyl (GelMA)‐based bioink is developed for printing 3D functional cardiac tissue constructs. The GNR concentration is adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentrations of GNR, the nanocomposite bioink has a low viscosity, similar to pristine inks, which allows for the easy integration of cells at high densities. As a result, rapid deposition of cell‐laden fibers at a high resolution is possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells show improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridge the electrically resistant pore walls of polymers, improve the cell‐to‐cell coupling, and promote synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering.
The Pfam protein families database

Pfam is a large collection of protein families and domains. Over the past 2 years the number of families in Pfam has doubled and now stands at 6190 (version 10.0). Methodology improvements for searching the Pfam collection locally as well as via the web are described. Other recent innovations include modelling of discontinuous domains allowing Pfam domain definitions to be closer to those found in structure databases. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://Pfam.cgb.ki.se/).
Patterns of renal disease in Indigenous Populations

In China, mesangial proliferative glomerulonephritis (MsPGN) is the most common cause in patients presenting with primary nephrotic syndrome (NS, 40%), with isolated proteinuria (IP) (45%), or with haematuria (HU, 80%). Once all recognized secondary causes of mesangial lesions are excluded (including the resolving stage of postinfectious glomerulonephritis, such as post-streptococcal glomerulonephritis, and the glomerular lesions of systemic diseases) the term of primary MsPGN is used. The predominant pathologic change is diffuse mesangial cell proliferation and mesangial matrix expansion to a variable extent. This is always combined with focal or extensive glomerulosclerosis, tubular atrophy and interstitial cellularity and fibrosis in the advanced cases. Immunopathological studies with special antibodies to PCNA and a-SM-actin confirmed the histopathological mesangial finding of cell proliferation. Further, study with antibodies to the different components of the extracellular matrix (ECM) (i.e. FN, LN, Col-111 and IV) revealed an increase of ECM, combined with increased expression of TGF-P in different stages of MsPGN. Two different patterns of immunoglobin are detected: predominant IgA deposition or predominant IgG, IgM, C3, Clq depositions. The clinical manifestation of IgA-positive MsPGN was different from non-IgA MsPGN. IgA MsPGN was seen mainly in HU patients (40% of our HU cases), but in a relatively small number of cases of NS and IP (10% of each group). In contrast, non-IgA MsPGN occurred in 30% of NS and 35% of IP in our cases. A uniquely high prevalence of IgG-predominant MsPGN can be found readily in Chinese medical articles (58.7% in our non-IgA MsPGN cases), which suggests that there might be an association of non-IgA MSPGN with some as yet unidentified environmental or toxic factor. The immunopathologic categories of rapidly progressive glomerulonephritis (RPGN ) have been examined in 29 hospitalized patients during January 1991 to October 1996. Among them, there were 4 cases of Type I (14%), 14 cases of Type I1 (48%), 9 cases of Type 111 (32%), and
Immune dysregulation of pemphigus in humans and mice

Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes that is caused by immunoglobulin (Ig)G autoantibodies against the cadherin‐type adhesion molecule desmoglein (Dsg)3 expressed on stratified epithelial cells. Interaction between antigen‐specific T and B cells, which is selectively achieved through T‐cell receptor/major histocompatibility complex–peptide complex association and subsequently corroborated by co‐stimulatory molecules such as CD40/CD154, is required for production of pathological anti‐desmoglein 3 antibody. Some genetically and environmentally susceptible individuals harbor desmoglein reactive B and T cells, and anti‐desmoglein antibodies were detected in their serum. Analysis of the anti‐desmoglein antibody clones derived from pemphigus patients or pemphigus model mice revealed that pathogenic antibodies mostly react with conformational epitopes on mature form desmogleins, whereas non‐pathogenic ones tend to react with non‐conformational epitopes. Surprisingly, antibodies to the Dsg1 precursor pro‐protein are also cloned from individuals without pemphigus. These observations suggest that active suppression by regulatory cell subsets is dominant in these susceptible individuals. In fact, Dsg‐reactive T‐inducible regulatory type 1 (Tr1) cells are readily detected in healthy carriers of pemphigus‐related human leukocyte antigen haplotypes, but rarely in pemphigus patients. These Tr1 cells can be functionally converted to T‐helper 2‐like cells which secrete interleukin‐2 by inactivation of Foxp3 through antisense oligonucleotides. Thus, delicate balance between self‐reactive lymphocytes and regulatory T cells may be a key element in determining whether individuals produce pathogenic antibodies and develop pemphigus phenotypes or not.
Efeito da administração do Allium sativum sobre as alterações cardiovasculares de ratos Wistar com infarto do miocárdio.

O alho (Allium sativum) apresenta varias acoes beneficas ao sistema circulatorio, tais como diminuicao dos niveis de colesterol total, LDL-colesterol e da pressao arterial, alem de efeito antioxidante. O objetivo deste estudo foi avaliar o efeito da administracao do Allium sativum sobre as alteracoes da hemodinâmica cardiovascular e estruturais macroscopicas do coracao de animais com infarto induzido experimentalmente. Ratos Wistar foram tratados, previamente e apos inducao do infarto, com homogeneizado de alho na dose de 125mg/Kg/dia durante 21 dias, por via oral (uma semana antes e duas depois do procedimento de infarto). Os grupos controle passaram por cirurgia ficticia (SHAM). Os animais foram divididos em grupos controles e infartados com (SHAMT, INFT; respectivamente) ou sem (SHAM, INF; respectivamente) tratamento com alho. Houve reducao da hipertrofia do ventriculo direito (INF=0,75±0,05 vs. INFT=0,61±0,03 mg/Kg; p<0,01), da area de infarto (INF=29,7±4,8% vs. INFT=20,4±1,4%; p<0,05) e regularizacao dos niveis de pressao arterial sistolica (PAS; INF=100±8 vs. INFT=127±7 mmHg; p<0,05) e media (PAM; INF=94±4 vs. INFT=110±6 mmHg; p<0,01) dos animais INFT comparados com os INF. Houve um menor numero de animais mortos apos o procedimento de infarto no grupo INFT em relacao ao grupo INF (20%, n=2; 45,5%, n=5; respectivamente). Esses achados indicam que o alho tem um importante papel na prevencao e no controle de alteracoes cardiovasculares, uma vez que houve reducao do numero de mortes pos-infarto e melhor perfil cardiovascular dos animais INFT. Palavras-chave: Allium sativum. Infarto do miocardio.Hipertrofia cardiaca. Hemodinâmica cardiovascular.
Underwater‐Transparent Nanodendritic Coatings for Directly Monitoring Cancer Cells

Underwater-transparent nanodendritic coatings are easily fabricated by a three-step template process. After modification with anti-EpCAM, the coatings exhibit the capability for efficiently capturing rare number of cancer cells from whole blood. On the other hand, the unique underwater transparency enables the coatings to directly monitor captured cancer cells by optical imaging.
Laser 3D Printing with Sub‐Microscale Resolution of Porous Elastomeric Scaffolds for Supporting Human Bone Stem Cells

A reproducible method is needed to fabricate 3D scaffold constructs that results in periodic and uniform structures with precise control at sub‐micrometer and micrometer length scales. In this study, fabrication of scaffolds by two‐photon polymerization (2PP) of a biodegradable urethane and acrylate‐based photoelastomer is demonstrated. This material supports 2PP processing with sub‐micrometer spatial resolution. The high photoreactivity of the biophotoelastomer permits 2PP processing at a scanning speed of 1000 mm s−1, facilitating rapid fabrication of relatively large structures (>5 mm3). These structures are custom printed for in vitro assay screening in 96‐well plates and are sufficiently flexible to enable facile handling and transplantation. These results indicate that stable scaffolds with porosities of greater than 60% can be produced using 2PP. Human bone marrow stromal cells grown on 3D scaffolds exhibit increased growth and proliferation compared to smooth 2D scaffold controls. 3D scaffolds adsorb larger amounts of protein than smooth 2D scaffolds due to their larger surface area; the scaffolds also allow cells to attach in multiple planes and to completely infiltrate the porous scaffolds. The flexible photoelastomer material is biocompatible in vitro and is associated with facile handling, making it a viable candidate for further study of complex 3D‐printed scaffolds.
Regulation of the large (∼1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn

Most cases of Angelman syndrome (AS) result from loss or inactivation of ubiquitin protein ligase 3A (UBE3A), a gene displaying maternal-specific expression in brain. Epigenetic silencing of the paternal UBE3A allele in brain appears to be mediated by a non-coding UBE3A antisense (UBE3A-ATS). In human, UBE3A-ATS extends approximately 450 kb to UBE3A from the small nuclear ribonucleoprotein N (SNURF/SNRPN) promoter region that contains a cis-acting imprinting center (IC). The concept of a single large antisense transcript is difficult to reconcile with the observation that SNURF/SNRPN shows a ubiquitous pattern of expression while the more distal part of UBE3A-ATS, which overlaps UBE3A, is brain specific. To address this problem, we examined murine transcripts initiating from several alternative exons dispersed within a 500 kb region upstream of Snurf/Snrpn. Similar to Ube3a-ATS, these upstream (U) exon-containing transcripts are expressed at neuronal stages of differentiation in a cell culture model of neurogenesis. These findings suggest the novel hypothesis that brain-specific transcription of Ube3a-ATS is regulated by the U exons rather than Snurf/Snrpn exon 1 as previously suggested from human studies. In support of this hypothesis, we describe U-Ube3a-ATS transcripts where U exons are spliced to Ube3a-ATS with the exclusion of Snurf-Snrpn. We also show that the murine U exons have arisen by genomic duplication of segments that include elements of the IC, suggesting that the brain specific silencing of Ube3a is due to multiple alternatively spliced IC-Ube3a-ATS transcripts.
Coupling Freshly Isolated CD44+ Infrapatellar Fat Pad‐Derived Stromal Cells with a TGF‐β3 Eluting Cartilage ECM‐Derived Scaffold as a Single‐Stage Strategy for Promoting Chondrogenesis

An alternative strategy to the use of in vitro expanded cells in regenerative medicine is the use of freshly isolated stromal cells, where a bioactive scaffold is used to provide an environment conducive to proliferation and tissue‐specific differentiation in vivo. The objective of this study is to develop a cartilage extracellular matrix (ECM)‐derived scaffold that could facilitate the rapid proliferation and chondrogenic differentiation of freshly isolated stromal cells. By freeze‐drying cryomilled cartilage ECM of differing concentrations, it is possible to produce scaffolds with a range of pore sizes. The migration, proliferation, and chondrogenic differentiation of infrapatellar fat pad‐derived stem cells (FPSCs) depend on the concentration/porosity of these scaffolds, with greater sulphated glycosaminoglycan (sGAG) accumulation observed in scaffolds with larger‐sized pores. It is then sought to determine if freshly isolated fat pad‐derived stromal cells, seeded onto a transforming growth factor (TGF)‐β3 eluting ECM‐derived scaffold, could promote chondrogenesis in vivo. While a more cartilage‐like tissue could be generated using culture expanded FPSCs compared to nonenriched freshly isolated cells, fresh CD44+ stromal cells are capable of producing a tissue in vivo that stained strongly for sGAGs and type II collagen. These findings open up new possibilities for in‐theatre cell‐based therapies for joint regeneration.
Flicker-Defined Forms in the Ternus Display

Odic and Pratt (2008, Perception, 37, 1790–1804) proposed that the type of movement seen in the bistable Ternus display depends on the elements' temporal summation of contrast relative to the background. To test this theory, participants viewed a flicker-defined Ternus display where the elements had no temporal summation of contrast. Participants also viewed a luminance-defined control condition. Five interstimulus intervals (ISIs) (0, 20, 40, 60, and 80 ms) and two stimulus durations (SDs) (200 and 400 ms) were used in each condition. If temporal summation of contrast does not influence perceived group and end-to-end movement in flicker-defined forms, it was expected that the frequency of their reports would be equal to those in the luminance- defined control condition at the same ISIs and SDs. As predicted, the main effect of condition was not significant and participants reported both percepts at expected rates in both conditions, contrary to the predictions of Odic and Pratt (2008).