Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical behavior in living cells consistent with the tensegrity model

Alternative models of cell mechanics depict the living cell as a simple mechanical continuum, porous filament gel, tensed cortical membrane, or tensegrity network that maintains a stabilizing prestress through incorporation of discrete structural elements that bear compression. Real-time microscopic analysis of cells containing GFP-labeled microtubules and associated mitochondria revealed that living cells behave like discrete structures composed of an interconnected network of actin microfilaments and microtubules when mechanical stresses are applied to cell surface integrin receptors. Quantitation of cell tractional forces and cellular prestress by using traction force microscopy confirmed that microtubules bear compression and are responsible for a significant portion of the cytoskeletal prestress that determines cell shape stability under conditions in which myosin light chain phosphorylation and intracellular calcium remained unchanged. Quantitative measurements of both static and dynamic mechanical behaviors in cells also were consistent with specific a priori predictions of the tensegrity model. These findings suggest that tensegrity represents a unified model of cell mechanics that may help to explain how mechanical behaviors emerge through collective interactions among different cytoskeletal filaments and extracellular adhesions in living cells.
Marshall J. Edwards: discoverer of maternal hyperthermia as a human teratogen.

In a series of animal studies performed over a career spanning 40 years at the University of Sydney, Professor Marshall J. Edwards investigated the hypothesis that maternal hyperthermia during gestation can be teratogenic to the developing fetus. He is one of few investigators to have discovered a known human teratogen primarily through animal studies. In 1970 he earned his Ph.D. from the University of Sydney, writing a doctoral thesis entitled "A Study of Some Factors Affecting Fertility of Animals with Particular Reference to the Effects of Hyperthermia on Gestation and Prenatal Development of the Guinea-Pig. " He went on to prove that hyperthermia-induced malformations in animals involve many organs and structures, particularly the central nervous system. Other defects include craniofacial anomalies, heart defects and hypodactyly, cataracts and coloboma, kyphoscoliosis, renal anomalies, dental agenesis, and abdominal wall defects. In a series of carefully planned and executed experiments, he demonstrated that the type of defect is related to the timing of the hyperthermic insult, and analyzed the underlying mechanisms. Cell death, membrane disruption, vascular disruption, and placental infarction were all implicated in causing embryonic damage. This special article reviews the scientific discoveries and personal philosophy of Marshall J. Edwards, the discoverer of maternal hyperthermia as a human teratogen.
Responses to Free Lipopolysaccharide and Escherichia coli by Normal Human Intestinal Macrophages, Following their Migration out of the Lamina Propria

Intestinal macrophage responses to luminal bacteria and their constituents are important in mucosal inflammatory responses. We investigated the responses of intestinal macrophages to free lipopolysaccharide (LPS) and Escherichia coli. Macrophages were isolated from normal terminal ileum and colon by allowing them to migrate out of the lamina propria of mucosal samples denuded of epithelial cells. Following exposure to free LPS or fluorescein‐labelled E. coli, responsiveness was studied by intracellular expression of tumour necrosis factor‐α (TNF‐α). CD14, CD33, CD68, TLR2 and TLR4 expression was studied by fluorescence‐activated cell sorter (FACS). TLR and NOD2 expression was confirmed by reverse‐transcriptase polymerase chain reaction (RT‐PCR). CD14 was expressed by 36.5 ± 4.0% of the macrophages obtained following migration out of the lamina propria. These cells also expressed TLR2, TLR4 and NOD2. Of cells exposed to free LPS or those that had taken up E. coli, a greater proportion of CD14+ than CD14– macrophages expressed intracellular TNF‐α. Moreover, a greater proportion of macrophages (CD14+ and CD14–) demonstrated responses to E. coli than free LPS. In conclusion, a proportion of macrophages obtained following migration out of the lamina propria of normal terminal ileal and colonic mucosal samples express CD14, TLR2 and TLR4. These cells respond to free LPS and E. coli, as demonstrated by the expression of TNF‐α.
The implantable loop recorder in children

Objective: To evaluate use of the implantable loop recorder in children. Setting: Royal Hospital for Sick Children, Glasgow, UK. Method: Retrospective study of children who had an implantable loop recorder between September 1998 and October 2005. Results: 38 devices were implanted in 34 children. Median age at implantation 11.3 years (range 1.8–17.6); median follow-up period 15 months (range 2–58). The main presenting complaint was syncope in 26 (76.5%), seizures in 6 (17.6%) and palpitations in 2 (5.9%). After implantation, 19 (55.9%) patients had symptom recurrence. Of these, 11 were shown to have sinus rhythm during symptoms and 8 had an abnormal ECG. Four patients had asystole >3 seconds and were diagnosed with reflex asystolic syncope; 2 had polymorphic ventricular tachycardia. One patient who already had a diagnosis of long QT syndrome was shown to have ventricular ectopy during symptoms and β-blockers were increased. One patient had transient complete heart block during symptoms but refused a pacemaker. In almost half the patients (44.1%), symptoms resolved after implantation. Complications requiring removal of the device occurred in 6 (15.8%) implants. Conclusions: In children with syncope and palpitations, the implantable loop recorder appears to be an excellent method of effecting a “cure” in almost 50% of subjects. For those who remain symptomatic, it is successful in determining cardiac rhythm during symptoms, but the complication rate in children may be higher than that of adults.
Optimized donor management and organ preservation before kidney transplantation

Kidney transplantation is a major medical improvement for patients with end‐stage renal disease, but organ shortage limits its widespread use. As a consequence, the proportion of grafts procured from extended criteria donors (ECD) has increased considerably, but this comes along with increased rates of delayed graft function (DGF) and a higher incidence of immune‐mediated rejection that limits organ and patient survival. Furthermore, most grafts are derived from brain dead organ donors, but the unphysiological state of brain death is associated with significant metabolic, hemodynamic, and pro‐inflammatory changes, which further compromise patient and graft survival. Thus, donor interventions to preserve graft quality are fundamental to improve long‐term transplantation outcome, but interventions must not harm other potentially transplantable grafts. Several donor pretreatment strategies have provided encouraging results in animal models, but evidence from human studies is sparse, as most clinical evidence is derived from single‐center or nonrandomized trials. Furthermore, ethical matters have to be considered especially concerning consent from donors, donor families, and transplant recipients to research in the field of donor treatment. This review provides an overview of clinically proven and promising preclinical strategies of donor treatment to optimize long‐term results after kidney transplantation.
The real response of bone to exercise

This review presents findings made in studies of large mammalian bones, especially from racehorse training experiments (2–8 years old, third metacarpal, tarsal) and human autopsy orthopaedic femoral implant retrievals and other human biopsy and autopsy cases. Samples were cleaned to analyse mineralized matrix in three dimensions, or poly methyl‐methacrylate embedded and micromilled to delete topography and study the superficial c. 0.5‐µm two‐dimensional section using quantitative backscattered electron imaging. With experimental implant studies in rabbits, observations were also made in vivo using confocal microscopy. Cracks in both calcified cartilage and bone may be removed by infilling with calcified matrix. This may be a general repair mechanism for calcified connective tissue crack repair. The fraction of the organ volume occupied by any form of bone tissue in equine distal third metacarpal extremities was increased in the more exercised groups by bone deposited within former marrow adipocytic space. Where deposited upon prior lamellar bone surfaces, this occurred without the intervention of prior resorption and without the formation of a hypermineralized cement line. Exercise inhibited osteoclastic resorption at external anatomical growth modelling sites where it normally occurs. Addition is not coupled to time‐wasting resorption: both internally and externally, it occurs both by layering on existing cancellous surfaces and by creation of new immature scaffold, with de novo incorporation of a rich, capillary blood vessel supply. The real response within bone organs subjected to mechanical overload exercise within normal physiological limits is to make more, and to lose less, bone.
Stress situation reveals an association between perfectionism and drive for thinness.

OBJECTIVE Several theorists have hypothesized that stress situations may trigger abnormal eating and even eating disorders in individuals with a perfectionistic personality. The purpose of this study was to assess whether a stress situation would reveal an association between perfectionism and measures of eating disorders among female high school students. METHODS A sample of 42 female high school students completed the Multidimensional Perfectionism Scale and the Eating Disorder Inventory three times: on an average school day, on the day of an examination, and on the day they received the evaluation of the examination. Linear regression analysis was calculated to verify whether the dimensions of perfectionism were associated with the measures of eating disorders. RESULTS Body Dissatisfaction was associated with perfectionism on all the three occasions, whereas Drive for Thinness was associated with perfectionism only on the day the students received the results of the examination. DISCUSSION The results suggest that among nonclinical female individuals, stress may make significant a previously absent association between perfectionism and an actual desire or plan to lose weight. Such a finding suggests that stress may stimulate behaviors related to eating disorders in individuals with a perfectionistic personality.
Enzyme-linked immunosorbent assay for detection of Staphylococcus epidermidis antibody in experimental S. epidermidis endocarditis

The immune response against Staphylococcus epidermidis, as determined by an enzyme-linked immunosorbent assay, was evaluated in experimental S. epidermidis infections in rabbits. Antigens from 8 of 10 clinical S. epidermidis strains detected significant antibody production in five rabbits immunized with different strains of S. epidermidis and in five of six rabbits with experimental endocarditis caused by four different strains. The antigens from two strains detected antibody production in all rabbits, and strain ATCC 14990 discriminated best between positive and negative samples. Consecutive blood samples from rabbits with endocarditis and control rabbits with bacteremia, which were successfully prevented from developing endocarditis by using prophylactic antibiotics, were examined by using an enzyme-linked immunosorbent assay and an ultrasonic extract of strain ATCC 14990 as the antigen. This assay discriminated between rabbits with endocarditis and rabbits with uncomplicated bacteremia. Antibody production was detected as early as 3 days after the onset of infection in rabbits with endocarditis.
The First Laparoscopic Cholecystectomy

Prof Dr Med Erich Mühe of Böblingen, Germany, performed the first laparoscopic cholecystectomy on September 12, 1985. The German Surgical Society rejected Mühe in 1986 after he reported that he had performed the first laparoscopic cholecystectomy, yet in 1992 he received their highest award, the German Surgical Society Anniversary Award. In 1990 in Atlanta, at the Society of American Gastrointestinal Surgeons (SAGES) Convention, Perissat, Berci, Cuschieri, Dubois, and Mouret were recognized by SAGES for performing early laparoscopic cholecystectomies, but Mühe was not. However, in 1999 he was recognized by SAGES for having performed the first laparoscopic cholecystectomy–sAGES invited Mühe to present the Storz Lecture. In Mühe's presentation, titled “The First Laparoscopic Cholecystectomy,” which he gave in March 1999 in San Antonio, Texas, he described the first procedure. Finally, Mühe had received the worldwide acclaim that he deserved for his pioneering work. One purpose of this article is to trace the development of the basic instruments used in laparoscopic cholecystectomy. The other purpose is to give Mühe the recognition he deserves for being the developer of the laparoscopic cholecystectomy procedure.
VeryGene: linking tissue-specific genes to diseases, drugs, and beyond for knowledge discovery.

In addition to many other genes, tissue-specific genes (TSGs) represent a set of genes of great importance for human physiology. However, the links among TSGs, diseases, and potential therapeutic agents are often missing, hidden, or too scattered to find. There is a need to establish a knowledgebase for researchers to share this and additional information in order to speed up discovery and clinical practice. As an initiative toward systems biology, the VeryGene web server was developed to fill this gap. A significant effort has been made to integrate TSGs from two large-scale data analyses with respective information on subcellular localization, Gene Ontology, Reactome, KEGG pathway, Mouse Genome Informatics (MGI) Mammalian Phenotype, disease association, and targeting drugs. The current release carefully selected 3,960 annotated TSGs derived from 127 normal human tissues and cell types, including 5,672 gene-disease and 2,171 drug-target relationships. In addition to being a specialized source for TSGs, VeryGene can be used as a discovery tool by generating novel inferences. Some inherently useful but hidden relations among genes, diseases, drugs, and other important aspects can be inferred to form testable hypotheses. VeryGene is available online at http://www.verygene. com.
Kinetic Analysis of Human Immunodeficiency Virus Type 1 Assembly Reveals the Presence of Sequential Intermediates

ABSTRACT The assembly and budding of lentiviruses, such as human immunodeficiency virus type 1 (HIV-1), are mediated by the Gag protein precursor, but the molecular details of these processes remain poorly defined. In this study, we have combined pulse-chase techniques with density gradient centrifugation to identify, isolate, and characterize sequential kinetic intermediates in the lentivirus assembly process. We show that newly synthesized HIV-1 Gag rapidly forms cytoplasmic protein complexes that are resistant to detergent treatment, sensitive to protease digestion, and degraded intracellularly. A subpopulation of newly synthesized Gag binds membranes within 5 to 10 min and over several hours assembles into membrane-bound complexes of increasing size and/or density that can be resolved on Optiprep density gradients. These complexes likely represent assembly intermediates because they are not observed with assembly-defective Gag mutants and can be chased into extracellular viruslike particles. At steady state, nearly all of the Gag is present as membrane-bound complexes in various stages of assembly. The identification of sequential assembly intermediates provides the first demonstration that HIV-1 particle assembly proceeds via an ordered process. Assembly intermediates should serve as attractive targets for the design of antiviral agents that interfere with the process of particle production.
Widespread immunoreactivity for neuronal nuclei in cultured human and rodent astrocytes

The monoclonal antibody (mAb) neuronal nuclei (NeuN) labels the nuclei of mature neurons in vivo in vertebrates. NeuN has also been used to define post‐mitotic neurons or differentiating neuronal precursors in vitro. In this study, we demonstrate that the NeuN mAb labels the nuclei of astrocytes cultured from fetal and adult human, newborn rat, and embryonic mouse brain tissue. A non‐neuronal fibroblast cell line (3T3) also displayed NeuN immunoreactivity. We confirmed that NeuN labels neurons but not astrocytes in sections of P10 rat brain. Western blot analysis of NeuN immunoreactive species revealed a distribution of bands in nucleus‐enriched fractions derived from the different cell lines that was similar, but not identical to adult rat brain homogenates. We then examined the hypothesis that the glial fibrillary acidic protein/NeuN‐double positive population of cells might correspond to neuronal precursors. Although the NeuN‐positive astrocytes were proliferating, no evidence of neurogenesis was detected. Furthermore, expression of additional neuronal precursor markers was not detected. Our results indicate that primary astrocytes derived from mouse, rat, and human brain express NeuN. Our findings are consistent with NeuN being a selective marker of neurons in vivo, but indicate that studies utilizing NeuN‐immunoreactivity as a definitive marker of post‐mitotic neurons in vitro should be interpreted with caution.
Membrane type-1 matrix metalloproteinase activity is regulated by the endocytic collagen receptor Endo180

The molecular interactions leading to organised, controlled extracellular matrix degradation are of central importance during growth, development and tissue repair, and when deregulated contribute to disease processes including cancer cell invasion. There are two major pathways for collagen degradation: one dependent on secreted and membrane-bound collagenases, the other on receptor-mediated collagen internalisation and intracellular processing. Despite the established importance of both pathways, the functional interaction between them is largely unknown. We demonstrate here, that the collagen internalisation receptor Endo180 (also known as CD280, uPARAP, MRC2) is a novel regulator of membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP-2 activation and urokinase plasminogen activator (uPA) activity. We show close correlation between Endo180 expression, collagen accumulation and regulation of MT1-MMP cell-surface localisation and activity. We directly demonstrate, using collagen inhibition studies and non-collagen-binding mutants of Endo180, that the molecular mechanism underlying this regulation is the ability of Endo180 to bind and/or internalise collagens, rather than by acting as an interaction partner for pro-uPA and its receptor uPAR. These studies strongly support a functional interaction between two distinct collagen degradation pathways, define a novel mechanism regulating MT1-MMP activity and might have important implications for organised collagen clearance in the pericellular environment.
Diversity, distribution and sources of bacteria in residential kitchens.

Bacteria readily colonize kitchen surfaces, and the exchange of microbes between humans and the kitchen environment can impact human health. However, we have a limited understanding of the overall diversity of these communities, how they differ across surfaces and sources of bacteria to kitchen surfaces. Here we used high-throughput sequencing of the 16S rRNA gene to explore biogeographical patterns of bacteria across > 80 surfaces within the kitchens of each of four households. In total, 34 bacterial and two archaeal phyla were identified, with most sequences belonging to the Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. Genera known to contain common food-borne pathogens were low in abundance but broadly distributed throughout the kitchens, with different taxa exhibiting distinct distribution patterns. The most diverse communities were associated with infrequently cleaned surfaces such as fans above stoves, refrigerator/freezer door seals and floors. In contrast, the least diverse communities were observed in and around sinks, which were dominated by biofilm-forming Gram-negative lineages. Community composition was influenced by conditions on individual surfaces, usage patterns and dispersal from source environments. Human skin was the primary source of bacteria across all kitchen surfaces, with contributions from food and faucet water dominating in a few specific locations. This study demonstrates that diverse bacterial communities are widely distributed in residential kitchens and that the composition of these communities is often predictable. These results also illustrate the ease with which human- and food-associated bacteria can be transferred in residential settings to kitchen surfaces.
Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters

The human T-lymphotropic viruses (HTLVs) types 1 and 2 originated independently and are related to distinct lineages of simian T-lymphotropic viruses (STLV-1 and STLV-2, respectively). These facts, along with the finding that HTLV-1 diversity appears to have resulted from multiple cross-species transmissions of STLV-1, suggest that contact between humans and infected nonhuman primates (NHPs) may result in HTLV emergence. We investigated the diversity of HTLV among central Africans reporting contact with NHP blood and body fluids through hunting, butchering, and keeping primate pets. We show that this population is infected with a wide variety of HTLVs, including two previously unknown retroviruses: HTLV-4 is a member of a phylogenetic lineage that is distinct from all known HTLVs and STLVs; HTLV-3 falls within the phylogenetic diversity of STLV-3, a group not previously seen in humans. We also document human infection with multiple STLV-1-like viruses. These results demonstrate greater HTLV diversity than previously recognized and suggest that NHP exposure contributes to HTLV emergence. Our discovery of unique and divergent HTLVs has implications for HTLV diagnosis, blood screening, and potential disease development in infected persons. The findings also indicate that cross-species transmission is not the rate-limiting step in pandemic retrovirus emergence and suggest that it may be possible to predict and prevent disease emergence by surveillance of populations exposed to animal reservoirs and interventions to decrease risk factors, such as primate hunting.
Maternal behaviour in sheep and its neuroendocrine regulation

Non‐parturient sheep, hormonally primed and presented with newborn lambs are, at best, indifferent to them and if approached by the lamb may show violent rejection. However, non‐gestant ewes primed with oestrogen and progesterone, but given vaginocervical stimulation, do show a rapid onset in maternal behaviour. This stimulation is ineffective in promoting maternal behaviour with epidural anaesthesia. Vaginocervical stimulation increases the release of oxytocin into cerebrospinal fluid and in‐vivo microdialysis has revealed high levels of oxytocin release in limbic brain areas known to be important for maternal behaviour. Oxytocin, when given intraventricularly, produces the full complement of acceptance and suckling behaviour in non‐gestant ewes. Although ineffective when given alone, opioids potentiate the release of oxytocin in the limbic brain and increase the intensity of maternal responding, while the opioid receptor blocker, naltrexone, prevents both maternal induction and oxytocin release. This neural basis for maternally motivated behaviour may be equally relevant to human behaviour, although the mechanisms available for addressing these peptidergic systems have clear differences.