julilili42/papers huggingface dataset:
Single‐Molecule Imaging: Defocused Wide‐field Imaging Unravels Structural and Temporal Heterogeneity in Complex Systems (Adv. Mater. 10–11/2009)
2009-03-12

The front cover shows an artist's impression of a conjugated polyfluorene polymer doped with perylene-diimide fluorophores. The blue luminescence of the fluorenes is transferred to the PDI moieties, allowing spectral tuning of the emission. This process is difficult to quantify due to the large structural freedom of the polymer chains. In their article on p. 1079, Johan Hofkens and co-workers describe how single-molecule imaging can tackle this complexity.
Aquaporins and their significance in otorhinolaryngology
2009-03-12

Fast and proper regulated water transport across cell membranes is important for the normal function of organs. Water channels, called aquaporins (AQPs), are involved in this process. AQPs play a role in the mucus and saliva secretion. They are also involved in maintaining inner ear fluid homeostasis. The discovery of AQPs gives new opportunities for the pharmacological treatment of rhinitis, bronchitis, mucoviscidosis, sialoadenitis and Sjögren’s syndrome. ---------------------------------------- Бързият и регулиран транспорт на водата през клетъчната мембрана е от изключителна важност за нормалното функциониране на органите. Той се осъществява от специализирани водни канали, наречени аквапорини (AQP). Аквапорините имат важно участие в секретирането на слуз и на слюнка. Те са ангажирани и в поддържане постоянството на състава и обема на системата от течности във вътрешното ухо. Откритието на аквапорините отваря възможности за разработване на нови терапевтични подходи при заболявания като ринит, бронхит, муковисцидоза, сиалоаденит и синдром на Sjögren.
Competition and a short growing season lead to ecotypic differentiation at the two extremes of the ecological range
2009-03-13

1 Local adaptation is a major factor shaping a species' range. Studies on adaptation to local abiotic conditions are numerous, but adaptation to neighbour conditions has been almost neglected, and these two have rarely been separated experimentally. We hypothesized that adaptation to abiotic stress (e.g. fast development, drought resistance) dominates at the stressful end of the gradient, while adaptation to competition (e.g. large plant size) is more common at the benign end of the distribution range. 2 We conducted a reciprocal sowing experiment coupled with a removal experiment in the field for two winter annual grass species Bromus fasciculatus C. Presl. and Brachypodium distachyon (L.) Beauv. from Mediterranean and arid populations in Jordan. The two species were also grown under standard conditions for evaluating whether traits indicative of competitive ability and tolerance to stress are more common for either of the ecotypes. 3 Adaptation to abiotic stress could not be tested because our experiment was performed in a favourable year where water was not limiting in either of the sites. Competition was intense in both sites for the two populations of each species but competitive exclusion was observed only in the Mediterranean site. Mediterranean populations produced consistently more biomass and exhibited later onset of flowering than arid populations, both in the field and under standard conditions. 4 Mediterranean populations also showed better competitive response ability however stress tolerance was no different to that of arid populations. 5 This study indicates that competition and length of the growing season are major selective constraints at the two extremes of the ecological range along aridity gradients. We suggest that drought stress increases in importance during dry years and studies on local adaptation along climatic gradients may help predict the effect of global change on future species' distributions.
Mast cells: novel clinical perspectives from recent insights
2009-03-13

Abstract: Mast cells are still generally viewed as mediators of type I allergic or pseudoallergic reactions. Research over the past 10 years revealed that our view was too small and that mast cells are of key importance in innate immunity and also types II, III and IV adaptive immune reactions. Understanding their role in modulating and amplifying of inflammatory responses provides important insights into the pathogenesis of skin diseases such as psoriasis, atopic dermatitis, bullous pemphigoid or the control of infections. This helps us to understand the course of these diseases, their trigger mechanisms, and, the new role of agents, which can modulate the function of mast cells. These insights will help to develop new therapeutic approaches.
cGMP-Dependent Protein Kinase I Is Crucial for Angiogenesis and Postnatal Vasculogenesis
2009-03-13

Our findings demonstrate that the cGMP-cGKI pathway is critical for postnatal neovascularization and establish a new role for cGKI in vasculogenesis, which is mediated by bone marrow-derived progenitors.
Modulation of suicidal erythrocyte cation channels by an AMPA antagonist
2009-03-13

Abstract In neurons alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors are heteromeric cation channels composed of different sub‐units, including GluA1‐GluA4. When expressed without GluA2, AMPA receptors function as Ca 2+ ‐permeable cation channels. In erythrocytes, activation of Ca 2+ ‐permeable cation channels triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with subsequent exposure of phosphatidylserine at the cell surface. Activators of the channels and thus eryptosis include removal of extracellular Cl − (replaced by gluconate) and energy depletion (removal of glucose). The present study explored whether GluA1 is expressed in human erythrocytes and whether pharmacological AMPA receptor inhibition modifies Ca 2+ entry and suicidal death of human erythrocytes. GluA1 protein abundance was determined by confocal microscopy, phosphatidylserine exposure was estimated from annexin V binding, cell volume from forward scatter in FACS analysis, cytosolic Ca 2+ concentration from Fluo3 fluorescence and channel activity by whole‐cell patch‐clamp recordings. As a result, GluA1 is indeed expressed in the erythrocyte cell membrane. The AMPA receptor antagonist NBQX (1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxo‐benzo[f]quinoxaline‐7‐sulfonamide) inhibited the cation channels following Cl − removal and the eryptosis following Cl − removal or energy depletion. The present study reveals a novel action of AMPA receptor antagonists and raises the possibility that GluA1 or a pharmacologically related protein participates in the regulation of Ca 2+ entry into and suicidal death of human erythrocytes.
A combined experimental and theoretical study of the pH‐dependent binding mode of NAD+ by water‐soluble molecular clips
2009-03-13

Abstract The highly selective recognition process of NAD + and NADH (as important cofactors of many redox enzymes) by molecular clips in aqueous solution is studied systematically by a combined experimental and quantum‐chemical approach. The strongly pH‐dependent complexation‐induced 1 H NMR shifts of the guest molecule indicate that in buffered aqueous solution at pH = 7.2 the nicotinamide ring, the active site of NAD + , is preferentially bound inside the cavity of the molecular clip, whereas in pure water under slightly acidic conditions both units (the nicotinamide ring as well as the adenine moiety) are located outside the cavity. The latter finding is explained by a competing self‐aggregation of NAD + which prohibits the recognition process. In addition, the investigation of the NAD + fragments NMNA, NMN, and AMP as well as the comparison of measured and computed chemical shieldings provides information on possible binding modes. Under equal conditions the binding of NADH to the molecular clip is significantly weaker than that of NAD + , so that the oxidation states (NAD + /NADH) can be distinguished by the molecular clips. The nucleotides NMN and AMP are bound less strongly by the molecular clips than NAD + . The weaker binding indicates that multiple aromatic π − π and cation− π host–guest interactions only possible in NAD + have a synergetic effect on the complex stability. In addition to the inhibition of the cofactor NAD + , a further implication is the development of sensors since a quenching of fluorescence is observed for specific molecular clips by the addition of NAD + . Copyright © 2009 John Wiley &amp; Sons, Ltd.
Germline variation of the melanocortin‐1 receptor does not explain shared risk for melanoma and thyroid cancer
2009-03-13

Background: Recently, germline variants of the melanocortin‐1 receptor (MC1R) have been shown to be associated with an increased risk for BRAF mutant but not BRAF wild‐type cutaneous melanoma. Similar to melanoma, BRAF mutations are also commonly found in papillary thyroid carcinomas. Furthermore, patients with melanoma have an increased risk for thyroid carcinoma and vice versa. Methods: To determine whether MC1R variation also represents a risk factor for BRAF mutant thyroid carcinomas, we sequenced BRAF and MC1R in two separate case–control cohorts. Results: We demonstrate that MC1R is expressed in normal and neoplastic thyroid epithelial cells, albeit at lower levels than in melanocytes. In the first cohort of 66 follicular and 62 papillary thyroid carcinomas (PTC), and 128 matched controls from the San Francisco Bay Area we found no association between the number of MC1R variant alleles and thyroid cancer. Patients with BRAF‐mutated tumors had a higher frequency of MC1R variant alleles than their matched controls ( P = 0.039). However, contrary to the findings in melanoma, the odds ratio for having a BRAF mutant cancer decreased from 3.9 for carriers of one MC1R allele to 1.5 for carriers of two or more alleles. As the frequency of MC1R alleles varies highly among different ethnic populations, we analysed a second, ethnically more homogeneous cohort from Spain and Portugal, and found no association with PTC nor with BRAF‐mutated PTC. Conclusion: Our data indicate that the strong association between BRAF mutations and MC1R variants previously found in melanoma does not extend to thyroid cancer.
Serum- and Glucocorticoid-inducible Kinases (SGK) regulate KCNQ1/KCNE potassium channels
2009-03-15

The stress reaction includes the release of stress hormones such as cortisol via the HPA axis4. One of the genes regulated by cortisol is the serum- and glucocorticoid-inducible kinase 1 (SGK1) a stimulator of the slow outward potassium channel KCNQ1/KCNE1-one of the major mediators of cardiac repolarization. Apart from KCNE1, several other KCNE beta subunits including KCNE3 and KCNE5 have been detected at the mRNA level in cardiac tissue as well as in the inner ear and the gastro-intestinal tract. Here, we extend our previous investigations to KCNQ1/KCNE3 channels and their modulation by SGKs. We show that these channels are not stimulated by any of the three SGK isoforms when expressed in a heterologous expression system. 3D docking simulations suggest that crucial residues within KCNQ1 and KCNE1 are co-localized to a region close to the putative inner phase of the membrane, suggesting a key region important for channel complex sorting into vesicles. Identification of the KCNQ1/KCNE recycling pathway and its modulation by SGK provides a mechanistic insight into stress-induced modulation of KCNQ1/KCNE channels.
PET Imaging of Prostate Cancer Xenografts with a Highly Specific Antibody against the Prostate-Specific Membrane Antigen
2009-03-16

Because of the high and specific uptake of (64)Cu-labeled mAb 3/A12 in PSMA-positive tumors, this ligand represents an excellent candidate for prostate cancer imaging and potentially for radioimmunotherapy.
Long-term effects of chondrospheres on cartilage lesions in an autologous chondrocyte implantation model as investigated in the SCID mouse model
2009-03-16

Microtraumata often lead to articular cartilage lesions. Due to the bradytrophic character of hyaline cartilage, these lesions are hardly repaired by the organism. Autologous chondrocyte implantation (ACI) was established for restoring isolated structural cartilage defects in knee joints. However, results are not always convincing. Human chondrocytes from patients undergoing total knee arthroplasty were cultured in monolayer followed by condensing single chondrocytes to spheroids (chondrospheres). The integrative capacity of chondrospheres was examined by implanting them into lesions in human articular cartilage specimens and co-implanting them into SCID mice. Mice were sacrificed after 4, 12 and 24 weeks. HE and safranin O staining as well as immunohistochemistry using anti-S100, anti-collagen I and II antibodies were performed and analyzed using semiquantitative scores. Integration of the chondrospheres with the (native) cartilage matrix was analyzed by determining the percentage of adhering surface. With respect to long-term stability, the chondrocytes within chondrospheres showed a typical chondrocytic morphology. Immunohistochemically, a high collagen II production was detected. Over a time period of 24 weeks, an increasing content of collagen type II, glycosaminoglycans and collagenous fibers were found. Importantly, the newly synthesized cartilaginous matrix integrated continuously with the native cartilage lesion border. In conclusion, the presented data demonstrate that chondrospheres are able to restore and conserve their phenotype for at least 24 weeks under in vivo conditions. Moreover, chondrospheres adhere to full-thickness cartilage defects and appear to produce a cartilaginous extracellular matrix which fuses with native cartilage thus generating an autologous cartilage-like repair tissue.
Prevalence of oral pathologic findings in an ancient pre‐Columbian archeologic site in the Atacama Desert
2009-03-16

Objective: To determine the prevalence of oral pathologic findings in an ancient culture that inhabited the Atacama Desert. Materials and methods: A systematic examination was performed on the remains of 83 individuals unearthed from a prehistoric burial ground. A total of 57 skeletal remains achieved appropriate inclusion criteria, from which estimated age at death, gender, ante‐ and postmortem tooth loss, prevalence and location of caries, apical periodontitis sequela, alveolar bone resorption and attrition were recorded. Results: From the analyzed skeletal remains (13 male, 22 female and 22 not identifiable), the mean age estimated was 29.9 ± 13.8 years. A total of 89.4% of them presented permanent dentition with a mean ante‐mortem tooth loss of 9.0 teeth and a postmortem mean tooth loss of 14.4 teeth per subject. In all, 46.4% of the postmortem remaining permanent teeth ( n = 237) showed caries lesions. Interproximal caries was most frequently observed (31.5%), followed by occlusal (25.9%) and cervical caries (19.4%). Root remnants were found in 23.1% of the cases. In addition, 58.0% of the adults presented attrition, 26.0% signs of apical periodontitis and 44.0% loss of alveolar bone support &gt;5 mm. Conclusion: The remains of jaws and teeth of the individuals examined in this study presented sequelae of severe oral health damage due to caries and periodontal disease.
Size matters: Increased grey matter in boys with conduct problems and callous–unemotional traits
2009-03-17

Brain imaging studies of adults with psychopathy have identified structural and functional abnormalities in limbic and prefrontal regions that are involved in emotion recognition, decision-making, morality and empathy. Among children with conduct problems, a small subgroup presents callous-unemotional traits thought to be antecedents of psychopathy. No structural brain imaging study has examined this subgroup of children. The present study used voxel-based morphometry to compare whole brain grey matter volumes and concentrations of boys with elevated levels of callous-unemotional conduct problems and typically developing boys and explored four a priori regions of interest. sMRI scans were collected from 23 boys with elevated levels of callous-unemotional conduct problems (mean age = 11 years 8 months) and 25 typically developing boys (mean age = 11 years 6 months) selected from a community sample of children. Data were analysed using optimized voxel-based morphometry. Study-specific probability maps were created and four a priori regions of interest identified (orbitofrontal, anterior cingulate and anterior insular cortices and amygdala). Both grey matter volume and concentration were examined controlling for cognitive ability and hyperactivity-inattention symptoms. Boys with callous-unemotional conduct problems, as compared with typically developing boys, presented increased grey matter concentration in the medial orbitofrontal and anterior cingulate cortices, as well as increased grey matter volume and concentration in the temporal lobes bilaterally. These findings may indicate a delay in cortical maturation in several brain areas implicated in decision making, morality and empathy in boys with callous-unemotional conduct problems.
Regulation of mprF in Daptomycin-Nonsusceptible Staphylococcus aureus Strains
2009-03-17

ABSTRACT We used a well-characterized isogenic set of clinical bloodstream Staphylococcus aureus strains to study (i) regulation of mprF -mediated phosphatidylglycerol lysinylation in the contexts of in vitro daptomycin (DAP) nonsuceptibility and (ii) the role of mprF mutation in endovascular virulence. We observed a correlation between increased expression of a mutant mprF gene and reduced in vitro DAP susceptibility. There were no detectable fitness differences between strains in experimental infective endocarditis.
Geographical distribution of cryptic genetic types in the planktonic foraminifer Globigerinoides ruber
2009-03-17

Abstract We present SSU rDNA data resolving the seasonal and geographical distribution of ‘cryptic’ genetic types of the planktonic foraminifer morphospecies Globigerinoides ruber in the eastern Atlantic Ocean and the Mediterranean Sea. Analysis of 262 sequences revealed the presence of five genetic types belonging to two distinct lineages. Although the morphospecies G. ruber occurs throughout the investigated region, its constituent ‘cryptic’ genetic types show a pattern of widespread exclusion, which is difficult to reconcile with the concept of ubiquitous dispersal. One of the newly discovered genetic types was exclusively found at stations in the Mediterranean Sea, possibly representing the smallest‐scale example of endemism known in planktonic foraminifera. In general, our results suggest that the geographical scale of mutual exclusion between the genotypes is negatively correlated with their phylogenetic relatedness: the most similar and most recently diverged pair of siblings showed the strongest evidence for small‐scale competitive exclusion. This pattern is consistent with the concept of niche partitioning, implying decreasing level of competition between genetic types with increasing degree of genetic divergence.
The use of an innovative femur neck prosthesis in case of complications after hip fracture surgery
2009-03-17

The surgeon can notice severe arthrotic changes of the articulating surfaces of the hip joint during the osteosynthesis procedure. Facing a fracture of the proximal femur the surgeon should as first treat the fracture, then wait until its bony consolidation afterwards he has to decide what to do to cure the arthrotic hip. Normally the implant should be completely removed after a period of 12 months when a solidly fracture healing can be found and a so-called conventional hip prosthesis (cemented or cementless) has to be implanted. All these femoral components are fixed in the intramedullary cavity of the proximal femur. In a lot of cases when the DMS or a similar device is removed a well incorporated plate and a stable connection between the plate and the bone is found. This frequent intraoperative observation led to the idea to leave this bone-implant connection untouched, to remove only the lag screw and place the DMP over it thus resulting a total hip replacement with an extramedullary fixation of the femoral part of the prosthesis.
Application of the Dynamic Martin Screw (DMS) in the intertrochanteric osteotomy
2009-03-17

The basic conditions for a functioning and permanent use of the hip joint are based on a normal joint anatomy and physiological functional parameters of load capacity. The pathophysiology of defective positions in the hip joint area therefore has to be regarded pre-operatively at first under the aspect of the objective value of morbidity. This can be seen on the one hand because of pain and functional disablement, on the other side out of aesthetic causes from the sight of the patient. Missing possibility of compensation being endangered by an arthrosis either of posttraumatic or degenerative causes manifest an actual and therefore at the same time prospective sign of morbidity. Any osteotomy which has the aim to create an embettering of an actual situation only makes sense when it is guaranteed that the unphysiological loads can be abolished. The correction of pathological joint overloading can involve the indication either by prophylactic as well as by therapeutic reasons.
The 31A 3-3 fracture: an unstable problem
2009-03-17

The increasing incidence of pertrochanteric and subtrochanteric femur fractures makes their treatment ever more challenging both medically and socioeconomically. The increasing life expectancy in our population brings with it a host of factors that complicate our treatment of proximal femur fractures in elderly people. In addition to a variety of medical conditions, these patients many times have a diminished physical and mental reserve. In order to prevent potentially fatal complications, early mobilization and weight bearing are critical determinants of our treatment. Owing to discerning inability of elderly people fractures of the lower extremity causes a longer phase of immobilisation, if the fracture is not treated in a full weight bearing, stable manner. Thus the risk of complication such as thrombosis, embolism, pneumonia or decubital ulcera increases and the physical decline will be accelerated.
Pathologic fractures and osteolyses at the femur
2009-03-17

The application of the angle-adaptable Dynamic Martin Screw (DMS) within framework of compound osteosynthesis will be presented in this chapter. In case of metastatic formations or in case of pathologic fractures in the prevalence of osteoporosis of the long tubular bone conventional osteosyntheses frequently offer an insufficient degree of exercise stability and weight bearing stability. The most frequent causes of these fractures are metastases of non-osseous tumours, osteoporosis and much less commonly primary bone tumours.
Distal femur fractures
2009-03-17

Fractures of the distal part of the femoral bone are a result of direct trauma. They are severe injuries caused by great violence and velocity. 35% of the patients had open soft tissue damage. One third of the patients suffer a polytrauma and two third are caused by traffic accidents.
Stabilization of intertrochanteric fractures with the Dynamic Martin Screw (DMS)
2009-03-17

Pertrochanteric femur fractures do usually heal unless the patient dies prematurely of other complications. Frequent concomitant factors of problems in proximal femur fracture patients are advanced age, pronounced osteoporosis and multiple morbidities. Fracture type and subsequent selection of stabilisation method and implant may also represent relevant factors in the outcome. On the basis of these specific problems in patients with proximal femur fractures, any therapeutic concept must aim to harmonize the type of fracture treatment with the severity of fracture occurring.