Magnetic fabric of Araguainha complex impact structure (Central Brazil): Implications for deformation mechanisms and central uplift formation

The weakening mechanisms involved in the collapse of complex impact craters are controversial. The Araguainha impact crater, in Brazil, exposes a complex structure of 40 km in diameter, and is an excellent object to address this issue. Its core is dominated by granite. In addition to microstructural observations, magnetic studies reveal its internal fabric acquired during the collapse phase. All granite samples exhibit impact-related planar deformation features (PDFs) and planar fractures (PFs), which were overprinted by cataclasis. Cataclastic deformation has evolved from incipient brittle fracturing to the development of discrete shear bands in the center of the structure. Fracture planes are systematically decorated by tiny grains (<10 mu m) of magnetite and hematite, and the orientation of magnetic lineation and magnetic foliation obtained by the anisotropies of magnetic susceptibility (AMS) and anhysteretic remanence (AAR) are perfectly coaxial in all studied sites. Therefore, we could track the orientation of deformation features which are decorated by iron oxides using the AMS and AAR. The magnetic fabrics show a regular pattern at the borders of the central peak, with orientations consistent with the fabric of sediments at the crater's inner collar and complex in the center of the structure. Both the cataclastic flow revealed from microstructural observations and the structural pattern of the magnetic anisotropy match the predictions from numerical models of complex impact structures. The widespread occurrence of cataclasis in the central peak, and its orientations revealed by magnetic studies indicate that acoustic fluidization likely operates at all scales, including the mineral scales. The cataclastic flow made possible by acoustic fluidization results in an apparent plastic deformation at the macroscopic scale in the core. (C) 2012 Elsevier B.V. All rights reserved.

Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from Complex I

Evidence accumulated in the last ten years has demonstrated that a large proportion of the mitochondrial respiratory chain complexes in a variety of organisms is arranged in supramolecular assemblies called supercomplexes or respirasomes. Besides conferring a kinetic advantage (substrate channeling) and being required for the assembly and stability of Complex I, indirect considerations support the view that supercomplexes may also prevent excessive formation of reactive oxygen species (ROS) from the respiratory chain. Following this line of thought we have decided to directly investigate ROS production by Complex I under conditions in which the complex is arranged as a component of the supercomplex I1III2 or it is dissociated as an individual enzyme. The study has been addressed both in bovine heart mitochondrial membranes and in reconstituted proteoliposomes composed of complexes I and III in which the supramolecular organization of the respiratory assemblies is impaired by: (i) treatment either of bovine heart mitochondria or liposome-reconstituted supercomplex I-III with dodecyl maltoside; (ii) reconstitution of Complexes I and III at high phospholipids to protein ratio. The results of this investigation provide experimental evidence that the production of ROS is strongly increased in either model; supporting the view that disruption or prevention of the association between Complex I and Complex III by different means enhances the generation of superoxide from Complex I . This is the first demonstration that dissociation of the supercomplex I1III2 in the mitochondrial membrane is a cause of oxidative stress from Complex I. Previous work in our laboratory demonstrated that lipid peroxidation can dissociate the supramolecular assemblies; thus, here we confirm that preliminary conclusion that primary causes of oxidative stress may perpetuate reactive oxygen species (ROS) generation by a vicious circle involving supercomplex dissociation as a major determinant.

Differentiation and extracellular matrix interactions of chondrocytes in response to signaling molecules and biomaterials for cartilage repair = Differenzierung und Interaktionen von Chondrozyten mit der extrazellulären Matrix als Reaktion auf Signalmoleküle und Biomaterialien für die Wiederinstandsetzung von Knorpel

Chondrocytes live isolated in the voluminous extracellular matrix of cartilage, which they secrete and is neither vascularized nor innervated. Nutrient and waste exchanges occur through diffusion leading to low oxygen tension around the cells. Consequently even normal cartilage under normal physiological conditions suffers from a poor reparative potential that predisposes to degenerative conditions, such as osteoarthritis of the joints, with significant clinical effects.rnOne of the key challenges in medicine is the structural and functional replacement of lost or damaged tissues. Current therapeutical approaches are to transplant cells, implant bioartificial tissues, and chemically induce regeneration at the site of the injury. None of them reproduces well the biological and biomechanical properties of hyaline cartilage.rnThis thesis investigates the re-differentiation of chondrocytes and the repair of cartilage mediated by signaling molecules, biomaterials, and factors provided in mixed cellular cultures (co-culture systems). As signaling molecules we have applied prostaglandin E2 (PGE2) and bone morphogenetic protein 1 (BMP-1) and we have transfected chondrocytes with BMP-1 expressing vectors. Our biomaterials have been hydrogels of type-I collagen and gelatin-based scaffolds designed to mimic the architecture and biochemistry of native cartilage and provide a suitable three-dimensional environment for the cells. We have brought chondrocytes to interact with osteosarcoma Cal 72 cells or with murine preosteoblastic KS483 cells, either in a cell-to-cell or in a paracrine manner.rnExogenous stimulation with PGE2 or BMP-1 did not improve the differentiation or the proliferation of human articular chondrocytes. BMP-1 induced chondrocytic de-differentiation in a dose-dependent manner. Prostaglandin stimulation from gelatin-based scaffolds (three-dimensional culture) showed a certain degree of chondrocyte re-differentiaton. Murine preosteoblastic KS483 cells had no beneficial effect on human articular chondrocytes jointly cultivated with them in hydrogels of type I collagen. Although the hydrogels provided the chondrocytes with a proper matrix in which the cells adopted their native morphology; additionally, the expression of chondrocytic proteoglycan increased in the co-cultures after two weeks. The co-culture of chondrocytes with osteoblast-like cells (in transwell systems) resulted in suppression of the regular de-differentiation program that passaged chondrocytes undergo when cultured in monolayers. Under these conditions, the extracellular matrix of the chondrocytes, rich in type-II collagen and aggrecan, was not transformed into the extracellular matrix characteristic of de-differentiated human articular chondrocytes, which is rich in type-I collagen and versican.rnThis thesis suggests novel strategies of tissue engineering for clinical attempts to improve cartilage repair. Since implants are prepared in vitro (ex-vivo) by expanding human articular chondrocytes (autologous or allogeneic), we conclude that it will be convenient to provide a proper three-dimensional support to the chondrocytes in culture, to supplement the culture medium with PGE2, and to stimulate chondrocytes with osteoblastic factors by cultivating them with osteoblasts.rn

EPR spectroscopy as a tool for the elucidation of non-covalent structuring principles in complex soft matter

This thesis aims at connecting structural and functional changes of complex soft matter systems due to external stimuli with non-covalent molecular interaction profiles. It addresses the problem of elucidating non-covalent forces as structuring principle of mainly polymer-based systems in solution. The structuring principles of a wide variety of complex soft matter types are analyzed. In many cases this is done by exploring conformational changes upon the exertion of external stimuli. The central question throughout this thesis is how a certain non-covalent interaction profile leads to solution condition-dependent structuring of a polymeric system.rnTo answer this question, electron paramagnetic resonance (EPR) spectroscopy is chosen as the main experimental method for the investigation of the structure principles of polymers. With EPR one detects only the local surroundings or environments of molecules that carry an unpaired electron. Non-covalent forces are normally effective on length scales of a few nanometers and below. Thus, EPR is excellently suited for their investigations. It allows for detection of interactions on length scales ranging from approx. 0.1 nm up to 10 nm. However, restriction to only one experimental technique likely leads to only incomplete pictures of complex systems. Therefore, the presented studies are frequently augmented with further experimental and computational methods in order to yield more comprehensive descriptions of the systems chosen for investigation.rnElectrostatic correlation effects in non-covalent interaction profiles as structuring principles in colloid-like ionic clusters and DNA condensation are investigated first. Building on this it is shown how electrostatic structuring principles can be combined with hydrophobic ones, at the example of host-guest interactions in so-called dendronized polymers (denpols).rnSubsequently, the focus is shifted from electrostatics in dendronized polymers to thermoresponsive alkylene oxide-based materials, whose structuring principles are based on hydrogen bonds and counteracting hydrophobic interactions. The collapse mechanism in dependence of hydrophilic-hydrophobic balance and topology of these polymers is elucidated. Complementarily the temperature-dependent phase behavior of elastin-like polypeptides (ELPs) is investigated. ELPs are the first (and so far only) class of compounds that is shown to feature a first-order inverse phase transition on nanoscopic length scales.rnFinally, this thesis addresses complex biological systems, namely intrinsically disordered proteins (IDPs). It is shown that the conformational space of the IDPs Osteopontin (OPN), a cytokine involved in metastasis of several kinds of cancer, and BASP1 (brain acid soluble protein one), a protein associated with neurite outgrowth, is governed by a subtle interplay between electrostatic forces, hydrophobic interaction, system entropy and hydrogen bonds. Such, IDPs can even sample cooperatively folded structures, which have so far only been associated with globular proteins.

Metformin inhibits human androgen production by regulating steroidogenic enzymes HSD3B2 and CYP17A1 and complex I activity of the respiratory chain

Metformin is treatment of choice for the metabolic consequences seen in polycystic ovary syndrome for its insulin-sensitizing and androgen-lowering properties. Yet, the mechanism of action remains unclear. Two potential targets for metformin regulating steroid and glucose metabolism are AMP-activated protein kinase (AMPK) signaling and the complex I of the mitochondrial respiratory chain. Androgen biosynthesis requires steroid enzymes 17α-Hydroxylase/17,20 lyase (CYP17A1) and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2), which are overexpressed in ovarian cells of polycystic ovary syndrome women. Therefore, we aimed to understand how metformin modulates androgen production using NCI-H295R cells as an established model of steroidogenesis. Similar to in vivo situation, metformin inhibited androgen production in NCI cells by decreasing HSD3B2 expression and CYP17A1 and HSD3B2 activities. The effect of metformin on androgen production was dose dependent and subject to the presence of organic cation transporters, establishing an important role of organic cation transporters for metformin's action. Metformin did not affect AMPK, ERK1/2, or atypical protein kinase C signaling. By contrast, metformin inhibited complex I of the respiratory chain in mitochondria. Similar to metformin, direct inhibition of complex I by rotenone also inhibited HSD3B2 activity. In conclusion, metformin inhibits androgen production by mechanisms targeting HSD3B2 and CYP17-lyase. This regulation involves inhibition of mitochondrial complex I but appears to be independent of AMPK signaling.

Uptake of bone-related matrix proteins into implanted deproteinized bovine bone mineral

Deproteinized bovine bone mineral (DBBM) (Bio-Oss®, Geistlich-Pharma, Wohlhusen, Switzerland) is widely used as a bone substitute for the preservation or augmentation of bone volume. After implantation near native bone, new bone may form around the DBBM particles. Since DBBM is very resistant to resorption, it will hardly ever be replaced by bone and, therefore, the mechanical stability largely depends on the extent of bridging between the newly formed bone and the DBBM particles. The molecular factors responsible for the deposition of new bone to the DBBM particles have not been determined. The aim of this study was, therefore, to test the hypothesis that DBBM implanted near bone take up bone-related matrix proteins that are involved in cell-matrix interactions. Cylindrical biopsies harvested from tooth extraction sites filled with DBBM particles were fixed in aldehydes, decalcified, and embedded in LR White resin. Thin sections were incubated with antibodies against bone sialoprotein (BSP) and osteopontin (OPN), two bone proteins involved in cell attachment, signaling, and mineralization. High-resolution immunogold labeling was used to examine protein distribution. BSP and OPN were immunodetected in all DBBM particles and yielded an identical distribution pattern. Most gold particles were found over the peripheral DBBM matrix, although some peripheral regions lacked immunolabeling. The bulk of the interior DBBM portion was mainly free of labeling with the exception of the peripheral matrix of some osteocyte lacunae and canaliculi. It is concluded that DBBM selectively takes up at least BSP and OPN after its implantation at a bone site. BSP and OPN or other molecules accommodating in DBBM may modulate events associated with cell attachment and differentiation.

The frozen elephant trunk: an interesting hybrid endovascular-surgical technique to treat complex pathologies of the thoracic aorta

The treatment of complex aortic pathologies involving the ascending aorta, the aortic arch, and the descending aorta remains a challenging issue in aortic surgery. The frozen elephant trunk procedure effectively combines surgical and interventional technologies in the treatment of extensive aortic aneurysms and dissections. We present two patients with complex aortic lesions involving all three segments of the thoracic aorta. The device used in our series is the new E-vita open hybrid prosthesis consisting of a proximal woven polyester tube and a distal self-expandable nitinol stent graft, which can be delivered antegrade into the descending aorta.

Treatment of multiple adjacent Miller Class I and II gingival recessions with collagen matrix and the modified coronally advanced tunnel technique

OBJECTIVE To clinically evaluate the treatment of Miller Class I and II multiple adjacent gingival recessions using the modified coronally advanced tunnel technique combined with a newly developed bioresorbable collagen matrix of porcine origin. METHOD AND MATERIALS Eight healthy patients exhibiting at least three multiple Miller Class I and II multiple adjacent gingival recessions (a total of 42 recessions) were consecutively treated by means of the modified coronally advanced tunnel technique and collagen matrix. The following clinical parameters were assessed at baseline and 12 months postoperatively: full mouth plaque score (FMPS), full mouth bleeding score (FMBS), probing depth (PD), recession depth (RD), recession width (RW), keratinized tissue thickness (KTT), and keratinized tissue width (KTW). The primary outcome variable was complete root coverage. RESULTS Neither allergic reactions nor soft tissue irritations or matrix exfoliations occurred. Postoperative pain and discomfort were reported to be low, and patient acceptance was generally high. At 12 months, complete root coverage was obtained in 2 out of the 8 patients and 30 of the 42 recessions (71%). CONCLUSION Within their limits, the present results indicate that treatment of Miller Class I and II multiple adjacent gingival recessions by means of the modified coronally advanced tunnel technique and collagen matrix may result in statistically and clinically significant complete root coverage. Further studies are warranted to evaluate the performance of collagen matrix compared with connective tissue grafts and other soft tissue grafts.

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Protein profiling of organic stone matrix and urine from dogs with urolithiasis

Two-thirds of the organic matrix in urinary stones consists of proteins. Their relationship to calculogenesis remains controversial with regard to their effect as inhibitors or promoters during stone formation. The purpose of the present study was to determine the differences in peptide and protein pattern between the urine of stone formers (n = 23) and control dogs (n = 12), as well as between organic matrix of different urinary stones (struvite n = 11, calcium oxalate n = 8, uric acid n = 4) using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Specific differences in protein and peptide profiles were found in the organic matrix of different mineral compositions. Characteristic differences were also found in urinary peptide and protein pattern especially in molecular masses below 20 kDa between affected and healthy dogs. Based on the obtained molecular masses they were in some cases tentatively identified as proteins that are known to be involved in stone formation in humans. The study shows that in dogs, specific-urinary peptides and proteins might be associated with urolithiasis. It indicates the importance to further characterize those proteins for possible diagnostic purposes in prognosis and therapy

Application of a computational model for complex fluvial ecosystems: The population dynamics of zebra mussel Dreissena polymorpha as a case study

The potential and adaptive flexibility of population dynamic P-systems (PDP) to study population dynamics suggests that they may be suitable for modelling complex fluvial ecosystems, characterized by a composition of dynamic habitats with many variables that interact simultaneously. Using as a model a reservoir occupied by the zebra mussel Dreissena polymorpha, we designed a computational model based on P systems to study the population dynamics of larvae, in order to evaluate management actions to control or eradicate this invasive species. The population dynamics of this species was simulated under different scenarios ranging from the absence of water flow change to a weekly variation with different flow rates, to the actual hydrodynamic situation of an intermediate flow rate. Our results show that PDP models can be very useful tools to model complex, partially desynchronized, processes that work in parallel. This allows the study of complex hydroecological processes such as the one presented, where reproductive cycles, temperature and water dynamics are involved in the desynchronization of the population dynamics both, within areas and among them. The results obtained may be useful in the management of other reservoirs with similar hydrodynamic situations in which the presence of this invasive species has been documented.

Complex pelvic traumas: Data linkage of the German Pelvic Injury Register and the TraumaRegister DGU®

BACKGROUND Complex pelvic traumas, i.e., pelvic fractures accompanied by pelvic soft tissue injuries, still have an unacceptably high mortality rate of about 18 %. PATIENTS AND METHODS We retrospectively evaluated an intersection set of data from the TraumaRegister DGU® and the German Pelvic Injury Register from 2004-2009. Patients with complex and noncomplex pelvic traumas were compared regarding their vital parameters, emergency management, stay in the ICU, and outcome. RESULTS From a total of 344 patients with pelvic injuries, 21 % of patients had a complex and 79 % a noncomplex trauma. Complex traumas were significantly less likely to survive (16.7 % vs. 5.9 %). Whereas vital parameters and emergency treatment in the preclinical setting did not differ substantially, patients with complex traumas were more often in shock and showed acute traumatic coagulopathy on hospital arrival, which resulted in more fluid volumes and transfusions when compared to patients with noncomplex traumas. Furthermore, patients with complex traumas had more complications and longer ICU stays. CONCLUSION Prevention of exsanguination and complications like multiple organ dysfunction syndrome still pose a major challenge in the management of complex pelvic traumas.

Childhood Trauma and Complex Posttraumatic Stress Disorder Symptoms in Older Adults: A Study of Direct Effects and Social-Interpersonal Factors as Potential Mediators

Childhood traumatic events may lead to long-lasting psychological effects and contribute to the development of complex posttraumatic sequelae. These might be captured by the diagnostic concept of complex posttraumatic stress disorder (CPTSD) as an alternative to classic posttraumatic stress disorder (PTSD). CPTSD comprises a further set of symptoms in addition to those of PTSD, namely, changes in affect, self, and interpersonal relationships. Previous empirical research on CPTSD has focused on middle-aged adults but not on older adults. Moreover, predictor models of CPTSD are still rare. The current study investigated the association between traumatic events in childhood and complex posttraumatic stress symptoms in older adults. The mediation of this association by 2 social-interpersonal factors (social acknowledgment as a survivor and dysfunctional disclosure) was investigated. These 2 factors focus on the perception of acknowledgment by others and either the inability to disclose traumatic experiences or the ability to do so only with negative emotional reactions. A total of 116 older individuals (age range = 59–98 years) who had experienced childhood traumatic events completed standardized self-report questionnaires indexing childhood trauma, complex trauma sequelae, social acknowledgment, and dysfunctional disclosure of trauma. The results showed that traumatic events during childhood were associated with later posttraumatic stress symptoms but with classic rather than complex symptoms. Social acknowledgment and dysfunctional disclosure partially mediated this relationship. These findings suggest that childhood traumatic stress impacts individuals across the life span and may be associated with particular adverse psychopathological consequences.

Retrospective assesment of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and early endometrioid endometrial cancer

Objective: The primary objective of this project was to describe the efficacy of the Levonorgestrel Intrauterine Device (LIUD) for treatment of Complex Endometrial Cancer (CAH) and Grade 1 Endometrial Cancer (G1EEC) in terms of rate of Complete Response (CR) and Partial Response (PR) after 6 months of therapy. Finally, we assessed if any clinical or pathologic features were associated with response to the LIUD. ^ Methods: This study was a retrospective case series designed to report the response rate of patients with CAH or G1EEC treated with LIUD therapy. In addition, this study has a laboratory component to assess molecular predictors of response to LIUD therapy. Retrospective data already collected from patients diagnosed with CAH or EEC grade 1 and treated with LIUD therapy at MD Anderson Cancer Center (MDACC) were used for this study. Patients from all ethnic and race groups were included. A Complete Response (CR) was defined in patients diagnosed with CAH if pathologic report at 6 months demonstrated either no evidence of hyperplasia or no atypia in the setting of simple or complex hyperplasia. Partial Response (PR) was recorded if disease downgraded to only CAH from G1EEC. No Response (NR) was recorded if pathologic report demonstrates no change (Stable Disease, SD) or progression to cancer (Progressive Disease, PD). We calculated the proportion of patients with complete response to LIUD therapy with 95% confidence interval. We compared the response rates (CR/PR vs NR) by obesity status (Obese if BMI > 40 kg/m2 vs non-obese if BMI <= 40 kg/m2) as well as other clinical and pathologic factors, such as age, uterine size (median size), and presence of exogenous progesterone effect. ^ Results: There were 39 patients diagnosed with either CAH or G1EEC treated with the LIUD. Of 39 patients, 12 did not have pathological results of biopsy at 6months time period. Of 27 evaluable patients, 17 were diagnosed with CAH and 10 with G1EEC. Overall response rate (RR) was 78% (95% CI = 62-94%) at 6 months, 18 patients had CR (4 in G1EEC; 14 in CAH), 3 patients had PR (3 in G1EEC), 3 had SD (1 in CAH; 2 in G1EEC), 3 had PD (2 in CAH; 1 in G1EEC). After histology stratification, RR at 6 months was 82.35% (14/17; 95%CI = 67.4-97.3%) in CAH and 70% (7/10; 95% CI = 41-98.4%) in G1EEC. ^ There was no difference in response (R) and no response (NR) based on BMI (p=0.56). He observed a trend showing association between age with response (p=0.1). There was no association between uterine size and response to therapy (p=0.17). We recorded strong association between exogenous progesterone effect and response. ^ Conclusion: LIUD therapy for the treatment of CAH and G1EEC may be effective and safe. Presence of exogenous progesterone effect may predict the response to LIUD therapy at earlier time points. There is need of further studies with larger sample size to explore the relationship of response with other clinical and pathologic factors^

Development of combined micro -preparation, separation, and mass spectrometry methods and application in the microdialysis study of neuropeptide metabolism

Two sets of mass spectrometry-based methods were developed specifically for the in vivo study of extracellular neuropeptide biochemistry. First, an integrated micro-concentration/desalting/matrix-addition device was constructed for matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) to achieve attomole sensitivity for microdialysis samples. Second, capillary electrophoresis (CE) was incorporated into the above micro-liquid chromatography (LC) and MALDI MS system to provide two-dimensional separation and identification (i.e. electrophoretic mobility and molecular mass) for the analysis of complex mixtures. The latter technique includes two parts of instrumentation: (1) the coupling of a preconcentration LC column to the inlet of a CE capillary, and (2) the utilization of a matrix-precoated membrane target for continuous CE effluent deposition and for automatic MALDI MS analysis (imaging) of the CE track.^ Initial in vivo data reveals a carboxypeptidase A (CPA) activity in rat brain involved in extracellular neurotensin metabolism. Benzylsuccinic acid, a CPA inhibitor, inhibited neurotensin metabolite NT1-12 formation by 70%, while inhibitors of other major extracellular peptide metabolizing enzymes increased NT1-12 formation. CPA activity has not been observed in previous in vitro experiments. Next, the validity of the methodology was demonstrated in the detection and structural elucidation of an endogenous neuropeptide, (L)VV-hemorphin-7, in rat brain upon ATP stimulation. Finally, the combined micro-LC/CE/MALDI MS was used in the in vivo metabolic study of peptide E, a mu-selective opioid peptide with 25 amino acid residues. Profiles of 88 metabolites were obtained, their identity being determined by their mass-to-charge ratio and electrophoretic mobility. The results indicate that there are several primary cleavage sites in vivo for peptide E in the release of its enkephalin-containing fragments. ^