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Species lists are widely used in legislation and regulation to manage and conserve biodiversity. In this paper, we explore the issues caused by the lack of an adequately governed and universally accepted list of the world’s species. These include lack of quality control, duplicated effort, conflicts of interest, lack of currency, and confusion in the scientific use of taxonomic information. If species lists are to fulfill their role efficiently, then the governance systems underlying their creation must keep pace. Fortunately, modernization of species list governance is now possible as a result of advances in biodiversity informatics and two decades of experience working to create the backbone of a global species list.

Background Distal lower extremity reconstruction can be challenging in terms of flap design. Bulky flaps result in limited mobility accompanied with the need of customized footwear. Raising the ALT-flap in a superficial fascial plane (thin ALT-flap) can be beneficial. This study evaluates thin ALT-flaps for lower distal extremity reconstruction. Methods In a retrospective study, patients that underwent microvascular extremity reconstruction at the level of the ankle and dorsal foot at the University of Freiburg from 2008–2018 were reviewed. Results 95 patients could be included in the study (35 perforator flaps, 8 fascia flaps and 54 muscle flaps).Among the perforator flaps, 21 ALT-flaps were elevated conventionally and 14 in the superficial fascial plane (thin ALT-flap). Among the conventional ALT-flaps, there was one flap loss (5%) and one successful revision (5%). 5(24%) flaps received secondary thinning. 57%(n = 12) were able to wear conventional footwear. There were 2(15%) successful revisions of thin ALT-flaps. 100% of thin ALT-flaps survived and 85%(n = 11) of the patients wore ordinary footwear after defect coverage.Among fascial flaps, 50%(n = 4) had to be revised with 2(25%) complete and 1 (13%) partial flap loss. All patients achieved mobility in ordinary shoes (n = 8).In muscle flaps, there were 7(13%) revisions and 5(9%) flap losses. 5(9%) flaps received secondary thinning. Only 33%(n = 18) were mobile in ordinary footwear. Conclusion The thin ALT-flap is a save one-stage evolution for lower distal extremity reconstruction with a favorable flap survival rate. Compared with conventional ALT-flaps it might be beneficial in reducing the need for expensive custom fitted shoes and secondary thinning procedures.

Taxonomy—the delimitation, naming, classification and documentation of species and other taxa—is an often-misunderstood discipline. Complex and at times contested, taxonomy occupies a sometimes discomforting intermediate position on a continuum from descriptive to hypothetico-deductive science. Two aspects of taxonomy that are striking to many observers and users are the degree to which taxonomists often disagree, and the degree of taxonomic revisionism (the replacement of one taxonomic classification with another, exemplified by the phrase ‘taxonomists are always changing the names of things’). Disagreements between taxonomists do not usually indicate taxonomic confusion or chaos, but rather often represent valid disagreements over the best, most effective and most meaningful way to interpret, describe and classify one of the most complex systems that scientists seek to describe and characterise—the patterns of variation of life on Earth. One way to partially manage disagreements among taxonomists is to develop a mechanism to synthesise the flux of taxonomic activity into agreed, broadly accepted, authoritative and scientifically robust global lists of the world’s species and other taxa. A sound understanding of some aspects of the nature of taxonomy is needed to appreciate the opportunities, complexities and limitations of the development and maintenance of such lists.

Direct tests of gene function have historically been performed in a limited number of model organisms. The CRISPR/Cas system is species-agnostic, offering the ability to manipulate genes in a range of models, enabling insights into evolution, development, and physiology. Astatotilapia burtoni, a cichlid fish from the rivers and shoreline around Lake Tanganyika, has been extensively studied in the laboratory to understand evolution and the neural control of behavior. Here we develop protocols for the creation of CRISPR-edited cichlids and create a broadly useful mutant line. By manipulating the Tyrosinase gene, which is necessary for eumelanin pigment production, we describe a fast and reliable approach to quantify and optimize gene editing efficiency. Tyrosinase mutants also remove a major obstruction to imaging, enabling visualization of subdermal structures and fluorophores in situ. These protocols will facilitate broad application of CRISPR/Cas9 to studies of cichlids as well as other non-traditional model aquatic species.

The Miocene convergence of the Sunda shelf, Sahul shelf and Wallacea facilitated the exchange of previously isolated floras across the Sunda–Sahul Convergence Zone (SSCZ). The SSCZ is a hotspot of biogeographical research; however, phytogeographical patterns across the region remain poorly understood. We conducted multivariate analysis on a comprehensive species checklist of SSCZ vascular plants to quantify the extent of exchange, characterize phytogeographical patterns and investigate their abiotic drivers. We found that Lydekker’s and Wallace’s Lines are not reflected in floristic composition at any taxonomic level, with 46% of genera distributed across these biogeographical lines. In contrast, environment is significantly correlated with floristic composition, with annual rainfall and seasonality being the strongest correlates. Mainland Asia, Borneo, the Philippines, New Guinea and Australia were major routes of exchange throughout the Cenozoic, possibly because these areas have been persistent landmasses throughout the entire period of convergence. We conclude that Sunda–Sahul floristic exchange has substantially influenced the assembly of the regional flora and that modern phytogeographical patterns have been influenced more by environmental variables and available landmass (i.e. establishment conditions) than by putative barriers to movement such as Wallace’s and Lydekker’s Lines (i.e. vagility).

We present BonZeb – a suite of modular Bonsai packages which allow high-resolution zebrafish tracking with dynamic visual feedback. Bonsai is an increasingly popular software platform that is accelerating the standardization of experimental protocols within the neurosciences due to its speed, flexibility, and minimal programming overhead. BonZeb can be implemented into novel and existing Bonsai workflows for online behavioral tracking and offline tracking with batch processing. We demonstrate that BonZeb can run a variety of experimental configurations used for gaining insights into the neural mechanisms of zebrafish behavior. BonZeb supports head-fixed closed-loop and free-swimming virtual open-loop assays as well as multi-animal tracking, optogenetic stimulation, and calcium imaging during behavior. The combined performance, ease of use and versatility of BonZeb opens new experimental avenues for researchers seeking high-resolution behavioral tracking of larval zebrafish.

Introduction: Resection of anorectal malignancies may result in extensive perineal/pelvic defects that require an interdisciplinary surgical approach involving reconstructive surgery. The myocutaneous gracilis flap (MGF) and the gluteal fold flap (GFF) are common options for defect coverage in this area. Here we report our experience with the MGF/GFF and compare the outcome regarding clinical key parameters. Methods: In a retrospective chart review, we collected data from the Department of Plastic Surgery of the University of Freiburg from December 2008-18 focusing on epidemiological, oncological, and therapy-related data including comorbidities (ASA Classification) and peri-/postoperative complications (Clavien-Dindo-System). Results: Twenty-nine patients were included with a mean follow-up of 17 months. Of the cases, 19 (65.5%) presented with recurrent disease, 21 (72.4%) received radiochemotherapy preoperatively, 2 (6.9%) received chemotherapy alone. Microscopic tumor free margins were achieved in 25 cases (86.2%). 17 patients (7 men, 10 women, rectal adenocarcinoma n = 11; anal squamous cell carcinoma n = 6; mean age 58.5 ± 10.68, mean BMI 23.1, mean ASA score 2.8) received a MGF (unilateral n = 10; bilateral n = 7). Twelve patients (7 men, 5 women, rectal adenocarcinoma n = 7; anal squamous cell carcinoma n = 4, proctodeal gland carcinoma n = 1, mean age 66.2 ± 9.2, mean BMI 23.6, mean ASA score 2.6) received coverage with a GFF (unilateral n = 4; bilateral n = 8). Mean operation time of coverage was 105 ± 9 min for unilateral and 163 ± 11 for bilateral MGFs, 70 ± 13 min for unilateral and 107 ± 14 for bilateral GFFs. Complications affected 62%. There was no significant difference in the complication rate between the MGF- and GFF-group. Complications were mainly wound healing disorders that did not extend the hospital stay. No flap loss and no complication that lead to long-lasting disability was documented (both groups). Pain-free sitting took more time in the GFF-group due to the location of the donor site. Conclusion: MG-flaps and GF-flaps prove to be reliable and robust techniques for perineal/pelvic reconstruction. Though flap elevation is significantly faster for GF-flaps, preoperative planning and intraoperative Doppler confirmation are advisable. With comparable complication rates, we suggest a decision-making based on distribution of adipose tissue for dead space obliteration, intraoperative patient positioning, and perforator vessel quality/distribution.

Kopfschmerzen gehoren weltweit zu den haufigsten Erkrankungen, die bei Betroffenen starke Schmerzen und Funktionseinschrankungen verursachen. Lebensqualitatseinschrankungen sowie erhebliche Kosten durch verschiedene, teure Therapien sind die Folge. Der vorliegende Beitrag beschaftigt sich mit der Frage: Ist Chiropraktik bei Kopfschmerzen im Vergleich zu anderen Therapien eine klinisch relevante, nachhaltige Behandlungsmethode und stellt sie somit eine Standardtherapie dar? Die Recherche erfolgte in der Datenbank PubMed. Der Evidenzlevel der einzelnen Studien wurde mithilfe der PEDro-Skala ermittelt. Die Studien mit Evidenzklasse I wurden nach dem PICO-Modell tabellarisch ausgewertet. Untersuchte Endpunkte waren Kopfschmerzfrequenz und -intensitat sowie Medikamenteneinnahme. Die Literaturrecherche ergab von 219 recherchierten Artikeln 30 zum Thema, davon 15 systematische Ubersichtsarbeiten und 15 randomisierte klinische Studien, von denen 12 Studien auswertbare Ergebnisse aufwiesen. Insgesamt wurden 21 verbesserte Werte der Endpunkte analysiert. Davon zeigten 11 durch chiropraktische Behandlungen beste Ergebnisse. Die Kombinationstherapien mit Chiropraktik und Physiotherapie lagen 3‑mal vorne, die Anwendung der Physiotherapie schnitt 3‑mal am besten ab und 4‑mal gab es keine Unterschiede der Ergebnisse beim Vergleich von Interventions- und Kontrollgruppen. Die chiropraktischen Behandlungen erreichten genau wie die Physiotherapie und die Kombination aus beiden Behandlungen beste Resultate bei den Verbesserungen der Endpunkte. Die Ergebnisunterschiede zwischen den Interventions- und Kontrollgruppen waren gering oder gar nicht vorhanden. Die untersuchten Studien wiesen methodische Schwachen auf. Die Ergebnisse zeigen, dass Chiropraktik bei Kopfschmerzen keine klinisch relevante, nachhaltige Behandlung und somit keine Standardtherapie aufgrund der ausgewerteten Studien darstellt.

Acyl carrier proteins (ACPs) are central hubs in polyketide and fatty acid biosynthetic pathways, but the fast motions of the ACP's phosphopantetheine (Ppant) arm make its conformational dynamics difficult to capture using traditional spectroscopic approaches. Here we report that converting the terminal thiol of Escherichia coli ACP's Ppant arm into a thiocyanate activates this site to form a selective cross-link with the active site cysteine of its partner ketoacyl synthase (FabF). The reaction releases a cyanide anion, which can be detected by infrared spectroscopy. This represents a practical and generalizable method for obtaining and visualizing ACP-protein complexes relevant to biocatalysis and will be valuable in future structural and engineering studies.

Viola banksii, the type species of section Erpetion, is endemic in eastern mainland Australia. In this paper we characterise morphological and anatomical features and assess genome size and genetic diversity in combination with the breeding system. V. banksii develops exclusively chasmogamous flowers. Ovules are anatropous, crassinucellate and bitegmic, the female gametophyte is of the Polygonum type, and the embryo is of Asterad type surrounded by nuclear endosperm. Pollen is non-heteromorphic, 3-aperturate, and highly viable. V. banksii grows in shade on moist, well drained, often sandy soils, and this is reflected in the anatomy of its organs, which includes a lack of subepidermal collenchyma in aerial parts, large leaf epidermal cells with thin cell walls, a narrow cuticle layer, and vascular bundles with xylem that are not rich in vessels. V. banksii is tolerant to zinc and lead based on phytotoxicity test. The high chromosome number (2n = 10x = 50) does not correspond to a small genome size (2C DNA = 1.27 pg). Low mean intra-populational gene diversity (HS = 0.077) detected by ISSR markers confirms the strong influence of selfing and clonal propagation by pseudostolons. Unique morphological traits of V. banksii include nyctinastic petal movement, the lack of a floral spur, the presence of gland-like protuberances on two stamens, and the presence of pseudostolons, which could be a synapomorphy for the whole section.

The incidence of scalp tumors requiring radical excision increases with age. Free flap surgery is the standard reconstructive option for large defects; however, there is an ongoing uncertainty about its safety in the elderly. We conducted a review of data and report on 19 patients aged ≥75 years and 13

Fragestellung: Fingeramputationsverletzungen der Zone 1 und 2 nach Tamai stellen gewöhnlich lediglich eine relative Replantationsindikation dar. Im Gegensatz zur primären Stumpfbildung sind Replantationen sehr aufwändig und erfordern spezielle supermikrochirurgische Fähigkeiten, [zum vollständigen Text gelangen Sie über die oben angegebene URL], 59. Kongress der Deutschen Gesellschaft für Handchirurgie

Introduction C-reactive protein circulates as a pentameric protein (pCRP). pCRP is a well-established diagnostic marker as plasma levels rise in response to tissue injury and inflammation. We recently described pro-inflammatory properties of CRP, which are mediated by conformational changes from pCRP to bioactive isoforms expressing pro-inflammatory neo-epitopes [pCRP* and monomeric C-reactive protein (mCRP)]. Here, we investigate the role of CRP isoforms in renal ischemia/reperfusion injury (IRI). Methods Rat kidneys in animals with and without intraperitoneally injected pCRP were subjected to IRI by the time of pCRP exposure and were subsequently analyzed for monocyte infiltration, caspase-3 expression, and tubular damage. Blood urea nitrogen (BUN) was analyzed pre-ischemia and post-reperfusion. CRP effects on leukocyte recruitment were investigated via intravital imaging of rat-striated muscle IRI. Localized conformational CRP changes were analyzed by immunohistochemistry using conformation specific antibodies. 1,6-bis(phosphocholine)-hexane (1,6-bisPC), which stabilizes CRP in its native pentameric form was used to validate CRP effects. Leukocyte activation was assessed by quantification of reactive oxygen species (ROS) induction by CRP isoforms ex vivo and in vitro through electron spin resonance spectroscopy. Signaling pathways were analyzed by disrupting lipid rafts with nystatin and subsequent ROS detection. In order to confirm the translational relevance of our findings, biopsies of microsurgical human free tissue transfers before and after IRI were examined by immunofluorescence for CRP deposition and co-localization of CD68+ leukocytes. Results The application of pCRP aggravates tissue damage in renal IRI. 1,6-bisPC reverses these effects via inhibition of the conformational change that leads to exposure of pro-inflammatory epitopes in CRP (pCRP* and mCRP). Structurally altered CRP induces leukocyte–endothelial interaction and induces ROS formation in leukocytes, the latter can be abrogated by blocking lipid raft-dependent signaling pathways with Nystatin. Stabilizing pCRP in its native pentameric state abrogates these pro-inflammatory effects. Importantly, these findings are confirmed in human IRI challenged muscle tissue. Conclusion These results suggest that CRP is a potent modulator of IRI. Stabilizing the native pCRP conformation represents a promising anti-inflammatory therapeutic strategy by attenuation of leukocyte recruitment and ROS formation, the primary pathomechanisms of IRI.

Die digitale Volumentomografie (DVT) stellt eine neue Moglichkeit der Schnittbildgebung in der Handchirurgie dar. Die Methode hat in der letzten Dekade eine weite Verbreitung in der Kopf-Hals-Bildgebung gefunden und ist in diesem Bereich ein etabliertes Standardverfahren, fur das eine, im Vergleich zur Computertomografie (MDCT), niedrigere Strahlenexposition beschrieben wird. Wir berichten uber 24 Monate klinische Erfahrung mit dem Einsatz der Methode in einer handchirurgischen Universitatsklinik. Die DVT wird bezuglich ihrer Technik sowie ihrer klinischen Eignung anhand von exemplarischen Falldarstellungen vorgestellt und evaluiert. Weiterhin werden ihre Vor- und Nachteile diskutiert und in den Kontext der aktuellen Literatur gesetzt.

C-reactive protein (CRP) is a pentraxin that has long been employed as a marker of inflammation in clinical practice. Recent findings brought up the idea of CRP to be not only a systemic marker but also a mediator of inflammation. New studies focused on structural changes of the plasma protein, revealing the existence of two distinct protein conformations associated with opposed inflammatory properties. Native, pentameric CRP (pCRP) is considered to be the circulating precursor form of monomeric CRP (mCRP) that has been identified to be strongly proinflammatory. Recently, a dissociation mechanism of pCRP has been identified on activated platelets and activated/apoptotic cells associated with the amplification of the proinflammatory potential. Correspondingly, CRP deposits found in inflamed tissues have been identified to exhibit the monomeric conformation by using conformation-specific antibodies. Here we review the current literature on the causal role of the dissociation mechanism of pCRP and the genesis of mCRP for the amplification of the proinflammatory potential in inflammatory reactions such as atherosclerosis and ischemia/reperfusion injury. The chance to prevent the formation of proinflammatory mediators in ubiquitous inflammatory cascades has pushed therapeutic strategies by targeting pCRP dissociation in inflammation. In this respect, the development of clinically applicable derivatives of the palindromic compound 1,6-bis(phosphocholine)-hexane (1,6-bis PC) should be a major focus of future CRP research.

PURPOSE Facial paralysis has a profound impact on functionality and esthetics of the oral region. In patients with strong skin laxity and soft tissue ptosis, functional smile reconstruction is challenging due to the accentuated asymmetry at rest. Thus, the purpose of the study was to analyze facial symmetry in this patient clientele following a combination of dynamic reanimation with fascial strips for static suspension compared to functional gracilis transfer alone. METHODS In 2014, we altered the single-stage approach for microsurgical smile reconstruction in patients with significant soft tissue ptosis by adding fascia lata grafts for static support. We evaluated 6 patients (mean age 57.8 ± 5.2, group A) who underwent the combined procedure, and compared their results to 6 patients with flaccid facial paralysis who were treated before 2014 and received a functional gracilis transfer alone (mean age 52.5 ± 7.5, group B). To test the efficacy of the technique, we retrospectively analyzed the correction of the oral asymmetry as well as nasal and philtral deviation by computer-assisted photograph analysis 6 months postoperatively. RESULTS The comparative analysis revealed a significant postoperative improvement of the oral asymmetry (A: 90.0 ± 5.0% relative correction at rest vs. B: 62.6 ± 17.2%, P

Genetic access to small, reproducible sets of neurons is key to an understanding of the functional wiring of the brain. Here we report the generation of a new Gal4- and Cre-driver resource for zebrafish neurobiology. Candidate genes, including cell type-specific transcription factors, neurotransmitter-synthesizing enzymes and neuropeptides, were selected according to their expression patterns in small and unique subsets of neurons from diverse brain regions. BAC recombineering, followed by Tol2 transgenesis, was used to generate driver lines that label neuronal populations in patterns that, to a large but variable extent, recapitulate the endogenous gene expression. We used image registration to characterize, compare, and digitally superimpose the labeling patterns from our newly generated transgenic lines. This analysis revealed highly restricted and mutually exclusive tissue distributions, with striking resolution of layered brain regions such as the tectum or the rhombencephalon. We further show that a combination of Gal4 and Cre transgenes allows intersectional expression of a fluorescent reporter in regions where the expression of the two drivers overlaps. Taken together, our study offers new tools for functional studies of specific neural circuits in zebrafish.

C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions., C-reactive protein is a pentameric protein secreted by the liver in response to injury and infection. Here Braig et al. show that conformational changes in CRP on the surface of monocyte-derived microvesicles enable binding of complement C1q and lead to activation of the complement cascade and aggravation of inflammation.

SummaryThe reticular formation in the brainstem controls motor output via axonal projections to the hindbrain and spinal cord. It remains unclear how individual groups of brainstem neurons contribute to specific motor functions. Here, we investigate the behavioral role of the nucleus of the medial longitudinal fasciculus (nMLF), a small group of reticulospinal neurons in the zebrafish midbrain. Calcium imaging revealed that nMLF activity is correlated with bouts of swimming. Optogenetic stimulation of neurons in the left or right nMLF activates the posterior hypaxial muscle and produces a graded ipsilateral tail deflection. Unilateral ablation of a subset of nMLF cells biases the tail position to the intact side during visually evoked swims, while sparing other locomotor maneuvers. We conclude that activity in the nMLF provides postural control of tail orientation and thus steers the direction of swimming. Our studies provide an example of fine-grained modularity of descending motor control in vertebrates.

Tissue damage in burn injury leads to a rapid increase of leukocytes and acute phase reactants. Plasma levels of C-reactive protein (CRP) rise within hours after the insult. No deficiency of this protein has been reported in humans, suggesting it plays a pivotal role in innate immunity. CRP in circulation is composed of five identical subunits [pentameric CRP (pCRP)]. Recently, deposits of structurally modified CRP (mCRP) have been found in inflammatory diseases. Little is known about this structural change and how it affects CRP functions. We analyzed CRP deposits in burn wounds and serum by immunohistochemistry, western blot and dot blot analysis. CRP was deposited in necrotic and inflamed tissue, but not in adjacent healthy tissue. Tissue deposited CRP was detected by mCRP-specific antibodies and structurally different from serum pCRP. mCRP but not pCRP induced reactive oxygen species production by monocytes and facilitated uptake of necrotic Jurkat cells by macrophages. In addition, it accelerated migration of keratinocytes in a scratch wound assay. The structural changes that occur in pCRP upon localization to damaged and inflamed tissue in burn wounds result in a functionally altered protein with distinct functions. mCRP exhibits opsonic, proinflammatory and promigratory properties which modulate wound healing.

Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms. DOI: http://dx.doi.org/10.7554/eLife.12572.001, eLife digest An animal’s ability to rapidly and efficiently locate new sources of food in its environment can mean the difference between life and death. As a result, animals have evolved foraging strategies that are adapted to the distribution and detectability of food sources. Organisms ranging from bacteria to humans use one such strategy, called random search, to locate food that cannot be detected at a distance and that is randomly distributed in their surroundings. The biological mechanisms that underpin random search are relatively well understood in single-cell organisms such as bacteria, but this information tells us little about the mechanisms that are used by animals, which use their nervous system to control their foraging behavior. Roberts et al. have now investigated the biological basis for random search behavior in a tiny roundworm called Caenorhabditis elegans. This worm forages for pockets of bacteria in decaying plant matter and has a simple and well-understood nervous system. Roberts et al. used information on how the cells in this worm’s nervous system connect together into so-called “neural circuits” to generate a mathematical model of random searching. The model revealed that the worm’s neural circuitry for random searching can be understood in terms of two groups of neuron-like components that switch randomly between “ON” and “OFF” states. While one group promotes forward movement, the other promotes backward movement, which is associated with a change in search direction. These two groups inhibit each other so that only one group usually is active at a given time. By adjusting this model to reproduce the behavioral records of real worms searching for food, Roberts et al. could predict the key neuronal connections involved. These predictions were then confirmed by taking electrical recordings from neurons. The model could also account for the unexpected behavioral effects that are seen when a neuron in one of these groups was destroyed or altered by a genetic mutation. These findings thus reveal a biological mechanism for random search behavior in worms that might operate in other animals as well. The findings might also provide future insight into the neural circuits involved in sleep and wakefulness in mammals, which is organized in a similar way. DOI: http://dx.doi.org/10.7554/eLife.12572.002

Recent evidence suggests that the prototypic acute phase reactant C-reactive protein (CRP) is not only a marker but also a potential contributor to inflammatory diseases. CRP belongs to the family of pentraxins and as such consists of five identical non-covalently linked subunits. Contradictory data on the characteristics of CRP as either being pro- or anti-inflammatory may be explained by the existence of two conformations of the protein: the circulating native, pentameric CRP (pCRP) and the monomeric isoform (mCRP), formed as a result of a dissociation process of pCRP. In vitro both isoforms exhibit a very distinct inflammatory profile. We recently identified a localized, physiologically relevant pCRP dissociation mechanism by activated platelets and apoptotic cells and showed the deposition of mCRP in inflamed tissue. Here we review the literature on the causal role of pCRP and mCRP in the light of our findings and critically analyze the current controversies around CRP. The novel understanding of the localized dissociation of circulating pentameric CRP to the distinctively pro-inflammatory monomeric CRP allows for a new view on CRP in inflammatory reactions and further highlights mCRP and the pCRP dissociation process as a potential therapeutic target.

Chemotaxis inCaenorhabditis elegansdepends critically on the rate of change of attractant concentration computed as the worm moves through its environment. This computation depends, in turn, on the neuron class ASE, a left–right pair of pair of chemosensory neurons that is functionally asymmetric such that the left neuron is an on-cell, whereas the right neuron is an off-cell. To determine whether this coding strategy is a general feature of chemosensation inC. elegans, we imaged calcium responses in all chemosensory neurons known or in a position to contribute to chemotaxis to tastants in this organism. This survey revealed one new class of on-cells (ADF) and one new class of off-cells (ASH). Thus, the ASE class is unique in having both an on-cell and an off-cell. We also found that the newly characterized on-cells and off-cells promote runs and turns, respectively, mirroring the pattern reported previously for ASEL and ASER. Our results suggest that theC. eleganschemotaxis network is specialized for the temporal differentiation of chemosensory inputs, as required for chemotaxis.

Chemotaxis in Caenorhabditis elegans, like chemotaxis in bacteria, involves a random walk biased by the time derivative of attractant concentration, but how the derivative is computed is unknown. Laser ablations have shown that the strongest deficits in chemotaxis to salts are obtained when the ASE chemosensory neurons (ASEL and ASER) are ablated, indicating that this pair has a dominant role. Although these neurons are left-right homologues anatomically, they exhibit marked asymmetries in gene expression and ion preference. Here, using optical recordings of calcium concentration in ASE neurons in intact animals, we demonstrate an additional asymmetry: ASEL is an ON-cell, stimulated by increases in NaCl concentration, whereas ASER is an OFF-cell, stimulated by decreases in NaCl concentration. Both responses are reliable yet transient, indicating that ASE neurons report changes in concentration rather than absolute levels. Recordings from synaptic and sensory transduction mutants show that the ON-OFF asymmetry is the result of intrinsic differences between ASE neurons. Unilateral activation experiments indicate that the asymmetry extends to the level of behavioural output: ASEL lengthens bouts of forward locomotion (runs) whereas ASER promotes direction changes (turns). Notably, the input and output asymmetries of ASE neurons are precisely those of a simple yet novel neuronal motif for computing the time derivative of chemosensory information, which is the fundamental computation of C. elegans chemotaxis. Evidence for ON and OFF cells in other chemosensory networks suggests that this motif may be common in animals that navigate by taste and smell.

Extracorporeal shockwave therapy (ESWT) is used in a number of indications in the medical field. A number of tendinopathies show good and excellent results due to evidence based medicine. The treatment of lateral epicondylitis is known to show conflicting results. This overview of the published RCT's on ESWT for lateral epicondylitis tries to show the reasons for this conflicting data-base and point out, why we think that this is still a main indication for extracorporeal shockwave therapy.

Extracorporeal shockwave therapy (ESWT) has gained acceptance in the medical field and in the treatment of non-unions and delayed bone healing. ESWT has been used effectively for many years as a noninvasive surgical procedure. The idea of treating Osteochondritis dissecans of knee and talus arose in the middle of the 1990's. OCD is known as a pre-arthritic factor in the long-term and still there is no consistent treatment. In the literature there is still only a small number of publications but international societies for shockwave treatment are convinced that ESWT on OCD shows to be an effective and safe method in the treatment of OCD in the early stages. We want to summarize the actual data on the treatment of OCD by ESWT.

Unilateral facial paralysis is a common disease that is associated with significant functional, aesthetic and psychological issues. Though idiopathic facial paralysis (Bell's palsy) is the most common diagnosis, patients can also present with a history of physical trauma, infectious disease, tumor, or iatrogenic facial paralysis. Early repair within one year of injury can be achieved by direct nerve repair, cross-face nerve grafting or regional nerve transfer. It is due to muscle atrophy that in long lasting facial paralysis complex reconstructive methods have to be applied. Instead of one single procedure, different surgical approaches have to be considered to alleviate the various components of the paralysis. The reconstruction of a spontaneous dynamic smile with a symmetric resting tone is a crucial factor to overcome the functional deficits and the social handicap that are associated with facial paralysis. Although numerous surgical techniques have been described, a two-stage approach with an initial cross-facial nerve grafting followed by a free functional muscle transfer is most frequently applied. In selected patients however, a single-stage reconstruction using the motor nerve to the masseter as donor nerve is superior to a two-stage repair. The gracilis muscle is most commonly used for reconstruction, as it presents with a constant anatomy, a simple dissection and minimal donor site morbidity. Here we demonstrate the pre-operative work-up, the post-operative management, and precisely describe the surgical procedure of single-stage microsurgical reconstruction of the smile by free functional gracilis muscle transfer in a step by step protocol. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly comprehend the procedure. We further discuss indications and limitations of the technique and demonstrate representative results.

The inflammatory sequelae of ischemia-reperfusion injury (IRI) are a major causal factor of tissue injury in various clinical settings. MicroRNAs (miRs) are short, non-coding RNAs, which regulate protein expression. Here, we investigated the role of miR-155 in IR-related tissue injury. Quantifying microRNA-expression levels in a human muscle tissue after IRI, we found miR-155 expression to be significantly increased and to correlate with the increased expression of TNF-α, IL-1β, CD105, and Caspase3 as well as with leukocyte infiltration. The direct miR-155 target gene SOCS-1 was downregulated. In a mouse model of myocardial infarction, temporary LAD ligation and reperfusion injury resulted in a smaller area of necrosis in miR-155-/- animals compared to wildtype animals. To investigate the underlying mechanisms, we evaluated the effect of miR-155 on inflammatory cell recruitment by intravital microscopy and on the generation of reactive oxygen species (ROS) of macrophages. Our intravital imaging results demonstrated a decreased recruitment of inflammatory cells in miR-155-/- animals during IRI. The generation of ROS in leukocytic cells of miR-155-/- animals was also reduced. RNA silencing of the direct miR-155 target gene SOCS-1 abrogated this effect. In conclusion, miR-155 aggravates the inflammatory response, leukocyte infiltration and tissue damage in IRI via modulation of SOCS-1-dependent generation of ROS. MiR-155 is thus a potential target for the treatment or prevention of IRI.

Einleitung: Zur Rekonstruktion der Mundwinkelmotilität bei Fazialisparese gilt das zweizeitige Vorgehen mit Crossface Nerve Graft (CFNG) und freiem funktionellen Muskeltransfer als “Gold-Standard”. Eine einzeitige Alternative ist der Anschluss des Muskels an den N. massetericus, einem[for full text, please go to the a.m. URL], 132. Kongress der Deutschen Gesellschaft für Chirurgie

Zebrafish larvae show characteristic prey capture behavior in response to small moving objects. The neural mechanism used to recognize objects as prey remains largely unknown. We devised a machine learning behavior classification system to quantify hunting kinematics in semi-restrained animals exposed to a range of virtual stimuli. Two-photon calcium imaging revealed a small visual area, AF7, that was activated specifically by the optimal prey stimulus. This pretectal region is innervated by two types of retinal ganglion cells, which also send collaterals to the optic tectum. Laser ablation of AF7 markedly reduced prey capture behavior. We identified neurons with arbors in AF7 and found that they projected to multiple sensory and premotor areas: the optic tectum, the nucleus of the medial longitudinal fasciculus (nMLF) and the hindbrain. These findings indicate that computations in the retina give rise to a visual stream which transforms sensory information into a directed prey capture response. DOI: http://dx.doi.org/10.7554/eLife.04878.001, eLife digest Our ability to recognize objects, and to respond instinctively to them, is something that is not fully understood. For example, seeing your favorite dessert could trigger an irresistible urge to eat it. Yet precisely how the image of the dessert could trigger an inner desire to indulge is a question that has so far eluded scientists. This compelling question also applies to the animal kingdom. Predators often demonstrate a typical hunting behavior upon seeing their prey from a distance. But just how the image of the prey triggers this hunting behavior is not known. Semmelhack et al. have now investigated this question by looking at the hunting behavior of zebrafish larvae. The larvae's prey is a tiny microbe that resembles a small moving dot. When the larvae encounter something that looks like their prey, they demonstrate a hardwired hunting response towards it. The hunting behavior consists of a series of swimming maneuvers to help the larvae successfully capture their prey. Semmelhack et al. used prey decoys to lure the zebrafish larvae, and video recordings to monitor the larvae's response. During the recordings, the larvae were embedded in a bed of jelly with only their tails free to move. The larvae's tail movements were recorded, and because the larvae are completely transparent, their brain activity could be visually monitored at the same time using calcium dyes. Using this approach, Semmelhack et al. identified a specific area of the brain that is responsible for triggering the larvae's hunting behavior. It turns out that this brain region forms a circuit that directly connects the retina at the back of the eye to nerve centers that control hunting maneuvers. So when the larva sees its prey, this circuit could directly trigger the larva's hunting behavior. When the circuit was specifically destroyed with a laser, this instinctive hunting response was impaired. These findings suggest that predators have a distinct brain circuit that hardwires their hunting response to images of their prey. Future studies would involve understanding precisely how this circuit coordinates the larvae's complex hunting behavior. DOI: http://dx.doi.org/10.7554/eLife.04878.002

Wahrend der Studie zur Wirkung der extrakorporalen Stoswellentherapie bei der adulten Osteochondrosis dissecans von Knie und Sprunggelenk fand sich der im Artikel beschriebene Fall. Ein 29-jahriger Hobbysportler litt uber 2 Jahre unter anhaltenden Schmerzen des Knies. Rontgen- und kernspintomographische Untersuchungen zeigten eine progrediente Osteochondrosis dissecans III. In der diagnostischen Arthroskopie zeigten sich eine ausgepragte Chondromalazie III–IV sowie ein freier Gelenkkorper. Nach weiteren histologischen und szintigraphischen Untersuchungen wurde eine hochenergetische Stoswellentherapie (ESWT) durchgefuhrt. Im Intervall von 3 Monaten erfolgten MRT-Kontrollen und nach einem halben Jahr erschien eine 2. hochenergetische Stoswellentherapie notwendig. Ein weiteres halbes Jahr spater, also 14 Monate nach der primaren diagnostischen Arthroskopie, zeigten sich in einer 2. diagnostischen Arthroskopie und in der MRT-Kontrolle die komplette Ausheilung des Knorpeldefekts mit hyalinen Knorpel sowie eine deutliche Verbesserung der osteochondralen Lasion.

Free muscle transfer innervated by a cross-facial nerve graft represents the criterion standard for smile reconstruction in facial paralysis. If primary reconstruction fails, a second muscle transfer is usually needed. Herein, we investigated the possibility of avoiding a second free muscle transfer by in situ coaptation of the gracilis muscle to the masseteric nerve.We report a series of 3 failed free muscle transfers for facial reanimation among 21 free flap transfers performed for facial reanimation between March 2008 and August 2013. To salvage the muscle, we performed coaptation of the neural pedicle from the cross-facial nerve graft to the masseteric nerve. This method allows for leaving the fixation sutures of the muscle at the oral commissure in place. All patients showed muscle contraction after 3 months and a smile with open mouth after 6 months. No significant difference in the range of commissure excursion was observed between the healthy and operated sides.Recoaptation of the neural pedicle from the cross-facial nerve graft to the masseteric nerve, leaving the muscle transplant in place, is a suitable salvage procedure after unsuccessful reconstruction with a cross-facial nerve graft, avoiding a second free muscle transfer.4.

Background— The relevance of the dissociation of circulating pentameric C-reactive protein (pCRP) to its monomeric subunits (mCRP) is poorly understood. We investigated the role of conformational C-reactive protein changes in vivo. Methods and Results— We identified mCRP in inflamed human striated muscle, human atherosclerotic plaque, and infarcted myocardium (rat and human) and its colocalization with inflammatory cells, which suggests a general causal role of mCRP in inflammation. This was confirmed in rat intravital microscopy of lipopolysaccharide-induced cremasteric muscle inflammation. Intravenous pCRP administration significantly enhanced leukocyte rolling, adhesion, and transmigration via localized dissociation to mCRP in inflamed but not noninflamed cremaster muscle. This was confirmed in a rat model of myocardial infarction. Mechanistically, this process was dependent on exposure of lysophosphatidylcholine on activated cell membranes, which is generated after phospholipase A2 activation. These membrane changes could be visualized intravitally on endothelial cells, as could the colocalized mCRP generation. Blocking of phospholipase A2 abrogated C-reactive protein dissociation and thereby blunted the proinflammatory effects of C-reactive protein. Identifying the dissociation process as a therapeutic target, we stabilized pCRP using 1,6-bis(phosphocholine)-hexane, which prevented dissociation in vitro and in vivo and consequently inhibited the generation and proinflammatory activity of mCRP; notably, it also inhibited mCRP deposition and inflammation in rat myocardial infarction. Conclusions— These results provide in vivo evidence for a novel mechanism that localizes and aggravates inflammation via phospholipase A2–dependent dissociation of circulating pCRP to mCRP. mCRP is proposed as a pathogenic factor in atherosclerosis and myocardial infarction. Most importantly, the inhibition of pCRP dissociation represents a promising, novel anti-inflammatory therapeutic strategy.

Wir untersuchten den Einsatz von CSE-Hemmern im klinischen Alltag bei Patienten nach akutem Myokardinfarkt in Deutschland bei 17732 konsekutiv eingeschlossenen Patienten der Myokardinfarktregister MIR-1 und MITRA-1. Eine klinische Nachbeobachtungsstudie wurde bei der MITRA-1-Studie durchschnittlich nach 18 Monaten durchgefuhrt. Insgesamt erhielten 30% der Patienten mit akutem Myokardinfarkt einen CSE-Hemmer bei Entlassung. Von 1994–1998 wurde eine Zunahme der Verordnung der CSE-Hemmer von 6% auf 44% beobachtet, aber auch 1998 erhielten noch weniger als die Halfte der Patienten mit akutem Myokardinfarkt einen CSE-Hemmer bei Entlassung. In einer logistischen Regressionsanalyse waren komplizierende Begleiterkrankungen wie Niereninsuffizienz (OR 0,7), Herzinsuffizienz (OR 0,7) und Diabetes mellitus (OR 0,9) mit einer geringen Verordnung von CSE-Hemmern assoziiert. Lebensalter >70 Jahre (OR 0,5) war ebenfalls mit einer geringeren Verordnung von CSE-Hemmern bei Entlassung aus der Klinik assoziiert. Die Patienten, die mit CSE-Hemmern entlassen worden waren, hatten eine niedrigere Langzeitmortalitat von 5,8% als die Patienten ohne CSE-Hemmer mit 12,9%. Nach Adjustierung fur Alter und Begleiterkrankungen war die CSE-Hemmer-Verordnung mit einer grenzwertig signifikanten Reduktion der Langzeit-Mortalitat assoziiert (multivariate OR 0,7, 95% KI 0,4–1,0). Eine Subgruppenanalyse des Therapienutzens, gemessen an der „number needed to treat” (NNT), der Zahl der Patienten, die mit CSE-Hemmern behandelt werden mussen, um einen Todesfall zu verhindern, wies bei den Patienten mit kardiovaskularen Risikofaktoren, wie Herzinsuffizienz (NNT 7,5), Diabetes mellitus (NNT 7,8) und Alter >70 Jahre (NNT 13,8), einen groseren Nutzen der Therapie nach als bei Patienten ohne diese Risikofaktoren (NNT 345). Die Hochrisikopatienten erhielten jedoch weniger CSE-Hemmer verordnet als Patienten ohne diese Risikofaktoren (Verordnungshaufigkeit 11,8% versus 19,8%).

In einer prospektiven klinischen Studie wurde der prognostische Vorhersagewert klinischer, laborchemischer und elektrophysiologischer Untersuchungsparameter bei komatosen Patienten nach kardiopulmonaler Reanimation evaluiert. Von 1997–1999 wurden 69Patienten, 21 Frauen und 48Manner, mittleres Alter 64 (17–90) Jahre eingeschlossen. 28Tage nach Reanimation waren 56,6% der Patienten verstorben, 43% der Uberlebenden entwickelten ein apallisches Syndrom. Ergebnisse: Das Fortbestehen einer komatosen Bewusstseinslage uber 48 Stunden nach Reanimation, persistierend hohe Serumkonzentrationen der Neuroproteine Neuronenspezifische Enolase (>30 ng/ml) und Sangtec 100 (>0,7 μg/l) und das Fehlen kortikaler Komplexe mittlerer Latenz (N70) bei Ableitung der Medianus-SEP zeigten mit hoher Spezifitat und Sensitivitat fruhzeitig eine individuell schlechte Prognose – Tod oder apallisches Syndrom – an. Dabei erwiesen sich die kortikalen Komplexe mittlerer Latenz allen anderen Parametern uberlegen. Schlussfolgerung: Die Autoren empfehlen fur die Prognosebeurteilung komatoser reanimierter Patienten auf der Intensivstation neben der taglichen klinisch-neurologischen Untersuchung die Ableitung der Medianus-SEP, und hier insbesondere der kortikalen Komplexe mittlerer Latenz sowie die Bestimmung der Serumkonzentration eines Neuroproteins NSE oder S 100 uber einen Zeitraum von 5 Tagen nach Reanimation.

BACKGROUND Critical illness polyneuropathy (CIP) remains a problem after open heart surgery. Recently, we reported about a retrospectively performed study pointing out that sepsis, the application of higher amounts of catecholamines and intervention such as chronic venovenous hemodiafiltration may be involved in the onset of CIP. A prospectively performed study is presented in order to evaluate the significance of risk factors initially after open heart surgery. METHODS From June 1997 until September 1998, patients undergoing open heart surgery and being ventilated beyond 3 days were prospectively enrolled in the study and underwent a standard protocol of electromyographic investigation in order to determine CIP. Several items were recorded: amount of catecholamines, serum levels of urea, creatinine, albumin, and glucose. The duration of sepsis and chronic venovenous hemodiafiltration were reevaluated. Additionally the age, the left ventricular end-diastolic pressure prior to the operation, the time of ICU stay and the time of ventilatory support were compared. RESULTS Within the observation period, 37 adult patients could be enrolled in the study, whereas 12 patients did develop CIP and 7 patients did not. Patients developing CIP required significantly different amounts of epinephrine (0.17 +/- 0.02 vs. 0.09 +/- 0.01 mg/kg/day, p < 0.05, t-test) higher amounts of norepinephrine (0.06 +/- 0.02 vs. 0.02 +/- 0.01 mg/kg/day, p

Im Beobachtungszeitraum von Mai 1993 bis Mai 1995 wurden 2 202 Patienten im Funktionsbereich Internistische Intensivtherapie der Klinik fur Innere Medizin behandelt, darunter waren 247 Patienten (11,2%) mit exogenen Intoxikationen. Von diesen Patienten verstarben 3% (n = 7). In einem zweijahrigen Vergleichszeitraum (1984–1985) wurden 2 121 Patienten betreut, davon 16% mit exogenen Intoxikationen; die Mortalitat lag bei 2%. Unter den verwendeten Noxen dominierte Alkohol allein (22%) oder in Kombination (27%). Bei den verbleibenden Fallen lagen Benzo-diazepine an erster Stelle, gefolgt von Hypnotika und Sedativa, Kardiaka, Pilzen und Gasen. Auch 1984–1985 war die Reihenfolge ahnlich (Sedativa und Hypnotika 32,2%, Transquilizer 24,8%, Analgetika 10,5%, Neuroleptika 6%). Stadtgasintoxikationen entfielen ganzlich. Die Situation hat sich bezuglich der Antidotgaben (z.B. Anticholium und Anexate) gebessert, so das die Verlaufe mit den Intoxikationen durch Anticholinergika und Benzodiazepine nicht mehr so schwer sind.

Critical illness polyneuropathy (CIP) is a recognized cause of muscle weakness and failure of weaning from a ventilator. In order to characterize the features of CIP, we have examined 28 consecutive surgical patients with severe sepsis using bedside electrophysiology. Of the 28 patients (median APACHE II score 31), 20 developed moderate to severe CIP, as shown by the presence of moderate to severe denervation activity on resting EMG. The median nerve compound muscle action potential (CMAP) amplitudes were reduced to 3.24 (SEM 0.48) mV, while sensory nerve action potential (SNAP) amplitudes obtained from the same nerve were normal (13.1 (1.9) microV). In approximately 50% of these patients, the reduction in CMAP exceeded 50% of the lower limit of normal. Similar results were obtained from stimulation of the ulnar nerve. We conclude that CIP is a major complication in patients with severe sepsis and prolonged artificial ventilation. It predominantly involves motor fibres and thus markedly interferes with weaning from the ventilator.

The zebrafish model system is helping researchers improve the health and welfare of people and animals and has become indispensable for advancing biomedical research. As genetic engineering is both resource intensive and time-consuming, sharing successfully developed genetically modified zebrafish lines throughout the international community is critical to research efficiency and to maximizing the millions of dollars in research funding. New restrictions on importation of zebrafish into Canada based on putative susceptibility to infection by the spring viremia of carp virus (SVCV) have been imposed on the scientific community. In this commentary, we review the disease profile of SVCV in fish, discuss the findings of the Canadian government's scientific assessment, how the interpretations of their assessment differ from that of the Canadian research community, and describe the negative impact of these regulations on the Canadian research community and public as it pertains to protecting the health of Canadians.

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, intestinal ischemia as well as following transplant and cardiovascular surgery. Reperfusion of previously ischemic tissue, while essential for the prevention of irreversible tissue injury, elicits excessive inflammation of the affected tissue. Adjacent to the production of reactive oxygen species, activation of the complement system and increased microvascular permeability, the activation of leukocytes is one of the principle actors in the pathological cascade of inflammatory tissue damage during reperfusion. Leukocyte activation is a multistep process consisting of rolling, firm adhesion and transmigration and is mediated by a complex interaction between adhesion molecules in response to chemoattractants such as complement factors, chemokines, or platelet-activating factor. While leukocyte rolling in postcapillary venules is predominantly mediated by the interaction of selectins with their counter ligands, firm adhesion of leukocytes to the endothelium is selectin-controlled via binding to intercellular adhesion molecules (ICAM) and vascular cellular adhesion molecules (VCAM). Gold standard for the in vivo observation of leukocyte-endothelial interaction is the technique of intravital microscopy, first described in 1968. Though various models of IRI (ischemia-reperfusion injury) have been described for various organs, only few are suitable for direct visualization of leukocyte recruitment in the microvascular bed on a high level of image quality. We here promote the digital intravital epifluorescence microscopy of the postcapillary venule in the cremasteric microcirculation of the rat as a convenient method to qualitatively and quantitatively analyze leukocyte recruitment for IRI-research in striated muscle tissue and provide a detailed manual for accomplishing the technique. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly appreciate, and safely perform the method. In a step by step protocol we depict how to get started with respiration controlled anesthesia under sufficient monitoring to keep the animal firmly anesthetized for longer periods of time. We then describe the cremasteric preparation as a thin flat sheet for outstanding optical resolution and provide a protocol for leukocyte imaging in IRI that has been well established in our laboratories.

Previous studies have reported that C-reactive protein (CRP) interacting with low-density lipoproteins (LDL) affects macrophage activation and LDL uptake. However, the physiological relevance of CRP-LDL interaction with circulating monocytes remains elusive. Moreover, recent studies have shown that CRP exists in two isoforms with partly opposing characteristics pentameric (pCRP) and monomeric CRP (mCRP). Here we investigated the effects of CRP interacting with minimally modified low-density lipoprotein (mmLDL) interaction in regard to events involved in formation of atherosclerotic plaque. We analyzed the effect of mmLDL on human monocytes and found a substantial increase in monocyte activation as evaluated by CD11b/CD18 expression and increased monocyte adhesion under static and under shear flow conditions to human endothelial cells. Monocyte adhesion and activation was attenuated by pCRP via the prevention of mmLDL binding to monocytes. These anti-inflammatory properties of pCRP were lost when it dissociates to the monomeric form. Our results elucidate the physiological relevance of the CRP-mmLDL interaction and furthermore confirm the importance of the previously described pCRP dissociation to mCRP as a localized inflammatory "activation" mechanism.

Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets.