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Complement research experienced a renaissance with the discovery of a third activation route, the lectin pathway. We developed a unique model of total lectin pathway deficiency, a mouse strain lacking mannan-binding lectin-associated serine protease-2 (MASP-2), and analyzed the role of MASP-2 in two models of postischemic reperfusion injury (IRI). In a model of transient myocardial IRI, MASP-2-deficient mice had significantly smaller infarct volumes than their wild-type littermates. Mice deficient in the downstream complement component C4 were not protected, suggesting the existence of a previously undescribed lectin pathway-dependent C4-bypass. Lectin pathway-mediated activation of C3 in the absence of C4 was demonstrated in vitro and shown to require MASP-2, C2, and MASP-1/3. MASP-2 deficiency also protects mice from gastrointestinal IRI, as do mAb-based inhibitors of MASP-2. The therapeutic effects of MASP-2 inhibition in this experimental model suggest the utility of anti-MASP-2 antibody therapy in reperfusion injury and other lectin pathway-mediated disorders.

The purpose of this dissertation is to study and examine the underlying reasons for police use of deadly force and potential deadly force, in Canada and the United States of America, during the period from 1980 through 2002. Within this context, the phenomenon of victim-precipitated homicide, also known as “suicide-by-cop,” is examined. The reader is first introduced to the various legal and policy provisions that exist within Canada and, the United States of America that control and regulate police use of deadly force. The reader is then provided with a review of the literature surrounding the explanations and predictors of police use of deadly force. Within this context, the dissertation also explores those theories that serve to explain the changing patterns of extreme violence and suicide within society. The methods utilized to obtain and discern the data for this dissertation are provided. This is followed by a “findings and interpretations” section of the dissertation. This dissertation analyzes 843 separate documented incidents where police personnel, within Canada (n = 409) and the United States of America (n = 434), have discharged their firearms typically while facing a lethal threat. In 417 of these incidents, the police have responded by discharging their firearm and killing a total of 419 people. The remaining cases that were examined reflect incidents in which police personnel responded with less-lethal force. Through the examination of police investigations, Coroner and Medical Examiner records, government data and, interviews with police officers and prison inmates, this dissertation reveals that, in roughly a third of the cases examined (n = 273), police officers reacted to a lethal threat of victim-precipitated homicide. These are incidents in which an individual, who is typically predisposed to suicide or mental illness, has in a calculated and deliberate manner forced a police officer to use potentially deadly force. In addition, this dissertation reveals the link between the phenomenon of police assisted suicide and the phenomenon of suicide as a result of police intervention. The latter one refers to instances in which an individual predisposed to suicide has suddenly taken his or her own life upon the intervention by police.

[...] weight training is a much safer activity than most sports, and can help improve your child's ability to handle the stresses of running, kicking and throwing during sports participation.

To determine the influence of time from injury to surgery on neurological recovery and length of stay (LOS) in an observational cohort of individuals with traumatic spinal cord injury (tSCI), we analyzed the baseline and follow-up motor scores of participants in the Rick Hansen Spinal Cord Injury Registry to specifically assess the effect of an early (less than 24 h from injury) surgical procedure on motor recovery and on LOS. One thousand four hundred and ten patients who sustained acute tSCIs with baseline American Spinal Injury Association Impairment Scale (AIS) grades A, B, C, or D and were treated surgically were analyzed to determine the effect of the timing of surgery (24, 48, or 72 h from injury) on motor recovery and LOS. Depending on the distribution of data, we used different types of generalized linear models, including multiple linear regression, gamma regression, and negative binomial regression. Persons with incomplete AIS B, C, and D injuries from C2 to L2 demonstrated motor recovery improvement of an additional 6.3 motor points (SE=2.8 p<0.03) when they underwent surgical treatment within 24 h from the time of injury, compared with those who had surgery later than 24 h post-injury. This beneficial effect of early surgery on motor recovery was not seen in the patients with AIS A complete SCI. AIS A and B patients who received early surgery experienced shorter hospital LOS. While the issues of when to perform surgery and what specific operation to perform remain controversial, this work provides evidence that for an incomplete acute tSCI in the cervical, thoracic, or thoracolumbar spine, surgery performed within 24 h from injury improves motor neurological recovery. Early surgery also reduces LOS.

Many natural silks produced by spiders and insects are unique materials in their exceptional toughness and tensile strength, while being lightweight and biodegradable–properties that are currently unparalleled in synthetic materials. Myriad approaches have been attempted to prepare artificial silks from recombinant spider silk spidroins but have each failed to achieve the advantageous properties of the natural material. This is because of an incomplete understanding of the in vivo spidroin-to-fiber spinning process and, particularly, because of a lack of knowledge of the true morphological nature of spidroin nanostructures in the precursor dope solution and the mechanisms by which these nanostructures transform into micrometer-scale silk fibers. Herein we determine the physical form of the natural spidroin precursor nanostructures stored within spider glands that seed the formation of their silks and reveal the fundamental structural transformations that occur during the initial stages of extrusion en route to fiber formation. Using a combination of solution phase diffusion NMR and cryogenic transmission electron microscopy (cryo-TEM), we reveal direct evidence that the concentrated spidroin proteins are stored in the silk glands of black widow spiders as complex, hierarchical nanoassemblies (∼300 nm diameter) that are composed of micellar subdomains, substructures that themselves are engaged in the initial nanoscale transformations that occur in response to shear. We find that the established micelle theory of silk fiber precursor storage is incomplete and that the first steps toward liquid crystalline organization during silk spinning involve the fibrillization of nanoscale hierarchical micelle subdomains.

Scar formation is a potentially detrimental process of tissue restoration in adults, affecting organ form and function. During fetal development, cutaneous wounds heal without inflammation or scarring at early stages of development; however, they begin to heal with significant inflammation and scarring as the skin becomes more mature. One possible cell type that could regulate the change from scarless to fibrotic healing is the mast cell. We show here that dermal mast cells in scarless wounds generated at embryonic day 15 (E15) are fewer in number, less mature, and do not degranulate in response to wounding as effectively as mast cells of fibrotic wounds made at embryonic day 18 (E18). Differences were also observed between cultured mast cells from E15 and E18 skin, with regard to degranulation and preformed cytokine levels. Injection of mast cell lysates into E15 wounds disrupted scarless healing, suggesting that mast cells interfere with scarless repair. Finally, wounds produced at E18, which normally heal with a scar, healed with significantly smaller scars in mast cell-deficient KitW/W-v mice compared with Kit+/+ littermates. Together, these data suggest that mast cells enhance scar formation, and that these cells may mediate the transition from scarless to fibrotic healing during fetal development.

Migratory cells use distinct motility modes to navigate different microenvironments, but it is unclear whether these modes rely on the same core set of polarity components. To investigate this, we disrupted actin-related protein 2/3 (Arp2/3) and the WASP-family verprolin homologous protein (WAVE) complex, which assemble branched actin networks that are essential for neutrophil polarity and motility in standard adherent conditions. Surprisingly, confinement rescues polarity and movement of neutrophils lacking these components, revealing a processive bleb-based protrusion program that is mechanistically distinct from the branched actin-based protrusion program but shares some of the same core components and underlying molecular logic. We further find that the restriction of protrusion growth to one site does not always respond to membrane tension directly, as previously thought, but may rely on closely linked properties such as local membrane curvature. Our work reveals a hidden circuit for neutrophil polarity and indicates that cells have distinct molecular mechanisms for polarization that dominate in different microenvironments.

PurposeStudies have shown that bracing is an effective treatment for patients with idiopathic scoliosis. According to the current classification, almost all braces fall in the thoracolumbosacral orthosis (TLSO) category. Consequently, the generalization of scientific results is either impossible or misleading. This study aims to produce a classification of the brace types. MethodsFour scientific societies (SOSORT, SRS, ISPO, and POSNA) invited all their members to be part of the study. Six level 1 experts developed the initial classifications. At a consensus meeting with 26 other experts and societies’ officials, thematic analysis and general discussion allowed to define the classification (minimum 80% agreement). The classification was applied to the braces published in the literature and officially approved by the 4 scientific societies and by ESPRM. ResultsThe classification is based on the following classificatory items: anatomy (CTLSO, TLSO, LSO), rigidity (very rigid, rigid, elastic), primary corrective plane (frontal, sagittal, transverse, frontal & sagittal, frontal & transverse, sagittal & transverse, three-dimensional), construction—valves (monocot, bivalve, multisegmented), construction—closure (dorsal, lateral, ventral), and primary action (bending, detorsion, elongation, movement, push-up, three points). The experts developed a definition for each item and were able to classify the 15 published braces into nine groups. ConclusionThe classification is based on the best current expertise (the lowest level of evidence). Experts recognize that this is the first edition and will change with future understanding and research. The broad application of this classification could have value for brace research, education, clinical practice, and growth in this field.

Vibrio cholerae biotype El Tor is perpetuating the longest cholera pandemic in recorded history. The genomic islands VSP-1 and VSP-2 distinguish El Tor from previous pandemic V. cholerae strains. Using a co-occurrence analysis of VSP genes in >200,000 bacterial genomes we built gene networks to infer biological functions encoded in these islands. This revealed that dncV , a component of the cyclic-oligonucleotide-based anti-phage signalling system (CBASS) anti-phage defence system, co-occurs with an uncharacterized gene vc0175 that we rename avcD for anti-viral cytodine deaminase. We show that AvcD is a deoxycytidylate deaminase and that its activity is post-translationally inhibited by a non-coding RNA named AvcI. AvcID and bacterial homologues protect bacterial populations against phage invasion by depleting free deoxycytidine nucleotides during infection, thereby decreasing phage replication. Homologues of avcD exist in all three domains of life, and bacterial AvcID defends against phage infection by combining traits of two eukaryotic innate viral immunity proteins, APOBEC and SAMHD1. Deoxynucleotide depletion by a family of dCTP deaminases defends bacteria against phage infection.

The study of biodiversity started as a single unified field that spanned both ecology and evolution and both macro and micro phenomena. But over the 20th century, major trends drove ecology and evolution apart and pushed an emphasis towards the micro perspective in both disciplines. Macroecology and macroevolution re-emerged as self-consciously distinct fields in the 1970s and 1980s, but they remain largely separated from each other. Here, we argue that despite the challenges, it is worth working to combine macroecology and macroevolution. We present 25 fundamental questions about biodiversity that are answerable only with a mixture of the views and tools of both macroecology and macroevolution.