Absence of MHC-II expression by lymph node stromal cells results in autoimmunity.

How lymph node stromal cells (LNSCs) shape peripheral T-cell responses remains unclear. We have previously demonstrated that murine LNSCs, lymphatic endothelial cells (LECs), blood endothelial cells (BECs), and fibroblastic reticular cells (FRCs) use the IFN-γ-inducible promoter IV (pIV) of the MHC class II (MHCII) transactivator CIITA to express MHCII. Here, we show that aging mice (>1 yr old) in which MHCII is abrogated in LNSCs by the selective deletion of pIV exhibit a significant T-cell dysregulation in LNs, including defective Treg and increased effector CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell frequencies, resulting in enhanced peripheral organ T-cell infiltration and autoantibody production. The proliferation of LN-Tregs interacting with LECs increases following MHCII up-regulation by LECs upon aging or after exposure to IFN-γ, this effect being abolished in mice in which LECs lack MHCII. Overall, our work underpins the importance of LNSCs, particularly LECs, in supporting Tregs and T-cell tolerance

Effects of Cage Enrichment on Behavior, Welfare and Outcome Variability in Female Mice

The manner in which laboratory rodents are housed is driven by economics (minimal use of space and resources), ergonomics (ease of handling and visibility of animals), hygiene, and standardization (reduction of variation). This has resulted in housing conditions that lack sensory and motor stimulation and restrict the expression of species-typical behavior. In mice, such housing conditions have been associated with indicators of impaired welfare, including abnormal repetitive behavior (stereotypies, compulsive behavior), enhanced anxiety and stress reactivity, and thermal stress. However, due to concerns that more complex environmental conditions might increase variation in experimental results, there has been considerable resistance to the implementation of environmental enrichment beyond the provision of nesting material. Here, using 96 C57BL/6 and SWISS female mice, respectively, we systematically varied environmental enrichment across four levels spanning the range of common enrichment strategies: (1) bedding alone; (2) bedding + nesting material; (3) deeper bedding + nesting material + shelter + increased vertical space; and (4) semi-naturalistic conditions, including weekly changes of enrichment items. We studied how these different forms of environmental enrichment affected measures of animal welfare, including home-cage behavior (time–budget and stereotypic behavior), anxiety (open field behavior, elevated plus-maze behavior), growth (food and water intake, body mass), stress physiology (glucocorticoid metabolites in fecal boluses and adrenal mass), brain function (recurrent perseveration in a two-choice guessing task) and emotional valence (judgment bias). Our results highlight the difficulty in making general recommendations across common strains of mice and for selecting enrichment strategies within specific strains. Overall, the greatest benefit was observed in animals housed with the greatest degree of enrichment. Thus, in the super-enriched housing condition, stereotypic behavior, behavioral measures of anxiety, growth and stress physiology varied in a manner consistent with improved animal welfare compared to the other housing conditions with less enrichment. Similar to other studies, we found no evidence, in the measures assessed here, that environmental enrichment increased variation in experimental results

A framework for the joint institutionalization of climate change mitigation and adaptation in city administrations

Cities are key actors in reducing both the causes of climate change (mitigation) and its impact (adaptation), and many have developed separate mitigation and adaptation strategies and measures. However, in order to maximize outcomes, both scholars and practitioners are increasingly calling for more integrated and synergetic approaches. Unfortunately, related research remains scarce and fragmented, and there is a lack of systematic investigation into the necessary institutional conditions and processes. Against this background, this paper develops a framework to assess and support the joint institutionalization of climate adaptation and mitigation—here called adaptigation—in city administrations. This pioneering framework draws upon four key features of bureaucracies: organizational structure, visions and goals, actors, and technology and tools. Illustrated by pilot applications to the cities of Würzburg (Germany) and Mwanza (Tanzania), the framework provides a robust basis for future research, policy recommendations, and the development of context-specific guidelines for national and local decision-makers and officials. It highlights the importance of (i) clearly defined procedures for the implementation of adaptigation into urban planning processes (e.g., with the active involvement of stakeholders in the form of working groups or roundtable discussions), (ii) locally relevant goals and visions, established in collaboration with stakeholders, and (iii) the creation of mitigation and adaptation structures that are supported by the appropriate level of human resources, both within and outside city administrations. In this context, global, supranational, and national institutions play an important role in supporting institutionalization by providing targeted funding and promoting adaptigation, which requires the development of integrated goals, visions, and legislation

Institutionalizing climate change mitigation and adaptation through city advisory committees: Lessons learned and policy futures

Municipal advisory committees are becoming increasingly influential in guiding decision-making processes that address climatic issues. According to the Adaptigation Institutionalization Framework (included in the recent IPCC report), the implementation of such participatory structures is vital for the effective, joint institutionalization of climate change mitigation and adaptation. However, there is a lack of empirical evidence to support this claim. Against this background, this paper tests the Adaptigation Framework using the example of municipal advisory committees in Germany. Based on a review of 107 cities, and social network analyses of 20 cities, we develop a typology of advisory committees, examine their stakeholder constellations, and assess how they influence municipalities’ capacity to institutionalize joint mitigation and adaptation goals in sector policy and planning. Our results and the developed social network analysis approach can be used by cities worldwide to systematically analyze and enhance participation structures to address climate change more effectively. We conclude with some recommendations for future research and polic

Enhancing structures for joint climate change mitigation and adaptation action in city administrations–Empirical insights and practical implications

Increasing impacts from climate change have prompted international calls for the development of synergetic mitigation and adaptation policies and measures. While cities are seen as key actors in the implementation of related actions, there is a lack of scientific knowledge on the organizational conditions required to achieve this in practice. Our paper addresses this gap. Specifically, we assess the impact of various organizational configurations on the initiation of joint mitigation and adaptation resolutions by city councils in Germany. Our results demonstrate that the joint organizational institutionalization of mitigation and adaptation (i.e. joint departments) can be considered both as a necessary and significant prerequisite for joint implementation, unlike joint climate action plans. The developed methodology and identified conditions present an innovative way forward to assess and improve the initiation of integrated resolutions. Our work contributes to organizational and climate policy integration theories, and can help cities worldwide to optimize their organizational configurations and enhance joint mitigation and adaptation actions

A hybrid lattice basis reduction and quantum search attack on LWE

\u3cp\u3eRecently, an increasing amount of papers proposing post-quantum schemes also provide concrete parameter sets aiming for concrete post-quantum security levels. Security evaluations of such schemes need to include all possible attacks, in particular those by quantum adversaries. In the case of lattice-based cryptography, currently existing quantum attacks are mainly classical attacks, carried out with quantum basis reduction as subroutine. In this work, we propose a new quantum attack on the learning with errors (LWE) problem, whose hardness is the foundation for many modern lattice-based cryptographic constructions. Our quantum attack is based on Howgrave-Graham’s Classical Hybrid Attack and is suitable for LWE instances in recent cryptographic proposals. We analyze its runtime complexity and optimize it over all possible choices of the attack parameters. In addition, we analyze the concrete post-quantum security levels of the parameter sets proposed for the New Hope and Frodo key exchange schemes, as well as several instances of the Lindner-Peikert encryption scheme. Our results show that – depending on the assumed basis reduction costs – our Quantum Hybrid Attack either significantly outperforms, or is at least comparable to all other attacks covered by Albrecht–Player– Scott in their work “On the concrete hardness of Learning with Errors”. We further show that our Quantum Hybrid Attack improves upon the Classical Hybrid Attack in the case of LWE with binary error.\u3c/p\u3

Pulmonary Echinococcus multilocularis metastasis in a dog.

A young adult Labrador retriever dog was presented for surgical debulking of hepatic alveolar echinococcosis. Computed tomography detected hepatomegaly with multiple large cavitary masses with extension of tissue from a lesion wall into the caudal vena cava and numerous nodules in all lung lobes. Following euthanasia, histology confirmed parasitic vesicles with granulomatous reaction in all lesions, and polymerase chain reaction (PCR) established the causative agent to be Echinococcus multilocularis. This report is the first to present imaging features of pulmonary E. multilocularis granulomata in a dog

Ataxie aufgrund eines vertebralen Hämangiosarkoms mit Metastasierung bei einer 20-jährigen Schweizer Warmblutstute

A 20-year old Swiss Warmblood mare was referred to the Swiss Institute of Equine Medicine with a history of poor performance, coughing and ataxia and hindlimb weakness which progressed to recumbency. Lung auscultation revealed pronounced wheezing, blood work showed signs of chronic inflammation and increased bone turnover and thoracic ultrasound indicated patchy pulmonary consolidation. Cerebrospinal fluid revealed only mild, unspecific changes allowing exclusion of meningoencephalomyelitis and clinically relevant bleeding. Despite medical treatment and support in a sling the mare did not improve and was euthanized. Necropsy revealed a poorly demarcated, non-encapsulated and invasively growing mass dorsally in the musculature at the level of the forth cervical vertebra (C4) infiltrating the vertebral body and the spinal canal at the level of C1–C2. Multiple nodular, firm masses were present in all lobes of the lung and appeared to be mainly located in vessels. Histologically the masses were composed of spindle cells with marked anisocytosis, anisocaryosis, a high mitotic activity and showed invasive growth. These neoplastic cells stained positive for CD31, an endothelial cell marker, which confirmed diagnosis of a hemangiosarcoma. Definite ante mortem diagnosis of hemangiosarcoma, which is rare in horses, is challenging. Besides the vertebral localization, disseminated, locally invasive and cutaneous forms of hemangiosarcoma exist and can be either acquired or congenital. Prognosis for equine hemangiosarcoma and response to treatment are usually poor and progression of clinical signs is rapid. Vertebral hemangiosarcoma is an uncommon cause of spinal ataxia in horses.Eine 20-jährige Schweizer Warmblutstute mit einer Vorgeschichte von Husten und Leistungsschwäche wurde wegen akuter Ataxie und Hinterhandschwäche festliegend eingeliefert. Über der Lunge war lautes Giemen auskultierbar, eine Blutuntersuchung zeigte Anzeichen einer chronischen Entzündung sowie eines erhöhten Knochenstoffwechsels, und im Lungenultraschall waren multiple, oberflächliche, konsolidierte Bereiche sichtbar. Der Liquor cerebrospinalis war nur leichtgradig entzündlich verändert, was den Ausschluss einer Meningoen- cephalomyelitis oder einer klinisch bedeutsamen Blutung erlaubte. Trotz eines intensiven medikamentellen Therapieversuchs inklusive Aufhängung in einem Netz verbesserte sich der Zustand der Stute nicht und sie musste euthanasiert werden. Bei der Sektion wurde in der Muskulatur dorsal des vierten Halswirbels (C4) eine den Wirbel, den Wirbelkanal und in Höhe des 1. / 2. Halswirbels auch das Rückenmark infiltrierende, schlecht begrenzte Masse gefunden. In allen Lungenlappen wurden multiple derbe, teils mit den Gefässen assoziierte Massen vorgefunden. Histologisch waren die Massen in Halsmuskulatur, Halswirbeln, Wirbelkanal und Rückenmark aus Spindelzellen mit deutlicher Anisozytose, Anisokaryose und hoher Mitoserate zusammengesetzt und zeigten invasives Wachstum. Sie färbten sich immunohistochemisch positiv für CD31, einen Endothelzellmarker, an, was die Diagnose eines Hämangiosarkoms bestätigte. Eine definitive ante mortem Diagnose kann beim Hämangiosarkom, einer beim Pferd seltenen Erkrankung, meist nicht gestellt werden. Neben der vertebralen Lokalisation existieren disseminierte, lokal invasive und kutane Formen des Hämangiosarkoms, die entweder erworben oder angeboren sein können. Die Prognose für ein equines Hämangiosarkom und das Ansprechen auf Therapie sind gewöhnlich schlecht und das Voranschreiten der klinischen Symptome schnell. Das vertebrale Hämangiosarkom ist eine äusserst seltene Ursache für spinale Ataxie beim Pferd

Bacteriophages Improve Outcome in Experimental Staphylococcus Aureus Ventilator Associated Pneumonia.

RATIONALE Infections caused by multidrug resistant bacteria are a major clinical challenge. Phage therapy is a promising alternative antibacterial strategy. OBJECTIVE To evaluate the efficacy of intravenous phage therapy for the treatment of ventilator associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats. METHODS A randomized blinded controlled experimental study compared intravenous teicoplanin (3mg/kg, n=12), a cocktail of four phages (2-3 x 10^9 plaque forming units/ml of 2003, 2002, 3A and K, n=12) and combination of both (n=11), given two, 12 and 24 hours after induction of pneumonia, then once daily for four days. The primary outcome was survival at day four. Secondary outcomes were bacterial and phage densities in lungs and spleen, histopathological scoring of infection within the lungs and inflammatory biomarkers in blood. MEASUREMENTS AND MAIN RESULTS Treatment with either phages or teicoplanin increased survival from 0% to 58% and 50% respectively (p<0.005). Combination of phage with antibiotics did not further improve outcome (45% survival). Animal survival correlated with reduced bacterial burden in the lung (1.2 x 10^6 CFU/g of tissue for survivors versus 1.2 x 10^9 CFU/g for non-surviving animals, p<0.0001), as well as improved histopathological outcomes. Phage multiplication within the lung occurred during treatment. IL-1β increased for all treatment groups over the course of therapy. CONCLUSIONS Phage therapy was as effective as teicoplanin in improving survival and decreasing bacterial load within the lungs of rats infected with methicillin-resistant S. aureus. Combining antibiotics with phage therapy did not further improve outcomes. Key Words: bacteriophage; antibiotic resistance, microbial; pneumonia, ventilator associated