Dual role for B-1a cells in immunity to influenza virus infection

B-1 cells are known to contribute most of the “natural antibodies” that are secreted in the steady state, antibodies which are crucial for protection against many pathogens including influenza virus. Whether the CD5+ B-1a subset plays a role during an active immune response is incompletely understood. In contrast to recent data suggesting a passive role for B-1a cells, data provided here show strong highly localized activation of B-1 cells in the draining lymph nodes of the respiratory tract after influenza infection. B-1 cells are identified as a major source for both steady state and infection-induced local virus-neutralizing IgM. The CD5+ B-1a subset is the main B-1 cell subset generating this response. B-1a cell responses are generated by their increased local accumulation rather than by antigen-specific expansion. Our study reveals that during infection with influenza, CD5-expressing B-1a cells respond to and contribute to protection, presumably without the need for B cell receptor–mediated antigen-specific signals, which are known to induce the death of B-1a cells rather than activation. With that, our data reveal fundamental differences in the response regulation of B-1 and B-2 cells during an infection

Chylous Leak During Posterior Approach to Juvenile Scoliosis Surgery: A Case Report.

CaseWe report the first documented case of chylous leak recognized intraoperatively during posterior spinal instrumentation and fusion for juvenile scoliosis in a female patient with a history of thoracotomy and decortication for an empyema.ConclusionsThoracic duct injury can lead to severe morbidity and mortality because of chylothorax formation. Although chylous leaks are a well-documented complication of the anterior approach to spine surgery, leaks during the posterior approach are rarely reported. When these chylous leaks are recognized intraoperatively, the likelihood of serious complications may be minimized by drain placement before closure

Entropic equality for worst-case work at any protocol speed

We derive an equality for non-equilibrium statistical mechanics in finite-dimensional quantum systems. The equality concerns the worst-case work output of a time-dependent Hamiltonian protocol in the presence of a Markovian heat bath. It has has the form "worst-case work = penalty - optimum". The equality holds for all rates of changing the Hamiltonian and can be used to derive the optimum by setting the penalty to 0. The optimum term contains the max entropy of the initial state, rather than the von Neumann entropy, thus recovering recent results from single-shot statistical mechanics. Energy coherences can arise during the protocol but are assumed not to be present initially. We apply the equality to an electron box.Comment: 4 page + 14 page appendix; 8 figures; AA

Regulation of miR-9 by Ethanol and the Effects of miR-9 Inhibition

Alcohol addiction is a complex disease that alters molecular pathways within the brain and leads to the development of alcohol tolerance. One of alcohol\u27s primary targets in the brain is BK potassium channels. BK channels are alternatively spliced and the splice variant expression is regulated by miR-9. Exposure to alcohol upregulates miR-9, an miRNA that modifies the cellular composition of BK channel isoforms and contributes to alcohol tolerance. The molecular mechanisms by which miR-9 is upregulated upon alcohol exposure are currently unknown. We hypothesize that miR-9 upregulation occurs at the transcriptional and/or post-transcriptional level and that inhibition of miR-9 will diminish the acute and long-term effects of alcoholism. We will investigate whether alcohol upregulates miR-9 through interactions with the miR-9 promoter and attempt to identify alcohol sensitive regions of the miR-9 promoter. Another mechanism by which alcohol may upregulate miR-9 is by directing post-transcriptional miRNA maturation through interactions with the enzymes Drosha or Dicer. Lastly, we will inhibit miR-9 expression through RNAi to characterize its role in ethanol sensitivity. Identification of the mechanism underlying miR-9 upregulation after exposure to alcohol will not only provide further insight into alcohol addiction, but may also contribute to the development of potential therapeutic treatments for alcoholism

5,7-Dibromo-2-methyl­quinolin-8-ol

In the title compound, C10H7Br2NO, the mol­ecule possesses a planar geometry with an r.m.s deviation of 0.0383 Å for all non-H atoms. The crystal structure displays O—H⋯N and C—H⋯O hydrogen bonding, as well as Br⋯Br contacts [3.6284 (4) Å]

Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice

INTRODUCTION: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which frequently develops in models of VILI, should be prevented. To study VILI in healthy mice, the authors used a MV model with clinically relevant ventilator settings, avoiding massive damage of lung structures and shock, and preventing metabolic acidosis. METHODS: Healthy C57Bl/6 mice (n = 66) or BALB/c mice (n = 66) were ventilated (tidal volume = 7.5 ml/kg or 15 ml/kg; positive end-expiratory pressure = 2 cmH2O; fraction of inspired oxygen = 0.5) for five hours. Normal saline or sodium bicarbonate were used to correct for hypovolaemia. Lung histopathology, lung wet-to-dry ratio, bronchoalveolar lavage fluid protein content, neutrophil influx and levels of proinflammatory cytokines and coagulation factors were measured. RESULTS: Animals remained haemodynamically stable throughout the whole experiment. Lung histopathological changes were minor, although significantly more histopathological changes were found after five hours of MV with a larger tidal volume. Lung histopathological changes were no different between the strains. In both strains and with both ventilator settings, MV caused higher wet-to-dry ratios, higher bronchoalveolar lavage fluid protein levels and more influx of neutrophils, and higher levels of proinflammatory cytokines and coagulation factors. Also, with MV higher systemic levels of cytokines were measured. All parameters were higher with larger tidal volumes. Correcting for metabolic acidosis did not alter endpoints. CONCLUSIONS: MV induces VILI, in the absence of a priming pulmonary insult and even with use of relevant (least injurious) ventilator settings. This model offers opportunities to study the pathophysiological mechanisms behind VILI and the contribution of MV to lung injury in the absence of pre-existing lung injury

A mouse model displays host and bacterial strain differences in Aerococcus urinae urinary tract infection

In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract