NAIP/NLRC4 inflammasome activation in MRP8+ cells is sufficient to cause systemic inflammatory disease.

Inflammasomes are cytosolic multiprotein complexes that initiate protective immunity in response to infection, and can also drive auto-inflammatory diseases, but the cell types and signalling pathways that cause these diseases remain poorly understood. Inflammasomes are broadly expressed in haematopoietic and non-haematopoietic cells and can trigger numerous downstream responses including production of IL-1β, IL-18, eicosanoids and pyroptotic cell death. Here we show a mouse model with endogenous NLRC4 inflammasome activation in Lysozyme2 + cells (monocytes, macrophages and neutrophils) in vivo exhibits a severe systemic inflammatory disease, reminiscent of human patients that carry mutant auto-active NLRC4 alleles. Interestingly, specific NLRC4 activation in Mrp8 + cells (primarily neutrophil lineage) is sufficient to cause severe inflammatory disease. Disease is ameliorated on an Asc -/- background, and can be suppressed by injections of anti-IL-1 receptor antibody. Our results provide insight into the mechanisms by which NLRC4 inflammasome activation mediates auto-inflammatory disease in vivo

The Role of Work Pressure in IT Task Groups: Identifying Theoretical Constructs

This paper introduces the study of group work pressure (GWP) in information technology (IT) task groups. We theorize that GWP arises from demands and resources in group work and that high levels of GWP inhibit group performance. To identify the constructs of a new group task demands-resources (GTD-R) model, we solicit subjects’ descriptions of factors associated with high and low pressure group work situations they have experienced. We find that GWP is composed of characteristics of the task, group, environment, and individuals in the environment. Group characteristics include expertise of the group, group history, and degree of interpersonal conflicts. Individual characteristics include task motivation, personal expertise, and positive/negative consequences. Task complexity, time pressure, and external resources available to the group complete the model tasks. The findings extend prior demands-resources research, suggesting a research model for future study and practical mechanisms for reducing undesirable effects of GWP

Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)

A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics

NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.

NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as Naip1-6(Δ/Δ) mice lacking all functional Naip genes. By challenging Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-) mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6(Δ/Δ) mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo

Parametric Analyses In Randomized Clinical Trials

One salient feature of randomized clinical trials is that patients are randomly allocated to treatment groups, but not randomly sampled from any target population. Without random sampling parametric analyses are inexact, yet they are still often used in clinical trials. Given the availability of an exact test, it would still be conceivable to argue convincingly that for technical reasons (upon which we elaborate) a parametric test might be preferable in some situations. Having acknowledged this possibility, we point out that such an argument cannot be convincing without supporting facts concerning the specifics of the problem at hand. Moreover, we have never seen these arguments made in practice. We conclude that the frequent preference for parametric analyses over exact analyses is without merit. In this article we briefly present the scientific basis for preferring exact tests, and refer the interested reader to the vast literature backing up these claims. We also refute the assertions offered in some recent publications promoting parametric analyses as being superior in some general sense to exact analyses. In asking the reader to keep an open mind to our arguments, we are suggesting the possibility that numerous researchers have published incorrect advice, which has then been taught extensively in schools. We ask the reader to consider the relative merits of the arguments, but not the frequency with which each argument is made

Fire effects on temperate forest soil C and N storage

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116995/1/eap20112141189.pd

Correspondence between geometrical and differential definitions of the sine and cosine functions and connection with kinematics

In classical physics, the familiar sine and cosine functions appear in two forms: (1) geometrical, in the treatment of vectors such as forces and velocities, and (2) differential, as solutions of oscillation and wave equations. These two forms correspond to two different definitions of trigonometric functions, one geometrical using right triangles and unit circles, and the other employing differential equations. Although the two definitions must be equivalent, this equivalence is not demonstrated in textbooks. In this manuscript, the equivalence between the geometrical and the differential definition is presented assuming no a priori knowledge of the properties of sine and cosine functions. We start with the usual length projections on the unit circle and use elementary geometry and elementary calculus to arrive to harmonic differential equations. This more general and abstract treatment not only reveals the equivalence of the two definitions but also provides an instructive perspective on circular and harmonic motion as studied in kinematics. This exercise can help develop an appreciation of abstract thinking in physics.Comment: 6 pages including 1 figur

The influence of meridional ice transport on Europa’s ocean stratification and heat content

Jupiter’s moon Europa likely hosts a saltwater ocean beneath its icy surface. Geothermal heating and rotating convection in the ocean may drive a global overturning circulation that redistributes heat vertically and meridionally, preferentially warming the ice shell at the equator. Here we assess the previously unconstrained influence of ocean‐ice coupling on Europa’s ocean stratification and heat transport. We demonstrate that a relatively fresh layer can form at the ice‐ocean interface due to a meridional ice transport forced by the differential ice shell heating between the equator and the poles. We provide analytical and numerical solutions for the layer’s characteristics, highlighting their sensitivity to critical ocean parameters. For a weakly turbulent and highly saline ocean, a strong buoyancy gradient at the base of the freshwater layer can suppress vertical tracer exchange with the deeper ocean. As a result, the freshwater layer permits relatively warm deep ocean temperatures.Key PointsCoupling of Europa’s ocean circulation and the ice shell impacts global stratificationA low‐latitude freshwater layer may suppress vertical heat and tracer transportParameter space is explored based on properties observed by future missionsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137725/1/grl56051.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137725/2/grl56051-sup-0001-TextS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137725/3/grl56051_am.pd