Simultaneous measurement of multiple parameters of a subwavelength structure based on the weak value formalism

A mathematical extension of the weak value formalism to the simultaneous measurement of multiple parameters is presented in the context of an optical focused vector beam scatterometry experiment. In this example, preselection and postselection are achieved via spatially-varying polarization control, which can be tailored to optimize the sensitivity to parameter variations. Initial experiments for the two-parameter case demonstrate that this method can be used to measure physical parameters with resolutions at least 1000 times smaller than the wavelength of illumination

Understanding How Lipopolysaccharide Impacts CD4 T Cell Immunity

Lipopolysaccharide (LPS) is a natural adjuvant synthesized by gram-negative bacteria that has profound effects on CD4 T cell responses. LPS stimulates cells through Toll-like receptor 4 (TLR4), causing the release of inflammatory cytokines and upregulation of costimulatory molecules on antigen presenting cells. The combination of signals from antigen, costimulation, and cytokines allow CD4 T cells to overcome suppressive barriers and accumulate in large numbers. T cells that are primed in an LPS-stimulated environment are programmed for long-term survival following clonal expansion. LPS is well-known for generating Th1 responses, however, under appropriate conditions it can also support differentiation into other T helper lineages, demonstrating its pleiotropic nature. Although molecular analyses have provided insights into how immune responses are controlled by LPS in vivo, its powerful adjuvant activity is also associated with toxicity. Research on partial TLR4 agonists such as monophosphoryl lipid A have demonstrated that toxicity and immunogenicity are not always linked, making them useful candidates for human vaccines. In this sense, many years of LPS research have ultimately contributed to vaccine design, and the next generation may involve studying how the balance between different CD4 T cell subsets is controlled

Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age.

The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain

Analysis of salmonid leukocytes purified by hypotonic lysis of erythrocytes

A technique that uses hypotonic lysis of erythrocytes was optimized for the purification of leukocytes from the peripheral blood and anterior kidney (pronephros) of rainbow trout Oncorhynchus mykiss. Comparisons of initial blood dilution (1:2, 1:4, and 1:6) and the time of exposure to hypotonic conditions (10, 20, and 40 s) revealed that a dilution of 1:2 provided the most complete hemolysis after 20 or 40 s in a hypotonic solution. For pronephros, a 1:5 (w:v) dilution and lysis in hypotonic solution for 10–40 s was effective in eliminating erythrocytes. Total leukocyte yield from the blood and pronephros by use of the hypotonic lysis method was comparable with that obtained by use of typical density gradient centrifugation, and cell viability was 97% or greater. Differential cell counts showed that hypotonic lysis resulted in a distribution of leukocyte cell types similar to that of density gradient separation. Hypotonic lysis of erythrocytes is a simple, rapid, and inexpensive method of purifying leukocytes from salmonid fish blood and pronephros

Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin

Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a β-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.Fil: Russo, Ashley J.. UConn Health School of Medicine; Estados UnidosFil: Vasudevan, Swathy O.. UConn Health School of Medicine; Estados UnidosFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kumari, Puja. UConn Health School of Medicine; Estados UnidosFil: Menoret, Antoine. UConn Health School of Medicine; Estados UnidosFil: Duduskar, Shivalee. Jena University Hospital; AlemaniaFil: Wang, Chengliang. UConn Health School of Medicine; Estados UnidosFil: Pérez Sáez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fettis, Margaret M.. University of Florida; Estados UnidosFil: Li, Chuan. UConn Health School of Medicine; Estados UnidosFil: Liu, Renjie. University of Florida; Estados UnidosFil: Wanchoo, Arun. University of Florida; Estados UnidosFil: Chandiran, Karthik. UConn Health School of Medicine; Estados UnidosFil: Ruan, Jianbin. UConn Health School of Medicine; Estados UnidosFil: Vanaja, Sivapriya Kailasan. UConn Health School of Medicine; Estados UnidosFil: Bauer, Michael. Jena University Hospital; AlemaniaFil: Sponholz, Christoph. Jena University Hospital; AlemaniaFil: Hudalla, Gregory A.. University of Florida; Estados UnidosFil: Vella, Anthony T.. UConn Health School of Medicine; Estados UnidosFil: Zhou, Beiyan. UConn Health School of Medicine; Estados UnidosFil: Deshmukh, Sachin D.. Jena University Hospital; AlemaniaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rathinam, Vijay A.. UConn Health School of Medicine; Estados Unido

Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age

Abstract: The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain

Malta : language, literacy and identity in a Mediterranean island society

Available documentation for the early modern period indicates that the Malta harbor towns achieved literacy earlier than the countryside. The Maltese townsmen lived on a trading route, and it was necessary for them to learn the lingua franca, as the language of trade in the Mediterranean. The educated elite were able to acquire fluent speaking knowledge, as well as the ability to write, Tuscan (a dialect then in the process of becoming standard Italian), while continuing to employ their local Maltese ‘dialect’ on numerous occasions. By and large, the erosion of the position of Maltese as the subordinate language was an inevitable by-product of this development. The Maltese language was able to attain the function of a literary language in the nineteenth century but it had no standard orthography until 1931 and was only adopted as Malta’s official language in 1964.peer-reviewe