Skin Dose Equivalent Measurement from Neutron-Deficient Isotopes.

Neutron-deficient-isotopes decay via positron emission and/or electron capture often followed by x-ray, gamma-ray, and 0.511 MeV photons from positron annihilation. For cases of significant area and/or personnel contamination with these isotopes, determination of skin dose equivalent (SDE) is required by 10CFR835. For assessment of SDE, we evaluated the MICROSPEC-2(TM) system manufactured by Bubble Technology Industries of Canada which uses three different probes for dose measurement. We used two probes: (1) the X-probe which measures lower energy (4 - 120 keV) photon energy distributions and determines deep dose equivalent, SDE and dose equivalent to eyes, and (2) the B-probe which measures electron (positron) energy distributions, and determines skin dose equivalent. Also, the measured photon and beta spectra can be used to identify radioactive isotopes in the contaminated area. Measurements with several neutron-deficient sources showed that this system provided reasonably accurate SDE rate measurements when compared with calculated benchmark SDE rates with an average percent difference of 40%. Variations were expected because of differences between the assumed geometries used by MlCROSPEC-2 and the calculations when compared to the measurement conditions

An Optogenetic Toolkit for Spatial and Temporal Control of the cAMP Dependent Protein Kinase

Cellular signaling is highly compartmentalized in both time and space as exemplified by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway. PKA and associated signaling proteins are sequestered to specific subcellular compartments by A-kinase anchoring proteins to generate distinct signaling microenvironments. These signaling nodes provide spatial specificity to PKA so that this otherwise ubiquitous signaling pathway is only activated in the right location and at the right time. Although many tools are available to manipulate cellular signaling on a global scale, it is difficult to control intracellular signaling with any degree of spatiotemporal resolution. Here, we present a set of optogenetic tools to control PKA signaling at the plasma membrane, cytoskeleton, and outer mitochondrial membrane. We used molecular engineering approaches in conjunction with biochemical and cell biology assays such as western blotting and fluorescent microscopy to show that activation of our optogenetic toolset in cells results in compartment specific PKA phosphorylation events upon stimulation with light, and that activity is localized to discrete locations within the cell using a PKA reporter system generated by our group. Abbreviations: Photoactivated adenylate cyclase (PAC, AC), Nucleus (Nu), Plasma Membrane (PM), Outer Mitochondrial Membrane (OMM), Vasodilator Stimulated Phosphoprotein (VASP

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages

A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJKIM) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJKIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJKIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways

Integrating Human Indoor Air Pollutant Exposure within Life Cycle Impact Assessment

Neglecting health effects from indoor pollutant emissions and exposure, as currently done in Life Cycle Assessment (LCA), may result in product or process optimizations at the expense of workers’ or consumers’ health. To close this gap, methods for considering indoor exposure to chemicals are needed to complement the methods for outdoor human exposure assessment already in use. This paper summarizes the work of an international expert group on the integration of human indoor and outdoor exposure in LCA, within the UNEP/SETAC Life Cycle Initiative. A new methodological framework is proposed for a general procedure to include human-health effects from indoor exposure in LCA. Exposure models from occupational hygiene and household indoor air quality studies and practices are critically reviewed and recommendations are provided on the appropriateness of various model alternatives in the context of LCA. A single-compartment box model is recommended for use as a default in LCA, enabling one to screen occupational and household exposures consistent with the existing models to assess outdoor emission in a multimedia environment. An initial set of model parameter values was collected. The comparison between indoor and outdoor human exposure per unit of emission shows that for many pollutants, intake per unit of indoor emission may be several orders of magnitude higher than for outdoor emissions. It is concluded that indoor exposure should be routinely addressed within LCA

Primary Extracranial Meningiomas: An Analysis of 146 Cases

Primary extracranial meningiomas are rare neoplasms, frequently misdiagnosed, resulting in inappropriate clinical management. To date, a large clinicopathologic study has not been reported. One hundred and forty-six cases diagnosed between 1970 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. Histologic features were reviewed, immunohistochemistry analysis was performed (n = 85), and patient follow-up was obtained (n = 110). The patients included 74 (50.7%) females and 72 (49.3%) males. Tumors of the skin were much more common in males than females (1.7:1). There was an overall mean age at presentation of 42.4 years, with a range of 0.3–88 years. The overall mean age at presentation was significantly younger for skin primaries (36.2 years) than for ear (50.1 years) and nasal cavity (47.1 years) primaries. Symptoms were in general non-specific and reflected the anatomic site of involvement, affecting the following areas in order of frequency: scalp skin (40.4%), ear and temporal bone (26%), and sinonasal tract (24%). The tumors ranged in size from 0.5 up to 8 cm, with a mean size of 2.3 cm. Histologically, the majority of tumors were meningothelial (77.4%), followed by atypical (7.5%), psammomatous (4.1%) and anaplastic (2.7%). Psammoma bodies were present in 45 tumors (30.8%), and bone invasion in 31 (21.2%) of tumors. The vast majority were WHO Grade I tumors (87.7%), followed by Grade II (9.6%) and Grade III (2.7%) tumors. Immunohistochemically, the tumor cells labeled for EMA (76%; 61/80), S-100 protein (19%; 15/78), CK 7 (22%; 12/55), and while there was ki-67 labeling in 27% (21/78), <3% of cells were positive. The differential diagnosis included a number of mesenchymal and epithelial tumors (paraganglioma, schwannoma, carcinoma, melanoma, neuroendocrine adenoma of the middle ear), depending on the anatomic site of involvement. Treatment and follow-up was available in 110 patients: Biopsy, local excision, or wide excision was employed. Follow-up time ranged from 1 month to 32 years, with an average of 14.5 years. Recurrences were noted in 26 (23.6%) patients, who were further managed by additional surgery. At last follow-up, recurrent disease was persistent in 15 patients (mean, 7.7 years): 13 patients were dead (died with disease) and two were alive; the remaining patients were disease free (alive 60, mean 19.0 years, dead 35, mean 9.6 years). There is no statistically significant difference in 5-year survival rates by site: ear and temporal bone: 83.3%; nasal cavity: 81.8%; scalp skin: 78.5%; other sites: 65.5% (P = 0.155). Meningiomas can present in a wide variety of sites, especially within the head and neck region. They behave as slow-growing neoplasms with a good prognosis, with longest survival associated with younger age, and complete resection. Awareness of this diagnosis in an unexpected location will help to avoid potential difficulties associated with the diagnosis and management of these tumors

A boom‐or‐bust approach — the ‘Glass Cannon’ hypothesis in host microbiomes

In Focus: Dunphy, CM, Vollmer, SV, Gouhier, TC. (2021) Host–microbial systems as glass cannons: Explaining microbiome stability in corals exposed to extrinsic perturbations. Journal of Animal Ecology, 90, 1044–1057. The importance of symbiotic microbial communities for the functioning of animal hosts is now well‐documented; however, the interactions between host microbiomes and stress are less well‐understood. Dunphy et al. used a common garden experiment to show that host–microbiomes vary in their resilience across different coral species. The authors then used mathematical modelling to provide novel evidence that species with microbiomes that are regulated by host processes are robust to perturbation from stressors, but that robustness comes at a higher cost to the host. Conversely, species with microbiomes that are regulated by microbial processes are generally much more resilient and cheaper to support, but when disrupted by external stressors, the communities break down entirely—these latter species are termed ‘glass cannons’. This novel hypothesis has important implications for how host microbiomes function in a rapidly changing world that exposes animal hosts to multiple biotic and abiotic perturbations