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\"A collection of writings by those who fought Hitler from within Nazi Germany. While the 'Valkyrie' plot by Nazi officers to kill Adolf Hitler is the best known instance of German opposition to his dictatorship, there were many other significant acts of resistance. Behind Valkyrie collects documents, letters, and testimonies of Germans who fought Hitler from within, making many of them available in their entirety and in English for the first time. Peter Hoffmann assembles the words of citizens protesting the National Socialists' dismantling of the first democratic German republic, socialists and conservatives arguing for civil liberties, and dissatisfied senior military officials. Behind Valkyrie's first-hand accounts of reactions to crimes by the SS, mistreatment of millions of Soviet prisoners of war, mass murder of Jews, and the mismanagement of military campaigns show that attempts to maintain freedom, justice, and human rights often came from unexpected sources. While not free of the prejudices of their time, these nearly forgotten voices help provide a more complete understanding of the range of dissent during one of history's most disturbing epochs\"--From publisher's website.

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

Significance The stimulation of certain surface receptors on immune cells triggers the release of calcium (Ca ²⁺) stored in the endoplasmic reticulum (ER). This Ca ²⁺ flux is required for efficient activation and function of immune cells, and involves the ER membrane Ca ²⁺ channel, the inositol 1,4,5-triphosphate receptor (IP3R). We found that stable expression of IP3R requires the addition of a fatty acid through a process called palmitoylation catalyzed by an enzyme complex composed of DHHC6 (letters represent the amino acids aspartic acid, histidine, histidine, and cysteine in the catalytic domain) and selenoprotein K (Selk) proteins. These findings provide new mechanistic insight into the selenium-sensitive fine-tuning of immune cell activation through posttranslational modification of the IP3R Ca ²⁺ channel. This study also reveals a novel DHHC6/Selk enzyme complex responsible for regulating stable expression of the IP3R. Calcium (Ca ²⁺) is a secondary messenger in cells and Ca ²⁺ flux initiated from endoplasmic reticulum (ER) stores via inositol 1,4,5-triphosphate (IP3) binding to the IP3 receptor (IP3R) is particularly important for the activation and function of immune cells. Previous studies demonstrated that genetic deletion of selenoprotein K (Selk) led to decreased Ca ²⁺ flux in a variety of immune cells and impaired immunity, but the mechanism was unclear. Here we show that Selk deficiency does not affect receptor-induced IP3 production, but Selk deficiency through genetic deletion or low selenium in culture media leads to low expression of the IP3R due to a defect in IP3R palmitoylation. Bioinformatic analysis of the DHHC (letters represent the amino acids aspartic acid, histidine, histidine, and cysteine in the catalytic domain) family of enzymes that catalyze protein palmitoylation revealed that one member, DHHC6, contains a predicted Src-homology 3 (SH3) domain and DHHC6 is localized to the ER membrane. Because Selk is also an ER membrane protein and contains an SH3 binding domain, immunofluorescence and coimmunoprecipitation experiments were conducted and revealed DHHC6/Selk interactions in the ER membrane that depended on SH3/SH3 binding domain interactions. DHHC6 knockdown using shRNA in stably transfected cell lines led to decreased expression of the IP3R and impaired IP3R-dependent Ca ²⁺ flux. Mass spectrophotometric and bioinformatic analyses of the IP3R protein identified two palmitoylated cysteine residues and another potentially palmitoylated cysteine, and mutation of these three cysteines to alanines resulted in decreased IP3R palmitoylation and function. These findings reveal IP3R palmitoylation as a critical regulator of Ca ²⁺ flux in immune cells and define a previously unidentified DHHC/Selk complex responsible for this process.

Background Ambient air pollution poses a major risk for the development and aggravation of respiratory diseases. Evidence suggests that even in low-level air pollution environments there is a risk for an increase in adverse respiratory symptoms. We examined whether variations in daily air pollution levels of nitrogen dioxide, ozone, or particulate matter in Berlin, Germany were associated with hospital admissions of chronic obstructive pulmonary disease (COPD) and asthma patients in a time series analysis. Methods We calculated single and multi-pollutant models, investigated possible lags in effect, and analysed the influence of meteorological variables on the results. Data from January 2005 through December 2015 were used to quantify the concentration–response. Results The risk ratio for asthma patients to be hospitalised on the same day of NO 2 exposure was 1.101 per 10 µg/m 3 NO 2 increase (95% CI: 1.013 to 1.195), for COPD patients 1.123 (95% CI: 1.081 to 1.168). Neither the exposure to ozone (95% CI: 0.904 to 1.020), PM 10 (95% CI: 0.990 to 1.127), nor PM 2.5 (95% CI: 0.981 to 1.148) was associated with an increased risk ratio for asthma patients to be hospitalised . Risk ratios for the hospital admission of COPD patients were also not increased due to ozone (95% CI: 0.981 to 1.033), PM 10 (95% CI: 0.988 to 1.032), or PM 2.5 (95% CI: 0.966 to 1.019) exposure. The presented risk ratios and confidence intervals relate to the day of exposure. We found no increased hospitalisation risks with a delayed occurrence on subsequent days. Conclusions A quantifiable, statistically significant increase in risk for asthma and COPD exacerbations owing to NO 2 exposure at levels well below European regulatory limit values was observed.

\"Moods by Yoel Hoffmann--\"Isreal's celebrated avant-garde genius\" (The Forward)--supplies the magic missing link between the infinitesimal and the infinite. Part novel and part memoir, Yoel Hoffmann's Moods is flooded with feelings--about his family, losses, loves, the soul's hidden powers, old phone books, and life in the Galilee, with its every scent, breeze, notable dog, and odd neighbor. Carrying these shards is a general tenderness accentuated by a new dimension brought along with \"that great big pill of Prozac.\" Literature's so pathetic. We peddle fabric with a sun painted on it and no one even looks up... Beautifully translated by Peter Cole, Moods is fiction for lovers of poetry and poetry for lovers of fiction--a small marvel of a book and, with its pockets of joy, a curiously cheerful book by an author who once called himself \"a praying mantis inclined to melancholy\" -- Provided by publisher.

The incidence of many infections is seasonal e.g. surgical site infections, urinary tract infection and bloodstream infections. We questioned whether there is seasonal variation even in climate-controlled hospitalized patients, and analyzed the influence of climate parameters on nosocomial bloodstream infections. The retrospective cohort study is based on two databases: The German national surveillance system for nosocomial infections in intensive care units (ICU-KISS) from 2001 to 2015 and aggregated monthly climate data. Primary bloodstream infection (PBSI) is defined as a positive blood culture with one (or more) pathogen(s) which are not related to an infection on another site and which were not present at admission. Monthly infection data were matched with postal code, calendar month and corresponding monthly climate and weather data. All analyses were exploratory in nature. 1,196 ICUs reported data on PBSI to KISS. The ICUs were located in 779 hospitals and in 728 different postal codes in Germany. The majority of the 19,194 PBSI were caused by gram-positive bacteria. In total, the incidence density of BSI was 17% (IRR 1.168, 95%CI 1.076-1.268) higher in months with high temperatures ([greater than or equal to]20°C) compared to months with low temperatures (<5°C). The effect was most prominent for gram-negatives; more than one third (38%) higher followed by gram-positives with 13%. Fungi reached their highest IRR at moderately warm temperatures between 15-20°C. At such temperatures fungi showed an increase of 33% compared to temperatures below 5°C. PBSI spiked in summer with a peak in July and August. PBSI differed by pathogen: The majority of bacteria increased with rising temperatures. Enterococci showed no seasonality. S. pneumoniae reached a peak in winter time. The association of the occurrence of PBSI and temperatures [greater than or equal to]20°C was stronger when the mean monthly temperature in the month prior to the occurrence of BSI was considered instead of the temperature in the month of the occurrence of BSI. High average temperatures [greater than or equal to]20°C increased the risk of the development of a PBSI by 16% compared with low temperatures <5°C. Most nosocomial infections are endogenous in nature; the microbiome plays a crucial role in host health. If gut and skin microbiome varies with season, environmental parameters will contribute to the observed incidence patterns. Similarly, the impact of global warming on both local weather patterns and extreme weather events may influence the acquisition of pathogens. A better understanding of the etiology of these infections is needed to provide guidance for future infection control strategies.

يرى الكثير من النشطاء البيئيين وعلماء الطاقة أن أمام البشرية فقط بضعة عقود من السنين قبل وقوع الكارثة لإجراء التحول الضروري والجسيم من حضارة اقتصاد الوقود الأحفوري الى حضارة اقتصاد الهيدروجين ويتطلب ذلك إقصاء استعمال الوقود الأحفوري بجميع مشتقاته واستبداله بمصادر الطاقة البديلة المستدامة مع استعمال الهيدروجين كناقل للطاقة وتستدعي هذه العملية تحولات كبيرة في الاقتصاد والسياسة والمجتمع ويساعد في ذلك الدخول في عصر المعلوماتية والأنترنت.

Many of the 25 members of the selenoprotein family function as enzymes that utilize their selenocysteine (Sec) residues to catalyze redox-based reactions. However, some selenoproteins likely do not exert enzymatic activity by themselves and selenoprotein K (SELENOK) is one such selenoprotein family member that uses its Sec residue in an alternative manner. SELENOK is an endoplasmic reticulum (ER) transmembrane protein that has been shown to be important for ER stress and for calcium-dependent signaling. Molecular mechanisms for the latter have recently been elucidated using knockout mice and genetically manipulated cell lines. These studies have shown that SELENOK interacts with an enzyme in the ER membrane, DHHC6 (letters represent the amino acids aspartic acid, histidine, histidine, and cysteine in the catalytic domain), and the SELENOK/DHHC6 complex catalyzes the transfer of acyl groups such as palmitate to cysteine residues in target proteins, i.e., palmitoylation. One protein palmitoylated by SELENOK/DHHC6 is the calcium channel protein, the inositol 1,4,5-trisphosphate receptor (IP3R), which is acylated as a means for stabilizing the tetrameric calcium channel in the ER membrane. Factors that lower SELENOK levels or function impair IP3R-driven calcium flux. This role for SELENOK is important for the activation and proliferation of immune cells, and recently, a critical role for SELENOK in promoting calcium flux for the progression of melanoma has been demonstrated. This review provides a summary of these findings and their implications in terms of designing new therapeutic interventions that target SELENOK for treating cancers like melanoma.