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Most SARS‐CoV‐2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41‐amino‐acid peptide. Here, we show that ORF3c is expressed in SARS‐CoV‐2‐infected cells and suppresses RIG‐I‐ and MDA5‐mediated IFN‐β induction. ORF3c interacts with the signaling adaptor MAVS, induces its C‐terminal cleavage, and inhibits the interaction of RIG‐I with MAVS. The immunosuppressive activity of ORF3c is conserved among members of the subgenus sarbecovirus, including SARS‐CoV and coronaviruses isolated from bats. Notably, however, the SARS‐CoV‐2 delta and kappa variants harbor premature stop codons in ORF3c, demonstrating that this reading frame is not essential for efficient viral replication in vivo and is likely compensated by other viral proteins. In agreement with this, disruption of ORF3c does not significantly affect SARS‐CoV‐2 replication in CaCo‐2, CaLu‐3, or Rhinolophus alcyone cells. In summary, we here identify ORF3c as an immune evasion factor of SARS‐CoV‐2 that suppresses innate sensing in infected cells. Synopsis: SARS‐CoV‐2‐encoded ORF3c is expressed in infected cells. This small viral protein is conserved among sarbecoviruses and suppresses the induction of IFN‐β by targeting the signaling adaptor protein MAVS.SARS‐CoV‐2 ORF3c is expressed in infected cells and suppresses IFN‐β induction.SARS‐CoV‐2 ORF3c interacts with the signaling adaptor MAVS.SARS‐CoV‐2 ORF3c induces C‐terminal cleavage of MAVS and inhibits its interaction with RIG‐I.The immunosuppressive activity of ORF3c is conserved among sarbecoviruses. [ABSTRACT FROM AUTHOR]

Cell‐intrinsic responses mounted in PBMCs during mild and severe COVID‐19 differ quantitatively and qualitatively. Whether they are triggered by signals emitted by productively infected cells of the respiratory tract or result from physical interaction with virus particles remains unclear. Here, we analyzed susceptibility and expression profiles of PBMCs from healthy donors upon ex vivo exposure to SARS‐CoV and SARS‐CoV‐2. In line with the absence of detectable ACE2 receptor expression, human PBMCs were refractory to productive infection. RT–PCR experiments and single‐cell RNA sequencing revealed JAK/STAT‐dependent induction of interferon‐stimulated genes (ISGs) but not proinflammatory cytokines. This SARS‐CoV‐2‐specific response was most pronounced in monocytes. SARS‐CoV‐2‐RNA‐positive monocytes displayed a lower ISG signature as compared to bystander cells of the identical culture. This suggests a preferential invasion of cells with a low ISG baseline profile or delivery of a SARS‐CoV‐2‐specific sensing antagonist upon efficient particle internalization. Together, nonproductive physical interaction of PBMCs with SARS‐CoV‐2‐ and, to a much lesser extent, SARS‐CoV particles stimulate JAK/STAT‐dependent, monocyte‐accentuated innate immune responses that resemble those detected in vivo in patients with mild COVID‐19. Synopsis: Human PBMCs, despite absent susceptibility to SARS‐CoV and SARS‐CoV‐2 infection, mount a JAK/STAT‐dependent innate immune response in monocytes upon exposure to SARS‐CoV‐2. ScRNA‐sequencing revealed an inverse relationship between SARS‐CoV‐2 RNA‐positivity and the IFN state.PBMCs are refractory and nonpermissive to SARS‐CoV and SARS‐CoV‐2 infection.Nevertheless, exposure of PBMCs to SARS‐CoV‐2 induces a JAK/STAT‐dependent cell‐intrinsic innate immune response that is most pronounced in monocytes.Monocytes positive for SARS‐CoV‐2 RNA display a lower IFN state as compared to RNA‐negative bystander cells, suggesting intracellular delivery of virion‐packaged IFN antagonists upon particle internalization. [ABSTRACT FROM AUTHOR]

The P‐stereogenic bis(phosphanes) 7 and 9, featuring pairs of P(Mes)‐ethynyl or vinyl substituents at the dimethyl xanthene backbone show rather low barriers of stereochemical inversion at phosphorus. π‐Conjugative effects are probably causing these low inversion barriers. Compound 7 reacted with B(C6F5)3 to form the nine‐membered heterocyclic product 10, featuring a [P]−C≡C−B(C6F5)3 substituent. Compound 7 was converted to the bis[P(Mes)vinyl] xanthene derivative 9, which gave the zwitterionic P(H)(Mes)−CH=CH−B(C6F5)3 containing product 16 upon treatment with B(C6F5)3. Thermally induced epimerization barriers at phosphorus of ca. 20 to 27 kcal mol−1 were calculated by DFT for the alkenyl‐ and alkynyl‐P derived systems 6 to 9, 15 and 16 and experimentally determined for the examples 7 and 16. [ABSTRACT FROM AUTHOR]

Attachment of a pair of P‐stereogenic mesityl(alkynyl)phosphanyl groups at the 4‐ and 5‐positions of a 9,9‐dimethylxanthene framework gave mixtures of the respective rac‐ and meso‐bisphosphanyl diastereoisomers. They slowly epimerized in a thermally induced reaction with Gibbs activation barriers of about 25 kcal mol−1 at room temperature (measured and DFT calculated). The reaction of the meso‐mesityl(tert‐butylethynyl)phosphanyl derivative with two molar equivalents of Piers′ borane [HB(C6F5)2] led to the formation of the alkylidene‐bridged geminal bisphosphane/borane‐frustrated Lewis pair system. The compound was obtained enriched (>85 %) in the rac diastereoisomer. With a variety of bifunctional donor substrates, the rac‐bis‐P/B FLP formed macrocyclic compounds. They were all formally derived from meso‐configurated diastereoisomers of the bisphosphanylxanthene backbone. [ABSTRACT FROM AUTHOR]

The current study aims to investigate corresponding self-control and self-control failures that are the result of ego depletion and its impact on police officers' decision to use force. For that purpose, a total of 200 German police recruits were randomly assigned to either an experimental or control group. Ego depletion was manipulated using the "e" crossing task. Participants then worked through a video-based scenario exercise, in which they encountered a provocative citizen. They were required to indicate the time that they would take to resort to using force to resolve the situation. Results showed that ego depleted officers intended to use force earlier than controls. This indicates that circumstances that produce ego depletion could lead to the inappropriate use of force by reducing self-control. This has major implications for the police use of force and how we understand police officers' decision making in response to provocation. [ABSTRACT FROM AUTHOR]

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (n = 3/4) and IgM (n = 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (n = 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays. [ABSTRACT FROM AUTHOR]

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A new pathway for the ring expansion reaction of antiaromatic boroles with organic azides is reported. While the reaction usually leads to 1,2‐azaborinines, it was diverted to the formation of a 1,2,3‐diazaborinine by changing the electronic characteristics of the reagents. The isolable azo‐azaborinine intermediate initially formed from the reaction of 1‐(2,3,4,5‐tetraphenylborolyl)ferrocene with 4‐azido‐N,N‐dimethylaniline gradually decomposed to a 1,2,3‐diazaborinine and benzonitrile. Both the spectroscopic properties and the reactivity of the heteroaromatic compound show analogies to pyridine, to which it is isoelectronic. Density functional theory (DFT) calculations provided insight into the mechanism of this unusual transformation. Nitrile & error: A new pathway for the ring expansion reaction of boroles with organic azides is presented, leading to a 1,2,3‐diazaborinine instead of the expected 1,2‐azaborinine. Mechanistic DFT calculations provided insight into the mechanism of formation of the BN2C3 heterocycle, and spectroscopic and reactivity studies demonstrated the analogies of the 1,2,3‐diazaborinine to pyridine. [ABSTRACT FROM AUTHOR]

Copyright of Nachrichten aus der Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Additive manufacturing is one of the key technologies of the 21st century. Additive manufacturing processes are often combined with subtractive manufacturing processes to create hybrid manufacturing because it is useful for manufacturing complex parts, for example, 3D printed sensor systems. Currently, several CNC machines are required for hybrid manufacturing: one machine is required for additive manufacturing and one is required for subtractive manufacturing. Disadvantages of conventional hybrid manufacturing methods are presented. Hybrid manufacturing with one CNC machine offers many advantages. It enables manufacturing of parts with higher accuracy, less production time, and lower costs. Using the example of fused layer modeling (FLM), we present a general approach for the integration of additive manufacturing processes into a numerical control for machine tools. The resulting CNC architecture is presented and its functionality is demonstrated. Its application is beyond the scope of this paper. [ABSTRACT FROM AUTHOR]

Compression bandaging is a major cornerstone in the treatment of chronic venous insufficiency. Its efficacy considerably depends on the applied pressure and it is therefore largely dependent on the individual applying the system. The sub-bandage pressure was measured under three consecutive compression bandages applied by 21 nurses before and after training and the introduction of a pressure monitor (Kikuhime®, MediTrade, Denmark). A questionnaire was used to evaluate the self-rating before and after the intervention. Before intervention, a questionnaire showed the confidence of the nurses in reaching sufficient sub-bandage pressure levels. However, 34·9% of all bandages were shown to be insufficient before intervention (< 20 or ≥ 60 mmHg) and only 17·5% after intervention, representing a statistically significant improvement through intervention. Of the insufficient bandages, 77·3% were applied by nurses with more than 10 years of working experience. Furthermore, the mean sub-bandage pressure in active standing position, a marker for the working pressure, was improved form 38·7 to 64·3 mmHg after intervention. Continuous awareness and training are necessary to maintain sufficient compression bandaging. The availability of a pressure monitor was helpful to reach this goal. Long work experience and self-rating alone is not sufficient to maintain adequate quality in compression bandaging. [ABSTRACT FROM AUTHOR]

Background: The G-DRG per case payments are calculated annually on the basis of present output and cost data provided from German hospitals. The economic valuation of dermatology-related DRGs depends largely on inpatients’ length of stay. At present, longitudinal analyses of dermatologic hospital data considering the development of length of stay under DRG conditions are not available. Methods: A multicenter, longitudinal study of clinical data from hospitals with different care levels was performed (n = 23). Frequent and relevant dermatologic diagnoses were grouped and analyzed over a time period of four years (2003–2006). The development of lengths of stay and of G-DRG cost weights were studied in detail. Descriptive statistical methods were applied. Results: After introduction of DRG, the data reveal a) reduction of length of stay in inpatient dermatology and b) after an initial abrupt rise, DRG valuation of dermatologic groups moderately decreased over time. Both trends changed most rapidly in the early years but reached a stable niveau in 2006. The study furthermore points out that not only length of stay, but also other type of costs influence DRG calculations. Conclusions: German dermatology reflects the international trend showing reductions of length of stay after introduction of a DRG-based hospital funding system. The DRG calculation and valuation of inpatient services depend on the duration of hospital stay. However, increasing per diem costs resulting from higher performances of every inpatient bed day are also taken into account. Further reduction of length of stay must not threaten the quality of inpatient care in dermatology. [ABSTRACT FROM AUTHOR]

The update of the G-DRG system for the year 2009 has been successfully negotiated. Like in the past years, changes are minimal and not dramatic, but they significantly enhance the quality of the DRG system. Once again, the German DRG system demonstrates its versatility and reliability for clinical reimbursement purposes. In the field of dermatology, several improvements or enhancements can be identified; the average case mix index that declined in the past years should now rise by 0.5 percent for 2009. Oncology cases are affected especially by this increase. Some refinements advanced for several years by the German Dermatologic Society (DDG) have been recognized –complex therapies like vacuum wound therapy, isolation due to multi-resistant infections and multiple primary tumors now have better cost weights. Although there still remain some minor problems like reimbursement of cost-intensive treatments, German dermatology is in summary very well prepared for the year 2009. [ABSTRACT FROM AUTHOR]

Background: In German-speaking countries, the specialty of dermatology is characterized by a large amount of subspecialties. Data providing information whether and to what extent these subspecialties are represented in German dermatology departments and clinics is not available. Methods: A national questionnaire survey was performed to determine the extent of involvement of dermatological subspecialties in dermatologic hospitals.Methods of descriptive statistics were applied. Results: Overall, 90 dermatologic departments participated in this survey with a response rate of 78.3 %.The subspecialties allergology, dermatooncology,and dermatologic surgery are represented in over 90 % of departments; the sub-specialties andrology, aesthetic dermatology, dermatopathology, microbiology,phlebology,photobiology,proctology, and wound healing are represented in over 50 % of clinics. Furthermore, the subspecialties allergology, dermato-oncology, photobiology, and dermatopathology have strong research or academic representation. Conclusions: The present survey demonstrates that dermatologic subspecialties are widely represented in dermatologic departments and clinics not only by individuals with specialty training but also by those in higher academic posts. This demonstrated high expertise should be maintained in German dermatology and could be promoted by academic programs. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The mature cysteine protease from Dermatophgoides pteronyssinus , Der p 1, is a major house dust mite allergen. Its enzymatic activity has been shown to have pro-inflammatory effects that could also negatively influence efficacy of allergen-specific immunotherapy. The aim of this study was to express recombinant pro-Der p 1 (rpro-Der p 1) in the yeast Pichia pastoris and to study its maturation. Expression was achieved at a concentration ranging from 45 mg·L-1 (methanol-induced expression) to 168 mg·L-1 (constitutive expression). No significant spontaneous maturation of the secreted proenzyme was observed. rpro-Der p 1 with a sequence-based molecular mass of 34 kDa was hyperglycosylated by the yeast, migrating at 50–60 kDa on SDS/PAGE. Compared with its natural counterpart (nDer p 1), the recombinant proenzyme demonstrated decreased IgE reactivity, resulting in a 30-fold lower capacity to induce histamine release from human basophils. Decreased immunoreactivity was also shown by competitive RIA and sandwich ELISA with Der p 1-specific antibody reagents. CD spectra of rpro-Der p 1 and nDer p 1 revealed significant structural differences. Deglycosylation of rpro-Der p 1 with endoglycosidase H resulted in a decrease in apparent molecular mass from 50 kDa to 34 kDa, but did not affect nDer p 1. On removal of N-glycans from rpro-Der p 1, which harbours two putative N-glycosylation sites in both propeptide and mature sequence, the mature rDer p 1 appeared. This suggests that hyperglycosylation hampers spontaneous maturation. Maturation of the recombinant pro-enzyme was also achieved by addition of the active natural cysteine protease, nDer p 1. In conclusion, high-level expression of rpro-Der p 1 in P. pastoris results in a stable hypoallergenic proenzyme with potential for use in allergen-specific immunotherapy. [ABSTRACT FROM AUTHOR]