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PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0262088
Author(s):  
Wael Yousef

Critical thinking is a requisite skill for college success, employability, and conducive active civic participation. Empirical studies have noted to the low achievement of Arab students on critical thinking assessments. Insufficient endeavors have attempted to propose effective interventions enhancing critical thinking abilities among Arab students. The current analysis provides a preliminary overview of a special course designed to improve critical thinking skills among Arab college students. Results indicated a great improvement in all areas of critical thinking including explanation of information, identification of strategies, implementing solutions, and formulating logical inferences. Students’ scores on a critical thinking assessment increased from sufficient to good as a result of participating in the program. The gains are consistent after controlling for gender, major, class seniority, and nationality. Notwithstanding these promising results, this paper is limited in several respects including the choice of critical thinking assessments represented by two questions, the highly contextualized setting making it difficult to be replicated, and the convenient sampling strategy used to recruit participants. This set of limitations, however, does not discourage proactive attempts like designing special courses to enhance students’ critical thinking acquisition in the Middle East.


2021 ◽  
Author(s):  
Aidan G.C. Wright ◽  
Whitney R. Ringwald

Widiger and Hines raise a number of significant concerns with the Alternative Model of Personality Disorders (AMPD). This places the major class of psychiatric difficulties represented by the personality disorders in a precarious position because the model used in prior editions of the Diagnostic and Statistical Manual of Mental Disorders and currently reprinted in Section II is moribund if not dead, and with the AMPD’s significant problems their future is unclear. Although we agree that Widiger and Hines’ criticisms have merit, they are not the whole picture. We review additional relevant research that supports the contention that what differentiates personality disorders from other psychopathology is the self and interpersonal dysfunction, as Criterion A of the AMPD currently states. We emphasize the importance of drawing a distinction between the conceptual model and its operationalization. We argue that paradoxically, to save personality disorders we need to do away with them and replace them with the “interpersonal disorders”. There is strong theory, empirical research, and ethical arguments in favor of this conceptual reframing.


2021 ◽  
Author(s):  
Kang Wang ◽  
Zijing Jia ◽  
Linlin Bao ◽  
Lei Wang ◽  
Lei Cao ◽  
...  

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine.


Atmosphere ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1617
Author(s):  
Addison B. McAlister ◽  
James I. Vesto ◽  
Aaron Huang ◽  
Kathryn A. Wright ◽  
Emily J. McLaughlin Sta. Maria ◽  
...  

β-hydroxynitrates (HN) are a major class of products formed during OH and NO3 initiated oxidation of terpenes. Their production contributes significantly to secondary organic aerosol (SOA) formation and NOx sequestration. However, studying the condensed phase reactions of this important class of molecules has been hindered by the lack of commercially available authentic standards. The goal of this work was to examine the influence of water concentration and solvent identity on product yields of a tertiary HN derived from 3-carene prepared in house. To assess the role of water on conversion chemistry, bulk-phase reactions were conducted in DMSO-d6, a non-nucleophilic solvent, with a gradient of water concentrations, and analyzed with 1H NMR. Product identifications were made by comparison with authentic standards prepared in house. Four major products were identified, including an unexpected diol produced from carbocation rearrangement, diol diastereomers, and trans-3-carene oxide, with varying yields as a function of water concentration. Product yields were also measured in two protic, nucleophilic solvents, MeOD-d4 and EtOD-d6. Finally, reactions with added chloride formed alkyl chloride products in yields approaching 30%. These results are among the first to highlight the complexities of nucleophilic reactions of hydroxynitrates in bulk, mixed aqueous/organic media and to identify new, unexpected products.


2021 ◽  
Vol 22 (22) ◽  
pp. 12385
Author(s):  
Nikola Gligorijevic ◽  
Mirjana Radomirovic ◽  
Olgica Nedic ◽  
Marija Stojadinovic ◽  
Urmila Khulal ◽  
...  

The worldwide outbreak of COVID-19 was caused by a pathogenic virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therapies against SARS-CoV-2 target the virus or human cells or the immune system. However, therapies based on specific antibodies, such as vaccines and monoclonal antibodies, may become inefficient enough when the virus changes its antigenicity due to mutations. Polyphenols are the major class of bioactive compounds in nature, exerting diverse health effects based on their direct antioxidant activity and their effects in the modulation of intracellular signaling. There are currently numerous clinical trials investigating the effects of polyphenols in prophylaxis and the treatment of COVID-19, from symptomatic, via moderate and severe COVID-19 treatment, to anti-fibrotic treatment in discharged COVID-19 patients. Antiviral activities of polyphenols and their impact on immune system modulation could serve as a solid basis for developing polyphenol-based natural approaches for preventing and treating COVID-19.


2021 ◽  
Author(s):  
Zewei Chen ◽  
Ziyi Zhao ◽  
Xinjie Hui ◽  
Junya Zhang ◽  
Yixue Hu ◽  
...  

The proteins secreted through type 1 secretion systems often play important roles in pathogenicity of various gram-negative bacteria. However, the type 1 secretion mechanism remains unknown. In this research, we observed the sequence features of RTX proteins, a major class of type 1 secreted substrates. We found striking non-RTX-motif amino acid composition patterns at the C-termini, most typically exemplified by the enriched '[FLI][VAI]' at the most C-terminal two positions. Machine-learning models, including deep-learning models, were trained using these sequence-based non-RTX-motif features, and further combined into a tri-layer stacking model, T1SEstacker, which predicted the RTX proteins accurately, with a 5-fold cross-validated sensitivity of ~0.89 at the specificity of ~0.94. Besides substrates with RTX motifs, T1SEstacker can also well distinguish non-RTX-motif type 1 secreted proteins, further suggesting their potential existence of common secretion signals. In summary, we made comprehensive sequence analysis on the type 1 secreted RTX proteins, identified common sequence-based features at the C-termini, and developed a stacking model that can predict type 1 secreted proteins accurately.


2021 ◽  
Vol 17 (10) ◽  
pp. e1009959
Author(s):  
Anna L. Gregory ◽  
Daniel A. Pensinger ◽  
Andrew J. Hryckowian

Clostridioides difficile is an opportunistic diarrheal pathogen responsible for significant morbidity and mortality worldwide. A disrupted (dysbiotic) gut microbiome, commonly engendered by antibiotic treatment, is the primary risk factor for C. difficile infection, highlighting that C. difficile–microbiome interactions are critical for determining the fitness of this pathogen. Here, we review short chain fatty acids (SCFAs): a major class of metabolites present in the gut, their production by the gut microbiome, and their impacts on the biology of the host and of C. difficile. We use these observations to illustrate a conceptual model whereby C. difficile senses and responds to SCFAs as a marker of a healthy gut and tunes its virulence accordingly in order to maintain dysbiosis. Future work to learn the molecular mechanisms and genetic circuitry underlying the relationships between C. difficile and SCFAs will help to identify precision approaches, distinct from antibiotics and fecal transplant, for mitigating disease caused by C. difficile and will inform similar investigations into other gastrointestinal pathogens.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroki Akiba ◽  
Tomoko Ise ◽  
Satoshi Nagata ◽  
Haruhiko Kamada ◽  
Hiroaki Ohno ◽  
...  

AbstractA major class of bispecific antibodies (BsAbs) utilizes heterodimeric Fc to produce the native immunoglobulin G (IgG) structure. Because appropriate pairing of heavy and light chains is required, the design of BsAbs produced through recombination or reassembly of two separately-expressed antigen-binding fragments is advantageous. One such method uses intein-mediated protein trans-splicing (IMPTS) to produce an IgG1-based structure. An extra Cys residue is incorporated as a consensus sequence for IMPTS in successful examples, but this may lead to potential destabilization or disturbance of the assay system. In this study, we designed a BsAb linked by IMPTS, without the extra Cys residue. A BsAb binding to both TNFR2 and CD30 was successfully produced. Cleaved side product formation was inevitable, but it was minimized under the optimized conditions. The fine-tuned design is suitable for the production of IgG-like BsAb with high symmetry between the two antigen-binding fragments that is advantageous for screening BsAbs.


Author(s):  
Seung Cho Lee ◽  
Robert A. Martienssen

Plant genomes are largely comprised of retrotransposons which can replicate through ‘copy and paste' mechanisms. Long terminal repeat (LTR) retrotransposons are the major class of retrotransposons in plant species, and importantly they broadly affect the expression of nearby genes. Although most LTR retrotransposons are non-functional, active retrotranspositions have been reported in plant species or mutants under normal growth condition and environmental stresses. With the well-defined reference genome and numerous mutant alleles, Arabidopsis studies have significantly expanded our understanding of retrotransposon regulation. Active LTR retrotransposon loci produce virus-like particles to perform reverse transcription, and their complementary DNA can be inserted into new genomic loci. Due to the detrimental consequences of retrotransposition, plants like animals, have developed transcriptional and post-transcriptional silencing mechanisms. Recently several different genome-wide techniques have been developed to understand LTR retrotransposition in Arabidopsis and different plant species. Transposome, methylome, transcriptome, translatome and small RNA sequencing data have revealed how host silencing mechanisms can affect multiple steps of retrotransposition. These recent advances shed light on future mechanistic studies of retrotransposition as well as retrotransposon diversity.


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