Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards Engineering an Orthogonal Protein Translation Initiation System

In the last two decades, methods to incorporate non-canonical amino acids (ncAAs) into specific positions of a protein have advanced significantly; these methods have become general tools for engineering proteins. However, almost all these methods depend on the translation elongation process, and strategies leveraging the initiation process have rarely been reported. The incorporation of a ncAA specifically at the translation initiation site enables the installation of reactive groups for modification at the N-termini of proteins, which are attractive positions for introducing abiological groups with minimal structural perturbations. In this study, we attempted to engineer an orthogonal protein translation initiation system. Introduction of the identity elements of Escherichia coli initiator tRNA converted an engineered Methanococcus jannaschii tRNATyr into an initiator tRNA. The engineered tRNA enabled the site-specific incorporation of O-propargyl-l-tyrosine (OpgY) into the amber (TAG) codon at the translation initiation position but was inactive toward the elongational TAG codon. Misincorporation of Gln was detected, and the engineered system was demonstrated only with OpgY. We expect further engineering of the initiator tRNA for improved activity and specificity to generate an orthogonal translation initiation system.
The Zygotic Division Regulator ZAR1 Plays a Negative Role in Defense Against Botrytis cinerea in Arabidopsis

A phosphorylation/dephosphorylation cycle at tyrosine 428 of CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) plays an essential role in chitin triggered immunity in Arabidopsis thaliana. In this study, we used a differential peptide pull-down (PPD) assay to identify factors that could participate downstream of this cycle. We identified ZYGOTIC ARREST 1 (ZAR1) and showed that it interacts with CERK1 specifically when the tyrosine 428 (Y428) residue of CERK1 is dephosphorylated. ZAR1 was originally characterized as an integrator for calmodulin and G-protein signals to regulate zygotic division in Arabidopsis. Our current results established that ZAR1 also negatively contributed to defense against the fungus Botrytis cinerea and played a redundant role with its homolog ZAR2 in this process. The zar1-3 zar2-1 double mutant exhibited stronger resistance to B. cinerea compared with zar1-3 single mutant, zar2-1 single mutant, and wild-type plants. Moreover, the inducible expression of numerous defense response genes upon B. cinerea infection was increased in the zar1-3zar2-1 double mutant, consistent with a repressive role for ZAR proteins in the defense response. Therefore, our findings provided insight into the function of ZAR1 in multiple defenses and developmental regulation pathways.
Identification of kinetic triplets by results of derivatographic analysis

The method for identification of the triplet of kinetic parameters of a heterogeneous reaction using the data of the derivatographic analysis is proposed. This method is characterized by high accuracy and relative simplicity and it can be effectively realized using MS Excel software. Metal nanopowder is one of the most prospective high-energy materials that is widely used in many spheres [1, 2]. This explains long and sustained interest in studying the features of metal nanopowder, in particular the kinetics of oxidation [3]. The proceeding heterogeneous reaction can be in full measure characterized by the so-called “kinetic triplet” – the frequency factor A, the activation energy EEaa and the mathematical description of the reaction mechanism f(α) [4, 5, 6]. To identify these three parameters, the data of the derivatographic experiment conducted in the non-isothermal mode are used, when the change in the degree of transformation of the material α over time t is described by the differential equation ddα dddd = AA ∙ exp (− EEaa RRRR) ∙ ff(α), RR = 8.3144621 J mol ∙ К . (1) Under the temperature-linear heating where the rate of temperature increase T with a given parameter β = ddRR dddd ⁄ and a specific mechanism ff(α) = (1 − α)nn, the kinetic equation (1) can be represented as ddα dddd = AA β ∙ exp (− EEaa RRRR) ∙ (1 − α) nn, (2) where n – order (index) of reaction. Equation (2) has no analytical solution and numerical methods or approximate analytical ones are used to determine the kinetic parameters. The aim of this paper is to represent a quantitative result analysis of the derivatographic study of oxidation on the basis of a new approach to calculating the kinetic parameters of a  Corresponding author: bvborisov@tpu.ru
From Economic Crisis to a Crisis of Representation? The Relationship Among Economic Conditions, Ideological Congruence, and Electoral Participation

Research indicates that ideological congruence between citizens and political parties increases the likelihood of turning out to vote. But does this relationship also hold in times of economic crisis? In this study, I investigate whether economic conditions moderate the effect of voter–party representation on turnout. I argue that ideological congruence has significant effects on electoral participation during “normal” times, but these are even more relevant when citizens face economic hardship. Thus, in times of crisis, citizens are more likely to vote if they have a party that represents their position. I empirically test this argument by analyzing large-scale cross-national survey data from the Comparative Study of Electoral Systems (CSES). Findings bear important implications for the relationship between economic conditions and the functioning of modern democracies.
The Spread of Plasmidic AmpC in a General Lebanese Hospital Over Nine Consecutive Years and the Relationship With Restricted Isolation Protocols

Background: The dreaded bacterial infection by extended-spectrum β-lactamases (ESBL)-producers has always troubled the medical field whether on the public, scientific, or clinical levels. One of the lesser known β-lactamases, which is capable of hydrolyzing broad and extended-spectrum cephalosporins—i.e., cephamycins plus oxyimino-β-lactams—are the AmpC β-lactamases. This group, which has also been termed occasionally—and incorrectly—as ESBL Class C, confers resistance to β-lactamase inhibitors. The prevalence of plasmidic AmpC (pAmpC) strains is possibly still a matter of debate considering the unevenly matched data between phenotypically-detected and molecularly-detected pAmpC. Aim: In the absence of any study in Lebanon addressing the AmpC, our intention was to determine the numbers and percentages of AmpC Enterobacteriaceae isolates, notably plasmid-mediated ones, across different wards at the Centre Hospitalier du Nord (CHN), Lebanon, and highlight the importance of infection control protocols. Materials and Methods: Carriage and infection with pAmpC Enterobacteriaceae were retrospectively investigated between 2011 and 2015 and prospectively between 2016 and 2019 at the Centre Hospitalier du Nord Hospital, North Lebanon. The rise or decline in the numbers of such strains, in concordance with the allegedly intensive isolation of the patients, were analyzed. Results: Intensive care unit (ICU) data shows an initial rise in infection isolates from 2012 to 2014 and in the carriage isolates from 2012 to 2013 with later notable overall decrease in the both isolates' numbers with the application of the isolation protocols at CHN from 2014 onwards. Floors 2, 3, and 4 seemed to house the bulk of the isolates as well. Conclusion: Preventive measures, such as on-going surveillance of the hospital wards by specialized healthcare personnel and strict implementation of infection control practices, should be a top priority in any medical center in order to isolate such strains and try to put a limit for the development and the dissemination of any possible multidrug resistant strains.
Transition of Serotype 35B Pneumococci From Commensal to Prevalent Virulent Strain in Children

In our community-based prospective cohort study in young children, we observed a significant increase in pneumococcal serotype 35B nasopharyngeal (NP) commensal colonization during the 2011–2014 timeframe, but these strains were not associated with disease. Beginning in 2015 and continuing through to the present, the serotype 35B virulence changed, and it became the dominant bacteria isolated and associated with pneumococcal acute otitis-media (AOM) in our cohort. We performed comparative analyses of 250 35B isolates obtained from 140 children collected between 2006 and 2019. Changes in prevalence, clonal-complex composition, and antibiotic resistance were analyzed. Seventy-two (29%) of 35B isolates underwent whole-genome sequencing to investigate genomic changes associated with the shift in virulence that resulted in increased rates of 35B-associated AOM disease. 35B strains that were commensals and AOM disease-causing were mainly associated with sequence type (ST) 558. Antibiotic concentrations of β-lactams and ofloxacin necessary to inhibit growth of 35B strains rose significantly (2006–2019) (p<0.005). However, only isolates from the 35B/ST558 showed significant increases in MIC50 of penicillin and ofloxacin between the years 2006–2014 and 2015–2019 (p=0.007 and p<0.0001). One hundred thirty-eight SNPs located in 34 different genes were significantly associated with post-2015 strains. SNPs were found in nrdG (metal binding, 10%); metP and metN (ABC transporter, 9%); corA (Mg2+ transporter, 6%); priA (DNA replication, 5%); and on the enzymic gene ldcB (LD-carboxypeptidase, 3%). Pneumococcal serotype 35B strains was a common NP commensal during 2010–2014. In 2015, a shift in increasing number of AOM cases occurred in young children caused by 35B, that was associated with changes in genetic composition and antibiotic susceptibility.
Grassification and Fast-Evolving Fire Connectivity and Risk in the Sonoran Desert, United States

In the southwestern United States, non-native grass invasions have increased wildfire occurrence in deserts and the likelihood of fire spread to and from other biomes with disparate fire regimes. The elevational transition between desertscrub and montane grasslands, woodlands, and forests generally occurs at ∼1,200 masl and has experienced fast suburbanization and an expanding wildland-urban interface (WUI). In summer 2020, the Bighorn Fire in the Santa Catalina Mountains burned 486 km2 and prompted alerts and evacuations along a 40-km stretch of WUI below 1,200 masl on the outskirts of Tucson, Arizona, a metropolitan area of >1M people. To better understand the changing nature of the WUI here and elsewhere in the region, we took a multidimensional and timely approach to assess fire dynamics along the Desertscrub-Semi-desert Grassland ecotone in the Catalina foothills, which is in various stages of non-native grass invasion. The Bighorn Fire was principally a forest fire driven by a long-history of fire suppression, accumulation of fine fuels following a wet winter and spring, and two decades of hotter droughts, culminating in the hottest and second driest summer in the 125-yr Tucson weather record. Saguaro (Carnegia gigantea), a giant columnar cactus, experienced high mortality. Resprouting by several desert shrub species may confer some post-fire resiliency in desertscrub. Buffelgrass and other non-native species played a minor role in carrying the fire due to the patchiness of infestation at the upper edge of the Desertscrub biome. Coupled state-and-transition fire-spread simulation models suggest a marked increase in both burned area and fire frequency if buffelgrass patches continue to expand and coalesce at the Desertscrub/Semi-desert Grassland interface. A survey of area residents six months after the fire showed awareness of buffelgrass was significantly higher among residents that were evacuated or lost recreation access, with higher awareness of fire risk, saguaro loss and declining property values, in that order. Sustained and timely efforts to document and assess fast-evolving fire connectivity due to grass invasions, and social awareness and perceptions, are needed to understand and motivate mitigation of an increasingly fire-prone future in the region.
Role of the Cervical Anterior Spinal Artery in the Endovascular Treatment of Vascular Diseases: Bystander, Accomplice, Victim, or Friend?

The cervical anterior spinal artery (ASA) is a very important artery arising from the intracranial vertebral artery (VA). It can play different roles in endovascular treatment (EVT) of spinal vascular diseases. The current understanding of these roles is incomplete; therefore, we performed this review. We found that cervical ASA can be involved in many spinal vascular diseases, such as arteriovenous fistula (AVF), arteriovenous malformation (AVM), and aneurysm, and can serve as a collateral channel in proximal VA occlusion. In AVF and AVM, when the cervical ASA is involved, it often plays the role of an accomplice or victim because it acts as the feeder or as a bystander that does not provide blood flow to the AVF and AVM. In cervical ASA aneurysm, the ASA is a victim. During EVT of VA aneurysms or stenoses, the cervical ASA ostia can be covered or occluded, resulting in ASA ischemia. In this situation, the ASA is a victim. In VA occlusion or the subclavian steal phenomenon, the cervical ASA can serve as a collateral channel to provide blood flow to the posterior circulation. In this case, the ASA plays the role of a friend. According to the role of the cervical ASA in spinal vascular diseases, EVT should be determined “case by case. ” Most importantly, when EVT is performed to treat these diseases, the cervical ASA axis must be preserved. Therefore, understanding the role of the cervical ASA in spinal vascular diseases is crucial.
Employing CRISPR/Cas Technology for the Improvement of Potato and Other Tuber Crops

New breeding technologies have not only revolutionized biological science, but have also been employed to generate transgene-free products. Genome editing is a powerful technology that has been used to modify genomes of several important crops. This review describes the basic mechanisms, advantages and disadvantages of genome editing systems, such as ZFNs, TALENs, and CRISPR/Cas. Secondly, we summarize in detail all studies of the CRISPR/Cas system applied to potato and other tuber crops, such as sweet potato, cassava, yam, and carrot. Genes associated with self-incompatibility, abiotic-biotic resistance, nutrient–antinutrient content, and post-harvest factors targeted utilizing the CRISPR/Cas system are analyzed in this review. We hope that this review provides fundamental information that will be useful for future breeding of tuber crops to develop novel cultivars.
Amelioration of Ambient Particulate Matter (PM2.5)-Induced Lung Injury in Rats by Aerobic Exercise Training

Ambient particulate matter (PM2.5), as an inflammation-inducing factor, increases the prevalence of lung injury. The aim of this study was to examine the protective effect and mechanism of aerobic exercise on PM2.5 exposure-induced lung injury. Forty Wistar rats were randomly divided into four groups: sedentary+PM2.5 exposure, exercise+PM2.5 exposure, sedentary, and exercise groups. All rats in the exercise-related groups underwent 8-week aerobic interval treadmill training (5daysweek−1, 1hday−1). PM-exposed rats were exposed to ambient PM2.5 (6h day−1) for 3weeks after the 8-week exercise intervention. Then, ventilation function, histopathological changes, and inflammation responses of pulmonary tissue were examined. Results showed that PM2.5 exposure induced lung injury as manifested by decreased pulmonary function, abnormal histopathological changes, and increased pro-inflammatory cytokine levels (tumor necrosis factor-α and Interleukin-1α). Aerobic exercise alleviated the airway obstruction, reduced respiratory muscle strength, bronchial mucosal exfoliation, ultrastructure damage, and inflammatory responses induced by PM2.5 in exercise-related groups. The benefits of exercise were related with the downregulation of p38-mitogen-activated protein kinase (MAPK), and the subsequent inhibition of the pathways of the cyclooxygenase 2 (COX-2) product, prostaglandin E2 (PGE2). Thus, pre-exercise training may be an effective way to protect against PM2.5-induced lung inflammatory injury in rats.
Insights Into the Genetic Diversity of Nordic Red Clover (Trifolium pratense) Revealed by SeqSNP-Based Genic Markers

Red clover (Trifolium pratense) is one of the most important fodder crops worldwide. The knowledge of genetic diversity among red clover populations, however, is under development. This study provides insights into its genetic diversity, using single nucleotide polymorphism (SNP) markers to define population structure in wild and cultivated red clover. Twenty-nine accessions representing the genetic resources available at NordGen (the Nordic gene bank) and Lantmännen (a Swedish agricultural company with a red clover breeding program) were used for this study. Genotyping was performed via SeqSNP, a targeted genotype by sequencing method that offers the capability to target specific SNP loci and enables de novo discovery of new SNPs. The SNPs were identified through a SNP mining approach based on coding sequences of red clover genes known for their involvement in development and stress responses. After filtering the genotypic data using various criteria, 623 bi-allelic SNPs, including 327 originally targeted and 296 de novo discovered SNPs were used for population genetics analyses. Seventy-one of the SNP loci were under selection considering both Hardy-Weinberg equilibrium and pairwise FST distributions. The average observed heterozygosity (HO), within population diversity (HS) and overall diversity (HT) were 0.22, 0.21 and 0.22, respectively. The tetraploids had higher average HO (0.35) than diploids (0.21). The analysis of molecular variance (AMOVA) showed low but significant variation among accessions (5.4%; P < 0.001), and among diploids and tetraploids (1.08%; P = 0.02). This study revealed a low mean inbreeding coefficient (FIS = −0.04) exhibiting the strict outcrossing nature of red clover. As per cluster, principal coordinate and discriminant analyses, most wild populations were grouped together and were clearly differentiated from the cultivated types. The cultivated types of red clover had a similar level of genetic diversity, suggesting that modern red clover breeding programs did not negatively affect genetic diversity or population structure. Hence, the breeding material used by Lantmännen represents the major genetic resources in Scandinavia. This knowledge of how different types of red clover accessions relate to each other and the level of outcrossing and heterozygosity will be useful for future red clover breeding.
Cerebellar Theta Burst Stimulation on Walking Function in Stroke Patients: A Randomized Clinical Trial

Objectives: The objective of this study was to explore the efficacy of cerebellar intermittent theta burst stimulation (iTBS) on the walking function of stroke patients. Methods: Stroke patients with walking dysfunction aged 25–80 years who had suffered their first unilateral stroke were included. A total of 36 patients [mean (SD) age, 53 (7.93) years; 10 women (28%)] were enrolled in the study. All participants received the same conventional physical therapy, including transfer, balance, and ambulation training, during admission for 50 min per day during 2 weeks (10 sessions). Every session was preceded by 3 min procedure of cerebellar iTBS applyed over the contralesional cerebellum in the intervention group or by a similar sham iTBS in control group. The groups were formed randomly and the baseline characteristics showed no significant difference. The primary outcome measure was Fugl–Meyer Assessment–Lower Extremity scores. Secondary outcomes included walking performance and corticospinal excitability. Measures were performed before the intervention beginning (T0), after the first (T1) and the second (T2) weeks. Results: The Fugl–Meyer Assessment for lower extremity scores slightly improved with time in both groups with no significant difference between the groups and over the time. The walking performance significantly improved with time and between group. Two-way mixed measures ANOVA showed that there was significant interaction between time and group in comfortable walking time (F2,68 = 6.5242, P = 0.0080, η2partial = 0.276, ε = 0.641), between-group comparisons revealed significant differences at T1 (P = 0.0072) and T2 (P = 0.0133). The statistical analysis of maximum walking time showed that there was significant interaction between time and groups (F2,68 = 5.4354, P = 0.0115, η2partial = 0.198, ε = 0.734). Compared with T0, the differences of maximum walking time between the two groups at T1 (P = 0.0227) and T2 (P = 0.0127) were statistically significant. However, both the Timed up and go test and functional ambulation category scale did not yield significant differences between groups (P > 0.05). Conclusion: Our results revealed that applying iTBS over the contralesional cerebellum paired with physical therapy could improve walking performance in patients after stroke, implying that cerebellar iTBS intervention may be a noninvasive strategy to promote walking function in these patients. This study was registered at ChiCTR, number ChiCTR1900026450.
PD-L2 glycosylation promotes immune evasion and predicts anti-EGFR efficacy

Background Combination therapy has been explored for advanced head and neck squamous cell carcinoma (HNSCC) owing to the limited efficacy of anti-epidermal growth factor receptor (EGFR) therapy. Increased expression and glycosylation of immune checkpoint molecules in tumors are responsible for cetuximab therapy refractoriness. The role of programmed death ligand 2 (PD-L2), a ligand of PD-1, in the immune function is unclear. Here, we examined the regulatory mechanism of PD-L2 glycosylation and its role in antitumor immunity and cetuximab therapy. Methods Single-cell RNA sequencing and immunohistochemical staining were used to investigate PD-L2 expression in cetuximab-resistant/sensitive HNSCC tissues. The mechanism of PD-L2 glycosylation regulation was explored in vitro. The effects of PD-L2 glycosylation on immune evasion and cetuximab efficacy were verified in vitro and using mice bearing orthotopic SCC7 tumors. Results The PD-L2 levels were elevated and N-glycosylated in patients with cetuximab-resistant HNSCC. Glycosylated PD-L2 formed a complex with EGFR, which resulted in the activation of EGFR/signal transducer and activator of transcription 3 (STAT3) signaling and decreased the cetuximab binding affinity to EGFR. The N-glycosyltransferase fucosyltransferase (FUT8), a transcriptional target of STAT3, was required for PD-L2 glycosylation. Moreover, glycosylation modification stabilized PD-L2 by blocking ubiquitin-dependent lysosomal degradation, which consequently promoted its binding to PD-1 and immune evasion. Inhibition of PD-L2 glycosylation using Stattic, a specific STAT3 inhibitor, or PD-L2 mutation blocking its binding to FUT8, increased cytotoxic T lymphocyte activity and augmented response to cetuximab. Conclusions Increased expression and glycosylation of PD-L2 in tumors are an important mechanism for cetuximab therapy refractoriness. Thus, the combination of PD-L2 glycosylation inhibition and cetuximab is a potential therapeutic strategy for cancer.