bluuebunny/crossref_metadata_2025 huggingface dataset:
Pain Relief with Combination Acetaminophen/Codeine or Ibuprofen following Third-Molar Extraction: A Systematic Review and Meta-Analysis
Authors: Watson Hunter , Hildebolt Charles , Rowland Kevin
Published: November 2021

Objective

The purpose of our study was to perform a systematic review and meta-analysis of randomized, blinded, placebo-controlled studies that, following third-molar extraction, utilized either a combination of acetaminophen (600 mg) with codeine (60 mg) or ibuprofen (400 mg) for pain management.

Design

We searched PubMed, and the trial registry ClinicalTrials.gov databases with the keywords “molar or molars,” “tooth or teeth,” “extraction,” and “pain.” Selected studies were: (1) randomized, blinded, placebo controlled, (2) utilized either a single-dose combination acetaminophen (600 mg) with codeine (60 mg) (A/C) or ibuprofen, and (3) recorded standardized pain relief (PR) at 6 hours, or summed total pain relief over 6 hours (TOTPAR6). Of the 2,949 articles that were identified, 79 were retrieved for full-text analysis, and 20 of these studies met our inclusion criteria.

Results

For A/C, the weighted, standardized mean difference (SMD) for TOTPAR6 was 0.796 (95% confidence interval [CI], 0.597–0.995), P < .001, and for PR at 6 hours, the SMD was 0.0186 (0.007 to 0.378; P = .059), whereas for ibuprofen the SMD for TOTPAR6 was 3.009 (1.283 to 4.735; P = .001), and for PR at 6 hours, the SMD was 0.854 (95% CI, 0.712–0.996; P < .001). A SMD of 0.8 or larger is indicative of a large effect.

Conclusions

Our data indicate that single dose of ibuprofen (400 mg) is an effective pain reducer for post third molar extraction pain.
Vascularized bone regeneration accelerated by 3D-printed nanosilicate-functionalized polycaprolactone scaffold
Authors: Xu Xiongcheng , Xiao Long , Xu Yanmei , Zhuo Jin , Yang Xue , Li Li , Xiao Nianqi , Tao Jing , Zhong Quan , Li Yanfen , Chen Yuling , Du Zhibin , Luo Kai
Published: November 2021

Critical oral-maxillofacial bone defects, damaged by trauma and tumors, not only affect the physiological functions and mental health of patients but are also highly challenging to reconstruct. Personalized biomaterials customized by 3D printing technology have the potential to match oral-maxillofacial bone repair and regeneration requirements. Laponite (LAP) nanosilicates have been added to biomaterials to achieve biofunctional modification owing to their excellent biocompatibility and bioactivity. Herein, porous nanosilicate-functionalized polycaprolactone (PCL/LAP) was fabricated by 3D printing technology, and its bioactivities in bone regeneration were investigated in vitro and in vivo. In vitro experiments demonstrated that PCL/LAP exhibited good cytocompatibility and enhanced the viability of bone marrow mesenchymal stem cells (BMSCs). PCL/LAP functioned to stimulate osteogenic differentiation of BMSCs at the mRNA and protein levels and elevated angiogenic gene expression and cytokine secretion. Moreover, BMSCs cultured on PCL/LAP promoted the angiogenesis potential of endothelial cells by angiogenic cytokine secretion. Then, PCL/LAP scaffolds were implanted into the calvarial defect model. Toxicological safety of PCL/LAP was confirmed, and significant enhancement of vascularized bone formation was observed. Taken together, 3D-printed PCL/LAP scaffolds with brilliant osteogenesis to enhance bone regeneration could be envisaged as an outstanding bone substitute for a promising change in oral-maxillofacial bone defect reconstruction.
Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T1–T2 dual-mode magnetic resonance imaging probes
Authors: Yang Li , Fu Shengxiang , Cai Zhongyuan , Liu Li , Xia Chunchao , Gong Qiyong , Song Bin , Ai Hua
Published: November 2021

The T1−T2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T1–T2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r1 (8.4 mM−1s−1), r2 (83.2 mM−1s−1) and relatively ideal r2/r1 ratio (9.9) were selected for T1–T2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.
Effects of Parkinson Disease on Blur-Driven and Disparity-Driven Vergence Eye Movements
Authors: Gupta Palak , Beylergil Sinem , Murray Jordan , Jacobs Jonathan , Kilbane Camilla , Shaikh Aasef G. , Ghasia Fatema F.
Published: November 2021

Synchronous movements of the 2 eyes in the opposite direction, disconjugate movements such as vergence, facilitate depth perception. The vergence eye movements are affected in Parkinson disease (PD). Visual blur (accommodation) and fusion (retinal disparity) are important triggers for the vergence. The neural circuit responsible for blur-driven and disparity-driven vergence is tightly coupled. We investigated the effect of PD on these 2 vergence paradigms. In the experiment involving 14 patients with PD and 6 healthy controls, substantial differences between blur-driven and disparity-driven vergence were found. The gain (ratio of actual vs desired eye movements) was reduced in patients with PD in case of disparity-driven vergence but not in blur-driven vergence. The latency of disparity-driven vergence onset was significantly longer for patients with PD compared with healthy controls. Four strategies were used to drive disparity-driven vergence: a) pure disconjugate vergence, b) conjugate saccadic movements, c) disconjugate vergence followed by saccadic movements, and d) conjugate saccades followed by disconjugate vergence movements. Blur-driven vergence had only 2 strategies: a) conjugate saccades followed by disconjugate vergence and b) conjugate saccadic movements only. The results are consistent with the prediction that PD primarily affects disparity-driven vergence, but there are some effects on the strategies to execute blur-driven vergence. We speculate that the deep cerebellar nuclei and the supraoculomotor area of the midbrain that carry the disparity-driven and blur-driven vergence are affected in PD. It is possible to modulate their function through projections to the subthalamic nuclei.
Transient analysis of power loss density with time-harmonic electromagnetic waves in Debye media
Authors: Zhong Jiaqi , Liang Shan , Chen Yong , Tan Jiajia
Published: November 2021

Due to the complex permittivity, it is difficult to directly clarify the transient mechanism between electromagnetic waves and Debye media. To overcome the above problem, the temporal relationship between the electromagnetic waves and permittivity is explicitly derived by applying the Fourier inversion and introducing the remnant displacement. With the help of the Poynting theorem and energy conservation equation, the transient power loss density is derived to describe the transient dissipation of electromagnetic field and the mechanism on phase displacement has been explicitly revealed. Besides, the unique solution can be obtained by applying the time-domain analysis method rather than involving the frequency-domain characteristics. The effectiveness of transient analysis is demonstrated by giving a comparison simulation on one-dimensional example.
Associations between vocal emotion recognition and socio-emotional adjustment in children
Authors: Neves Leonor , Martins Marta , Correia Ana Isabel , Castro São Luís , Lima César F.
Published: November 2021

The human voice is a primary channel for emotional communication. It is often presumed that being able to recognize vocal emotions is important for everyday socio-emotional functioning, but evidence for this assumption remains scarce. Here, we examined relationships between vocal emotion recognition and socio-emotional adjustment in children. The sample included 141 6- to 8-year-old children, and the emotion tasks required them to categorize five emotions (anger, disgust, fear, happiness, sadness, plus neutrality), as conveyed by two types of vocal emotional cues: speech prosody and non-verbal vocalizations such as laughter. Socio-emotional adjustment was evaluated by the children's teachers using a multidimensional questionnaire of self-regulation and social behaviour. Based on frequentist and Bayesian analyses, we found that, for speech prosody, higher emotion recognition related to better general socio-emotional adjustment. This association remained significant even when the children's cognitive ability, age, sex and parental education were held constant. Follow-up analyses indicated that higher emotional prosody recognition was more robustly related to the socio-emotional dimensions of prosocial behaviour and cognitive and behavioural self-regulation. For emotion recognition in non-verbal vocalizations, no associations with socio-emotional adjustment were found. A similar null result was obtained for an additional task focused on facial emotion recognition. Overall, these results support the close link between children's emotional prosody recognition skills and their everyday social behaviour.
Devosia equisanguinis sp. nov., isolated from horse blood
Authors: Kämpfer Peter , Busse Hans-Jürgen , Clermont Dominique , Criscuolo Alexis , Glaeser Stefanie P.
Published: November 2021

A Gram-stain-negative, aerobic, non-endospore-forming organism isolated from horse blood was studied for its taxonomic allocation. On the basis of 16S rRNA gene sequence similarity comparisons, strain M6-77T grouped within the genus

Devosia

and was most closely related to

Devosia elaeis

(97.6 %) and

Devosia indica

(97.55 %). The 16S rRNA gene sequence similarity to type strains of other

Devosia

species was below 97.5 %. The average nucleotide identity and digital DNA–DNA hybridization values between the M6-77T genome assembly and those of the closest relative

Devosia

type strains were <85 and <25 %, respectively. Strain M6-77T grew optimally at 25–37 °C (range: 10–36 °C), at a pH range of pH 6.5–10.5 and in the presence of up to 3 % (w/v) NaCl. The fatty acid profile from whole-cell hydrolysates supported the allocation of the strain to the genus

Devosia

. Major fatty acids were C18 : 1
 ω7c, 11-methyl C18 : 1
 ω7c and C16 : 0. The quinone system consisted exclusively of ubiquinone Q-10. The polar lipid profile was composed of the major lipids diphosphatidylglycerol, phosphatidylglycerol and three unidentified glycolipids. In the polyamine pattern, putrescine was predominant and spermidine was detected in moderate amounts. The diamino acid of the peptidoglycan was meso-diaminopimelic acid. In addition, the results of physiological and biochemical tests also allowed phenotypic differentiation of strain M6-77T from the closely related species. Hence, M6-77T represents a new species of the genus

Devosia

, for which we propose the name Devosia equisanguinis sp. nov., with M6-77T (=CIP 111628T=LMG 30659T=CCM 8868T) as the type strain.
Home literacy environment mediates the relationship between socioeconomic status and white matter structure in infants
Authors: Turesky Ted K. , Sanfilippo Joseph , Zuk Jennifer , Ahtam Banu , Gagoski Borjan , Lee Ally , Garrisi Kathryn , Dunstan Jade , Carruthers Clarisa , Vanderauwera Jolijn , Yu Xi , Gaab Nadine
Published: November 2021

The home literacy environment (HLE) in infancy has been associated with subsequent pre-literacy skill development and HLE at pre-school age has been shown to correlate with white matter organization in tracts that subserve prereading and reading skills. Furthermore, childhood socioeconomic status (SES) has been linked with both HLE and white matter organization. It is also important to understand whether the relationships between environmental factors such as HLE and SES and white matter organization can be detected as early as infancy, as this period is characterized by rapid brain development that may make white matter pathways particularly susceptible to these early experiences. Here, we hypothesized (1) an association between HLE and white matter organization in pre-reading and reading-related tracts in infants, and (2) that this association mediates a link between SES and white matter organization. To test these hypotheses, infants (mean age: 9.2 ± 2.5 months, N = 18) underwent diffusion-weighted imaging MRI during natural sleep. Fractional anisotropy (FA) was estimated from the left superior longitudinal fasciculus (SLF) and left arcuate fasciculus using the automated fiber-tract quantification method. HLE was measured with the Reading subscale of the StimQ and SES was measured with years of maternal education. Self-reported maternal reading ability was also quantified and applied to all statistical models to control for confounding genetic effects. The Reading subscale of the StimQ positively related to FA in left SLF and mediated the association between maternal education and FA in the left SLF. Taken together, these findings underscore the importance of considering HLE from the start of life and may inform novel prevention and intervention strategies targeted at low-SES families to support developing infants during a period of heightened brain plasticity.
Whokaryote: distinguishing eukaryotic and prokaryotic contigs in metagenomes based on gene structure
Authors: Pronk Lotte J. U. , Medema Marnix H.
Published: November 2021

Metagenomics has become a prominent technology to study the functional potential of all organisms in a microbial community. Most studies focus on the bacterial content of these communities, while ignoring eukaryotic microbes. Indeed, many metagenomics analysis pipelines silently assume that all contigs in a metagenome are prokaryotic. However, because of marked differences in gene structure, prokaryotic gene prediction tools fail to accurately predict eukaryotic genes. Here, we developed a classifier that distinguishes eukaryotic from prokaryotic contigs based on foundational differences between these taxa in gene structure. We first developed a random forest classifier that uses intergenic distance, gene density and gene length as the most important features. We show that, with an estimated accuracy of 97%, this classifier with principled features grounded in biology can perform almost as well as the classifiers EukRep and Tiara, which use k-mer frequencies as features. By re-training our classifier with Tiara predictions as additional feature, weaknesses of both types of classifiers are compensated; the result is an enhanced classifier that outperforms all individual classifiers, with an F1-score of 1.00 on precision, recall and accuracy for both eukaryotes and prokaryotes, while still being fast. In a reanalysis of metagenome data from a disease-suppressive plant endosphere microbial community, we show how using Whokaryote to select contigs for eukaryotic gene prediction facilitates the discovery of several biosynthetic gene clusters that were missed in the original study. Our enhanced classifier, which we call ‘Whokaryote’, is wrapped in an easily installable package and is freely available from https://git.wageningenur.nl/lotte.pronk/whokaryote.
Rhythmic auditory stimulation rescues cognitive flexibility in mutant mice with impaired gamma synchrony
Authors: Shi Jingcheng , Phensy Aarron J. , Sohal Vikaas S.
Published: November 2021

Neural synchronization at gamma (∼40 Hz) frequencies is believed to contribute to brain function and be deficient in disorders including Alzheimer’s disease and schizophrenia. Gamma-frequency sensory stimulation has been proposed as a non-invasive treatment for deficient gamma synchrony and associated cognitive deficits, and has been shown to be effective in mouse models of Alzheimer’s disease. However, both the mechanism and applicability of this approach remain unclear. Here we tested this approach using mutant (Dlx5/6+/-) mice which have deficits in gamma synchrony and the ability to learn to shift between rules which use different types of cues to indicate reward locations. 40 Hz auditory stimulation rescues rule shifting in Dlx5/6+/- mice. However, this improvement does not outlast the period of stimulation, and is not associated with normalized gamma synchrony, measured using genetically encoded voltage indicators. These results show how gamma-frequency sensory stimulation may improve behavior without fully restoring normal circuit function.
Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and protection of anaphylaxis
Authors: Le Thanh Nha Uyen , Nguyen Toan Q. , Nguyen Yen Thi Kim , Tan Clarissa Kai Hui , Tukijan Farhana , Couty Ludovic , Hasan Zafrul , Kalailingam Pazhanichamy , Wenk Markus , Cazenave-Gassiot Amaury , Camerer Eric , Nguyen Long N.
Published: November 2021

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is secreted by several cell types to induce signaling. We recently showed that Mfsd2b is an S1P transporter from hematopoietic cells, which contributes approximately 50% plasma S1P. To further determine the sources of plasma S1P, here, we report the characterizations of compound deletions of Mfsd2b and Spns2, another S1P transporter from endothelial cells. Global deletion of Mfsd2b and Spns2 (gDKO) resulted in embryonic lethality between E13.5 and E14.5 with severe hemorrhage that largely recapitulated the phenotypes from global S1P1 knockout mice, indicating that together with Mfsd2b, Spns2 also provides embryonic source of S1P for S1P1 stimulation. The hemorrhagic phenotypes in gDKO embryos were accompanied by increased angiogenesis and defects of tight junction proteins, indicating that S1P from Mfsd2b and Spns2 is essential for blood vessel integrity and maturation. The various sources of S1P in postnatal stages are yet to be fully understood. Postnatal ablation of S1P synthesis enzymes using Mx1Cre shows that Mx1Cre-sensitive cells provide most of plasma S1P. Interestingly, we showed that compound postnatal deletion of Mfsd2b and Spns2 using Mx1Cre (ctDKO-Mx1Cre) resulted in maximal reduction of 80% plasma S1P. Thus, a small amount of plasma S1P is supplied from other sources independent of Mfsd2b and Spns2. Nevertheless, the vasculature in the lung of ctDKO-Mx1Cre mice was compromised. Furthermore, ctDKO-Mx1Cre mice also exhibited severe susceptibility to anaphylaxis, indicating that S1P from Mfsd2b and Spns2 is indispensable during vascular stress. Together, our results show that Mfsd2b and Spns2 provide a critical source of S1P for embryonic development and they also provide a majority of plasma S1P for vascular homeostasis.
Direct regulation of cell cycle regulatory gene expression by NtrX to promote Sinorhizobium meliloti cell division
Authors: Xing Shenghui , Zhang Lanya , An Fang , Huang Leqi , Yang Xinwei , Zeng Shuang , Li Ningning , Zheng Wenjia , Ouenzar Khadidja , Yu Liangliang , Luo Li
Published: November 2021

Cell division of the alfalfa symbiont, Sinorhizobium meliloti, is regulated by the CtrA signaling network. The gene expression of regulatory proteins in the network is affected by nutrient signaling. In this study, we found that NtrX, one of the regulators of nitrogen metabolic response, can directly regulate the expression of several regulatory genes from the CtrA signaling network. Three sets of S. meliloti ntrX mutants, including the plasmid insertion strain, the depletion strain and the substitution of the 53rd aspartate (ntrXD53E) from a plasmid in the wild-type strain (Sm1021), showed similar cell division defects, such as slow growth, abnormal morphology of partial cells and delayed DNA synthesis. Transcript quantitative evaluation indicated that the transcription of genes such as ctrA and gcrA was up-regulated, while the transcription of genes such as dnaA and ftsZl was down-regulated in the insertion mutant and the strain of Sm1021 expressing ntrXD53E. Correspondingly, inducible transcription of ntrX activates the expression of dnaA and ftsZ1, but represses ctrA and gcrA in the depletion strain. The expression levels of CtrA and GcrA were confirmed by western blotting, which were consistent with the transcription data. The transcriptional regulation of these genes requires phosphorylation of the conserved 53rd aspartate in the NtrX protein. The NtrX protein binds directly to the promoter regions of ctrA, gcrA, dnaA and ftsZ1 by recognizing the characteristic sequence CAAN2-5TTG Our findings reveal that NtrX is a novel transcriptional regulator of the CtrA signaling pathway genes, and positively affects bacterial cell division, associated with nitrogen metabolism.

IMPORTANCE

Sinorhizobium meliloti infects the host alfalfa and induces formation of nitrogen-fixing nodules. Proliferation of rhizobia in plant tissues and cells is strictly controlled in the early stage of symbiotic interactions. However, the control mechanism is not very clear. Cell division of S. meliloti in the free-living state is regulated by the CtrA signaling network, but molecular mechanisms by which the CtrA system is associated with environmental nutrient signals (e.g., ammonia nitrogen) need to be further explored. This study demonstrates that NtrX, a regulator of nitrogen metabolism, required for symbiotic nodulation and nitrogen fixation by S. meliloti 1021, can act as a transcriptional regulator of the CtrA signaling system. It may link nitrogen signaling to cell cycle regulation in Rhizobium species.
Antenna modification leads to enhanced nitrogenase activity in a high light tolerant cyanobacterium
Authors: Bandyopadhyay Anindita , Ye Zi , Benedikty Zuzana , Trtilek Martin , Pakrasi Himadri B.
Published: November 2021

Biological nitrogen fixation is an energy intensive process that contributes significantly towards supporting life on this planet. Among nitrogen-fixing organisms, cyanobacteria remain unrivaled in their ability to fuel the energetically expensive nitrogenase reaction with photosynthetically harnessed solar energy. In heterocystous cyanobacteria light-driven, photosystem I (PSI)-mediated ATP synthesis plays a key role in propelling the nitrogenase reaction. Efficient light transfer to the photosystems rely on phycobilisomes (PBS), the major antenna protein complexes. PBS undergo degradation as a natural response to nitrogen starvation. Upon nitrogen availability, these proteins are resynthesized back to normal levels in vegetative cells, but their occurrence and function in heterocysts remains inconclusive. Anabaena 33047 is a heterocystous cyanobacterium that thrives under high light, harbors higher amounts of PBS in its heterocysts and fixes nitrogen at higher rates compared to other heterocystous cyanobacteria. To assess the relationship between PBS in heterocysts and nitrogenase function, we engineered a strain that retains high amounts of the antenna proteins in its heterocysts. Intriguingly, under high light intensities the engineered strain exhibited unusually high rates of nitrogenase activity compared to the wild type. Spectroscopic analysis revealed altered PSI kinetics in the mutant, with increased cyclic electron flow around PSI, a route that contributes to ATP generation and nitrogenase activity in heterocysts. Retaining higher levels of PBS in heterocysts appears to be an effective strategy to enhance nitrogenase function in cyanobacteria that are equipped with the machinery to operate under high light intensities.

Importance

The function of phycobilisomes, the large antenna protein complexes in heterocysts has long been debated. This study provides direct evidence of the involvement of these proteins in supporting nitrogenase activity in Anabaena 33047, a heterocystous cyanobacterium that has affinity for very high light intensities. This strain was previously known to be recalcitrant to genetic manipulation and hence despite its many appealing traits, remained largely unexplored. We developed a genetic modification system for this strain and generated a ΔnblA mutant that exhibited resistance to phycobilisome degradation upon nitrogen starvation. Physiological characterization of the strain indicated that PBS degradation is not essential for acclimation to nitrogen deficiency and retention of PBS is advantageous for nitrogenase function.
Comparative genomics on cultivated and uncultivated, freshwater and marine Candidatus Manganitrophaceae species implies their worldwide reach in manganese chemolithoautotrophy
Authors: Yu Hang , Chadwick Grayson L. , Lingappa Usha F. , Leadbetter Jared R.
Published: November 2021

Chemolithoautotrophic manganese oxidation has long been theorized, but only recently demonstrated in a bacterial co-culture. The majority member of the co-culture, Candidatus Manganitrophus noduliformans, is a distinct but not yet isolated lineage in the phylum Nitrospirota (Nitrospirae). Here, we established two additional MnCO3-oxidizing cultures using inocula from Santa Barbara (USA) and Boetsap (South Africa). Both cultures were dominated by strains of a new species, designated Candidatus Manganitrophus morganii. The next abundant members differed in the available cultures, suggesting that while Ca. Manganitrophus species have not been isolated in pure culture, they may not require a specific syntrophic relationship with another species. Phylogeny of cultivated Ca. Manganitrophus and related metagenome-assembled genomes revealed a coherent taxonomic family, Candidatus Manganitrophaceae, from both freshwater and marine environments and distributed globally. Comparative genomic analyses support this family being Mn(II)-oxidizing chemolithoautotrophs. Among the 895 shared genes were a subset of those hypothesized for Mn(II) oxidation (Cyc2 and PCC_1) and oxygen reduction (TO_1 and TO_2) that could facilitate Mn(II) lithotrophy. An unusual, plausibly reverse Complex 1 containing 2 additional pumping subunits was also shared by the family, as were genes for the reverse TCA carbon fixation cycle, which could enable Mn(II) autotrophy. All members of the family lacked genes for nitrification found in Nitrospira species. The results suggest that Ca. Manganitrophaceae share a core set of candidate genes for the newly discovered manganese dependent chemolithoautotrophic lifestyle, and likely have a broad, global distribution.

Importance

Manganese (Mn) is an abundant redox-active metal that cycled in many of Earth’s biomes. While diverse bacteria and archaea have been demonstrated to respire Mn(III/IV), only recently have bacteria been implicated in Mn(II) oxidation dependent growth. Here, two new Mn(II)-oxidizing enrichment cultures originated from two continents and hemispheres were examined. By comparing the community composition of the enrichments and performing phylogenomic analysis on the abundant Nitrospirota therein, new insights are gleaned on cell interactions, taxonomy, and machineries that may underlie Mn(II)-based lithotrophy and autotrophy.
Impact of SARS-CoV-2 Vaccines on Covid-19 Incidence and Mortality in the United States
Authors: Fang Fang , Clemens John David , Zhang Zuo-Feng , Brewer Timothy F.
Published: November 2021

Background

Despite safe and effective vaccines to prevent Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infections and disease, a substantial minority of the US remains resistant to getting vaccinated. It is imperative to know if expanding vaccination rates could reduce community-wide Coronavirus 2019 (COVID-19) disease, not just among those vaccinated.

Methods

Negative binomial models were used to estimate associations between U.S. county-level vaccination rates and county-wide COVID-19 incidence and mortality between April 23rd and September 30th, 2021. A two-week lag and a four-week lag were introduced to assess vaccination rate impact on incidence and mortality, respectively. Stratified analyses were performed for county vaccination rates 40%, and before and after Delta became the dominant variant.

Findings

Among 3,070 counties, each percentage increase in population vaccination rates reduced county-wide COVID-19 incidence by 0·9% (relative risk (RR) 0. 9910 (95% CI: 0·9869, 0·9952)) and mortality by 1·9% (RR 0·9807 (95% CI: 0·9745, 0·9823)). Among counties with vaccination coverage >40%, each percentage increase in vaccination rates reduced COVID-19 disease by 1·5%, RR 0·9850 (95% CI: 0·9793, 0·9952) and mortality by 2·7% (RR 0·9727 (95% CI: 0·9632, 0·9823)). These associations were not observed among counties with <40% vaccination rates. Increasing vaccination rates from 40% to 80% would have reduced COVID-19 cases by 45·4% (RR 0·5458 (95% CI: 0·4335, 0·6873)) and deaths by 67·0% (RR 0·3305 (95% CI: 0·2230, 0·4898)). An estimated 5,989,952 COVID-19 cases could have been prevented and 127,596 lives saved had US population vaccination rates increased from 40% to 80%.

Interpretations

Increasing U.S. SARS-CoV-2 vaccination rates results in population-wide reductions in COVID-19 incidence and mortality. Furthermore, increasing vaccination rates above 40% has protective effects among non-vaccinated persons. Given ongoing vaccine hesitancy in the U.S., increasing vaccination rates could better protect the entire community and potentially reach herd immunity.

Funding

National Cancer Institute
Extreme temperatures and mortality in 326 Latin American cities
Authors: Kephart Josiah L. , Sánchez Brisa N. , Moore Jeffrey , Schinasi Leah H. , Bakhtsiyarava Maryia , Ju Yang , Gouveia Nelson , Caiaffa Waleska T , Dronova Iryna , Arunachalam Saravanan , Roux Ana V. Diez , Rodríguez Daniel A.
Published: November 2021

Background

Climate change and urbanization are rapidly increasing human exposure to extreme ambient temperatures, yet few studies have examined the impact of temperature on mortality across Latin America, where 80% of residents live in urban areas.

Methods

We used distributed lag nonlinear conditional Poisson models to estimate city-specific associations between daily temperatures above (“heat”) and below (“cold”) each city-specific minimum mortality temperature and all-cause mortality, overall and stratified by age and cause of death. We estimated the percentage of total deaths attributable to heat or cold (excess death fraction [EDF]) and the difference in mortality per 1°C higher daily mean temperature above the 95th percentile of observed daily temperature.

Results

We analyzed data from 326 cities in nine Latin American countries between 2002-2015, representing 15,431,532 deaths from 249 million residents. The EDF of total deaths from heat was 0.67% (95% confidence interval [CI] 0.58%, 0.74%), and from cold was 5.09% (95% CI 4.64%, 5.47%). EDFs from heat and cold were particularly high among individuals aged 65+ years (0.81% [95% CI 0.75%, 0.86%] and 6.82% [95% CI 6.41%, 7.18%], respectively). The relative risk of death per 1°C increase above the city-specific 95th percentile daily temperature was 1.057 (95% CI 1.046, 1.067).

Conclusions

In Latin American cities, a substantial proportion of deaths are attributable to non-optimal ambient temperatures. Older populations are particularly vulnerable. Marginal increases in observed hot temperatures are associated with steep increases in mortality risk. Projected increases in temperature from climate change may have a substantial impact on mortality.

SIGNIFICANCE STATEMENT

Latin America has a large population at risk of urban heat exposure, yet little is known about the linkages between ambient temperature and health in the region. We analyzed over 15 million deaths in 326 Latin American cities to characterize the relationship between ambient temperature and mortality, overall and by age and cause of death. We found that 5.75% of all deaths are associated with non-optimal temperatures, older individuals are particularly vulnerable, and cardiorespiratory deaths are especially affected. A single degree increase (1°C) in daily temperature was associated with a 5.7% higher mortality among hot days, suggesting that projected increases in temperature from climate change may have a substantial impact on mortality.
The Direct and Indirect Effects of a Global Pandemic on US Fishers and Seafood Workers
Authors: White Easton , Levine Jill , Moeser Amanda , Sorensen Julie
Published: November 2021

The United States’ seafood industry experienced major shifts in consumer demand and COVID-19 social-distancing restrictions starting in March 2020, when the early stages of the pandemic were unfolding. However, the specific effects on workers across seafood value chains are less well known. According to the US Centers for Disease Control and Protection (CDC), fishers and seafood workers face an increased risk of workplace exposure to COVID-19 given the close proximity to others in processing facilities and on fishing vessels, long work hours, and communal housing, living, and transportation arrangements associated with seasonal employment. To explore this hypothesis, and given a lack of data on the sector, we reviewed news articles, scientific articles, and white papers to identify the various effects of COVID-19 on US seafood workers and to track COVID-19 cases and outbreaks. Here, we show that most COVID-19 cases among seafood workers were reported during the summer of 2020 and during the beginning of 2021 with outbreaks primarily occurring in seafood processing. COVID-19 cases were documented throughout coastal areas, with Alaska experiencing the largest number of cases and outbreaks. Based on news reports, seafood workers were about twice as likely to contract COVID-19 as workers in other parts of the overall US food system. By examining news articles and scientific literature, we also documented several indirect effects of the pandemic. Social-distancing restrictions limited crew size and number of workers on processing lines, resulting in longer work hours and more physical and mental taxation. Economic consequences of the pandemic were reportedly a primary concern for fishers and aquaculture businesses, including changes in markets, supply, and demand, in addition to revenue loss, price fluctuations, supply chain issues, and labor shortages. Fewer outlets interviewed workers in seafood processing; however, concerns about workplace safety, contracting COVID-19, access to medical services, vaccination, and paid sick leave were all noted. We also highlight several inequities in COVID-19 responses within the seafood sector, both along racial and gender lines. Peer-reviewed studies and news coverage all point to diverse direct and indirect effects of the COVID-19 pandemic on workers across seafood value chains. The summary of these effects can serve as a foundation for future work on infection control and occupational outreach to workers in the seafood sector.
The sequences of 150,119 genomes in the UK biobank
Authors: Halldorsson Bjarni V. , Eggertsson Hannes P. , Moore Kristjan H.S. , Hauswedell Hannes , Eiriksson Ogmundur , Ulfarsson Magnus O. , Palsson Gunnar , Hardarson Marteinn T. , Oddsson Asmundur , Jensson Brynjar O. , Kristmundsdottir Snaedis , Sigurpalsdottir Brynja D. , Stefansson Olafur A. , Beyter Doruk , Holley Guillaume , Tragante Vinicius , Gylfason Arnaldur , Olason Pall I. , Zink Florian , Asgeirsdottir Margret , Sverrisson Sverrir T. , Sigurdsson Brynjar , Gudjonsson Sigurjon A. , Sigurdsson Gunnar T. , Halldorsson Gisli H. , Sveinbjornsson Gardar , Norland Kristjan , Styrkarsdottir Unnur , Magnusdottir Droplaug N. , Snorradottir Steinunn , Kristinsson Kari , Sobech Emilia , Jonsson Helgi , Geirsson Arni J. , Olafsson Isleifur , Jonsson Palmi , Pedersen Ole Birger , Erikstrup Christian , Brunak Søren , Ostrowski Sisse Rye ,   DBDS Genetic Consortium, Thorleifsson Gudmar , Jonsson Frosti , Melsted Pall , Jonsdottir Ingileif , Rafnar Thorunn , Holm Hilma , Stefansson Hreinn , Saemundsdottir Jona , Gudbjartsson Daniel F. , Magnusson Olafur T. , Masson Gisli , Thorsteinsdottir Unnur , Helgason Agnar , Jonsson Hakon , Sulem Patrick , Stefansson Kari
Published: November 2021

We describe the analysis of whole genome sequences (WGS) of 150,119 individuals from the UK biobank (UKB). This constitutes a set of high quality variants, including 585,040,410 SNPs, representing 7.0% of all possible human SNPs, and 58,707,036 indels. The large set of variants allows us to characterize selection based on sequence variation within a population through a Depletion Rank (DR) score for windows along the genome. DR analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UKB, a large British Irish cohort (XBI) and smaller African (XAF) and South Asian (XSA) cohorts. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large scale WGS studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on exome sequencing and/or imputation.
Reversible regulation of Cas12a activities by AcrVA5-mediated acetylation and CobB-mediated deacetylation
Authors: Kang Xiaoman , Yin Lei , Zhuang Songkuan , Hu Tianshuai , Wu Zhile , Zhao Guoping , Chen Yijian , Xu Yong , Wang Jin
Published: November 2021

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated (Cas) system protects bacteria and archaea from the invasion of foreign genetic elements. To cope with the host CRISPR systems, phages have evolved many strategies, including the anti-CRISPR (Acr) proteins, to inactivate the Cas nucleases. Recently, it has been reported that the type V-A Cas12a effector can be acetylated and inactivated by AcrVA5, which is a GNAT-family acetyltransferase. However, it is unclear whether the host has any coping strategies to reactivate the defense system. Here we show that the AcrVA5-acetylated Cas12a can be deacetylated by bacterial deacetylase CobB, reactivating Cas12a for both in vitro cleavage of target DNA sequences and in vivo protection of the host from invasion of foreign nucleic acids. Therefore, this study not only shows the reversible regulation of Cas12a activities by post-translational modification but also reveals CobB as a secondary safeguard to bacterial CRISPR defense systems. In addition, we demonstrate that AcrVA5 is a wide-spectrum acetyltransferase, acetylating a large number of target proteins besides Cas12a, and the AcrVA5-acetylated targets can also be deacetylated by CobB.
Identification of diverse viruses associated with grasshoppers unveils phylogenetic congruence between hosts and viruses
Authors: Xu Yao , Jiang Jingyi , Lin Xiaoju , Shi Wangpeng , Cao Chuan
Published: November 2021

Locusts and grasshoppers are one of the most dangerous agricultural pests. Environmentally benign microbial pesticides are increasingly desirable for controlling locust outbreaks in fragile ecosystems. Here we use metagenomic sequencing to profile the rich viral communities in 34 grasshopper species and report 322 viruses, including 202 novel species. Most of the identified viruses are related to other insect viruses and some are targeted by antiviral RNAi pathway, indicating they infect grasshoppers. Some plant/fungi/vertebrate associated viruses are also abundant in our samples. Our analysis of relationships between host and virus phylogenies suggests that the composition of viromes is closely allied with host evolution, and there is significant phylogenetic relatedness between grasshoppers and viruses from Lispiviridae, Partitiviridae, Orthomyxoviridae, Virgaviridae and Flaviviridae. Overall, this study is a thorough exploration of viruses in grasshoppers and provide an essential evolutionary and ecological context for host-virus interaction in Acridoidea.

Author Summary

Locusts are the most destructive migratory pest in the world and continue to cause massive damages that endanger food security and threaten millions of people in 21st century. While chemical pesticides are still heavily relied on, biological pesticides developed from natural pathogens offer a reliable, less harmful alternative for controlling locust outbreaks in fragile ecosystems. Unfortunately, little is known about natural pathogens infecting this pest. In this study, we profile the viral communities in 34 grasshopper species include some major swarming species. While we identified as many as 202 novel viral species associated with grasshoppers, some of them are of potential to be developed as biocontrol agents. Our analysis of relatedness of phylogenies of grasshoppers and associated viruses helps to shed light on the eco-evolutionary interactions between insects and viruses. This work provides a valuable dataset of both academic and applied interest.
Stimulation of immunity-linked genes by membrane disruption is linked to Golgi function and the ARF-1 GTPase
Authors: Fanelli Matthew J. , Welsh Christofer M. , Lui Dominique S. , Smulan Lorissa J. , Walker Amy K.
Published: November 2021

Immunity-linked genes (ILGs) are activated by pathogens but also may respond to imbalances in lipids. Why pathogen attack and metabolic changes both impact ILG activation is unclear. We find that ILGs are activated when membrane phosphatidylcholine ratios change in secretory organelles inC. elegans. RNAi targeting of the ADP-ribosylation factor ARF-1, which disrupts the Golgi, also activates ILG expression, suggesting that activation of this membrane stress response could occur outside the ER. Our data argue that ILG upregulation is a coordinated response to changes in trafficking resulting from intrinsic cues (changes in membrane lipids) or extrinsic stimulation (increased secretion during immune response). Indeed, a focused RNAi screen of ILGs uncovered defects in secretion of two GFP reporters as well as accumulation of a pathogen-responsive CUB-domain fusion protein. These results also suggests that genes shared between the classical pathogen responses and lipid stress may act to counteract stress on secretory function.

Teaser

Pathogen response genes are also activated by lipid imbalances, which we suggest occurs because both processes put stress on the secretory pathway.
Building an RNA-based Toggle Switch using Inhibitory RNA Aptamers
Authors: Climent-Catala Alicia , Ouldridge Thomas E. , Stan Guy-Bart V. , Bae Wooli
Published: November 2021

Synthetic RNA systems offer unique advantages such as faster response, increased specificity, and programmability compared to conventional protein-based networks. Here, we demonstrate an in-vitro RNA-based toggle switch using RNA aptamers capable of inhibiting the transcriptional activity of T7 or SP6 RNA polymerases. The activities of both polymerases are monitored simultaneously by using Broccoli and Malachite green light-up aptamer systems. In our toggle switch, a T7 promoter drives the expression of SP6 inhibitory aptamers, and an SP6 promoter expresses T7 inhibitory aptamers. We show that the two distinct states originating from the mutual inhibition of aptamers can be toggled by adding DNA sequences to sequester the RNA inhibitory aptamers. Finally, we assessed our RNA-based toggle switch in cell-like conditions by introducing controlled degradation of RNAs using a mix of RNases. Our results demonstrate that the RNA-based toggle switch could be used as a control element for nucleic acid networks in synthetic biology applications.

Graphical TOC Entry
Rev1 promotes replication through UV lesions in conjunction with DNA polymerases η, ι, and κ but not DNA polymerase ζ
Authors: Yoon Jung-Hoon , Park Jeseong , Conde Juan , Wakamiya Maki , Prakash Louise , Prakash Satya
Published: November 2021

Translesion synthesis (TLS) DNA polymerases (Pols) promote replication through DNA lesions; however, little is known about the protein factors that affect their function in human cells. In yeast, Rev1 plays a noncatalytic role as an indispensable component of Polζ, and Polζ together with Rev1 mediates a highly mutagenic mode of TLS. However, how Rev1 functions in TLS and mutagenesis in human cells has remained unclear. Here we determined the role of Rev1 in TLS opposite UV lesions in human and mouse fibroblasts and showed that Rev1 is indispensable for TLS mediated by Polη, Polι, and Polκ but is not required for TLS by Polζ. In contrast to its role in mutagenic TLS in yeast, Rev1 promotes predominantly error-free TLS opposite UV lesions in humans. The identification of Rev1 as an indispensable scaffolding component for Polη, Polι, and Polκ, which function in TLS in highly specialized ways opposite a diverse array of DNA lesions and act in a predominantly error-free manner, implicates a crucial role for Rev1 in the maintenance of genome stability in humans.
Influence of role models on the entrepreneurial skills of science and technology undergraduates
Authors: Rajchamaha Kittichai , Prapojanasomboon Jatupat
Published: November 2021

Purpose

This study examines the perspectives of undergraduate science and technology students in Thailand regarding the influence of various role models on their entrepreneurial skills.

Design/methodology/approach

This study employed the single case study research method. Purposive sampling was used to select the participants. The sample consisted of 142 key informants, whose responses were analysed using a direct content analysis method.

Findings

From the students' perspectives, entrepreneurial role models indirectly influenced their entrepreneurial skills.

Practical implications

The findings have clear implications for educators and policymakers. Educational institutions should design and implement educational strategies that help connect informal learning gained from the family with formal training at higher education institutions. On-the-job or apprenticeship training should also be included as a component of course content.

Originality/value

Our findings regarding the influence of role models differ from those of previous studies in relation to two of the four role models considered here. First, according to the students, their family environment has no direct impact on their entrepreneurial skills. In addition, science- and technology-based educational environments should adopt an entrepreneurial orientation to help students understand various market and business pressures, which will enable them to make a positive contribution to the workplace.