bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro and macroevolution of sea anemone venom phenotype
Authors: Smith Edward G. , Surm Joachim M. , Macrander Jason , Simhi Adi , Amir Guy , Sachkova Maria Y. , Lewandowska Magda , Reitzel Adam M. , Moran Yehu
Published: January 2023

Venom is a complex trait with substantial inter- and intraspecific variability resulting from strong selective pressures acting on the expression of many toxic proteins. However, understanding the processes underlying toxin expression dynamics that determine the venom phenotype remains unresolved. By interspecific comparisons we reveal that toxin expression in sea anemones evolves rapidly and that in each species different toxin family dictates the venom phenotype by massive gene duplication events. In-depth analysis of the sea anemone,Nematostella vectensis, revealed striking variation of the dominant toxin (Nv1) diploid copy number across populations (1-24 copies) resulting from independent expansion/contraction events, which generate distinct haplotypes.Nv1copy number correlates with expression at both the transcript and protein levels with one population having a near-complete loss of Nv1 production. Finally, we establish the dominant toxin hypothesis which incorporates observations in other venomous lineages that animals have convergently evolved a similar strategy in shaping their venom.
Preferential molecular recognition of heterochiral guests within a cyclophane receptor
Authors: Weh Manuel , Shoyama Kazutaka , Würthner Frank
Published: January 2023

The discrimination of enantiomers by natural receptors is a well-established phenomenon. In contrast the number of synthetic receptors with the capability for enantioselective molecular recognition of chiral substrates is scarce and for chiral cyclophanes indicative for a preferential binding of homochiral guests. Here we introduce a cyclophane composed of two homochiral core-twisted perylene bisimide (PBI) units connected by p-xylylene spacers and demonstrate its preference for the complexation of [5]helicene of opposite helicity compared to the PBI units of the host. The pronounced enantio-differentiation of this molecular receptor for heterochiral guests can be utilized for the enrichment of the P-PBI-M-helicene-P-PBI epimeric bimolecular complex. Our experimental results are supported by DFT calculations, which reveal that the sterically demanding bay substituents attached to the PBI chromophores disturb the helical shape match of the perylene core and homochiral substrates and thereby enforce the formation of syndiotactic host-guest complex structures. Hence, the most efficient substrate binding is observed for those aromatic guests, e. g. perylene, [4]helicene, phenanthrene and biphenyl, that can easily adapt in non-planar axially chiral conformations due to their inherent conformational flexibility. In all cases the induced chirality for the guest is opposed to those of the embedding PBI units, leading to heterochiral host-guest structures.
Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol
Authors: Yang Ming , Qi Xiaoqiang , Li Nan , Kaifi Jussuf T. , Chen Shiyou , Wheeler Andrew A. , Kimchi Eric T. , Ericsson Aaron C. , Rector R. Scott , Staveley-O’Carroll Kevin F. , Li Guangfu
Published: January 2023

The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-β1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis.
Deep mutational scanning of essential bacterial proteins can guide antibiotic development
Authors: Dewachter Liselot , Brooks Aaron N. , Noon Katherine , Cialek Charlotte , Clark-ElSayed Alia , Schalck Thomas , Krishnamurthy Nandini , Versées Wim , Vranken Wim , Michiels Jan
Published: January 2023

Deep mutational scanning is a powerful approach to investigate a wide variety of research questions including protein function and stability. Here, we perform deep mutational scanning on three essential E. coli proteins (FabZ, LpxC and MurA) involved in cell envelope synthesis using high-throughput CRISPR genome editing, and study the effect of the mutations in their original genomic context. We use more than 17,000 variants of the proteins to interrogate protein function and the importance of individual amino acids in supporting viability. Additionally, we exploit these libraries to study resistance development against antimicrobial compounds that target the selected proteins. Among the three proteins studied, MurA seems to be the superior antimicrobial target due to its low mutational flexibility, which decreases the chance of acquiring resistance-conferring mutations that simultaneously preserve MurA function. Additionally, we rank anti-LpxC lead compounds for further development, guided by the number of resistance-conferring mutations against each compound. Our results show that deep mutational scanning studies can be used to guide drug development, which we hope will contribute towards the development of novel antimicrobial therapies.
A database of experimentally measured lithium solid electrolyte conductivities evaluated with machine learning
Authors: Hargreaves Cameron J. , Gaultois Michael W. , Daniels Luke M. , Watts Emma J. , Kurlin Vitaliy A. , Moran Michael , Dang Yun , Morris Rhun , Morscher Alexandra , Thompson Kate , Wright Matthew A. , Prasad Beluvalli-Eshwarappa , Blanc Frédéric , Collins Chris M. , Crawford Catriona A. , Duff Benjamin B. , Evans Jae , Gamon Jacinthe , Han Guopeng , Leube Bernhard T. , Niu Hongjun , Perez Arnaud J. , Robinson Aris , Rogan Oliver , Sharp Paul M. , Shoko Elvis , Sonni Manel , Thomas William J. , Vasylenko Andrij , Wang Lu , Rosseinsky Matthew J. , Dyer Matthew S.
Published: January 2023

The application of machine learning models to predict material properties is determined by the availability of high-quality data. We present an expert-curated dataset of lithium ion conductors and associated lithium ion conductivities measured by a.c. impedance spectroscopy. This dataset has 820 entries collected from 214 sources; entries contain a chemical composition, an expert-assigned structural label, and ionic conductivity at a specific temperature (from 5 to 873 °C). There are 403 unique chemical compositions with an associated ionic conductivity near room temperature (15–35 °C). The materials contained in this dataset are placed in the context of compounds reported in the Inorganic Crystal Structure Database with unsupervised machine learning and the Element Movers Distance. This dataset is used to train a CrabNet-based classifier to estimate whether a chemical composition has high or low ionic conductivity. This classifier is a practical tool to aid experimentalists in prioritizing candidates for further investigation as lithium ion conductors.
Ancient DNA reveals admixture history and endogamy in the prehistoric Aegean
Authors: Skourtanioti Eirini , Ringbauer Harald , Gnecchi Ruscone Guido Alberto , Bianco Raffaela Angelina , Burri Marta , Freund Cäcilia , Furtwängler Anja , Gomes Martins Nuno Filipe , Knolle Florian , Neumann Gunnar U. , Tiliakou Anthi , Agelarakis Anagnostis , Andreadaki-Vlazaki Maria , Betancourt Philip , Hallager Birgitta P. , Jones Olivia A. , Kakavogianni Olga , Kanta Athanasia , Karkanas Panagiotis , Kataki Efthymia , Kissas Konstantinos , Koehl Robert , Kvapil Lynne , Maran Joseph , McGeorge Photini J. P. , Papadimitriou Alkestis , Papathanasiou Anastasia , Papazoglou-Manioudaki Lena , Paschalidis Kostas , Polychronakou-Sgouritsa Naya , Preve Sofia , Prevedorou Eleni-Anna , Price Gypsy , Protopapadaki Eftychia , Schmidt-Schultz Tyede , Schultz Michael , Shelton Kim , Wiener Malcolm H. , Krause Johannes , Jeong Choongwon , Stockhammer Philipp W.
Published: January 2023

The Neolithic and Bronze Ages were highly transformative periods for the genetic history of Europe but for the Aegean—a region fundamental to Europe’s prehistory—the biological dimensions of cultural transitions have been elucidated only to a limited extent so far. We have analysed newly generated genome-wide data from 102 ancient individuals from Crete, the Greek mainland and the Aegean Islands, spanning from the Neolithic to the Iron Age. We found that the early farmers from Crete shared the same ancestry as other contemporaneous Neolithic Aegeans. In contrast, the end of the Neolithic period and the following Early Bronze Age were marked by ‘eastern’ gene flow, which was predominantly of Anatolian origin in Crete. Confirming previous findings for additional Central/Eastern European ancestry in the Greek mainland by the Middle Bronze Age, we additionally show that such genetic signatures appeared in Crete gradually from the seventeenth to twelfth centuries bc, a period when the influence of the mainland over the island intensified. Biological and cultural connectedness within the Aegean is also supported by the finding of consanguineous endogamy practiced at high frequencies, unprecedented in the global ancient DNA record. Our results highlight the potential of archaeogenomic approaches in the Aegean for unravelling the interplay of genetic admixture, marital and other cultural practices.
A modality-independent proto-organization of human multisensory areas
Authors: Setti Francesca , Handjaras Giacomo , Bottari Davide , Leo Andrea , Diano Matteo , Bruno Valentina , Tinti Carla , Cecchetti Luca , Garbarini Francesca , Pietrini Pietro , Ricciardi Emiliano
Published: January 2023

The processing of multisensory information is based upon the capacity of brain regions, such as the superior temporal cortex, to combine information across modalities. However, it is still unclear whether the representation of coherent auditory and visual events requires any prior audiovisual experience to develop and function. Here we measured brain synchronization during the presentation of an audiovisual, audio-only or video-only version of the same narrative in distinct groups of sensory-deprived (congenitally blind and deaf) and typically developed individuals. Intersubject correlation analysis revealed that the superior temporal cortex was synchronized across auditory and visual conditions, even in sensory-deprived individuals who lack any audiovisual experience. This synchronization was primarily mediated by low-level perceptual features, and relied on a similar modality-independent topographical organization of slow temporal dynamics. The human superior temporal cortex is naturally endowed with a functional scaffolding to yield a common representation across multisensory events.
[11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial
Authors: Wu Xilin , Senanayake Russell , Goodchild Emily , Bashari Waiel A. , Salsbury Jackie , Cabrera Claudia P. , Argentesi Giulia , O’Toole Samuel M. , Matson Matthew , Koo Brendan , Parvanta Laila , Hilliard Nick , Kosmoliaptsis Vasilis , Marker Alison , Berney Daniel M. , Tan Wilson , Foo Roger , Mein Charles A. , Wozniak Eva , Savage Emmanuel , Sahdev Anju , Bird Nicholas , Laycock Kate , Boros Istvan , Hader Stefan , Warnes Victoria , Gillett Daniel , Dawnay Anne , Adeyeye Elizabeth , Prete Alessandro , Taylor Angela E. , Arlt Wiebke , Bhuva Anish N. , Aigbirhio Franklin , Manisty Charlotte , McIntosh Alasdair , McConnachie Alexander , Cruickshank J. Kennedy , Cheow Heok , Gurnell Mark , Drake William M. , Brown Morris J.
Published: January 2023

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA (NCT02945904) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = −6.5 to 24.1%) and 3.8% (95% confidence interval = −11.9 to 9.4) lay within the pre-specified −17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.
Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer
Authors: Kotani Daisuke , Oki Eiji , Nakamura Yoshiaki , Yukami Hiroki , Mishima Saori , Bando Hideaki , Shirasu Hiromichi , Yamazaki Kentaro , Watanabe Jun , Kotaka Masahito , Hirata Keiji , Akazawa Naoya , Kataoka Kozo , Sharma Shruti , Aushev Vasily N. , Aleshin Alexey , Misumi Toshihiro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Mori Masaki , Yoshino Takayuki
Published: January 2023

Despite standard-of-care treatment, more than 30% of patients with resectable colorectal cancer (CRC) relapse. Circulating tumor DNA (ctDNA) analysis may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making. We report results from GALAXY, which is an observational arm of the ongoing CIRCULATE-Japan study (UMIN000039205) that analyzed presurgical and postsurgical ctDNA in patients with stage II–IV resectable CRC (n = 1,039). In this cohort, with a median follow-up of 16.74 months (range 0.49–24.83 months), postsurgical ctDNA positivity (at 4 weeks after surgery) was associated with higher recurrence risk (hazard ratio (HR) 10.0, P < 0.0001) and was the most significant prognostic factor associated with recurrence risk in patients with stage II or III CRC (HR 10.82, P < 0.001). Furthermore, postsurgical ctDNA positivity identified patients with stage II or III CRC who derived benefit from ACT (HR 6.59, P < 0.0001). The results of our study, a large and comprehensive prospective analysis of ctDNA in resectable CRC, support the use of ctDNA testing to identify patients who are at increased risk of recurrence and are likely to benefit from ACT.
Unsupervised EEG preictal interval identification in patients with drug-resistant epilepsy
Authors: Leal Adriana , Curty Juliana , Lopes Fábio , Pinto Mauro F. , Oliveira Ana , Sales Francisco , Bianchi Anna M. , Ruano Maria G. , Dourado António , Henriques Jorge , Teixeira César A.
Published: January 2023

Typical seizure prediction models aim at discriminating interictal brain activity from pre-seizure electrographic patterns. Given the lack of a preictal clinical definition, a fixed interval is widely used to develop these models. Recent studies reporting preictal interval selection among a range of fixed intervals show inter- and intra-patient preictal interval variability, possibly reflecting the heterogeneity of the seizure generation process. Obtaining accurate labels of the preictal interval can be used to train supervised prediction models and, hence, avoid setting a fixed preictal interval for all seizures within the same patient. Unsupervised learning methods hold great promise for exploring preictal alterations on a seizure-specific scale. Multivariate and univariate linear and nonlinear features were extracted from scalp electroencephalography (EEG) signals collected from 41 patients with drug-resistant epilepsy undergoing presurgical monitoring. Nonlinear dimensionality reduction was performed for each group of features and each of the 226 seizures. We applied different clustering methods in searching for preictal clusters located until 2 h before the seizure onset. We identified preictal patterns in 90% of patients and 51% of the visually inspected seizures. The preictal clusters manifested a seizure-specific profile with varying duration (22.9 ± 21.0 min) and starting time before seizure onset (47.6 ± 27.3 min). Searching for preictal patterns on the EEG trace using unsupervised methods showed that it is possible to identify seizure-specific preictal signatures for some patients and some seizures within the same patient.
Imaging features of localized IDH wild-type histologically diffuse astrocytomas: a single-institution case series
Authors: Kibe Yuji , Motomura Kazuya , Ohka Fumiharu , Aoki Kosuke , Shimizu Hiroyuki , Yamaguchi Junya , Nishikawa Tomohide , Saito Ryuta
Published: January 2023

Isocitrate dehydrogenase wild-type (IDHwt) diffuse astrocytomas feature highly infiltrative patterns, such as a gliomatosis cerebri growth pattern with widespread involvement. Among these tumors, localized IDHwt histologically diffuse astrocytomas are rarer than the infiltrative type. The aim of this study was to assess and describe the clinical, radiographic, histopathological, and molecular characteristics of this rare type of IDHwt histologically diffuse astrocytomas and thereby provide more information on how its features affect clinical prognoses and outcomes. We retrospectively analyzed the records of five patients with localized IDHwt histologically diffuse astrocytomas between July 2017 and January 2020. All patients were female, and their mean age at the time of the initial treatment was 55.0 years. All patients had focal disease that did not include gliomatosis cerebri or multifocal disease. All patients received a histopathological diagnosis of diffuse astrocytomas at the time of the initial treatment. For recurrent tumors, second surgeries were performed at a mean of 12.4 months after the initial surgery. A histopathological diagnosis of glioblastoma was made in four patients and one of gliosarcoma in one patient. The initial status of IDH1, IDH2, H3F3A, HIST1H3B, and BRAF was “wild-type” in all patients. TERT promoter mutations (C250T or C228T) were detected in four patients. No tumors harbored a 1p/19q codeletion, EGFR amplification, or chromosome 7 gain/10 loss (+ 7/ − 10). We assessed clinical cases of localized IDHwt histologically diffuse astrocytomas that resulted in malignant recurrence and a poor clinical prognosis similar to that of glioblastomas. Our case series suggests that even in patients with histologically diffuse astrocytomas and those who present with radiographic imaging findings suggestive of a localized tumor mass, physicians should consider the possibility of IDHwt histologically diffuse astrocytomas.
The telomerase activator TA-65 protects from cigarette smoke-induced small airway remodeling in mice through extra-telomeric effects
Authors: Tiendrébéogo Arnaud Jean Florent , Soumagne Thibaud , Pellegrin François , Dagouassat Maylis , Tran Van Nhieu Jeanne , Caramelle Philippe , Paul Emmanuel N. , Even Benjamin , Zysman Maeva , Julé Yvon , Samb Abdoulaye , Boczkowski Jorge , Lanone Sophie , Schlemmer Frédéric
Published: January 2023

Small airway remodeling (SAR) is a key phenomenon of airflow obstruction in smokers, leading to chronic obstructive pulmonary disease (COPD). SAR results in an increased thickness of small airway walls, with a combination of peribronchiolar fibrosis with increased fibrous tissue and accumulation of mesenchymal and epithelial cells. SAR pathogenesis is still unclear but recent data suggest that alterations in telomerase activity could represent a possible underlying mechanism of SAR. Our study was dedicated to identify a potential protective role of TA-65, a pharmacological telomerase activator, in a cigarette smoke (CS) model of SAR in mice, and to further precise if extra-telomeric effects of telomerase, involving oxidative stress modulation, could explain it. C57BL/6J mice were daily exposed to air or CS during 4 weeks with or without a concomitant administration of TA-65 starting 7 days before CS exposure. Morphological analyses were performed, and mucus production, myofibroblast differentiation, collagen deposition, as well as transforming growth factor-β1 (TGF-β1) expression in the small airway walls were examined. In addition, the effects of TA-65 treatment on TGF-β expression, fibroblast-to-myofibroblast differentiation, reactive oxygen species (ROS) production and catalase expression and activity were evaluated in primary cultures of pulmonary fibroblasts and/or mouse embryonic fibroblasts in vitro. Exposure to CS during 4 weeks induced SAR in mice, characterized by small airway walls thickening and peribronchiolar fibrosis (increased deposition of collagen, expression of α-SMA in small airway walls), without mucus overproduction. Treatment of mice with TA-65 protected them from CS-induced SAR. This effect was associated with the prevention of CS-induced TGF-β expression in vivo, the blockade of TGF-β-induced myofibroblast differentiation, and the reduction of TGF-β-induced ROS production that correlates with an increase of catalase expression and activity. Our findings demonstrate that telomerase is a critical player of SAR, probably through extra-telomeric anti-oxidant effects, and therefore provide new insights in the understanding and treatment of COPD pathogenesis.
Attention-deficit hyperactivity disorder traits are a more important predictor of internalising problems than autistic traits
Authors: Hargitai Luca D. , Livingston Lucy A. , Waldren Lucy H. , Robinson Ross , Jarrold Christopher , Shah Punit
Published: January 2023

Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) are both linked to internalising problems like anxiety and depression. ASD and ADHD also often co-occur, making their individual statistical contributions to internalising disorders difficult to investigate. To address this issue, we explored the unique associations of self-reported ASD traits and ADHD traits with internalising problems using a large general population sample of adults from the United Kingdom (N = 504, 49% male). Classical regression analyses indicated that both ASD traits and ADHD traits were uniquely associated with internalising problems. Dominance and Bayesian analyses confirmed that ADHD traits were a stronger, more important predictor of internalising problems. However, brief depression and anxiety measures may not provide a comprehensive index of internalising problems. Additionally, we focused on recruiting a sample that was representative of the UK population according to age and sex, but not ethnicity, a variable that may be linked to internalising disorders. Nevertheless, our findings indicate that while ASD and ADHD uniquely predict internalising problems, ADHD traits are a more important statistical predictor than ASD traits. We discuss potential mechanisms underlying this pattern of results and the implications for research and clinical practice concerning neurodevelopmental conditions.
Genetic and ecological drivers of molt in a migratory bird
Authors: Contina Andrea , Bossu Christen M. , Allen Daniel , Wunder Michael B. , Ruegg Kristen C.
Published: January 2023

The ability of animals to sync the timing and location of molting (the replacement of hair, skin, exoskeletons or feathers) with peaks in resource availability has important implications for their ecology and evolution. In migratory birds, the timing and location of pre-migratory feather molting, a period when feathers are shed and replaced with newer, more aerodynamic feathers, can vary within and between species. While hypotheses to explain the evolution of intraspecific variation in the timing and location of molt have been proposed, little is known about the genetic basis of this trait or the specific environmental drivers that may result in natural selection for distinct molting phenotypes. Here we take advantage of intraspecific variation in the timing and location of molt in the iconic songbird, the Painted Bunting (Passerina ciris) to investigate the genetic and ecological drivers of distinct molting phenotypes. Specifically, we use genome-wide genetic sequencing in combination with stable isotope analysis to determine population genetic structure and molting phenotype across thirteen breeding sites. We then use genome-wide association analysis (GWAS) to identify a suite of genes associated with molting and pair this with gene-environment association analysis (GEA) to investigate potential environmental drivers of genetic variation in this trait. Associations between genetic variation in molt-linked genes and the environment are further tested via targeted SNP genotyping in 25 additional breeding populations across the range. Together, our integrative analysis suggests that molting is in part regulated by genes linked to feather development and structure (GLI2andCSPG4) and that genetic variation in these genes is associated with seasonal variation in precipitation and aridity. Overall, this work provides important insights into the genetic basis and potential selective forces behind phenotypic variation in what is arguably one of the most important fitness-linked traits in a migratory bird.
Rapid, multiplex detection of SARS-CoV-2 using isothermal amplification coupled with CRISPR-Cas12a
Authors: Figueiredo Diogo , Cascalheira António , Goncalves Joao
Published: January 2023

In December 2019 an outbreak erupted due to the beta coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 in Wuhan, China. The disease caused by this virus (COVID-19) rapidly spread to all parts of the globe leading to a global pandemic. Efforts to combat the pandemic rely on RT-qPCR diagnostic tests that have high turnaround times (~ 24 h), are easily contaminated, need specialized equipment, facilities, and personnel that end up increasing the overall costs of this method. Loop-mediated isothermal amplification (LAMP) coupled with a reverse transcription step (RT-LAMP) is an alternative diagnostic method that can easily overcome these obstacles, when coupled with CRISPR/Cas it can eliminate false positives. Here we report a fast (~ 40 min), highly sensitive, point-of-care multiplex RT-LAMP and CRISPR/Cas12a assay to detect SARS-CoV-2. This fluorescence-based test achieved 100% specificity and 93% sensitivity using 25 positives and 50 negative patient samples for Ct < 35. Our reported LoD of 3 copies/µL will enable the robust, fast detection of the virus in a dedicated equipment which is a major step towards population-wide accessible testing.
A desire for distraction: uncovering the rates of media multitasking during online research studies
Authors: Drody Allison C. , Pereira Effie J. , Smilek Daniel
Published: January 2023

Interpretations of task performance in many cognitive studies rest on the assumption that participants are fully attentive to the tasks they agree to complete. However, with research studies being increasingly conducted online where monitoring participant engagement is difficult, this assumption may be inaccurate. If participants were found to be engaging in off-task behaviours while participating in these studies, the interpretation of study results might be called into question. To investigate this issue, we conducted a secondary data analysis across nearly 3000 participants in various online studies to examine the prevalence of one form of off-task behaviour: media multitasking. Rates of media multitasking were found to be high, averaging 38% and ranging from 9 to 85% across studies. Our findings broadly raise questions about the interpretability of results from online studies and urge researchers to consider the likelihood that participants are simultaneously engaging in off-task behaviours while completing online research tasks.
Monitoring phage-induced lysis of gram-negatives in real time using a fluorescent DNA dye
Authors: Egido Julia E. , Toner-Bartelds Catherine , Costa Ana Rita , Brouns Stan J. J. , Rooijakkers Suzan H. M. , Bardoel Bart W. , Haas Pieter-Jan
Published: January 2023

Bacteriophages (phages) are viruses that specifically attack bacteria. Their use as therapeutics, which constitutes a promising alternative to antibiotics, heavily relies on selecting effective lytic phages against the pathogen of interest. Current selection techniques are laborious and do not allow for direct visualization of phage infection dynamics. Here, we present a method that circumvents these limitations. It can be scaled for high-throughput and permits monitoring of the phage infection in real time via a fluorescence signal readout. This is achieved through the use of a membrane-impermeant nucleic acid dye that stains the DNA of damaged or lysed bacteria and new phage progeny. We have tested the method on Pseudomonas aeruginosa and Klebsiella pneumoniae and show that an increase in fluorescence reflects phage-mediated killing. This is confirmed by other techniques including spot tests, colony plating, flow cytometry and metabolic activity measurements. Furthermore, we illustrate how our method may be used to compare the activity of different phages and to screen the susceptibility of clinical isolates to phage. Altogether, we present a fast, reliable way of selecting phages against Gram-negative bacteria, which may be valuable in optimizing the process of selecting phages for therapeutic use.
Effects of population age structure on parenteral antimicrobial use estimations
Authors: Koizumi Ryuji , Kusama Yoshiki , Asai Yusuke , Tsuzuki Shinya , Aoyagi Kensuke , Ishikane Masahiro , Muraki Yuichi , Ohmagari Norio
Published: January 2023

Antimicrobial use (AMU) is conventionally reported as unadjusted defined daily doses (DDDs) or population-adjusted DDDs per 1000 inhabitants per day (DID). DID is frequently used to monitor national AMU trends, this metric does not intrinsically take temporal changes in population age structure into account. We examined the effects of population age structure on DID estimates of parenteral AMU in Japan, and predicted future trends in DDDs based on population projections. Parenteral AMU data from 2013 to 2018 were acquired from a national claims database. We assessed temporal trends in parenteral AMU by age group (children aged < 15 years, working-age persons aged 15–64 years, and older persons aged ≥ 65 years) using both DID and DDDs. In addition, we modeled DDD predictions based on age-specific population projections from 2019 to 2030. DID values for older persons were 8.08–10.15 times and 5.43–5.63 times higher than in children and working-age persons, respectively. DID was stable, but DDDs increased in older persons. The prediction models showed that DDDs will continue to increase until 2030 if DID remains steady or decreases. DID estimates were skewed by the older population. More rigorous antimicrobial stewardship efforts targeting geriatric care are needed to counter the aging-associated increase in AMU.
Intravenous fentanyl self-administration in male and female C57BL/6J and DBA/2J mice
Authors: Leonardo Michael , Brunty Sarah , Huffman Jessica , Kastigar Alexis , Dickson Price E.
Published: January 2023

The genetic mechanisms underlying fentanyl addiction, a highly heritable disease, are unknown. Identifying these mechanisms will lead to better risk assessment, early diagnosis, and improved intervention. To this end, we used intravenous fentanyl self-administration to quantify classical self-administration phenotypes and addiction-like fentanyl seeking in male and female mice from the two founder strains of the BXD recombinant inbred mouse panel (C57BL/6J and DBA/2J). We reached three primary conclusions from these experiments. First, mice from all groups rapidly acquired intravenous fentanyl self-administration and exhibited a dose–response curve, extinction burst, and extinction of the learned self-administration response. Second, fentanyl intake (during acquisition and dose response) and fentanyl seeking (during extinction) were equivalent among groups. Third, strain effects, sex effects, or both were identified for several addiction-like behaviors (cue-induced reinstatement, stress-induced reinstatement, escalation of intravenous fentanyl self-administration). Collectively, these data indicate that C57BL/6J and DBA/2J mice of both sexes were able to acquire, regulate, and extinguish intravenous fentanyl self-administration. Moreover, these data reveal novel strain and sex effects on addiction-like behaviors in the context of intravenous fentanyl self-administration in mice and indicate that the full BXD panel can be used to identify and dissect the genetic mechanisms underlying these effects.
Detecting the socio-economic drivers of confidence in government with eXplainable Artificial Intelligence
Authors: Bellantuono Loredana , Palmisano Flaviana , Amoroso Nicola , Monaco Alfonso , Peragine Vitorocco , Bellotti Roberto
Published: January 2023

The European Quality of Government Index (EQI) measures the perceived level of government quality by European Union citizens, combining surveys on corruption, impartiality and quality of provided services. It is, thus, an index based on individual subjective evaluations. Understanding the most relevant objective factors affecting the EQI outcomes is important for both evaluators and policy makers, especially in view of the fact that perception of government integrity contributes to determine the level of civic engagement. In our research, we employ methods of Artificial Intelligence and complex systems physics to measure the impact on the perceived government quality of multifaceted variables, describing territorial development and citizen well-being, from an economic, social and environmental viewpoint. Our study, focused on a set of regions in European Union at a subnational scale, leads to identifying the territorial and demographic drivers of citizens’ confidence in government institutions. In particular, we find that the 2021 EQI values are significantly related to two indicators: the first one is the difference between female and male labour participation rates, and the second one is a proxy of wealth and welfare such as the average number of rooms per inhabitant. This result corroborates the idea of a central role played by labour gender equity and housing policies in government confidence building. In particular, the relevance of the former indicator in EQI prediction results from a combination of positive conditions such as equal job opportunities, vital labour market, welfare and availability of income sources, while the role of the latter is possibly amplified by the lockdown policies related to the COVID-19 pandemics. The analysis is based on combining regression, to predict EQI from a set of publicly available indicators, with the eXplainable Artificial Intelligence approach, that quantifies the impact of each indicator on the prediction. Such a procedure does not require any ad-hoc hypotheses on the functional dependence of EQI on the indicators used to predict it. Finally, using network science methods concerning community detection, we investigate how the impact of relevant indicators on EQI prediction changes throughout European regions. Thus, the proposed approach enables to identify the objective factors at the basis of government quality perception by citizens in different territorial contexts, providing the methodological basis for the development of a quantitative tool for policy design.
Multiplex recombinase polymerase amplification for high-risk and low-risk type HPV detection, as potential local use in single tube
Authors: Wongsamart Rungdawan , Bhattarakasol Parvapan , Chaiwongkot Arkom , Wongsawaeng Doonyapong , Okada Pilailuk Akkapaiboon , Palaga Tanapat , Leelahavanichkul Asada , Khovidhunkit Weerapan , Dean Deborah , Somboonna Naraporn
Published: January 2023

High rates of new cervical cancer cases and deaths occur in low- and middle-income countries yearly, and one reason was found related to limitation of regular cervical cancer screening in local and low-resource settings. HPV has over 150 types, yet certain 14–20 high-risk and 13–14 low-risk types are common, and, thus, most conventional HPV nucleic acid assays, for examples, Cobas 4800 HPV test (Roche Diagnostics, New Jersey, USA) and REBA HPV-ID (Molecules and Diagnostics, Wonju, Republic of Korea) were developed to cover these types. We thereby utilized bioinformatics combined with recent isothermal amplification technique at 35–42 °C to firstly describe multiplex recombinase polymerase amplification assay that is specific to these common 20 high-risk and 14 low-risk types, and also L1 and E6/E7 genes that target different stages of cervical cancer development. Multiplex primer concentrations and reaction incubation conditions were optimized to allow simultaneous two gene detections at limit of detection of 1000 copies (equivalent to 2.01 fg) for L1 and 100 copies (0.0125 fg) for E6/E7, respectively. The assay was validated against urogenital and other pathogens, normal flora, and human control. In 130 real clinical sample tests, the assay demonstrated 100% specificity, 78% diagnostic accuracy, and 75% sensitivity compared with REBA HPV-ID test, and is much more rapid (15–40 min), less expensive (~ 3–4 USD/reaction) and does not require instrumentation (35–42 °C reaction condition so hand holding or tropical temperature is possible). Hence, the developed novel assay provides alternative screening tool for potential local screening. Furthermore, as this assay uses safe chemical reagents, it is safe for users.
Impaired placental hemodynamics and function in a non-human primate model of gestational protein restriction
Authors: Lo Jamie O. , Schabel Matthias C. , Gaffney Jessica , Lewandowski Katherine S. , Kroenke Christopher D. , Roberts Charles T. , Scottoline Brian P. , Frias Antonio E. , Sullivan Elinor L. , Roberts Victoria H. J.
Published: January 2023

Maternal malnutrition increases fetal and neonatal morbidity, partly by affecting placental function and morphology, but its impact on placental hemodynamics are unknown. Our objective was to define the impact of maternal malnutrition on placental oxygen reserve and perfusion in vivo in a rhesus macaque model of protein restriction (PR) using advanced imaging. Animals were fed control (CON, 26% protein), 33% PR diet (17% protein), or a 50% PR diet (13% protein, n = 8/group) preconception and throughout pregnancy. Animals underwent Doppler ultrasound and fetal biometry followed by MRI at gestational days 85 (G85) and 135 (G135; term is G168). Pregnancy loss rates were 0/8 in CON, 1/8 in 33% PR, and 3/8 in 50% PR animals. Fetuses of animals fed a 50% PR diet had a smaller abdominal circumference (G135, p < 0.01). On MRI, placental blood flow was decreased at G135 (p < 0.05) and placental oxygen reserve was reduced (G85, p = 0.05; G135, p = 0.01) in animals fed a 50% PR diet vs. CON. These data demonstrate that a 50% PR diet reduces maternal placental perfusion, decreases fetal oxygen availability, and increases fetal mortality. These alterations in placental hemodynamics may partly explain human growth restriction and stillbirth seen with severe PR diets in the developing world.
Total acoustic transmission in a honeycomb network empowered by compact acoustic isolator
Authors: Zhang Haixiao , Li Rong , Bao Yu , Liu Xiaoli , Zhang Yiwei
Published: January 2023

In recent years, acoustic metamaterials have exhibited extraordinary potential for manipulating the propagation of sound waves. However, it has been a challenge to control the propagation of sound waves through arbitrary pathways in a network. In this work, we designed a compact three-port isolator that can produce giant acoustic nonreciprocity by introducing actively controlled CNT films to the device without altering the geometric symmetry of it. This concept is subsequently applied to construct a 4 × 7 honeycomb network, in which, total transmission of sound wave in arbitrary pathway can be slickly achieved. Unlike the acoustic topological insulator, which only supports total transmission of arbitrary pathway in the band gap, our method provides more degrees of freedom and can be realized at any frequency. This ability opens up a new method for routing sound waves and exhibits promising applications ranging from acoustic communication to energy transmission.
Single molecule imaging simulations with advanced fluorophore photophysics
Authors: Bourgeois Dominique
Published: January 2023

Advanced fluorescence imaging techniques such as single-molecule localization microscopy (SMLM) fundamentally rely on the photophysical behavior of the employed fluorophores. This behavior is generally complex and impacts data quality in a subtle manner. A simulation software named Single-Molecule Imaging Simulator (SMIS) is introduced that simulates a widefield microscope and incorporates fluorophores with their spectral and photophysical properties. With SMIS, data collection schemes combining 3D, multicolor, single-particle-tracking or quantitative SMLM can be implemented. The influence of advanced fluorophore characteristics, imaging conditions, and environmental parameters can be evaluated, facilitating the design of real experiments and their proper interpretation.
Dihydroartemisinin imposes positive and negative regulation on Treg and plasma cells via direct interaction and activation of c-Fos
Authors: Li Qilong , Jiang Ning , Zhang Yiwei , Liu Yize , Su Ziwei , Yuan Quan , Sang Xiaoyu , Chen Ran , Feng Ying , Chen Qijun
Published: January 2023

Dihydroartemisinin (DHA), a potent antimalarial drug, also exhibits distinct property in modulation on Treg and B cells, which has been recognized for decades, but the underlying mechanisms remain understood. Herein we revealed that DHA could promote Treg proliferation, meanwhile, suppress B cell expansion in germinal centers, and consequently decrease the number of circulating plasma cells and the content of serum immunoglobulins. Further, DHA-activated Treg significantly mitigated lipopolysaccharide-induced and malaria-associated inflammation. All these scenarios were attributed to the upregulation of c-Fos expression by DHA and enhancement of its interaction with target genes in both Treg and circulating plasma cells with bilateral cell fates. In Treg, the c-Fos-DHA complex upregulated cell proliferation-associated genes and promoted cell expansion; whereas in plasma cells, it upregulated the apoptosis-related genes resulting in decreased circulating plasma cells. Thus, the bilateral immunoregulatory mechanism of DHA was elucidated and its application in the treatment of autoimmune diseases is further justified.
Influence of point defects and multiscale pores on the different phonon transport regimes
Authors: Wei Han , Hu Yue , Bao Hua
Published: January 2023

A common strategy to tailor the thermal conductivity of a material is to introduce structural features that modulate phonon scattering, such as atomic-scale defects and nano- and macro-sized pores. However, particle-like and wave-like phonon transport and scattering during a crossover in thermal transport regimes is not well understood. Here, we perform a rigorous quantitative comparison of the thermal conductivity obtained from molecular dynamics simulations and phonon Boltzmann transport equations, taking graphene as an example. We observe a generally increasing trend in thermal conductivity when the pore size increases from point defect to nanopore, due to a transition from Rayleigh scattering to geometric scattering and reduced boundary density. The thermal conductivity further converges to the diffusive limit for macropores because of the dominant effect of phonon-phonon scattering over phonon-boundary scattering. Moreover, we identify a critical interpore distance for the crossover from dependent to independent phonon-pore scattering and a critical pore size for the crossover from point defect scattering to boundary scattering. This work provides a comprehensive understanding of phonon transport in materials containing defects and pores.
Conical shell illumination incorporating a moving aperture for depth-resolved high-energy X-ray diffraction
Authors: Spence Daniel , Dicken Anthony , Downes David , Rogers Keith , Evans Paul
Published: January 2023

To retrieve crystallographic information from overlapping sample volumes requires a high-energy probe using a point detector.
Proteomics and metabolomics analysis of the lignin degradation mechanism of lignin-degrading fungus Aspergillus fumigatus G-13
Authors: Zhu Xudong , Zhou Zijing , Guo Gaijuan , Li Jinda , Yan Hong , Li Fen
Published: January 2023

Aspergillus fumigatus has the potential to degrade lignocellulosic biomass, but the degradation mechanism is not clear.
O-GalNAc glycosylation affects the immunogenicity of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein
Authors: Rong Yongheng , Wang Xingyun , Mao Weian , Chen Min , Wang Shengjun , Wang Peng George , He Yunjiao , Kong Yun
Published: January 2023

Herein, O-GalNAc glycosylated RBD (Tn-RBD) was synthesized as antigen via in vitro glycosylation reactions. The inhibition ability against hACE2 binding of antibodies induced with Tn-RBD was 30–40% increased.
Effect of pressure on the electronic structure of antiferromagnetic and paramagnetic YNiO3: the role of disproportionation
Authors: Wlazło Mateusz , Malyi Oleksandr I.
Published: January 2023

We successfully describe the pressure-dependent electronic structure of YNiO3 phases by accounting for energy-lowering symmetry breaking and pressure-dependent distribution of local motifs.
Chemical deactivation of titanosilicate catalysts caused by propylene oxide in the HPPO process
Authors: Liu Dongxu , Wang Rui , Yu Yunkai , Chen Zhen , Fang Nan , Liu Yueming , He Mingyuan
Published: January 2023

Reducing the bidentate ether species formed from the chemisorption between PO and acid sites in the TS/H2O2system is key to achieving stable operation of the HPPO process.
Ten years of Environmental Science: Processes & Impacts
Authors: McNeill Kristopher
Published: January 2023

Editor-in-Chief Kristopher McNeill reflects on 10 years of Environmental Science: Processes & Impacts.
Both live and heat-killed Bifidobacterium animalis J-12 alleviated oral ulcers in LVG golden Syrian hamsters by gavage by directly intervening in the intestinal flora structure
Authors: Jing Nanqing , Liu Fudong , Wang Ran , Zhang Yan , Yang Jianjun , Hou Yubing , Zhang Hongxing , Xie Yuanhong , Liu Hui , Ge Shaoyang , Jin Junhua
Published: January 2023

It is feasible by gavage live and heat-killed bifidobacterium animalis J-12 to intervene in oral ulcers caused by methyl viologen dichloride modeling.
Hydrogen bonding network-enabled Brønsted acid-catalyzed Friedel–Crafts reactions: a green approach to access unsymmetrical diaryl- and triarylmethanes
Authors: Singh Sanjay , Mondal Sankalan , Vodnala Nagaraju , Hazra Chinmoy Kumar
Published: January 2023

The title paper describes the synthesis of unsymmetrical di and triarylmethanes in one pot through catalyst activation reducing the conventional six-step cross-coupling approach to one step Friedel–Crafts approach.