bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved pig behavior analysis by optimizing window sizes for individual behaviors on acceleration and angular velocity data
Authors: Alghamdi Saleh , Zhao Zhuqing , Ha Dong S , Morota Gota , Ha Sook S
Published: September 2022

This paper presents the application of machine learning algorithms to identify pigs’ behaviors from data collected using the wireless sensor nodes mounted on pigs. The sensor node attached to a pig’s back senses the acceleration and angular velocity in three axes, and the sensed data are transmitted to a host computer wirelessly. Two video cameras, one attached to the ceiling of the pigpen and the other one to a fence, provided ground truth for data annotations. The data were collected from pigs for 131 h over 2 mo. As the typical behavior period depends on the behavior type, we segmented the acceleration data with different window sizes (WS) and step sizes (SS), and tested how the classification performance of different activities varied with different WS and SS. After exploring the possible combinations, we selected the optimum WS and SS. To compare performance, we used five machine learning algorithms, specifically support vector machine, k-nearest neighbors, decision trees, naive Bayes, and random forest (RF). Among the five algorithms, RF achieved the highest F1 score for four major behaviors consisting of 92.36% in total. The F1 scores of the algorithm were 0.98 for “eating,” 0.99 for “lying,” 0.93 for “walking,” and 0.91 for “standing” behaviors. The optimal WS was 7 s for “eating” and “lying,” and 3 s for “walking” and “standing.” The proposed work demonstrates that, based on the length of behavior, the adaptive window and step sizes increase the classification performance.
The effect of benzoic acid with or without a direct-fed microbial on the nutrient metabolism and gas emissions of growing pigs
Authors: Humphrey Dalton C , Bergstrom Jon R , Calvo Estefania Pérez , Trabue Steven L , Scoggin Kenwood D , Greiner Laura L
Published: September 2022

Twenty-four gilts (PIC 337 × 1050, PIC Genus, Hendersonville, TN) with an initial body weight (BW) of 33.09 ± 1.33 kg were used to investigate the effects of benzoic acid (BA) and a Bacillus-based direct-fed microbial (DFM) on the nutrient metabolism and manure gas emissions of growing pigs. Pigs were blocked by BW, placed into metabolism stalls, and randomly assigned to one of four dietary treatments: basal control (PC), low nitrogen (NC), PC plus 0.3% BA (PC+BA; VevoVitall, DSM Nutritional Products), and PC plus 0.3% BA and 0.025% DFM (PC+BA+DFM; PureGro, DSM Nutritional Products). Pigs were fed a common diet from day 0 to 14, and the experimental diets were fed in two phases (day 14 to 28 and day 28 to 53). The experiment consisted of four collection periods, with each period subdivided into two subperiods to collect samples for gas emissions and nutrient balance. Firstly, manure samples were collected for 72 h. Twice daily, urine and feces were weighed, and urine pH was measured. After each period, manure was subsampled and taken to the lab to measure gas emissions. Secondly, urine and feces were quantitatively collected for 96 h to allow for measurement of nutrient digestibility (ATTD) and retention. Data were analyzed as repeated measures in SAS 9.4 (SAS Inst., Cary, NC) with fixed effects of treatment, collection period, and block. Pig was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.05 < P ≤ 0.10. Pigs fed PC+BA had the greatest ADG compared to pigs fed NC (P = 0.016), with intermediate ADG for pigs fed PC or PC+BA+DFM (P ≥ 0.148). The ATTD of dry matter, gross energy, P, and N did not differ between treatments (P ≥ 0.093). However, the ATTD of Ca was reduced in pigs fed PC+BA+DFM compared to pigs fed PC+BA (P = 0.012). Pigs fed PC+BA or NC excreted less urinary N compared to PC and PC+BA+DFM (P ≤ 0.034), which contributed to greater nitrogen retention in PC+BA compared to PC (P = 0.016). Furthermore, decreased manure pH from pigs fed PC+BA or NC resulted in lower ammonia (NH3) emissions compared to pigs fed PC+BA+DFM or PC. There was no effect of dietary treatment on manure hydrogen sulfide, methane, or carbon dioxide emissions. In conclusion, supplementing 0.3% BA improved N retention and reduced manure pH and NH3 emissions, similar to feeding pigs low N, but improved the ADG of pigs when compared to feeding a low N diet.
“Moroccan” Artek: Colonized Textiles within 1930s Modernist Interiors
Authors: Burlando Daniele
Published: September 2022

Shortly after opening in 1936, the Finnish interior design company Artek organized two exhibitions in Helsinki: a model apartment showroom and a display within its shop, both involving a substantial presence of Amazigh carpets from the French protectorate of Morocco. This article analyses these rugs within Artek identifying them as “colonized textiles.” This proposed concept aims to highlight textiles within the appropriation of non-Western cultural fragments by structures of imperialism and coloniality, while parallelly problematizing the inclusion of Amazigh rugs within architectural modernism. The movement of Amazigh rugs from Morocco to Finland, and their transition from Amazigh communities to European modernist interiors, are described through key events and exhibitions from the interwar era. The involvement of Artek actors and the process leading to the founding of Artek are highlighted within this context. Exhibitions are presented as a stage for the interaction of discourses on modernism and imperialism, and for the reiteration of constructed narrations directed by élite circles, supporting the appropriation and commodification of colonized textiles in Europe. Political agendas of cultural supervision within the French protectorate of Morocco are described while situating Amazigh rugs in this context. Parallelly, the relevance of textiles is highlighted within discussions on architectural modernism.
Reference genome of the rubber boa,Charina bottae(Serpentes: Boidae)
Authors: Grismer Jesse L , Escalona Merly , Miller Courtney , Beraut Eric , Fairbairn Colin W , Marimuthu Mohan P A , Nguyen Oanh , Toffelmier Erin , Wang Ian J , Shaffer H Bradley
Published: September 2022

The rubber boa, Charina bottae is a semi-fossorial, cold-temperature adapted snake that ranges across the wetter and cooler ecoregions of the California Floristic Province. The rubber boa is 1 of 2 species in the family Boidae native to California and currently has 2 recognized subspecies, the Northern rubber boa C. bottae bottae and the Southern rubber boa C. bottae umbratica. Recent genomic work on C. bottae indicates that these 2 subspecies are collectively composed of 4 divergent lineages that separated during the late Miocene. Analysis of habitat suitability indicates that C. bottae umbratica montane sky-island populations from southern California will lose the majority of their habit over the next 70 yr, and is listed as Threatened under the California Endangered Species Act. Here, we report a new, chromosome-level assembly of C. bottae bottae as part of the California Conservation Genomics Project (CCGP). Consistent with the reference genome strategy of the CCGP, we used Pacific Biosciences HiFi long reads and Hi-C chromatin-proximity sequencing technology to produce a de novo assembled genome. The assembly comprises 289 scaffolds covering 1,804,944,895 bp, has a contig N50 of 37.3 Mb, a scaffold N50 of 97 Mb, and BUSCO completeness score of 96.3%, and represents the first reference genome for the Boidae snake family. This genome will enable studies of genetic differentiation and connectivity among C. bottae bottae and C. bottae umbratica populations across California and help manage locally endemic lineages as they confront challenges from human-induced climate warming, droughts, and wildfires across California.
A brief history of population genetic research in California and an evaluation of its utility for conservation decision-making
Authors: Beninde Joscha , Toffelmier Erin , Shaffer H Bradley
Published: September 2022

A recently published macrogenetic dataset of California’s flora and fauna, CaliPopGen, comprehensively summarizes population genetic research published between 1985 and 2020. Integrating these genetic data into the requisite “best available science” upon which conservation professionals rely should facilitate the prioritization of populations based on genetic health. We evaluate the extent to which the CaliPopGen Dataset provides genetic diversity estimates that are 1) unbiased, 2) sufficient in quantity, 3) cover entire species’ ranges, and 4) include potentially adaptive loci. We identified genetic diversity estimates for 4,462 spatially referenced populations of 432 species, confirming California’s rich published history of population genetics research. Most recent studies used microsatellites markers, which have uniquely high levels of variation, and estimates of all genetic metrics varied significantly across marker types. Most studies used less than 10 loci for inferences, rendering parameter estimates potentially unreliable, and covered small spatial extents that include only a fraction of the studied species’ California distribution (median 16.3%). In contrast, the ongoing California Conservation Genomics Project (CCGP) aims to cover the full geographical and environmental breadth of each species’ occupied habitats, and uses a consistent approach based on whole-genome data. However, the CCGP will sequence only 12% of the number of individuals, and covers only about half the evolutionary diversity, of the CaliPopGen Database. There is clearly a place in the evaluation of the genetic health of California for both approaches going forward, especially if differences among studies can be minimized, and overlap emphasized. A complementary use of both datasets is warranted to inform optimal conservation decision-making. Finally, a synopsis of the available population genetic data for California, all other US states and 241 other countries, allows us to identify states and countries for which meaningful data summaries, such as CaliPopGen, could be collated and others, which have limited published data available and are prime targets for future, empirical work.
Determining Time to Positivity of Blood Cultures in a Neonatal Unit
Authors: Arias-Felipe Ana , Ramírez-Berrios Jesús , Recio-Martinez Raúl , Orellana-Miguel Maria Angeles , Fontiveros-Escalona Diego , Bergón-Sendín Elena , de Alba-Romero Concepción
Published: September 2022

Blood cultures are the gold standard for detecting bacteremia. We have studied the time to positivity of blood cultures in our neonatal unit to reduce antibiotic doses in patients with a negative blood culture. Empirical antibiotic treatment of neonatal sepsis could be withdrawn 24 hours after obtaining blood cultures.
The colonization of land was a likely driving force for the evolution of mitochondrial retrograde signalling in plants
Authors: Khan Kasim , Van Aken Olivier
Published: September 2022

Most retrograde signalling research in plants was performed using Arabidopsis, so an evolutionary perspective on mitochondrial retrograde regulation (MRR) is largely missing. Here, we used phylogenetics to track the evolutionary origins of factors involved in plant MRR. In all cases, the gene families can be traced to ancestral green algae or earlier. However, the specific subfamilies containing factors involved in plant MRR in many cases arose during the transition to land. NAC transcription factors with C-terminal transmembrane domains, as observed in the key regulator ANAC017, can first be observed in non-vascular mosses, and close homologs to ANAC017 can be found in seed plants. Cyclin-dependent kinases (CDKs) are common to eukaryotes, but E-type CDKs that control MRR also diverged in conjunction with plant colonization of land. AtWRKY15 can be traced to the earliest land plants, while AtWRKY40 only arose in angiosperms and AtWRKY63 even more recently in Brassicaceae. Apetala 2 (AP2) transcription factors are traceable to algae, but the ABI4 type again only appeared in seed plants. This strongly suggests that the transition to land was a major driver for developing plant MRR pathways, while additional fine-tuning events have appeared in seed plants or later. Finally, we discuss how MRR may have contributed to meeting the specific challenges that early land plants faced during terrestrialization.
Homoeologous exchange enables rapid evolution of tolerance to salinity and hyper-osmotic stresses in a synthetic allotetraploid wheat
Authors: Wang Bin , Lv Ruili , Zhang Zhibin , Yang Chunwu , Xun Hongwei , Liu Bao , Gong Lei
Published: September 2022

The link between polyploidy and enhanced adaptation to environmental stresses could be a result of polyploidy itself harbouring higher tolerance to adverse conditions, or polyploidy possessing higher evolvability than diploids under stress conditions. Natural polyploids are inherently unsuitable to disentangle these two possibilities. Using selfed progenies of a synthetic allotetraploid wheat AT3 (AADD) along with its diploid parents, Triticum urartu TMU38 (AA) and Aegilops tauschii TQ27 (DD), we addressed the foregoing issue under abiotic salinity and hyper-osmotic (drought-like) stress. Under short duration of both stresses, euploid plants of AT3 showed intermediate tolerance of diploid parents; under life-long duration of both stresses, tolerant individuals to either stress emerged from selfed progenies of AT3, but not from comparable-sized diploid parent populations. Tolerance to both stresses were conditioned by the same two homoeologous exchanges (HEs; 2DS/2AS and 3DL/3AL), and at least one HE needed to be at the homozygous state. Transcriptomic analyses revealed that hyper-up-regulation of within-HE stress responsive genes of the A sub-genome origin is likely responsible for the dual-stress tolerant phenotypes. Our results suggest that HE-mediated inter-sub-genome rearrangements can be an important mechanism leading to adaptive evolution in allopolyploids as well as a promising target for genetic manipulation in crop improvement.
Effects of nutrient heterogeneity on root foraging and plant growth at the individual and community level
Authors: Wang Peng , Mou Pu , Hu Lingyan , Hu Shuijin
Published: September 2022

Plants enhance nutrient uptake in heterogeneous nutrient environments through selective root placement. Many studies have documented that plants grow better under heterogeneous than under homogeneous nutrient distribution, but comprehensive syntheses are relatively few. In a meta-analysis, we examined the effects of patch scale and contrast on plant responses by synthesizing the effects of nutrient heterogeneity on root foraging and plant growth in 131 comparative studies. Plant responses to nutrient heterogeneity were phylogenetically conserved, and the response in shoot biomass was significantly correlated with the response in root biomass but not with root foraging precision. Root precision depended on the competition regime, and plants had lower precision in interspecific than in conspecific competition. Community-level growth was significantly promoted by nutrient heterogeneity and was less variable than individual-level responses. Along with increasing patch scale, overall shoot and root responses of individuals increased but root foraging precision declined. In addition, moderate patch contrast induced the highest root responses. Our results indicate that plants optimize nutrient acquisition from heterogeneous patches mainly through increasing root growth, and plant communities exploit heterogeneous nutrients more effectively than individuals. Understanding the roles of patch attributes in nutrient-heterogeneity effects may help in designing fertilization practices to promote productivity and conserve biodiversity.
Multiomics reveals an essential role of long-distance translocation in regulating plant cadmium resistance and grain accumulation in allohexaploid wheat (Triticum aestivum)
Authors: Hua Ying-peng , Chen Jun-fan , Zhou Ting , Zhang Tian-yu , Shen Dan-dan , Feng Ying-na , Guan Pan-feng , Huang Shao-min , Zhou Zheng-fu , Huang Jin-yong , Yue Cai-peng
Published: September 2022

Cadmium (Cd) is a highly toxic heavy metal that readily enters cereals, such as wheat, via the roots and is translocated to the shoots and grains, thereby posing high risks to human health. However, the vast and complex genome of allohexaploid wheat makes it challenging to understand Cd resistance and accumulation. In this study, a Cd-resistant cultivar of wheat, ‘ZM1860’, and a Cd-sensitive cultivar, ‘ZM32’, selected from a panel of 442 accessions, exhibited significantly different plant resistance and grain accumulation. We performed an integrated comparative analysis of the morpho-physiological traits, ionomic and phytohormone profiles, genomic variations, transcriptomic landscapes, and gene functionality in order to identify the mechanisms underlying these differences. Under Cd toxicity, ‘ZM1860’ outperformed ‘ZM32’, which showed more severe leaf chlorosis, poorer root architecture, higher accumulation of reactive oxygen species, and disordered phytohormone homeostasis. Ionomics showed that ‘ZM32’ had a higher root-to-shoot translocation coefficient of Cd and accumulated more Cd in the grains than ‘ZM1860’. Whole-genome re-sequencing (WGS) and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in abiotic stress responses and ion transport between the two genotypes. Combined ionomics, transcriptomics, and functional gene analysis identified the plasma membrane-localized heavy metal ATPase TaHMA2b-7A as a crucial Cd exporter regulating long-distance Cd translocation in wheat. WGS- and PCR-based analysis of sequence polymorphisms revealed a 25-bp InDel site in the promoter region of TaHMA2b-7A, and this was probably responsible for the differential expression. Our multiomics approach thus enabled the identification of a core transporter involved in long-distance Cd translocation in wheat, and it may provide an elite genetic resource for improving plant Cd resistance and reducing grain Cd accumulation in wheat and other cereal crops.
SARS-CoV-2 Omicron Variant: Clinical Presentation and Occupational Implications in Young and Healthy IDF Soldiers
Authors: Akavian Inbal , Nitzan Itay , Talmy Tomer , Nitecki Maya , Gendler Sami , Besor Omri
Published: September 2022

Introduction

To this date, there is little known about the symptoms, their duration, and occupational implications of Coronavirus disease (COVID-19) in the military population. Decisions regarding implementing precaution measures are based on data deriving from the general population. Moreover, the Omicron variant seems to cause a disease with lesser severity than previous variants. We aimed to describe the clinical presentation and estimate the loss of workdays due to mild COVID-19 during an Omicron predominant wave among a young, healthy, and mostly vaccinated military population.

Materials and Methods

A cross-sectional, survey-based study among IDF soldiers who replied to an online questionnaire following recovery from COVID-19. Data included self-reported vaccination status, symptoms presentation and duration, and service-related sick days. Student’s t-test and chi-square test of independence were used to compare differences in continuous and categorical variables, respectively. A binary logistic regression analysis was performed to estimate the odds ratio and 95% CIs for prolonged symptom duration (4 days and above) by participants’ characteristics. The IDF medical corps institutional review board approved this study.

Results

A total of 199 soldiers, with a mean age of 21.9 years, were included in the study. Upper respiratory tract symptoms, headache, and constitutional symptoms were found to be the most common among symptomatic soldiers. The median reported time for inability to continue the daily routine, including work, was 5 days [Interquartile range (IQR), 0-10]. Median duration of symptoms was 4 days (IQR, 0-10). In addition, women were found to have longer symptomatic disease (odds ratio = 2.34; 95% CI, 1.20-4.52).

Conclusions

Our findings demonstrate that even among a young and fully vaccinated population, COVID-19 caused by the Omicron variant may result in substantial medical leave from military service, compared to common cold or influenza virus infection. Our study sample was relatively small; however, the response rate was high and our results shed light on the yet-to-be fully characterized Omicron variant-related COVID-19. Despite the current common perception of COVID-19 as a self-limiting mild disease with low burden of symptoms, our findings show the potential occupational burden of infection with COVID-19 on military units and their readiness and could be considered when discussing public health restrictions and further steps taken to minimize outbreaks ramifications.
iTRAQ-based proteomics revealed baicalein enhanced oxidative stress of Candida albicans by upregulating CPD2 expression
Authors: Lv Quan-Zhen , Zhang Xiao-long , Gao Lu , Yan Lan , Jiang Yuan-Ying
Published: September 2022

Baicalein could inhibit the growth and biofilm formation of Candida albicans, the most common clinical fungal pathogen. However, the antifungal mechanism of baicalein has not been elucidated. In this study, isobaric tags for relative and absolute quantification (iTRAQ) was used to verify the mechanism of antifungal fluconazole and baicalein. A total of 58 common proteins were detected in cells treated with fluconazole. These proteins encompassed fluconazole-targeted sterol synthesis pathway, including Erg11p, Erg6p, Erg3p, Erg25p, Erg5p, Erg10p, and Ncp1p. Next, iTRAQ was applied to the comparison of baicalein-treated C. albicans proteins, which detected 16 common proteins. The putative NADH dehydrogenase Cpd2p and the ATP-binding cassette transporter Snq2p were the most upregulated proteins with the treatment of baicalein. Our results showed that CPD2 disruption elevated C. albicans resistance to baicalein significantly both in vitro and in vivo. Further in-depth studies revealed that CPD2 disruption reduced the activation of C. albicans metacaspase and partially restored the mitochondrial membrane potential reduction caused by the treatment of baicalein, which indicated that CPD2 was involved in the apoptosis induced by baicalein. Consistently, under the treatment of baicalein, CPD2Δ/Δ mutant produced lower reactive oxygen species that was critical in causing oxidative damage and apoptosis in C. albicans. These results indicated that baicalein could increase intracellular oxidative damage by upregulating the expression of Cpd2p so as to inhibit the growth of C. albicans, which provides new insights for investigating the antifungal target of baicalein.
J-PLUS: a catalogue of globular cluster candidates around the M 81/M 82/NGC 3077 triplet of galaxies
Authors: Chies-Santos Ana L , de Souza Rafael S , Caso Juan P , Ennis Ana I , de Souza Camila P E , Barbosa Renan S , Chen Peng , Javier Cenarro A , Ederoclite Alessandro , Cristóbal-Hornillos David , Hernández-Monteagudo Carlos , López-Sanjuan Carlos , Marín-Franch Antonio , Moles Mariano , Varela Jesús , Vázquez Ramió Héctor , Dupke Renato , Sodré Laerte , Angulo Raul E
Published: September 2022

Globular clusters (GCs) are proxies of the formation assemblies of their host galaxies. However, few studies exist targeting GC systems of spiral galaxies up to several effective radii. Through 12-band Javalambre Photometric Local Universe Survey (J-PLUS) imaging, we study the point sources around the M 81/M 82/NGC 3077 triplet in search of new GC candidates. We develop a tailored classification scheme to search for GC candidates based on their similarity to known GCs via a principal component analysis projection. Our method accounts for missing data and photometric errors. We report 642 new GC candidates in a region of 3.5 deg2 around the triplet, ranked according to their Gaia astrometric proper motions when available. We find tantalizing evidence for an overdensity of GC candidate sources forming a bridge connecting M 81 and M 82. Finally, the spatial distribution of the GC candidates (g − i) colours is consistent with halo/intra-cluster GCs, i.e. it gets bluer as they get further from the closest galaxy in the field. We further employ a regression-tree-based model to estimate the metallicity distribution of the GC candidates based on their J-PLUS bands. The metallicity distribution of the sample candidates is broad and displays a bump towards the metal-rich end. Our list increases the population of GC candidates around the triplet by threefold, stresses the usefulness of multiband surveys in finding these objects, and provides a testbed for further studies analysing their spatial distribution around nearby (spirals) galaxies.
The winking eye of a very massive star: WR 21a revealed as an eclipsing binary by TESS
Authors: Barbá Rodolfo H , Gamen Roberto C , Martín-Ravelo Pablo , Arias Julia I , Morrell Nidia I
Published: September 2022

WR 21a was known as a massive spectroscopic binary composed of an O2.5 If*/WN6ha primary and an O3 V((f*))z secondary. Although a minimum value, the mass estimated for the primary placed it as one of the most massive stars found in our Galaxy. We report the discovery of photometric variations in the time series observations carried out by the Transiting Exoplanet Survey Satellite (TESS). These light variations are interpreted as formed by two main components: a sharp partial eclipse of the O3 secondary by the O2.5/WN6 star, and tidally excited oscillations. Based on the light minima, a new ephemeris for the system is calculated. The system configuration is detached and the observed eclipse corresponds to the periastron passage. During the eclipse, the light curve shape suggests the presence of the heartbeat effect. The frequencies derived for the tidally excited oscillations are harmonics of the orbital period. Combining new and previously published radial velocity measurements, a new spectroscopic orbital solution is also obtained. Using the phoebe code we model the TESS light curve and determine stellar radii of RO2.5/WN6 = 23.4 R⊙ and RO3 = 14.3 R⊙ and an orbital inclination i = 62${_{.}^{\circ}}$2 ± 0${_{.}^{\circ}}$9. The latter combined with the spectroscopic minimum masses lead to absolute masses of MO2.5/WN6 = 93.2 M⊙ and MO3 = 52.9 M⊙, which establishes WR 21a as belonging to the rare group of the very massive stars.
UVIT view of Centaurus A: a detailed study on positive AGN feedback
Authors: Joseph Prajwel , Sreekumar P , Stalin C S , Paul K T , Mondal Chayan , George Koshy , Mathew Blesson
Published: September 2022

Supermassive black holes at the centre of active galactic nuclei (AGNs) produce relativistic jets that can affect the star formation characteristics of the AGN hosts. Observations in the ultraviolet (UV) band can provide an excellent view of the effect of AGN jets on star formation. Here, we present a census of star formation properties in the Northern Star-forming Region (NSR) that spans about 20 kpc of the large radio source Centaurus A hosted by the giant elliptical galaxy NGC 5128. In this region, we identified 352 UV sources associated with Cen A using new observations at an angular resolution of <1.5 arcsec observed with the Ultra-Violet Imaging Telescope (UVIT) onboard AstroSat. These observations were carried out in one far-ultraviolet (FUV; λmean = 1481 Å) and three near-ultraviolet (NUV; with λmean of 2196, 2447, and 2792 Å, respectively) bands. The star-forming sources identified in UV tend to lie in the direction of the jet of Cen A, thereby suggesting jet triggering of star formation. Separating the NSR into Outer and Inner regions, we found the stars in the Inner region to have a relatively younger age than the Outer region, suggesting that the two regions may have different star formation histories. We also provide the UVIT source catalogue in the NSR.
Protein Conformational Space at the Edge of Allostery: Turning a Nonallosteric Malate Dehydrogenase into an “Allosterized” Enzyme Using Evolution-Guided Punctual Mutations
Authors: Iorio Antonio , Brochier-Armanet Céline , Mas Caroline , Sterpone Fabio , Madern Dominique
Published: September 2022

We unveil the intimate relationship between protein dynamics and allostery by following the trajectories of model proteins in their conformational and sequence spaces. Starting from a nonallosteric hyperthermophilic malate dehydrogenase, we have tracked the role of protein dynamics in the evolution of the allosteric capacity. Based on a large phylogenetic analysis of the malate (MalDH) and lactate dehydrogenase (LDH) superfamily, we identified two amino acid positions that could have had a major role for the emergence of allostery in LDHs, which we targeted for investigation by site-directed mutagenesis. Wild-type MalDH and the single and double mutants were tested with respect to their substrate recognition profiles. The double mutant displayed a sigmoid-shaped profile typical of homotropic activation in LDH. By using molecular dynamics simulations, we showed that the mutations induce a drastic change in the protein sampling of its conformational landscape, making transiently T-like (inactive) conformers, typical of allosteric LDHs, accessible. Our data fit well with the seminal key concept linking protein dynamics and evolvability. We showed that the selection of a new phenotype can be achieved by a few key dynamics-enhancing mutations causing the enrichment of low-populated conformational substates.
A multicentre, large-scale, observational study of tocilizumab in patients with Takayasu arteritis in Japan: The ACTEMRA® (ACT)-Bridge study
Authors: Harigai Masayoshi , Miyamae Takako , Hashimoto Hideyuki , Yoshida Amika , Yamashita Katsuhisa , Nakaoka Yoshikazu
Published: September 2022

Objectives

We evaluated the real-world tolerability and effectiveness of tocilizumab in Japanese patients with Takayasu arteritis (TAK).

Methods

Patients with TAK who had not received tocilizumab in the previous 6 months were enrolled in ACTEMRA® (ACT)-Bridge, a phase 4, observational study, from 66 Japanese institutions (enrolment period, September 2017 to September 2020) and received weekly subcutaneous tocilizumab 162 mg (observation period, 52 weeks).

Results

Among 120 patients included (mean age, 38.4 years; mean disease duration, 7.7 years; treated for relapse, 50.8%; previous immunosuppressant use, 57.5%; glucocorticoid use at baseline, 97.5%), 49 (40.8%) reported adverse events. The most common adverse event of special interest was serious infection (7.5%). Relapse was observed in 24 (20.0%) patients (0.8%, 2.5%, and 16.7% reporting ≥3, 2, and 1 relapses, respectively). The reasons for diagnosing relapse included chest and back pain (45.8%), neck pain (25.0%), fatigue (16.7%), fever and headache (12.5% each), abnormal imaging findings (50.0%), and elevated inflammatory markers (16.7%). At the last observation, 83.0% of relapse-free patients recorded a concomitant glucocorticoid dose (prednisolone equivalent) <10 mg/day.

Conclusions

This study demonstrated the effectiveness of tocilizumab in patients with TAK, with no new safety concerns. Tocilizumab plus glucocorticoids may be considered a treatment option for TAK.
National Cohort Study of Homebound Persons Living With Dementia: Antibiotic Prescribing Trends and Opportunities for Antibiotic Stewardship
Authors: Datta Rupak , Fried Terri , O’Leary John R , Zullo Andrew R , Allore Heather , Han Ling , Juthani-Mehta Manisha , Cohen Andrew
Published: September 2022

Background

Over 7 million older Americans are homebound. Managing infections in homebound persons presents unique challenges that are magnified among persons living with dementia (PLWD). This work sought to characterize antibiotic use in a national cohort of PLWD who received home-based primary care (HBPC) through the Veterans Health Administration.

Methods

Administrative data identified veterans aged ≥65 years with ≥2 physician home visits in a year between 2014 and 2018 and a dementia diagnosis 3 years before through 1 year after their initial HBPC visit. Antibiotics prescribed orally, intravenously, intramuscularly, or by enema within 3 days of an HBPC visit were assessed from the initial HBPC visit to death or December 31, 2018. Prescription fills and days of therapy (DOT) per 1000 days of home care (DOHC) were calculated.

Results

Among 39 861 PLWD, the median age (interquartile range [IQR]) was 85 (78–90) years, and 15.0% were Black. Overall, 16 956 (42.5%) PLWD received 45 122 prescription fills. The antibiotic use rate was 20.7 DOT per 1000 DOHC. Telephone visits and advanced practice provider visits were associated with 30.9% and 42.0% of fills, respectively. Sixty-seven percent of fills were associated with diagnoses for conditions where antibiotics are not indicated. Quinolones were the most prescribed class (24.3% of fills). The overall median length of therapy (IQR) was 7 (7–10) days. Antibiotic use rates varied across regions. Within regions, the median annual antibiotic use rate decreased from 2014 to 2018.

Conclusions

Antibiotic prescriptions were prevalent in HBPC. The scope, appropriateness, and harms of antibiotic use in homebound PLWD need further investigation.
Factors Associated With Acceptance of Telehealth-Based Antimicrobial Stewardship Program Recommendations in a Community Hospital Health System
Authors: Shively Nathan R , Jacobs Max W , Moffa Matthew A , Schorr Rebecca E , Walsh Thomas L
Published: September 2022

Background

Telehealth-based antimicrobial stewardship programs (TeleASPs) have led to reduced broad-spectrum antimicrobial utilization. Data on factors associated with acceptance of stewardship recommendations are limited.

Methods

A TeleASP, facilitated by remote infectious disease physicians and local pharmacists, was implemented in 2 community hospitals from February 2018 through July 2020. Variables potentially affecting acceptance of TeleASP recommendations were tracked. Odds ratios of acceptance were determined utilizing multiple logistic regression.

Results

During the 30-month period, 4863 (91.2%) of the total 5333 recommendations were accepted. Factors associated with a higher odds of acceptance in multivariable analysis were recommendations for antimicrobial dose/frequency adjustment (odds ratio [OR], 2.63; 95% CI, 1.6–4.3) and order for labs/tests (OR, 3.30; 95% CI, 2.1–5.2), while recommendations for antimicrobial de-escalation (OR, 0.75; 95% CI, 0.60–0.95) and antimicrobial discontinuation (OR, 0.57; 95% CI, 0.42–0.76) were associated with lower odds of acceptance. Female physicians were more likely to accept recommendations compared with males (93.1% vs 90.3% acceptance; OR, 1.65; 95% CI, 1.3–2.2). Compared with physicians with <3 years of experience, who had the highest acceptance rate (96.3%), physicians with ≥21 years of experience had the lowest (87.1%; OR, 0.26; 95% CI, 0.15–0.45).

Conclusions

TeleASP recommendations were accepted at a high rate. Acceptance rates were higher among female physicians, and recommendations to stop or de-escalate antimicrobials led to lower acceptance. Recommendations made to the most experienced physicians were the least accepted, which may be an important factor for stewardship programs to consider in education and intervention efforts.
The Johnes of Glasgow: Searching, Plague and Early Modern Municipal Power
Authors: Johnson Bethany L
Published: September 2022

Recent scholarship highlights the importance of public health policy in the early modern era. Long before the arrival of the plague, municipal governments instituted a range of policies to protect the health of the commonweal. In the last quarter of the sixteenth century, town councils in both Glasgow and London approved searching during outbreaks. Searchers could view residents for signs of sickness, and tabulate infections and cause of death. Previous studies describe the unique position of female searchers in London, who enjoyed increased economic security without commensurate legal or political power. Glasgow’s burgh records reveal a different model of searching, first recorded in 1574, conducted by men of economic and political influence who were imbued with significant legal power. Searchers were vital to ongoing municipal efforts to slow plague outbreaks in the British Isles, but the nature of their work and the extent of their power was a matter of gender.
Recovery ofBrucellain raw milk Minas artisanal cheese approved for consumption by official inspection agency in Brazil: assessment of prevalence and risk factors through One Health integrated approaches
Authors: Silva Marcio Roberto , Duch André Almeida Santos , Lage Rômulo Tadeu Pace de Assis , de Faria Letícia Scafutto , Menezes Liliane Denize Miranda , Ribeiro João Batista , de Souza Guilherme Nunes , Filho Paulo Martins Soares , Preis Ingred Sales , Sales Érica Bravo , de Souza Patrícia Gomes , Araújo Flábio Ribeiro , Guimarães Ricardo José de Paula Souza e , Mendes Tulio , Pettan-Brewer Christina , Fonseca-Júnior Antônio Augusto
Published: September 2022

Background

Minas artisanal cheese (MAC) from the Serro region is a Brazilian intangible cultural heritage. Produced from raw milk, it may carry zoonotic pathogens such as Brucella. This study included a randomized survey for the prevalence of Brucella-positive MAC and its associated factors.

Methods

MAC samples (n=55), each one from a different rural family-based cheese-processing agroindustry, were analysed for Brucella by direct polymerase chain reaction (PCR) species-specific DNA detection and cultivation-based approaches.

Results

Among 55 MACs that were analysed, we found 17 Brucella DNA-positive samples (30.9% [95% confidence interval {CI} 18.7 to 43.1]) by PCR and, for the first time, from one MAC (1.8% [95% CI 0.5 to 9.7]), viable Brucella abortus was recovered by cultivation. Higher values for two variables, the number of lactating cows per herd (p=0.043) and daily milk production per herd (p=0.043), were each associated with Brucella-positive MAC, which concentrated in three high-risk and one low-risk spatial clusters.

Conclusions

MAC may be a source of Brucella for humans, since the positive samples were from batches that were sold by cheesemakers. This should be of concern and encourage cooperation between the health and agriculture sectors in order to mitigate this public health risk through One Health integrated approaches.
Monotreme-specific conserved putative proteins derived from retroviral reverse transcriptase
Authors: Kitao Koichi , Miyazawa Takayuki , Nakagawa So
Published: September 2022

Endogenous retroviruses (ERVs) have played an essential role in the evolution of mammals. ERV-derived genes are reported in the therians, many of which are involved in placental development; however, the contribution of the ERV-derived genes in monotremes, which are oviparous mammals, remains to be uncovered. Here, we conducted a comprehensive search for possible ERV-derived genes in platypus and echidna genomes and identified three reverse transcriptase-like genes named RTOM1, RTOM2, and RTOM3 clustered in the GRIP2 intron. Comparative genomic analyses revealed that RTOM1, RTOM2, and RTOM3 are strongly conserved and are under purifying selection between these species. These could be generated by tandem duplications before the divergence of platypus and echidna. All RTOM transcripts were specifically expressed in the testis, possibly suggesting their physiological importance. This is the first study reporting monotreme-specific de novo gene candidates derived from ERVs, which provides new insights into the unique evolution of monotremes.
Differences Between Employed and Retired Older Adults in Information and Communication Technology Use and Attitudes
Authors: Schuster Amy M , Cotten Shelia R
Published: September 2022

Older adults, 65 years and older, are a heterogeneous group in terms of their information and communication technology (ICT) use. Few studies, however, have examined how ICT use patterns may vary between employed older adults versus those who are no longer in the workforce. We expand research on this topic by examining whether variations in ICT use, as well as attitudes toward ICTs and online self-efficacy, exist between these 2 groups. Key outcomes include online self-efficacy, attitudes towards new technology, length of time online, average daily hours online, and number of ICTs used. Data were collected in 2017 through an online survey from a national sample of U.S. older adults (N = 1,142) matched with the demographic characteristics of the 2010 U.S. Census for individuals aged 65 and older based on age, race, sex, and education. Data were analyzed using OLS regression, binary logistic regression, and mediation analysis. Employed older adults, compared to retired older adults, had higher online self-efficacy, more positive attitudes towards new technology, spent more time online (years), and were more likely to use 2 or more ICTs. Being retired was associated with fewer years online, which was mediated by more negative attitudes toward technology and less online self-efficacy. Longitudinal research is needed which examines the types of technologies used in the workforce by older adults, the exposure to others’ uses of technologies, and how use changes over time—all of which may potentially affect older adults’ technology skills and attitudes.
Conjugation of bisphosphonates with scorpion venom enhanced apoptotic activities in pancreatic cancer cells
Authors: Alhakamy Nabil A. , Al-Rabia Mohammed W. , Rizg Waleed Y. , Alghaith Adel F. , Ahmed Osama A. A. , Fahmy Usama A.
Published: September 2022

Background

In recent times, prevalence and the incidence of pancreatic cancer (PC) have increased exponentially. Among of the major issues of PC are the asymptotic manifestation that delays diagnosis, and scarcity of therapeutic means.

Methodology

To provide an effective therapeutic approach, current study was executed, in which an optimized alendronate sodium (ALS) and scorpion venom (SV) nanoconjugate (ALS-SV nanoconjugate) was selected via experimental design applying size and zeta potential as the selected factors. Additionally, efficacy against PANC1 cells was determined by analysis of IC50, cell cycle, annexin V staining, Bcl-2, Bax, p53, etc.

Results

The particle size of the optimized nanoconjugate was found to be 28.4± 1.2 nm and the zeta potential to be +26.2± 0.8 mV. The cytotoxicity in terms of IC50 ALS-SV nanoconjugate was found better (2.73 ± 0.2 µg/mL) than ALS alone (22.3 ± 0.2 µg/mL) and SV alone (6.23 ± 0.4 µg/mL). Besides, outcomes of cell cycle analysis exhibited maximum efficacy for nanoconjugate in the G2-M phase. Annexin V staining, Bax, Bcl-2, p53, and caspase 3 estimation also showed superior apoptotic activity for ALS-SV nanoconjugate. However, as compared to ALS alone and SV alone, nanoconjugate showed elevated expression levels of TNF-α. The apoptotic activity was enhanced by the ALS-SV nanoconjugate as confirmed by MMP analysis.

Conclusion

Accordingly, the current study revealed an enhancement in the anti-PC effects of the ALS-SV nanoconjugate that is considered as a novel approach against PC.
Network-informed discovery of multidrug combinations for ERα+/HER2-/PI3Kα-mutant breast cancer
Authors: Hany Dina , Zoetemelk Marloes , Bhattacharya Kaushik , Nowak-Sliwinska Patrycja , Picard Didier
Published: September 2022

Breast cancer is a persistent threat to women worldwide. A large proportion of breast cancers are dependent on estrogen receptor α (ERα) for tumor progression. Therefore, targeting ERα with antagonists, such as tamoxifen, remains standard therapy for ERα+ breast cancer. The clinical benefits of monotherapy are often counterbalanced by off-target toxicity and development of resistance. Combinations of more than two drugs might be of great therapeutic value to prevent resistance, and to reduce doses, and hence, toxicity. We mined data from the literature and public repositories to construct a network of potential drug targets for synergistic multidrug combinations. With 9 drugs, we performed a phenotypic combinatorial screen with ERα+ breast cancer cell lines. We identified two optimized low-dose combinations of 3 and 4 drugs of high therapeutic relevance to the frequent ERα+/HER2-/PI3Kα- mutant subtype of breast cancer. Moreover, we validated the efficacy of the combinations in tamoxifen-resistant cell lines, patient-derived organoids, and xenograft experiments. Thus, we propose multidrug combinations that have the potential to overcome the standard issues of current monotherapies.
MAM-STAT3-induced upregulation of mitochondrial Ca+2 causes immunosenescence in patients with type A mandibuloacral dysplasia
Authors: Padhiar Arshad Ahmed , Yang Xiaohong , Li Zhu , Liao Jinqi , Ali Ilyas , Shu Wei , Chishti AA , He Liangge , Alam Gulzar , Faqeer Abdullah , Zhou Yan , Zhang Shuai , Wang Ting , Liu Tao , Zhou Meiling , Wang Gang , Zou Xuenong , Zhou Guangqian
Published: September 2022

Homozygous lamina/c p.R527C mutations result in severe mandibuloacral dysplasia (MAD) and progeroid syndrome, but the underlying molecular pathology remains unknown. Here, we report on three patients with MAD, all displaying severe systemic inflammaging and characterized the major molecular pathways involved in the manifestation of this disease. Analysis of induced pluripotent stem cell (IPSC)-derived mesenchymal stem cells (MAD-iMSCs) obtained from the patients revealed that increased mitochondrial Ca+2 loading was the root cause of lost mitochondrial membrane potential, abnormal fission/fusion and fragmentation, which then participated in inflammaging by inducing the inflammasome. These alterations in Ca+2 homeostasis were mediated by signal transducer and activator of transcription 3 (STAT3), which is located on the mitochondrial associated membrane (MAM). STAT3 function could be rescued by treatment with clinically-approved IL-6 blockers, or by correction of R527C mutations. In addition, extracellular vesicles (EVs) obtained from MAD-iMSCs displayed reduced immunomodulatory function, being unable to rescue bleomycin-induced lung fibrosis and triggering mitochondrial dysfunction, senescence, and fibrosis in healthy cells. Our results provide new insights into the pathology of complex lamin-associated MAD with systemic immunosenescence, and suggest that targeting defective mitochondrial Ca+2 homeostasis may represent a promising novel therapy for this condition.