bluuebunny/crossref_metadata_2025 huggingface dataset:
Allosteric modulators enhance agonist efficacy by increasing the residence time of a GPCR in the active state
Authors: Cao Anne-Marinette , Quast Robert B. , Fatemi Fataneh , Rondard Philippe , Pin Jean-Philippe , Margeat Emmanuel
Published: January 2021

Much hope in drug development comes from the discovery of positive allosteric modulators (PAM) that display target subtype selectivity, and act by increasing agonist potency and efficacy. How such compounds can allosterically influence agonist action remains unclear. Metabotropic glutamate receptors (mGlu) are G protein-coupled receptors that represent promising targets for brain diseases, and for which PAMs acting in the transmembrane domain have been developed. Here, we explore the effect of a PAM on the structural dynamics of mGlu2 in optimized detergent micelles using single molecule FRET at submillisecond timescales. We show that glutamate only partially stabilizes the extracellular domains in the active state. Full activation is only observed in the presence of a PAM or the Gi protein. Our results provide important insights on the role of allosteric modulators in mGlu activation, by stabilizing the active state of a receptor that is otherwise rapidly oscillating between active and inactive states.
Interferon alpha-based combinations suppress SARS-CoV-2 infection in vitro and in vivo
Authors: Ianevski Aleksandr , Yao Rouan , Zusinaite Eva , Lello Laura Sandra , Wang Sainan , Jo Eunji , Yang Jaewon , Ravlo Erlend , Wang Wei , Lysvand Hilde , Løseth Kirsti , Oksenych Valentyn , Tenson Tanel , Windisch Marc P. , Poranen Minna , Nieminen Anni I. , Nordbø Svein Arne , Fenstad Mona Høysæter , Grødeland Gunnveig , Aukrust Pål , Trøseid Marius , Kantele Anu , Vitkauskiene Astra , Legrand Nicolas , Merits Andres , Bjørås Magnar , Kainov Denis E.
Published: January 2021

There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. In the present study, we found that recombinant human interferon-alpha (IFNa) triggers intrinsic and extrinsic cellular antiviral responses, as well as reduces replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. Although IFNa alone was insufficient to completely abolish SARS-CoV-2 replication, combinations of IFNa with remdesivir or other antiviral agents (EIDD-2801, camostat, cycloheximide, or convalescent serum) showed strong synergy and effectively inhibited SARS-CoV-2 infection in human lung epithelial Calu-3 cells. Furthermore, we showed that the IFNa-remdesivir combination suppressed virus replication in human lung organoids, and that its single prophylactic dose attenuated SARS-CoV-2 infection in lungs of Syrian hamsters. Transcriptome and metabolomic analyses showed that the combination of IFNa-remdesivir suppressed virus-mediated changes in infected cells, although it affected the homeostasis of uninfected cells. We also demonstrated synergistic antiviral activity of IFNa2a-based combinations against other virus infections in vitro. Altogether, our results indicate that IFNa2a-based combination therapies can achieve higher efficacy while requiring lower dosage compared to monotherapies, making them attractive targets for further pre-clinical and clinical development.
Divergent metabolism betweenTrypanosoma congolenseandTrypanosoma bruceiresults in differential drug sensitivity
Authors: Steketee P. C. , Dickie E. A. , Iremonger J. , Crouch K. , Paxton E. , Jayaraman S. , Alfituri O. A. , Awuah-Mensah G. , Ritchie R. , Schnaufer A. , de Koning H. P. , Gadelha C. , Wickstead B. , Barrett M. P. , Morrison L. J.
Published: January 2021

Animal African Trypanosomiasis (AAT) is a debilitating livestock disease prevalent across sub-Saharan Africa, a main cause of which is the protozoan parasiteTrypanosoma congolense. In comparison to the well-studiedT. brucei, there is a major paucity of knowledge regarding the biology ofT. congolense. Here, we use a combination of omics technologies and novel genetic tools to characterise core metabolism inT. congolensemammalian-infective bloodstream-form parasites, and test whether metabolic differences compared toT. bruceiimpact upon drug sensitivity. LikeT. brucei, glycolysis plays a major part inT. congolenseenergy metabolism. However, the rate of glucose uptake is significantly reduced inT. congolense, with cells remaining viable when cultured in concentrations as low as 2 mM. Instead of pyruvate, the primary glycolytic endpoints are succinate, malate and acetate. Comparative transcriptomics analysis showed higher levels of activity associated with the mitochondrial pyruvate dehydrogenase complex, acetate generation and the succinate shunt inT. congolense. However, based on omics analysis and chemical inhibition, there does not appear to be significant levels of oxidative phosphorylation. Stable-isotope labelling of glucose enabled the comparison of carbon usage betweenT. bruceiandT. congolense, highlighting differences in nucleotide and fatty acid metabolism. To validate the metabolic similarities and differences, both species were treated with pharmacological inhibitors, confirming a lack of essential electron transport chain activity inT. congolense,but increased sensitivity to inhibition of mitochondrial pyruvate import. Strikingly,T. congolenseexhibited significant resistance to inhibitors of fatty acid synthesis, including a 780-fold greater EC50against the lipase and fatty acid synthase inhibitor Orlistat, compared toT. brucei. These data highlight that bloodstream formT. congolensediverges fromT. bruceiin key areas of metabolism, with several features that are intermediate between bloodstream- and insect-stageT. brucei. These results have implications for drug development, mechanisms of drug resistance and host-pathogen interactions.
Relocation of rDNA repeats for repair is dependent on SUMO-mediated nucleolar release by the Cdc48/p97 segregase
Authors: Capella Matías , Mandemaker Imke K. , den Brave Fabian , Caballero Lucía Martín , Pfander Boris , Ladurner Andreas G. , Jentsch Stefan , Braun Sigurd
Published: January 2021

Ribosomal RNA genes (rDNA) are highly unstable and susceptible to rearrangement due to active transcription and their repetitive nature. Compartmentalization of rDNA in the nucleolus suppresses uncontrolled recombination. However, broken repeats must be released to the nucleoplasm to allow repair by homologous recombination. The process of rDNA relocation is conserved from yeast to humans, but the underlying molecular mechanisms are currently unknown. Here we show that DNA damage induces phosphorylation of the CLIP-cohibin complex, releasing membrane-tethered rDNA from the nucleolus inSaccharomyces cerevisiae. Downstream of phosphorylation, SUMOylation targets CLIP-cohibin for disassembly mediated by the Cdc48/p97 chaperone, which recognizes SUMOylated CLIP-cohibin through its cofactor, Ufd1. Consistent with a conserved mechanism, UFD1L depletion impairs rDNA release in human cells. The dynamic and regulated assembly and disassembly of the rDNA-tethering complex is therefore a key determinant of nucleolar rDNA release and genome integrity.
Extracellular matrix changes in colorectal carcinoma and correlation with lymph node metastasis
Authors: Theodoro Thérèse Rachell , Serrano Rodrigo Lorenzetti , Turke Karine Corcione , Saad Sarhan Sydney , Ribeiro Junior Marcelo Augusto Fontenelle , Waisberg Jaques , Pinhal Maria Aparecida Silva
Published: January 2021

The process of proliferation and invasion of tumor cells depends on changes in the extracellular matrix (ECM) through the activation of enzymes and alterations in the profile of ECM components. We aimed to investigate the mRNA and protein expression of ECM components such as heparanase (HPSE), heparanase-2 (HPSE2), matrix metalloproteinase-9 (MMP-9), and syndecan-1 (SYND1) in neoplastic and non-neoplastic tissues of patients with colorectal carcinoma (CRC). It is a cross-sectional study in which twenty-four adult patients that had CRC were submitted to resection surgery. We analyzed the expression of HPSE, HPSE2, MMP-9, and SYND1 by quantitative RT-PCR and immunohistochemistry. Differing from most of the studies that compare the mRNA expression between tumor samples and non-neoplastic tissues, we decided to investigate whether variations exist in the expression of the ECM components between the affected tissue and nontumoral tissue collected from the same patient with CRC. We removed both tissue samples immediately after the surgical resection of CRC. The data showed higher mRNA and protein expression of HPSE2 (P = 0.0058), MMP-9 (P = 0.0268), and SYND1 (P = 0.0002) in tumor samples compared to the non-neoplastic tissues, while there was only an increase in the level of HPSE protein in tumor tissues. A greater expression of HPSE2 was observed in patients with lymph node metastasis (P = 0.048), suggesting that such protein can be a marker of lymph node metastasis in CRC.
Seroprevalence and associated risk factors ofToxoplasma gondiiinfections among pregnant women in Makassar, Indonesia
Authors: Polanunu Nurul Fadilah Ali , Wahyuni Sitti , Hamid Firdaus
Published: January 2021

The protozoan parasite,Toxoplasma gondiiis estimated to infect one-third of the world’s population. Infection in pregnant women can cause severe conditions for their babies. Until now, there is no data regardingToxoplasmainfection from Makassar pregnant mothers. This study aims to obtain information onToxoplasmaspecific antibodies and to measure the risk factor associate with parasite infection. This cross-sectional study conducted in 9 of 47 primary health centres (Puskesmas) in Makassar. Blood samples and questionnaires were collected from 184 pregnant women aged 15-42 years old from September to October 2020. ELISA technique was used to examine the IgG and IgM antibodies. Univariable and multivariable analyses were carried out to measure factors that independently associate withToxoplasmaantibody positivity. Our result showed the range ofToxoplasmaIgM and IgG are 0.06-1.01 and 0.09-3.01, respectively. While no one of our participants has an acuteToxoplasma gondiiinfection (IgM positive), we found 32,6% pregnant mothers are exposed to parasite (positive IgG). Contact with cats [OR(95CI): 8.04 (3.09-20.87)], consume chicken satay [OR(95CI): 7.46(3.06-18.21)] and consume un-boiled water [OR(95CI): 5.23(1.57-17.38)] are independently associate with positiveToxoplasmaIgG antibody. Based on the result, we conclude that pregnant women in Makassar are exposed toT. gondiiand the cyst of parasite contaminates food and water in Makassar.
Crystallographic molecular replacement using anin silico-generated search model of SARS-CoV-2 ORF8
Authors: Flower Thomas G. , Hurley James H.
Published: January 2021

The majority of crystal structures are determined by the method of molecular replacement (MR). The range of application of MR is limited mainly by the need for an accurate search model. In most cases, pre-existing experimentally determined structures are used as search models. In favorable cases,ab initiopredicted structures have yielded search models adequate for molecular replacement. The ORF8 protein of SARS-CoV-2 represents a challenging case for MR using anab initioprediction because ORF8 has an all β-sheet fold and few orthologs. We previously determined experimentally the structure of ORF8 using the single anomalous dispersion (SAD) phasing method, having been unable to find an MR solution to the crystallographic phase problem. Following a report of an accurate prediction of the ORF8 structure, we assessed whether the predicted model would have succeeded as an MR search model. A phase problem solution was found, and the resulting structure was refined, yielding structural parameters equivalent to the original experimental solution.
Proteomic interrogation of the pathogen-host interface in cholera
Authors: Zoued Abdelrahim , Zhang Hailong , Zhang Ting , Giorgio Rachel T. , Kuehl Carole J. , Fakoya Bolutife , Sit Brandon , Waldor Matthew K.
Published: January 2021

The microbial cell surface is a critical site of microbe-host interactions that often control infection outcomes. Here, using the infant rabbit model of cholera, which provides an abundant source ofin vivo Vibrio choleraecells and diarrheal fluid, we investigated the proteomic composition of this interface. Bulk diarrheal fluid proteomes revealed that cholera toxin accounts for the vast majority of the host proteins present during infection. We developed a surface biotinylation protocol to purify and quantify both bacterial and host proteins present on the surface of diarrheal fluid-derivedV. cholerae. We found that SP-D, a toxin-dependent host protein that directly binds theV. choleraesurface, is a novel intestinal defense factor. OtherV. cholerae-bound host proteins also bound distinct taxa of the murine intestinal microbiota. Proteomic investigation of the microbial surface-host interface should be a valuable tool for probing microbe-host interactions and their influence on homeostasis and infection.
Long term impact on lung function of patients with moderate and severe COVID-19. A prospective cohort study
Authors: Qureshi Sonia , Nasir Nosheen , Rashid Naveed Haroon , Ahmed Naveed , Haq Zoya , Qamar Farah Naz
Published: January 2021

Introduction

A significant number of patients continue to recover from COVID-19; however, little is known about the lung function capacity among survivors. We aim to determine the long-term impact on lung function capacity in patients who have survived moderate or severe COVID-19 disease in a resource-poor setting.

Methods and analysis

This prospective cohort study will include patients aged 15 years and above and have reverse transcriptase-polymerase chain reaction (RT-PCR) positive for COVID 19 (nasopharyngeal or oropharyngeal). Patients with a pre-existing diagnosis of obstructive or interstitial lung disease, lung fibrosis and cancers, connective tissue disorders, autoimmune conditions affecting the lungs, underlying heart disease, history of syncope and refuse to participate will be excluded. Pulmonary function will be assessed using spirometry and diffusion lung capacity for carbon monoxide (DLCO) at three- and six-months interval. A chest X-ray at three and six-month follow-up and CT-chest will be performed if clinically indicated after consultation with the study pulmonologist or Infectious Disease (ID) physician. Echocardiogram (ECHO) to look for pulmonary hypertension at the three months visit and repeated at six months if any abnormality is identified initially. Data analysis will be performed using standard statistical software.

Ethics and dissemination

The proposal was reviewed and approved by ethics review committee (ERC) of the institution (ERC reference number 2020-4735-11311). Informed consent will be obtained from each study participant. The results will be disseminated among study participants, institutional, provincial and national level through seminars and presentations. Moreover, the scientific findings will be published in high-impact peer-reviewed medical journals.

Strengths and Limitations of this study

-

The study has the potential to develop context-specific evidence on the long-term impact on lung function among COVID-19 survivors

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Findings will play key role in understanding the impact of the disease on vital functions and help devise rehabilitative strategies to best overcome the effects of disease

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This is a single-center, study recruiting only a limited number of COVID-19 survivors

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The study participants may loss-to-follow up due to uncertain conditions and disease reemergence
Synthesis, structure and photophysical properties of two tetranuclear copper(I) iodide complexes based on acetylpyridine and diphosphine mixed ligands
Authors: Cao Bing-Jun , Li Ran , Huang Xi-He
Published: January 2021

Two copper(I) iodide tetramers, namely, [μ2-1,3-bis(diphenylphosphanyl)propane-κ2
P:P′]di-μ3-iodido-di-μ2-iodido-[1-(pyridin-3-yl)ethan-1-one-κN]tetracopper(I) dichloromethane disolvate, [Cu4I4(C6H7NO)2(C27H26P2)2]·2CH2Cl2 (Cu

L

3
), and [μ2-1,3-bis(diphenylphosphanyl)propane-κ2
P:P′]di-μ3-iodido-di-μ2-iodido-[1-(pyridin-4-yl)ethan-1-one-κN]tetracopper(I), [Cu4I4(C6H7NO)2(C27H26P2)2] (Cu

L

4
), have been synthesized from reactions of CuI, 1,3-bis(diphenylphosphanyl)propane (dppp) and 3- or 4-acetylpyridine (3/4-acepy). The complexes were characterized by elemental analysis, IR spectroscopy, single-crystal X-ray diffraction (XRD), powder XRD and photoluminescence spectroscopy. Both complexes possess a stair-step [Cu4I4] cluster structure with a crystallographic inversion centre located in the middle of a Cu2I2 ring (Z′ = 1/2). The dppp ligands each adopt a bidentate coordination mode that bridges two CuI centres on one side of the [Cu4I4] cluster and the acepy ligands act as terminal ligands. The solid-state samples of similar complexes show highly efficiency thermally activated delayed fluorescence (TADF) at room temperature. At ambient temperature, both Cu

L

3
and Cu

L

4
exhibit photoluminescence, with a maximum emission in the region 560–580 nm and with short emissive decay times, but only phosphorescence was observed at 77 K. The narrow gaps between the higher lying singlet state and the triplet state, ΔE(S
1 − T
1), also confirm the presence of TADF. Structure analysis and consideration of photoluminescence indicates that the position of the acetyl group on the heterocyclic ligand has an obvious influence on the structural arrangement, on intermolecular interactions and on the observed photophysical properties.
Fertilization alters protistan consumers and parasites in crop‐associated microbiomes
Authors: Sun Anqi , Jiao Xiao‐Yan , Chen Qinglin , Trivedi Pankaj , Li Zixin , Li Fangfang , Zheng Yong , Lin Yongxin , Hu Hang‐Wei , He Ji‐Zheng
Published: January 2021

Crop plants carry an enormous diversity of microbiota that provide massive benefits to hosts. Protists, as the main microbial consumers and a pivotal driver of biogeochemical cycling processes, remain largely understudied in the plant microbiome. Here, we characterized the diversity and composition of protists in sorghum leaf phyllosphere, and rhizosphere and bulk soils, collected from an 8‐year field experiment with multiple fertilization regimes. Phyllosphere was an important habitat for protists, dominated by Rhizaria, Alveolata and Amoebozoa. Rhizosphere and bulk soils had a significantly higher diversity of protists than the phyllosphere, and the protistan community structure significantly differed among the three plant–soil compartments. Fertilization significantly altered specific functional groups of protistan consumers and parasites. Variation partitioning models revealed that soil properties, bacteria and fungi predicted a significant proportion of the variation in the protistan communities. Changes in protists may in turn significantly alter the compositions of bacterial and fungal communities from the top‐down control in food webs. Altogether, we provide novel evidence that fertilization significantly affects the functional groups of protistan consumers and parasites in crop‐associated microbiomes, which have implications for the potential changes in their ecological functions under intensive agricultural managements.
A high‐throughput ultrasonic spraying inoculation method promotes colony cultivation of rare microbial species
Authors: Huang Xizhi , Li Pengjie , Zhou Mengfan , Li Yiwei , Ou Xiaowen , Chen Peng , Guggenberger Georg , Liu Bi‐Feng
Published: January 2021

Current method for obtaining microbial colonies still relies on traditional dilution and spreading plate (DSP) procedures, which is labor‐intensive, skill‐dependent, low‐throughput and inevitably causing dilution‐to‐extinction of rare microorganisms. Herein, we proposed a novel ultrasonic spraying inoculation (USI) method that disperses microbial suspensions into millions of aerosols containing single cells, which lately be deposited freely on a gel plate to achieve high‐throughput culturing of colonies. Compared with DSP, USI significantly increased both distributing uniformity and throughput of the colonies on agar plates, improving the minimal colony‐forming abundance of rare Escherichia coli mixed in a lake sample from 1% to 0.01%. Applying this novel USI to a lake sample, 16 cellulose‐degrading colonies were screened out among 4766 colonies on an enlarged 150‐mm‐diameter LB plate. Meanwhile, they could only be occasionally observed when using commonly used DSP procedures. 16S rRNA sequencing further showed that USI increased colony‐forming species from 11 (by DSP) to 23, including seven completely undetectable microorganisms in DSP‐reared communities. In addition to avoidance of dilution‐to‐extinction, operation‐friendly USI efficiently inoculated microbial samples on the agar plate in a high‐throughput and single‐cell form, which eliminated masking or out‐competition from other species in associated groups, thereby improving rare species cultivability.
Cross‐linguistic contributions of acoustic cues and prosodic awareness to first and second language vocabulary knowledge
Authors: Chung Wei‐Lun , Jarmulowicz Linda , Bidelman Gavin M.
Published: January 2021

Background

Several studies have revealed that prosody contributes to reading acquisition. However, the relation between awareness of prosodic patterns and different facets of language ability (e.g., vocabulary knowledge) in school‐age children remains unclear. This study measured awareness of prosodic patterns using non‐speech and speech stimuli.

Methods

Hierarchical regression equations were computed to examine links among auditory cues (e.g., amplitude rise time, pitch contour and interval), language‐specific prosodic awareness and children's vocabulary knowledge in Mandarin as a first language (L1) and English as a second language (L2) after controlling for age and nonverbal IQ.

Results

Results revealed that (1) amplitude envelope rise time discrimination predicted Mandarin L1 and English L2 vocabulary knowledge, (2) Mandarin tone perception and rhyme awareness did not predict Mandarin L1 vocabulary and (3) English rhyme awareness better predicted English L2 vocabulary than did stress production.

Conclusion

Our findings suggest that (1) amplitude rise time, which signals syllable boundaries, is a cross‐linguistic predictor of vocabulary knowledge and (2) the development of English L2 vocabulary may depend on phonological more than prosodic awareness.
The impact of chymosin and plant‐derived proteases on the acid‐induced gelation of milk
Authors: Beltrán‐Espinoza Jesús A , Domínguez‐Lujan Berenice , Gutiérrez‐Méndez Néstor , Chávez‐Garay Dely R , Nájera‐Domínguez Carolina , Leal‐Ramos Martha Y
Published: January 2021

This work aimed to study milk gel formation during a slow fermentation process and the simultaneous action of different proteases like bovine chymosin, recombinant camel chymosin, ficin and bromelain. The acid‐induced gels with bovine chymosin and recombinant camel chymosin were firmer than the control gels without proteases or the gels added with plant proteases. However, the acid‐induced gels with chymosins had a considerable water release and shrunk in volume as the milk fermentation progressed. In contrast, the acid‐induced gels added with bromelain and ficin were softer and showed less syneresis, even at acidic pHs.
Father Absence in Pregnancy or During Childhood and Pubertal Development in Girls and Boys: A Population‐Based Cohort Study
Authors: Gaml‐Sørensen Anne , Brix Nis , Ernst Andreas , Lunddorf Lea Lykke Harrits , Ramlau‐Hansen Cecilia Høst
Published: January 2021

This cohort study, including 15,810 children born 2000–2003 in Denmark, aimed to investigate the association between father absence in pregnancy or during childhood and pubertal development in girls and boys. The children were followed from 11 years of age and throughout pubertal development. Mean age differences according to exposure groups were estimated for each pubertal marker separately and for a combined pubertal marker. The results suggested that father absence in pregnancy and during childhood was associated with earlier pubertal development in girls, and father absence from late childhood was associated with earlier pubertal development in boys. The paternal investment theory, the psychosocial acceleration theory and the energetics theory were explored, and did not seem to explain the observed associations.
Unilateral solid‐cystic renal mass in an infant: Highlighting the cytological mimics
Authors: Gupta Parikshaa , Peters Nitin James , Trehan Amita , Gupta Kirti
Published: January 2021

Clear cell sarcoma of the kidney (CCSK) is the second most common primary renal malignancy in children, accounting for 3%‐5% of all primary paediatric renal tumours. Owing to its well‐known histopathological diversity, it is one of the most commonly misdiagnosed renal tumours. Establishing a cytological diagnosis of CCSK is challenging due to its rarity as well as the lack of knowledge about its cytological features. Described are the cytological features of a CCSK diagnosed in a male infant.
Assessing mandatory stay‐at‐home and business closure effects on the spread of COVID‐19
Authors: Bendavid Eran , Oh Christopher , Bhattacharya Jay , Ioannidis John P. A.
Published: January 2021

Background and Aims

The most restrictive nonpharmaceutical interventions (NPIs) for controlling the spread of COVID‐19 are mandatory stay‐at‐home and business closures. Given the consequences of these policies, it is important to assess their effects. We evaluate the effects on epidemic case growth of more restrictive NPIs (mrNPIs), above and beyond those of less‐restrictive NPIs (lrNPIs).

Methods

We first estimate COVID‐19 case growth in relation to any NPI implementation in subnational regions of 10 countries: England, France, Germany, Iran, Italy, Netherlands, Spain, South Korea, Sweden and the United States. Using first‐difference models with fixed effects, we isolate the effects of mrNPIs by subtracting the combined effects of lrNPIs and epidemic dynamics from all NPIs. We use case growth in Sweden and South Korea, 2 countries that did not implement mandatory stay‐at‐home and business closures, as comparison countries for the other 8 countries (16 total comparisons).

Results

Implementing any NPIs was associated with significant reductions in case growth in 9 out of 10 study countries, including South Korea and Sweden that implemented only lrNPIs (Spain had a nonsignificant effect). After subtracting the epidemic and lrNPI effects, we find no clear, significant beneficial effect of mrNPIs on case growth in any country. In France, for example, the effect of mrNPIs was +7% (95% CI: −5%‐19%) when compared with Sweden and + 13% (−12%‐38%) when compared with South Korea (positive means pro‐contagion). The 95% confidence intervals excluded 30% declines in all 16 comparisons and 15% declines in 11/16 comparisons.

Conclusions

While small benefits cannot be excluded, we do not find significant benefits on case growth of more restrictive NPIs. Similar reductions in case growth may be achievable with less‐restrictive interventions.
Long‐term efficacy and safety of erenumab in migraine prevention: Results from a 5‐year, open‐label treatment phase of a randomized clinical trial
Authors: Ashina Messoud , Goadsby Peter J. , Reuter Uwe , Silberstein Stephen , Dodick David W. , Xue Fei , Zhang Feng , Paiva da Silva Lima Gabriel , Cheng Sunfa , Mikol Daniel D.
Published: January 2021

Background and purpose

Although erenumab has demonstrated significant reduction in migraine frequency and improved quality of life in studies lasting 3 to 12 months, little is known about long‐term therapy.

Methods

This study was an open‐label, 5‐year treatment phase following a 12‐week, double‐blind, placebo‐controlled trial in adults with episodic migraine. Patients initially received open‐label erenumab 70 mg, which increased to 140 mg following a protocol amendment. Efficacy analyses included change from baseline in monthly migraine days (MMDs), monthly acute migraine‐specific medication (AMSM) days, and health‐related quality of life.

Results

Of 383 patients enrolled, 250 switched to 140 mg; 215 (56.1%) completed open‐label treatment. Mean (standard error) change in MMDs from baseline of 8.7 (0.2) days was −5.3 (0.3) days; an average reduction of 62.3% at year 5. Among patients using AMSM at baseline (6.3 [2.8] treatment days), mean change in monthly AMSM days was −4.4 (0.3) days at the end of 5 years. Patient‐reported outcomes indicated stable improvements in disability, headache impact, and migraine‐specific quality of life. Exposure‐adjusted patient incidence rates of adverse events (AEs) were 123.0/100 patient‐years; AEs were most frequently nasopharyngitis, upper respiratory tract infection, and influenza. Serious AEs (SAEs) reported by 49 patients (3.8/100 patient‐years) were mostly single occurrence. Two fatal adverse events were reported. There were no increases in incidence of AEs, SAEs, or AEs leading to treatment discontinuation over 5 years of exposure.

Conclusions

Treatment with erenumab was associated with reductions in migraine frequency and improvements in health‐related quality of life that were maintained for at least 5 years. No new safety signals were observed.
Expression and regulation of ccBAX by miR‐124 in the caudal fin cell of C. auratus gibelio upon cyprinid herpesvirus 2 infection
Authors: Yu Lu , Chen Qikang , Chu Xin , Luo Yang , Feng Zizhao , Lu Liqun , Zhang Ye , Xu Dan
Published: January 2021

Bcl2 family proteins play a critical role in cell death or survival. BAX, the death‐promoting protein of bcl2 family, mediated mitochondrial pathway inducing cells’ apoptosis in mammal. MiRNAs have been implicated as negative regulators down‐regulating genes’ expression after post‐transcriptional level. At present, little is known about the regulatory mechanism of miRNA on the Bcl2 family proteins during CyHV‐2 infection in silver crucian carp (Carassius auratus gibelio). In this study, the ccBAX (silver crucian carp BAX) gene was cloned and expressed, and polyclonal antibodies were raised in mouse against the purified ccBAX‐GST fusion protein. The structure analysis indicated that ccBAX protein included four conserve domains (BH1, BH2, BH3 and transmembrane domains) and the expression of ccBAX protein occurred throughout the cells. Furthermore, two miRNAs (miR‐124 and miRNA‐29b) were identified to negatively regulate ccBAX gene expression in GiCF cell. miR‐124 was found to suppress the expression of WT‐ccBAX (wild type), but not the MT‐ccBAX (mutant). Overall, the results demonstrated that the expression of the ccBAX gene was significantly down‐regulated by miR‐124 in silver crucian carp (Carassius auratus gibelio) during CyHV‐2 infection.
Trends and hotspots of family nursing research based on Web of Science: A bibliometric analysis
Authors: Huang Qi , Ronghuang Qi , Yinhuang Rui , Fanghuang Yan , Yansun Hong
Published: January 2021

Objective

Family nursing is an essential component of nursing practice. The number of articles that researchers must be familiar with is increasing, along with the importance of selective searching and summarization. This study aims to explore the development trend and research spotlight through the analysis of literature related to family nursing from 1986 to 2018.

Methods

Science Citation Index literatures about family nursing in Web of Science Core Collection (WoSCC) were searched by subject terms. The function of database document statistics and analysis, cite space visualization software and Excel were used to measure and analyze the included documents and draw the visualization atlas. Each article was evaluated for the following characteristics: authors, institution, country, keyword, reference, cited‐author, cited‐journal, grant.

Results

A total of 1,224 literatures from 68 countries and regions as well as 1,749 research institutions, 331 journals, 833 funded institutions and 4,007 first authors and collaborators were included. There is an increasing trend in the amount of papers published in family nursing research. Among them, the United States (275, 22.47%), Brazil (196, 16.01%), and the University of São Paulo (63, 5.15%) share the highest number of publications. < JOURNAL OF FAMILY NURSING > (IF = 1.889) was the most published journal (126, 10.29%). BELL JM was the highest published author (29, 2.37%), SVAVARSDOTTIR EK was highly cited (181 citation). At present, the research spotlight in this field focus on the traditional research directions such as “NURSING”, “FAMILY”, “NURSE” and “CARE”. But there are also new directions such as “QUALIFY OF LIFE”, “PALLIATIVE”, “CAREGIVER”, “CHILD” and “DEMENTIA”. The focus of research extends from “DRUGS, MEDICINE, CLINICAL, PSYCHOLIGY, EDUCATION, HEALTH” to “NURSING, SOCIETY”.

Conclusion

Family nursing started late, and its exploration was limited. Although family nursing was growing in certain countries, the fields involved in the research are still relatively narrow and lack interdisciplinary cross‐fusion. The research field of family nursing needs to be further explored and refined in future practice.
Attentional blink suppresses both stimulus‐driven and representation‐driven cross‐modal spread of attention
Authors: Zhao Song , Feng Chengzhi , Liao Yu , Huang Xinyin , Feng Wenfeng
Published: January 2021

Previous studies have shown that visual attention effect can spread to the task‐irrelevant auditory modality automatically through either the stimulus‐driven binding process or the representation‐driven priming process. Using an attentional blink paradigm, the present study investigated whether the long‐latency stimulus‐driven and representation‐driven cross‐modal spread of attention would be inhibited or facilitated when the attentional resources operating at the post‐perceptual stage of processing are inadequate, whereas ensuring all visual stimuli were spatially attended and the representations of visual target object categories were activated, which were previously thought to be the only endogenous prerequisites for triggering cross‐modal spread of attention. The results demonstrated that both types of attentional spreading were completely suppressed during the attentional blink interval but were highly prominent outside the attentional blink interval, with the stimulus‐driven process being independent of, whereas the representation‐driven process being dependent on, audiovisual semantic congruency. These findings provide the first evidence that the occurrences of both stimulus‐driven and representation‐driven spread of attention are contingent on the amount of post‐perceptual attentional resources responsible for the late consolidation processing of visual stimuli, whereas the early detection of visual stimuli and the top‐down activation of the visual representations are not the sole endogenous prerequisites for triggering any types of cross‐modal attentional spreading.
Blood donation by men who have sex with men: using evidence to change policy
Authors: Davison Katy L. , Reynolds Claire A. , Andrews Nick , Brailsford Susan R. ,   the UK Blood Donor Survey Steering Group
Published: January 2021

Background

In 2011 in the United Kingdom (UK), excluding Northern Ireland, the deferral of men who have sex with men (MSM) changed from lifetime to 12 months. We describe MSM who donated before and after this to inform further policy reviews.

Materials and Methods

Characteristics and sexual behaviours of donors identifying as male from routine surveillance are described. Rates of infections are compared pre‐ and post‐implementation of a 12‐month deferral. Donors are compared with screen negative male donors responding to a large‐scale survey during 2013/2014.

Results

Comparing the five years pre‐ and post‐change, the rate of confirmed positives for markers of HBV, HCV, HIV and syphilis decreased by 6·9% from 14·1 to 13·1/100 000 donations. The rate of recent infections was unchanged (1·72/100 000). Of 22 776 survey responses identifying as male, MSM disclosed sex between men over 12 months ago giving 99·35% compliance among male donors. Two‐thirds of the 72 non‐compliant MSM reported one to two partners and one‐third had no new partners within 12 months. The most commonly reported reason for non‐compliance from MSM both positive and negative for infection was ‘not important to declare’ (37·2% and 40·7%). Test seeking was rare (9·3% and 2·1%).

Conclusion

Compliance with the 12‐month MSM deferral policy was very high. The very low rates of infections post‐change demonstrated the effectiveness of the policy. These data were an important part of the 2017 review of all sexual behaviour deferrals.
Review of fossil heterostigmatic mites (Acari: Heterostigmata) from late Eocene Rovno Amber. I. Families Tarsocheylidae, Dolichocybidae and Acarophenacidae

Authors: Khaustov Alexander A. , Vorontsov Dmitry D. , Perkovsky Evgeny E. , Lindquist Evert E.
Published: January 2021

The present article represents the first part of a review of fossil heterostigmatic mites collected from late Eocene Rovno amber. Here, mites of the families Tarsocheylidae, Dolichocybidae, and Acarophenacidae are described, with Tarsocheylidae and Dolichocybidae recorded for the first time from amber. A new genus and four new species are described, namely, Hoplocheylus similis sp. nov. (Tarsocheylidae), Dolichocybe elongata sp. nov. (Dolichocybidae), Proadactylidium fossibilis gen. and sp. nov. and Paradactylidium sineunguis sp. nov. (Acarophenacidae). The extant species Acarophenax lacunatus Cross and Krantz, 1964 and A. assanovi Livshitz and Mitrofanov, 1974 are transferred to the new genus Proadactylidium. A revised key to the genera of Acarophenacidae is presented. The homologies of prodorsal setae in Acarophenacidae are reconsidered and reviewed.
Integrating phylogeny, ontogeny and systematics of the mite family Smarididae (Prostigmata, Parasitengona): Classification, identification key, and description of new taxa

Authors: Costa Samuel Geremias Dos Santos , Welbourn Cal , Klimov Pavel , Pepato Almir Rogério
Published: January 2021

Unlike most terrestrial parasitengone mites (chiggers, erythraeids), known mostly from parasitic and easy-to-collect larvae, smaridid systematics are mainly based on the post larval instar. Larvae are rarely collected, and their biology and host associations are virtually unknown. Here we infer phylogenetic relationships of Smarididae based on 50 morphological characters using both larval and post larval instars, including data on the larval morphology of Trichosmaris obtained through rearing. The subfamily Smaridinae, as currently understood, was recovered paraphyletic: the genus Smaris was rendered as basal smaridid lineage, while the genus Fessonia (Smaridinae) was sister to Hirstiosomatinae, albeit with moderate support. Our analysis suggests that the genus Surasmaris Southcott, 1995 is a junior synonym of Trichosmaris Southcott, 1963 (syn. nov.), and two Sphaerotarsus species should be placed into Hirstiosoma: Hirstiosoma baenai (Mayoral & Barranco, 2017) comb. nov., Hirstiosoma quercus (Yazdanpanah, Saboori & Hakimitabar, 2016) comb. nov. Sphaerotarsus monticolus Southcott, 1997 and S. leptopilus were recovered as independent lineages, and hence, a new genus Southcottiana gen. nov. is proposed to include Southcottiana monticola comb. nov (Southcott, 1997). We describe two new species, Trichosmaris paulensis sp. nov. (adults, larvae) and T. calcarensis sp. nov. (larva), and present the first description of larval T. dispar, the type species of Trichosmaris, previously known only from post larval instars. Based on the above results, we give a key to larval genera of Smarididae and a key to species of Trichosmaris (larval and postlarval instars).
Molecular beam epitaxy growth of low-bandgap material thick films using a molybdenum disilicide coated backing plate for substrate temperature control
Authors: Podpirka Adrian , Brupbacher Michael , Zgrabik Christine , Gagnon Jarod C. , Shrekenhamer David
Published: January 2021

Molecular beam epitaxial (MBE) deposition allows for the epitaxial growth of materials requiring atomically precise control of nanometer thick layers. A key concern with the growth of smaller bandgap materials on larger bandgap substrates via MBE is the radiative coupling of the deposited layer with the heater, which can lead to uncontrolled increases in temperature if not properly accommodated for. In this work, we demonstrate the ability to decouple the radiative component of the heater with the substrate and layer deposition through the incorporation of a molybdenum disilicide coated molybdenum backing plate. We demonstrate that the novel coating allows for highly efficient coupling with the heater while providing improved temperature control at the growth surface, leading to stable growth conditions. We demonstrate the stable growth and film characteristics through the growth of germanium telluride thin films on (100) gallium arsenide substrates.
Feit's seminal article on radiation of sound by a vibrating plate
Authors: Pierce Allan D. , Garrelick Joel M.
Published: January 2021

The Reflections series takes a look back on historical articles from The Journal of the Acoustical Society of America that have had a significant impact on the science and practice of acoustics.
Structure of cyanobacterial phycobilisome core revealed by structural modeling and chemical cross-linking
Authors: Liu Haijun , Zhang Mengru M. , Weisz Daniel A. , Cheng Ming , Pakrasi Himadri B. , Blankenship Robert E.
Published: January 2021

Cyanobacterial light-harvesting complex features efficient energy capture, transmission, and regulation to reaction centers.
Human population dynamics and
Yersinia pestis
in ancient northeast Asia
Authors: Kılınç Gülşah Merve , Kashuba Natalija , Koptekin Dilek , Bergfeldt Nora , Dönertaş Handan Melike , Rodríguez-Varela Ricardo , Shergin Dmitrij , Ivanov Grigorij , Kichigin Dmitrii , Pestereva Kjunnej , Volkov Denis , Mandryka Pavel , Kharinskii Artur , Tishkin Alexey , Ineshin Evgenij , Kovychev Evgeniy , Stepanov Aleksandr , Dalén Love , Günther Torsten , Kırdök Emrah , Jakobsson Mattias , Somel Mehmet , Krzewińska Maja , Storå Jan , Götherström Anders
Published: January 2021

Ancient genomes reveal a complex demographic picture since the post-LGM in northeast Asia and report the presence of
Y. pestis
.
Acoustohydrodynamic tweezers via spatial arrangement of streaming vortices
Authors: Zhu Haodong , Zhang Peiran , Zhong Zhanwei , Xia Jianping , Rich Joseph , Mai John , Su Xingyu , Tian Zhenhua , Bachman Hunter , Rufo Joseph , Gu Yuyang , Kang Putong , Chakrabarty Krishnendu , Witelski Thomas P. , Huang Tony Jun
Published: January 2021

Decomposition and control of acoustic streaming enable contact-free manipulation of bioanalytes and digitalized liquid handling.
Carbon isotope evidence for the global physiology of Proterozoic cyanobacteria
Authors: Hurley Sarah J. , Wing Boswell A. , Jasper Claire E. , Hill Nicholas C. , Cameron Jeffrey C.
Published: January 2021

Carboxysomes evolved due to rising O
2
, not falling CO
2
, enabling planktic cyanobacteria to flourish during earth’s middle age.
Critical role of synovial tissue–resident macrophage niche in joint homeostasis and suppression of chronic inflammation
Authors: Huang Qi-Quan , Doyle Renee , Chen Shang-Yang , Sheng Qicong , Misharin Alexander V. , Mao Qinwen , Winter Deborah R. , Pope Richard M.
Published: January 2021

Using a novel model of rheumatoid arthritis, we identified a critical role for reduced tissue-resident macrophages.
Rotational Doppler cooling and heating
Authors: Pan Deng , Xu Hongxing , García de Abajo F. Javier
Published: January 2021

Rotational Doppler cooling and heating are generalized from their translational counterparts, revealing dissimilar physics.
Acoustic spin Hall effect in strong spin-orbit metals
Authors: Kawada Takuya , Kawaguchi Masashi , Funato Takumi , Kohno Hiroshi , Hayashi Masamitsu
Published: January 2021

We have found the acoustic spin Hall effect that facilitates lattice motion-induced spin current in strong spin-orbit metals.
Observation of chiral edge states in gapped nanomechanical graphene
Authors: Xi Xiang , Ma Jingwen , Wan Shuai , Dong Chun-Hua , Sun Xiankai
Published: January 2021

We experimentally realized quantum valley Hall chiral edge states in nanomechanical graphene by tuning the boundary potential.
Dynamic thermal trapping enables cross-species smart nanoparticle swarms
Authors: Li Tongtao , Chan Kwok Hoe , Ding Tianpeng , Wang Xiao-Qiao , Cheng Yin , Zhang Chen , Lu Wanheng , Yilmaz Gamze , Qiu Cheng-Wei , Ho Ghim Wei
Published: January 2021

Smart nanoparticle swarm allows dynamic multimaterials integration to access distinctive functions.
Isomer-specific kinetics of the C
+
+ H
2
O reaction at the temperature of interstellar clouds
Authors: Yang Tiangang , Li Anyang , Chen Gary K. , Yao Qian , Suits Arthur G. , Guo Hua , Hudson Eric R. , Campbell Wesley C.
Published: January 2021

An important interstellar hydrocarbon chemical reaction has been measured in a laboratory.
Mass spectrometry imaging identifies abnormally elevated brain
l
-DOPA levels and extrastriatal monoaminergic dysregulation in
l
-DOPA–induced dyskinesia
Authors: Fridjonsdottir Elva , Shariatgorji Reza , Nilsson Anna , Vallianatou Theodosia , Odell Luke R. , Schembri Luke S. , Svenningsson Per , Fernagut Pierre-Olivier , Crossman Alan R. , Bezard Erwan , Andrén Per E.
Published: January 2021

l
-DOPA–induced dyskinesia is caused by elevated
l
-DOPA levels and dysregulated
l
-DOPA metabolism throughout the brain.
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection
Authors: Dan Jennifer M. , Mateus Jose , Kato Yu , Hastie Kathryn M. , Yu Esther Dawen , Faliti Caterina E. , Grifoni Alba , Ramirez Sydney I. , Haupt Sonya , Frazier April , Nakao Catherine , Rayaprolu Vamseedhar , Rawlings Stephen A. , Peters Bjoern , Krammer Florian , Simon Viviana , Saphire Erica Ollmann , Smith Davey M. , Weiskopf Daniela , Sette Alessandro , Crotty Shane
Published: January 2021

Variable memory

Immune memory against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) helps to determine protection against reinfection, disease risk, and vaccine efficacy. Using 188 human cases across the range of severity of COVID-19, Dan
et al.
analyzed cross-sectional data describing the dynamics of SARS-CoV-2 memory B cells, CD8
+
T cells, and CD4
+
T cells for more than 6 months after infection. The authors found a high degree of heterogeneity in the magnitude of adaptive immune responses that persisted into the immune memory phase to the virus. However, immune memory in three immunological compartments remained measurable in greater than 90% of subjects for more than 5 months after infection. Despite the heterogeneity of immune responses, these results show that durable immunity against secondary COVID-19 disease is a possibility for most individuals.

Science
, this issue p.
eabf4063
Genome Sequence of Bifidobacterium breve INIA P734 (CECT 8178), a Strain Isolated from Human Breast Milk
Authors: Rodrigo-Torres Lidia , Rodríguez Eva , Peirotén Ángela , Langa Susana , Medina Margarita , Arahal David R. , Aznar Rosa , Arqués Juan L.
Published: January 2021

The draft genome sequence of
Bifidobacterium breve
INIA P734, a strain shared by mother and child, is reported. It consists of 50 contigs, with 2,391,925 bp, 2,099 genes, and a G+C content of 58.8%. The genome analysis revealed the absence of antibiotic resistance and pathogenicity-related genes.
Draft Genome Sequences of Eight Campylobacter volucris Isolates from Freshwater Sources in Victoria, Australia
Authors: Davis Agnus M. , McCarthy David. T. , Bulach Dieter M. , Henry Rebekah
Published: January 2021

Campylobacter
spp. can survive and be transmitted from a range of environments. Here, we examine eight draft genome sequences of
Campylobacter volucris
, identified as part of an examination of waterborne
Campylobacter
species. This is the first report of environmental survival of
C. volucris
outside gull species.