bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic Donor-derived Malignancies Following Simultaneous Pancreas-kidney Transplant: Three Case Reports and Management Strategies
Authors: Amara Dominic , Wisel Steven A. , Braun Hillary J. , Collisson Eric A. , Friedlander Terence , Worner Giulia , Roll Garret R. , Hirose Ryutaro , Stock Peter G.
Published: March 2021

Background.

Stopping immunosuppression in a transplant patient with donor-derived malignancy offers the theoretical benefit that reconstitution of the patient’s immune system will allow “rejection” of the malignancy, as the malignancy also originates from allogeneic tissue. However, this option exists with the caveat that the patient’s allograft(s) will likely be rejected too. In simultaneous pancreas-kidney (SPK) recipients, the normal continued functioning and possible absence of malignancy in either the unaffected kidney or pancreas further complicate this decision.

Methods.

The charts of 3 patients with donor-derived metastatic malignancies after SPK were retrospectively reviewed in detail. We provide treatment and management recommendations based on successful outcomes and a review of the existing literature.

Results.

Consistent with a broad review of the literature, in all 3 cases, complete immunosuppression cessation, removal of both grafts, and in 1 case treatment with an immune checkpoint inhibitor to augment the immune response was successful. One patient is doing well 1 year after successfully undergoing kidney retransplantation, while a second patient is active on the waitlist for SPK retransplantation after no evidence of metastatic disease for 2 years.

Conclusion.

The successful management of metastatic donor-derived malignancies requires allograft removal, immunosuppression cessation, and adjuvant therapy that includes occasional use of checkpoint inhibitors to augment the immune response.
Prediction of Postoperative Risk of Raised Intracranial Pressure After Spontaneous Skull Base Cerebrospinal Fluid Leak Repair
Authors: Buchowicz Bryce , Chen Benson S. , Bidot Samuel , Bruce Beau B. , Newman Nancy J. , Saindane Amit M. , Levy Joshua M. , Biousse Valérie ,   for the CSF-Leak Study Group
Published: March 2021

Background:

A relationship between idiopathic intracranial hypertension and spontaneous skull base cerebrospinal fluid (CSF) leaks has been proposed, by which CSF leak decreases intracranial pressure (ICP) and masks the symptoms and signs of elevated ICP. These patients are at risk of developing papilledema, symptoms of elevated ICP, or a recurrent CSF leak after CSF leak repair. The objective of this study was to assess whether radiographic signs of raised ICP on preoperative magnetic resonance or computed venography (MRI or CTV) are predictors of postoperative papilledema, recurrence of CSF leak, or need for CSF shunt surgery.

Methods:

We performed a retrospective review of systematically collected demographics, fundus examination, and presurgical brain MRI and magnetic resonance venography/computed tomography venography (MRV/CTV) in patients seen at 1 institution between 2013 and 2019 with spontaneous skull base CSF leak repair. Patients were divided into 2 groups depending on whether they developed papilledema, recurrent CSF leak, or required CSF shunting (Group 1) or not (Group 2).

Results:

Fifty-seven patients were included, among whom 19 were in Group 1. There was no difference in demographic characteristics or clinical features between patients in Group 1 and Group 2. Controlling for other imaging features, bilateral transverse venous sinus stenosis (TVSS) on preoperative imaging increased the odds of being in Group 1 by 4.2 times (95% confidence interval [CI], 1.04–21.2, P = 0.04), optic nerve tortuosity decreased the odds of being in Group 1 by 8.3 times (95% CI: 1.4–74.6, P = 0.02).

Conclusion:

Imaging of the intracranial venous system with MRV or CTV is warranted before repair of spontaneous CSF leak, as bilateral TVSS is an independent risk factor for postoperative papilledema, CSF leak recurrence, or need for a CSF shunting procedure.
Comparative effects of viral-transport-medium heat inactivation upon downstream SARS-CoV-2 detection in patient samples
Authors: Thompson Jamie L. , Downie Ruiz Velasco Angela , Cardall Alice , Tarbox Rebecca , Richardson Jaineeta , Clarke Gemma , Lister Michelle , Howson-Wells Hannah C. , Fleming Vicki M. , Khakh Manjinder , Sloan Tim , Duckworth Nichola , Walsh Sarah , Denning Chris , McClure C. Patrick , Benest Andrew V. , Seedhouse Claire H.
Published: March 2021

Introduction. The COVID-19 pandemic, which began in 2020 is testing economic resilience and surge capacity of healthcare providers worldwide. At the time of writing, positive detection of the SARS-CoV-2 virus remains the only method for diagnosing COVID-19 infection. Rapid upscaling of national SARS-CoV-2 genome testing presented challenges: (1) Unpredictable supply chains of reagents and kits for virus inactivation, RNA extraction and PCR-detection of viral genomes. (2) Rapid time to result of <24 h is required in order to facilitate timely infection control measures.

Hypothesis. Extraction-free sample processing would impact commercially available SARS-CoV-2 genome detection methods.

Aim. We evaluated whether alternative commercially available kits provided sensitivity and accuracy of SARS-CoV-2 genome detection comparable to those used by regional National Healthcare Services (NHS).

Methodology. We tested several detection methods and tested whether detection was altered by heat inactivation, an approach for rapid one-step viral inactivation and RNA extraction without chemicals or kits.

Results. Using purified RNA, we found the CerTest VIASURE kit to be comparable to the Altona RealStar system currently in use, and further showed that both diagnostic kits performed similarly in the BioRad CFX96 and Roche LightCycler 480 II machines. Additionally, both kits were comparable to a third alternative using a combination of Quantabio qScript one-step Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) mix and Centre for Disease Control and Prevention (CDC)-accredited N1 and N2 primer/probes when looking specifically at borderline samples. Importantly, when using the kits in an extraction-free protocol, following heat inactivation, we saw differing results, with the combined Quantabio-CDC assay showing superior accuracy and sensitivity. In particular, detection using the CDC N2 probe following the extraction-free protocol was highly correlated to results generated with the same probe following RNA extraction and reported clinically (n=127; R2=0.9259).

Conclusion. Our results demonstrate that sample treatment can greatly affect the downstream performance of SARS-CoV-2 diagnostic kits, with varying impact depending on the kit. We also showed that one-step heat-inactivation methods could reduce time from swab receipt to outcome of test result. Combined, these findings present alternatives to the protocols in use and can serve to alleviate any arising supply-chain issues at different points in the workflow, whilst accelerating testing, and reducing cost and environmental impact.
Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice
Authors: Liu Pengpeng , Liang Shun-Qing , Zheng Chunwei , Mintzer Esther , Zhao Yan G. , Ponnienselvan Karthikeyan , Mir Aamir , Sontheimer Erik J. , Gao Guangping , Flotte Terence R. , Wolfe Scot A. , Xue Wen
Published: March 2021

Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). However, the efficacy of prime editing in adult mice has not been established. Here we report an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency in both fluorescent reporter cells and at endogenous loci in cultured cell lines. Using this genome modification system, we could also seed tumor formation through somatic cell editing in the adult mouse. Finally, we successfully utilize dual adeno-associated virus (AAVs) for the delivery of a split-intein prime editor and demonstrate that this system enables the correction of a pathogenic mutation in the mouse liver. Our findings further establish the broad potential of this genome editing technology for the directed installation of sequence modificationsin vivo, with important implications for disease modeling and correction.
3D models of Alzheimer’s disease patient microglia recapitulate disease phenotype and show differential drug responses compared to 2D
Authors: Cuní-López Carla , Quek Hazel , Oikari Lotta E. , Stewart Romal , Nguyen Tam Hong , Sun Yifan , Guo Christine C. , Lupton Michelle K. , White Anthony R.
Published: March 2021

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain’s resident immune cells, are an attractive target for potentially more effective therapeutic strategies. However, there is no currentin vitromodel system that faithfully recapitulates patient-specific microglial characteristics. To address this shortcoming, we developed novel 3D models of monocyte-derived microglia-like cells (MDMi) from AD patients. MDMi in 3D exhibited mature microglial features, including a highly branched morphology and enhanced bonafide microglial marker expression compared to 2D. Moreover, AD MDMi in 3D co-cultures with neuro-glial cells showed altered cell-to-cell interactions, growth factor and cytokine secretion profiles and responses to amyloid-β. Drug screening assays in 3D AD MDMi revealed different cytokine responses compared to 2D. Our study demonstrates disease- and drug-specific responses in 3D MDMi models that are not apparent in 2D and presents a new 3D platform for more effective and personalised drug testing.
Heterochrony inorthodenticleexpression is associated with ommatidial size variation betweenDrosophilaspecies
Authors: Torres-Oliva Montserrat , Buchberger Elisa , Buffry Alexandra D. , Kittelmann Maike , Guerrero Genoveva , Sumner-Rooney Lauren , Gaspar Pedro , Bullinger Georg C. , Figueras Jimenez Javier , Casares Fernando , Arif Saad , Posnien Nico , Nunes Maria D. S. , McGregor Alistair P. , Almudi Isabel
Published: March 2021

The compound eyes of insects exhibit extensive variation in ommatidia number and size, which affects how they see and underlies adaptations in their vision to different environments and lifestyles. However, very little is known about the genetic and developmental bases of differences in compound eye size. We previously showed that the larger eyes ofDrosophila mauritianacompared toD. simulansis generally caused by differences in ommatidia size rather than number. Furthermore, we identified an X-linked chromosomal region inD. mauritianathat results in larger eyes when introgressed intoD. simulans. Here, we used a combination of fine-scale mapping and gene expression analysis to further investigate positional candidate genes on the X chromosome. We found earlier expression oforthodenticle (otd)during ommatidial maturation in third instar larvae inD. mauritianathan inD. simulans, and we show that this gene is required for the correct organisation and size of ommatidia inD. melanogaster. We discovered that the activity of anotdeye enhancer is consistent with the difference in the expression of this gene between species, with theD. mauritianaenhancer sequence driving earlier expression than that ofD. simulans. We also identified potential direct targets of Otd that are differentially expressed betweenD. mauritianaandD. simulansduring ommatidial maturation. Taken together, our results suggest that differential timing ofotdexpression contributes to natural variation in ommatidia size betweenD. mauritianaandD. simulans,which provides new insights into the mechanisms underlying the regulation and evolution of compound eye size in insects.
Characterisation of a novel ACE2-based therapeutic with enhanced rather than reduced activity against SARS-CoV2 variants
Authors: Ferrari Mathieu , Mekkaoui Leila , Ilca F. Tudor , Akbar Zulaikha , Bughda Reyisa , Lamb Katarina , Ward Katarzyna , Parekh Farhaan , Karattil Rajeev , Allen Christopher , Wu Philip , Baldan Vania , Mattiuzzo Giada , Bentley Emma M. , Takeuchi Yasuhiro , Sillibourne James , Datta Preeta , Kinna Alexander , Pule Martin , Onuoha Shimobi C.
Published: March 2021

The human angiotensin-converting enzyme 2 acts as the host cell receptor for SARS-CoV-2 and the other members of theCoronaviridaefamily SARS-CoV-1 and HCoV-NL63. Here we report the biophysical properties of the SARS-CoV-2 spike variants D614G, B.1.1.7 and B.1.351 with affinities to the ACE2 receptor and infectivity capacity, revealing weaknesses in the developed neutralising antibody approaches. Furthermore, we report a pre-clinical characterisation package for a soluble receptor decoy engineered to be catalytically inactive and immunologically inert, with broad neutralisation capacity, that represents an attractive therapeutic alternative in light of the mutational landscape of COVID-19. This construct efficiently neutralised four SARS-CoV-2 variants of concern. The decoy also displays antibody-like biophysical properties and manufacturability, strengthening its suitability as a first-line treatment option in prophylaxis or therapeutic regimens for COVID-19 and related viral infections.
Tree canopy influences ground level atmospheric electrical and biogeochemical variability
Authors: Hunting Ellard R. , England Sam J. , Robert Daniel
Published: March 2021

Static electric fields in the atmosphere are increasingly recognized to interact with various organisms over several levels of biological organization. Recently, a link between atmospheric electrical variations and biogeochemical processes has been established in the context of open fields, yet biological structures like trees produce substantial alterations in atmospheric electric properties. Here, we assess whether these structural changes affect the dynamics of both biogenic and abiotic electrical landscapes and their relation to geochemical processes. To this end, we theoretically assess how trees alter their surrounding electric fields and empirically compare the temporal dynamics of atmospheric potential gradients, positive ions in the near-ground level atmosphere and soil electrochemical properties in an open field and under a tree. The developed model of electric fields around trees provides insight into the extent to which trees shield underlying electric landscape, revealing that a substantial increase in atmospheric potential gradient only marginally affects the electric field under the canopy. We further show that soil electrochemical properties are tied to temporal dynamics of positive ions in the near-ground level atmosphere, and that the presence of a tree reduces the temporal variability in both ground level positive ions concentrations and soil redox potential. This suggests that a tree can have a stabilizing effect on drivers of temporal variability in atmospheric electricity and soil electro-chemistry, thereby likely indirectly influencing soil microorganisms and processes as well as electro-sensitive organisms that perceive and utilize atmospheric electric fields.
Co-condensation of proteins with single- and double-stranded DNA
Authors: Renger Roman , Morin Jose A. , Lemaitre Regis , Ruer-Gruss Martine , Jülicher Frank , Hermann Andreas , Grill Stephan W.
Published: March 2021

Biomolecular condensates provide distinct compartments that can localize and organize biochemistry inside cells. Recent evidence suggests that condensate formation is prevalent in the cell nucleus. To understand how different components of the nucleus interact during condensate formation is an important challenge. In particular, the physics of co-condensation of proteins together with nucleic acids remains elusive. Here, we use optical tweezers to study how the prototypical prion-like protein Fused-in-Sarcoma (FUS) forms liquid-like assemblies in vitro, by co-condensing together with individual DNA molecules. Through progressive DNA unpeeling, buffer exchange and force measurements, we show that FUS adsorbing in a single layer on DNA effectively generates a sticky FUS-DNA polymer that can collapse to form a liquid-like FUS-DNA co-condensate. Condensation occurs at constant DNA tension for double-stranded DNA, which is a signature of phase separation. We suggest that co-condensation mediated by protein adsorption on nucleic acids is an important mechanism for intracellular compartmentalization.
Proprioception-based movement goals support imitation and are disrupted in apraxia
Authors: Isaacs Mitchell W. , Buxbaum Laurel J. , Wong Aaron L.
Published: March 2021

The ability to imitate observed actions serves as an efficient method for learning novel movements and is specifically impaired (without concomitant gross motor impairments) in the neurological disorder of limb apraxia, a disorder common after left hemisphere stroke. Research with apraxic patients has advanced our understanding of how people imitate. However, the role of proprioception in imitation has been rarely assessed directly. Prior work has proposed that proprioceptively sensed body position is transformed into a visual format, supporting the attainment of a desired imitation goal represented visually (i.e., how the movement should look when performed). In contrast, we hypothesized a more direct role for proprioception: we suggest that movement goals are also represented proprioceptively (i.e., how a desired movement should feel when performed), and the ability to represent or access such proprioceptive goals is deficient in apraxia. Using a novel imitation task in which a robot cued meaningless trajectories proprioceptively or visually, we probed the role of each sensory modality. We found that patients with left hemisphere stroke were disproportionately worse than controls at imitating when cued proprioceptively versus visually. This proprioceptive versus visual disparity was associated with apraxia severity as assessed by a traditional imitation task, but could not be explained by general proprioceptive impairment or speed-accuracy trade-offs. These data suggest that successful imitation depends in part on the ability to represent movement goals in terms of how those movements should feel, and that deficits in this ability contribute to imitation impairments in patients with apraxia.
Testing for evolutionary change in restoration: a genomic comparison betweenex situ, native and commercial seed sources ofHelianthus maximiliani
Authors: Braasch Joseph E , Di Santo Lionel N , Tarble Zach , Prasifka Jarrad R , Hamilton Jill A
Published: March 2021

Globally imperiled ecosystems often depend upon collection, propagation, and storage of seed material for use in restoration. However, during the restoration process demographic changes, population bottlenecks, and selection can alter the genetic composition of seed material, with potential impacts for restoration success. The evolutionary outcomes associated with these processes have been demonstrated using theoretical and experimental frameworks, but no studies to date have examined the impact these processes have had on the seed material maintained for conservation and restoration. In this study, we compare genomic variation across seed sources used in conservation and restoration for the perennial prairie plantHelianthus maximiliani, a key component of restorations across North American grasslands. We compare individuals sourced from contemporary wild populations,ex situconservation collections, commercially produced restoration material, and two populations selected for agronomic traits. Overall, we observed thatex situand contemporary wild populations exhibited a similar genomic composition, while four of five commercial populations and selected lines were differentiated from each other and other seed source populations. Genomic differences across seed sources could not be explained solely by isolation by distance nor directional selection. We did find evidence of sampling effects forex situcollections, which exhibited significantly increased coancestry relative to commercial populations, suggesting increased relatedness. Interestingly, commercially sourced seed appeared to maintain an increased number of rare alleles relative toex situand wild contemporary seed sources. However, while commercial seed populations were not genetically depauperate, the genomic distance between wild and commercially produced seed suggests differentiation in the genomic composition could impact restoration success. Our results point towards the importance of genetic monitoring of species used for conservation and restoration as they are expected to be influenced by the evolutionary processes that contribute to divergence during the restoration process.
The radish Ogura fertility restorer impedes translation elongation along its cognate CMS-causing mRNA
Authors: Wang Chuande , Lezhneva Lina , Arnal Nadège , Quadrado Martine , Mireau Hakim
Published: March 2021

The control of mRNA translation has been increasingly recognized as a key regulatory step for gene control but clear examples in eukaryotes are still scarce. Nucleo-cytoplasmic male sterilities (CMS) represent ideal genetic models to dissect genetic interactions between the mitochondria and the nucleus in plants. This trait is determined by specific mitochondrial genes and is associated with a pollen sterility phenotype that can be suppressed by nuclear genes known as restorer-of-fertility (Rf) genes. In the study, we focused on the Ogura CMS system in rapeseed and showed that the suppression to male sterility by the PPR-B fertility restorer (also called Rfo) occurs through a specific inhibition of the translation of the mitochondria-encoded CMS-causing mRNAorf138. We also demonstrate that PPR-B binds within the coding sequence oforf138and acts as a ribosome blocker to specifically impede translation elongation along theorf138mRNA. Rfo is the first recognized fertility restorer shown to act this way. These observations will certainly facilitate the development of synthetic fertility restorers for CMS systems in which efficient natural Rfs are lacking.
REST is a major negative regulator of endocrine differentiation during pancreas organogenesis
Authors: Rovira Meritxell , Atla Goutham , Maestro Miguel Angel , Grau Vane , García-Hurtado Javier , Maqueda Maria , Mosquera Jose Luis , Kerr-Conte Julie , Pattou Francois , Ferrer Jorge
Published: March 2021

Understanding genomic regulatory mechanisms of pancreas differentiation is relevant to the pathophysiology of diabetes mellitus, and to the development of replacement therapies. Numerous transcription factors promote β cell differentiation, although less is known about negative regulators. Earlier epigenomic studies suggested that the transcriptional repressor REST could be a suppressor of endocrine gene programs in the embryonic pancreas. However, pancreaticRestknock-out mice failed to show increased numbers of endocrine cells, suggesting that REST is not a major regulator of endocrine differentiation. Using a different conditional allele that enables profound REST inactivation, we now observe a marked increase in the formation of pancreatic endocrine cells. REST inhibition also promoted endocrinogenesis in zebrafish and mouse early postnatal ducts, and induced β-cell specific genes in human adult duct-derived organoids. Finally, we define REST genomic programs that suppress pancreatic endocrine differentiation. These results establish a crucial role of REST as a negative regulator of pancreatic endocrine differentiation.
MLL3/MLL4 Histone Methyltranferase Activity Dependent Chromatin Organization at Enhancers during Embryonic Stem Cell Differentiation
Authors: Kubo Naoki , Hu Rong , Ye Zhen , Ren Bing
Published: March 2021

MLL3 (KMT2C) and MLL4 (KMT2D), the major mono-methyltransferases of histone H3 lysine 4 (H3K4), are required for cellular differentiation and embryonic development in mammals. We previously observed that MLL3/4 promote long-range chromatin interactions at enhancers, however, it is still unclear how their catalytic activities contribute to enhancer-dependent gene activation in mammalian cell differentiation. To address this question, we mapped histone modifications, long-range chromatin contacts as well as gene expression in MLL3/4 catalytically deficient mouse embryonic stem (ES) cells undergoing differentiation toward neural precursor cells. We showed that MLL3/4 activities are responsible for deposition of H3K4me1 modification and formation of long-range enhancer-promoter contacts at a majority of putative enhancers gained during cell differentiation, but are dispensable for most candidate enhancers found in undifferentiated ES cells that persist through differentiation. While transcriptional induction at most genes is unaltered in the MLL3/4 catalytically deficient cells, genes making more contacts with MLL3/4-dependent putative enhancers are disproportionately affected. These results support that MLL3/4 contributes to cellular differentiation through histone-methyltransferase-activity dependent induction of enhancer-promoter contacts and transcriptional activation at a subset of lineage-specific genes.
Engineering the AEG1 promoter from cotton to develop male sterile lines
Authors: Soni Kamlesh Kumar , Mehrotra Amita Kush , Burma Pradeep Kumar
Published: March 2021

This work reports on modifying the Upstream Regulatory Module (URM, 1.5 Kb region upstream of the open reading frame) ofAnther Expressing Gene 1(AEG1) from cotton to achieve anther specific activity.AEG1was identified in a previous study aimed to isolate a promoter with tapetum specific activity. Such a promoter could then be used to expressbarnaseandbarstargenes for developing male sterile and restorer lines for hybrid seed production in cotton. The AEG1 URM was observed to be active in tapetum as well as in roots making it unusable to drive the expression ofbarnasegene. Analysis of the URM showed the presence of several root specific motifs. Two modified AEG1 URMs were developed, by removing or mutating these motifs and its activity checked in tobacco. The activity of one of the modified URMs, AEG1(ΔBmut) was restricted to the anther tissue as observed using the reporter geneß-glucuronidase. The study also demonstrates that male sterile lines could be developed in tobacco using the AEG1(ΔBmut) URM to express thebarnasegene. This work thus shows the possibility of engineering promoters to achieve tissue specificity and to develop male sterile lines in cotton.
Dynamic modulation of enhancer responsiveness by core promoter elements in livingDrosophilaembryo
Authors: Yokoshi Moe , Cambón Manuel , Fukaya Takashi
Published: March 2021

Regulatory interactions between enhancers and core promoters are fundamental for the temporal and spatial specificity of gene expression in development. The central role of core promoters is to initiate productive transcription in response to enhancer’s activation cues. However, it has not been systematically assessed how individual core promoter elements affect the induction of transcriptional bursting by enhancers. Here, we provide evidence that each core promoter element dynamically alters “enhancer responsiveness” by changing functional parameters of transcriptional bursting in developingDrosophilaembryos. Quantitative live imaging analysis revealed that the timing and the continuity of burst induction are common regulatory steps on which core promoter elements impact. We also show that core promoters use the upstream TATA box as an amplifier of transcriptional bursting upon interaction with enhancers. Genome editing analysis of the pair-rule genefushi tarazufurther revealed that the endogenous TATA box and the downstream core promoter element are both essential for the correct expression and the function of key developmental genes in early embryos. We suggest that core promoter elements serve as a key regulatory module in converting enhancer activity into transcription dynamics during animal development.
Genomics-informed insights into microbial degradation ofN,N-dimethylformamide
Authors: Li Junhui , Dijkstra Paul , Lu Qihong , Wang Shanquan , Chen Shaohua , Li Deqiang , Wang Zhiheng , Jia Zhenglei , Wang Lu , Shim Hojae
Published: March 2021

Effective degradation ofN,N-Dimethylformamide (DMF), an important industrial waste product, is challenging as only few bacterial isolates are known to be capable of degrading DMF. Aerobic remediation of DMF has typically been used, whereas anoxic remediation attempts are recently made, using nitrate as one electron acceptor, and ideally include methane as a byproduct. Here, we analyzed 20,762 complete genomes and 28 constructed draft genomes for the genes associated with DMF degradation. We identified 952 genomes that harbor genes involved in DMF degradation, expanding the known diversity of prokaryotes with these metabolic capabilities. Our findings suggest acquisition of DMF-degrading gene via plasmids are important in the order Rhizobiales and genusParacoccus, but not in most other lineages. Degradation pathway analysis reveals that most putative DMF degraders using aerobic Pathway I will accumulate methylamine intermediate, while members ofParacoccus, Rhodococcus, Achromobacter, andPseudomonascould potentially mineralize DMF completely under aerobic conditions. The aerobic DMF degradation via Pathway II is more common than thought and is primarily present in α-and β-Proteobacteria and Actinobacteria. Most putative DMF degraders could grow with nitrate anaerobically (Pathway III), however, genes for the use of methyl-CoM to produce methane were not found. These analyses suggest that microbial consortia could be more advantageous in DMF degradation than pure culture, particularly for methane production under the anaerobic condition. The identified genomes and plasmids form an important foundation for optimizing bioremediation of DMF-containing wastewaters.

Importance

DMF is extensively used as a solvent in industries, and is classified as a probable carcinogen. DMF is a refractory compound resistant to degradation, and until now, only few bacterial isolates have been reported to degrade DMF. To achieve effective microbial degradation of DMF from wastewater, it is necessary to identify genomic diversity with the potential to degrade DMF and characterize the genes involved in two aerobic degradation pathways and potential anaerobic degradation for methane production. A wide diversity of organisms has the potential to degrade DMF. Plasmid-mediated degradation of DMF is important for Rhizobiales andParacoccus. Most DMF degraders could grow anaerobically with nitrate as electron acceptor, while co-cultures are required to complete intermediate methanogenesis for methane production. This is the first genomics-based global investigation into DMF degradation pathways. The genomic database generated by this study provides an important foundation for the bioremediation of DMF in industrial waste waters.

Abstract Figure
Myocarditis in naturally infected pets with the British variant of COVID-19
Authors: Ferasin Luca , Fritz Matthieu , Ferasin Heidi , Becquart Pierre , Legros Vincent , Leroy Eric M.
Published: March 2021

Domestic pets can contract SARS-CoV-2 infection but, based on the limited information available to date, it is unknown whether the new British B.1.1.7 variant can more easily infect certain animal species or increase the possibility of human-to-animal transmission. In this study, we report the first cases of infection of domestic cats and dogs by the British B.1.1.7 variant of SARS-CoV-2 diagnosed at a specialist veterinary hospital in the South-East of England. Furthermore, we discovered that many owners and handlers of these pets had developed Covid-19 respiratory symptoms 3-6 weeks before their pets became ill and had also tested PCR positive for Covid-19. Interestingly, all these B.1.1.7 infected pets developed atypical clinical manifestations, including severe cardiac abnormalities secondary to myocarditis and a profound impairment of the general health status of the patient but without any primary respiratory signs. Together, our findings demonstrate for the first time the ability for companion animals to be infected by the B.1.1.7 variant of SARS-CoV-2 and raise questions regarding its pathogenicity in these animals. Moreover, given the enhanced infectivity and transmissibility of B.1.1.7 variant for humans, these findings also highlights more than ever the risk that companion animals may potentially play a significant role in SARS-CoV-2 outbreak dynamics than previously appreciated.
All Holographic Four-Point Functions in All Maximally Supersymmetric CFTs
Authors: Alday Luis F. , Zhou Xinan
Published: March 2021

The anti-de Sitter/conformal field theory (AdS/CFT) correspondence is a remarkable tool for analytically studying strongly coupled physics. Thanks to the AdS/CFT correspondence, strongly correlated quantum systems can be understood as weakly coupled gravity theories, which live in a holographic spacetime with an extra emergent dimension and constant negative curvature. Fundamental observables such as correlation functions are identified with scattering amplitudes in curved spacetime, which, in principle, can be computed by using standard perturbation theory. Unfortunately, such holographic calculations are notoriously difficult, even for tree-level processes involving four external particles. Despite relentless efforts over the past two decades, a full solution to this problem was not found. In this article, we introduce a powerful new method that solves this long-standing problem. We give a closed-form formula for all such four-point functions in a class of theories that constitute the best-known paradigms of AdS/CFT. These models exhaust the theories compatible with maximal supersymmetry, and they live in three, four, and six dimensions. Pivotal to our construction is the use of symmetries. We show that in a judiciously chosen limit, symmetry principles dictate a drastic simplification in holographic correlators, allowing them to be directly computed. Having solved this limit, we further show that the full correlators can be recovered from this special configuration by using only symmetries. In addition to providing valuable explicit expressions that have a wide range of applications in AdS/CFT, our analysis leads to several important conceptual lessons. Our results point out remarkable simplicities underlying the holographic correlators, as well as concrete ways to search for such structures. Moreover, our construction identifies previously unknown elegant underlying organizing principles for holographic correlators. These qualitative features of holographic correlators also echo the exciting progress in the scattering amplitude program in flat space, suggesting tantalizing prospects of future cross-fertilization of ideas.

Published by the American Physical Society
2021
Removal of spurious data in Bragg coherent diffraction imaging: an algorithm for automated data preprocessing
Authors: Pelzer Kenley , Schwarz Nicholas , Harder Ross
Published: March 2021

Bragg coherent diffraction imaging (BCDI) provides a powerful tool for obtaining high-resolution structural information from nanocrystalline materials. Here a BCDI sample consisting of a large number of randomly oriented nanoscale crystals is considered. Ideally, only one crystal is oriented to produce a Bragg peak on the detector. However, diffraction from other crystals often produces additional signals on the detector. Before the measured diffraction patterns can be processed into structural images, scientists routinely need to manually identify and remove the `alien' intensities from sources other than the intended crystal. With the development of modern high-coherence storage rings, such as the upgraded Advanced Photon Source (APS), the already slow process of manual preprocessing will be untenable for the large volumes of data that will be produced. An automated method of identifying and deleting alien intensities is proposed. This method exploits the fact that BCDI of a perfect crystal produces diffraction data with inversion symmetry around the Bragg peak. This approach uses the machine learning clustering method DBSCAN to distinguish between diffraction from multiple sources, and then calculates cluster size and inversion symmetry to assess whether clusters of intensity belong to desired data or alien signals. This approach can dramatically reduce the amount of time spent manually processing data, allowing BCDI data processing capabilities to keep pace with the technological advances of fourth-generation synchrotron light sources.
Crystal orientation and detector distance effects on resolving pseudosymmetry by electron backscatter diffraction
Authors: Pang Edward L. , Schuh Christopher A.
Published: March 2021

Accurately indexing pseudosymmetric materials has long proven challenging for electron backscatter diffraction. The recent emergence of intensity-based indexing approaches promises an enhanced ability to resolve pseudosymmetry compared with traditional Hough-based indexing approaches. However, little work has been done to understand the effects of sample position and orientation on the ability to resolve pseudosymmetry, especially for intensity-based indexing approaches. Thus, in this work the effects of crystal orientation and detector distance in a model tetragonal ZrO2 (c/a = 1.0185) material are quantitatively investigated. The orientations that are easiest and most difficult to correctly index are identified, the effect of detector distance on indexing confidence is characterized, and these trends are analyzed on the basis of the appearance of specific zone axes in the diffraction patterns. The findings also point to the clear benefit of shorter detector distances for resolving pseudosymmetry using intensity-based indexing approaches.
Exploring job crafting as a response to abusive supervision
Authors: Masood Huda , Karakowsky Len , Podolsky Mark
Published: March 2021

Purpose

The purpose of this qualitative exploratory study was to investigate the capacity of job crafting to serve as a viable response to abusive supervision. Although considerable literature has emerged on employee reactions to abusive supervision, the role of job crafting as a coping mechanism has received relatively little attention.

Design/methodology/approach

Using qualitative exploration, we conducted semi-structured interviews to examine how individuals engage in job crafting as a means to respond to or cope with abusive supervision. Critical Incident Interview Technique (CIIT) was used to obtain in-depth details of this topic. We analyzed the interview-based data using the thematic analysis (TA) technique. We also integrated topic modeling to cluster the identified categories of job crafting behaviors within our TA. The cultural context of our findings was further analyzed using interpretive phenological analysis (IPA).

Findings

The results of our thematic analysis led to four recurring themes in the interview-data: (1) Job crafting as a viable coping response to abusive supervision; (2) The type of coping relates to the type of crafting: Approach and Avoidance; (3) The role of perceived control; (4) Emotions play a role in the type of crafting employed. Findings from our IPA generated the following super-ordinate themes. (1) Job crafting fluidity, (2) effectiveness of job crafting, (3) resilience and (4) cultural dynamics.

Research limitations/implications

This research reveals the ways in which individuals may turn to job crafting behaviors as a means to cope following instances of abusive supervision. Given the qualitative exploration of our research approach, we identify generalizability to be an issue.

Practical implications

Job crafting is a proactive phenomenon that equips employees with coping abilities in the workplace. While Wrzesniewski and Dutton (2001) suggested that job crafting behaviors tend to be hidden from management, there may be merit in organizations explicitly acknowledging the benefits of allowing employees to be active agents in their work, capable of using multiple domains of job crafting to improve their personal and professional lives (Petrouet al., 2017).

Originality/value

The current research reveals the ways in which individuals may turn to job crafting behaviors as a means to cope, following instances of abusive supervision. We further fine-grained our analysis to explicate employee job crafting behaviors in response to abusive supervision within a cross-cultural domain.
Human resources flexibility as a mediating mechanism between high-performance work systems and organizational performance: a multilevel quasi-longitudinal study
Authors: Katou Anastasia A.
Published: March 2021

Purpose

The purpose of this study is to investigate the impact of high-performance work systems (HPWS) on organizational performance through the mediating role of human resources (HR) flexibility (expressed by functional flexibility, skills malleability and behavioural flexibility).

Design/methodology/approach

The study examines theoretical relationships in the Greek context, which reflects changing economic and financial crisis, based on multilevel structural equation modelling estimation, using three waves of sample data collected in years 2014, 2016 and 2018 from organizations operating in the private sector.

Findings

The study finds that although HPWS positively influences all three HR flexibility dimensions, this positive effect is not transferred equally to organizational performance. The dominant effect on organizational performance is attributed to skills malleability, a smaller effect to behavioural flexibility and a negligible effect to functional flexibility.

Research limitations/implications

Although the data collected refer to three different years, most of the companies and individuals responded to sampling were different. As such, the study does not allow for dynamic causal inferences due to its quasi-longitudinal nature.

Practical implications

The findings of this study may influence managerial decisions in developing bundles of HPWS policies and practices in relation to HR flexibility attributes.

Originality/value

Since most studies consider HR flexibility as an aggregated construct, this study is possibly one of the very few studies that is examining the differential impact of the HR flexibility dimensions on organizational performance in turbulent times.
Institutional factors for faculty members' implementation of blended learning in higher education
Authors: Anthony Jnr. Bokolo
Published: March 2021

Purpose

The aim of this study is to develop a model grounded by the institutional theory to investigate blended learning (BL) implementation among faculty members in higher education and further validate the model.

Design/methodology/approach

Quantitative methodology was employed, and data were gathered through questionnaires among 188 e-learning directors, managers and coordinators at faculty/department in institutions, which implement BL.

Findings

Findings reveal that BL implementation by faculty members is significantly influenced by coercive, normative and mimetic pressures. Findings from this study also identified institutional initiatives that influence BL implementation. Accordingly, findings from this study provide insights into the institutional theory perspective toward BL. The findings support higher education to plan and initiate BL policies.

Research limitations/implications

Data were collected from faculty members in universities, colleges and polytechnics only. Besides, this research is one of the limited studies that explore BL deployment from the lens of faculty members.

Practical implications

This research contributes to the existing literature on the institutional theory and BL by presenting significant initiatives as practical suggestions for educationalist and policymakers. Therefore, this study provides practical implications to better understand BL initiatives by providing insights into how institutions can improve faculty members' satisfaction levels, improving course management, enriching teaching quality and enhancing learning content.

Social implications

The findings provided in this study can be employed to design practices, policies and a culture that support continuance use of BL systems among faculty members to achieve an effective institutional outcome.

Originality/value

This study contributes to existing BL adoption and develops a model to examine faculty member implementation of BL approach. This research has several suggestions for higher education in terms of practice to support adoption of BL. The developed model can also be employed by academics, administration and institutions to determine success initiatives for achieving an appropriate change in adopting BL in their institutions.
Chiller system performance management with market basket analysis
Authors: Ho Wai Tung , Yu Fu Wing
Published: March 2021

Purpose

This study aims to apply association rule mining (ARM) to uncover specific associations between operating components of a chiller system and improve its coefficient of performance (COP), hence reducing the electricity use of buildings with central air conditioning.

Design/methodology/approach

First, 13 operating variables were identified, comprising measures of temperatures and flow rates of system components and their switching statuses. The variables were grouped into four bins before carrying out ARM. Strong rules were produced to associate the variables and switching statuses with different COP classes.

Findings

The strong rules explain existing constraints on practising chiller sequencing and prioritise variables for optimisation. Based on strong rules for the highest COP class, the optimal operating strategy involves rescheduling chillers and their associated components in pairs during a high load operation. Resetting the chilled water supply temperature is the next best strategy, followed by resetting the condenser water entering temperature, subject to operating constraints.

Research limitations/implications

This study considers the even frequency method with four bins only. Replication work can be done with other discretisation methods and different numbers of classes to compare potential differences in the bin ranges of the optimised variables.

Practical implications

The strong rules identified by ARM highlight associations between variables and high or low COPs. This supports the selection of critical variables and the operating status of system components to maximise the COP. Tailor-made optimisation strategies and the associated electricity savings can be further evaluated.

Originality/value

Previous studies applied ARM for chiller fault detection but without considering system performance under the interaction of different components. The novelty of this study is its demonstration of ARM’s intelligence at discovering associations in past operating data. This enables the identification of tailor-made energy management opportunities, which are essential for all engineering systems. ARM is free from the prediction errors of typical regression and black-box models.