bluuebunny/crossref_metadata_2025 huggingface dataset:
The Marmoset: The Next Frontier in Understanding the Development of the Human Brain
Authors: Homman-Ludiye Jihane , Bourne James A
Published: January 2021

Rodent models, particularly mice, have dominated the field of developmental neuroscience for decades, like they have in most fields of biomedicine research. However, with 80 million years since rodents and primates last shared a common ancestor, the use of mice to model the development of the human brain is not without many shortcomings. The human brain diverges from the mouse brain in many aspects and is comprised of novel structures as well as diversified cellular subtypes. While these newly evolved features have no equivalent in rodents, they are observed in nonhuman primates. Therefore, elucidating the cellular mechanisms underlying the development and maturation of the healthy and diseased human brain can be achieved using less complex nonhuman primates. Historically, macaques were the preferred nonhuman primate model. However, over the past decade, the New World marmoset monkey (Callithrix jacchus) has gained more importance, particularly in the field of neurodevelopment. With its small size, twin or triplet birth, and prosocial behavior, the marmoset is an ideal model to study normal brain development as well as neurodevelopmental disorders, which are often associated with abnormal social behaviors. The growing interest in the marmoset has prompted many comparative studies, all demonstrating that the marmoset brain closely resembles that of the human and is perfectly suited to model human brain development. The marmoset is thus poised to extend its influence in the field of neurodevelopment and will hopefully fill the gaps that the mouse has left in our understanding of how our brain forms and how neurodevelopmental disorders originate.
H∞ estimation for non-linear positive switched systems with time-varying delay
Authors: Li Shuo , Chen Yun , Xue Anke
Published: January 2021

For non-linear positive switched systems (NPSSs) with time-varying delay, the $H_{\infty }$ estimation problem is addressed in this paper. Firstly, in light of T-S fuzzy modeling method, the considered NPSS is equivalently transformed into a switched positive T-S fuzzy system. Then, a less conservative $H_{\infty }$ performance co1ndition is provided for the error system via presenting a new piecewise quadratic copositive Lyapunov–Krasovskii functional. Furthermore, an observer is constructed to make the underlying system exponentially stable with a preset $H_{\infty }$ performance and an iterative optimization algorithm is proposed to obtain the observer parameters. To verify the effectiveness of the theoretical results, two examples are finally presented.
Cytokine Augmentation Reverses Transplant Recipient Neutrophil Dysfunction Against the Human Fungal Pathogen Candida albicans
Authors: Barros Nicolas , Alexander Natalie , Viens Adam , Timmer Kyle , Atallah Natalie , Knooihuizen Sally A I , Hopke Alex , Scherer Allison , Dagher Zeina , Irimia Daniel , Mansour Michael K
Published: January 2021

Background

Solid organ transplant (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts. Here, we measure neutrophil anti-Candida activity.

Methods

Twenty-one SOT and 19 SCT recipients were enrolled 2–4 months posttransplant and compared to 23 healthy control patients (HC). Neutrophils were coincubated with Candida albicans, and percentage killing and swarming responses were measured.

Results

Neutrophils from transplant patients had decreased fungicidal capacity compared to HC (42%, 43%, and 72% for SCT, SOT, and HC, respectively; SCT vs HC: P < .0001; SOT vs HC: P < .0001; SOT vs SCT: P = .8), including diminished ability to control hyphal growth (HC vs SOT: 0.1455 vs 0.3894, P ≤ .001; HC vs SCT: 0.1455 vs 0.6295, P ≤ .0001, respectively). Serum from SCT, but not SOT, recipients, inhibited the ability of HC neutrophils to control C. albicans (37%, 45%, and 55% for SCT, SOT, and HC, respectively). Neutrophils’ control of hyphal growth was partially restored with granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor.

Conclusions

Despite normal circulating numbers, our data suggest that neutrophils from SOT and SCT recipients mount dysfunctional responses against C. albicans. Intrinsic neutrophil changes and extrinsic serum factors may be responsible for the dysfunction, which is partially reversed with cytokine augmentation.
Characteristics and Long-term Prognosis of Danish Patients With Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared With the Background Population
Authors: Omland Lars H , Vestergaard Hanne T , Dessau Ram B , Bodilsen Jacob , Andersen Nanna S , Christiansen Claus B , Ellermann-Eriksen Svend , Nielsen Lene , Andersen Christian Ø , Lebech Anne-Mette , Obel Niels
Published: January 2021

Background

Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown.

Methods

We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes.

Results

Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort.

Conclusions

Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity.
Emergence of MDR invasive Neisseria meningitidis in El Salvador, 2017–19
Authors: Marín José Eduardo Oliva , Villatoro Esmeralda , Luna María Jose , Barrientos Ana María , Mendoza Elmer , Lemos Ana Paula S , Camargo Carlos H , Sacchi Claudio T , Cunha Marcos Paulo V , Galas Marcelo , Gabastou Jean-Marc
Published: January 2021

Background

Invasive meningococcal disease (IMD) is an acute, highly transmissible and potentially fatal disease caused by Neisseria meningitidis. Prompt antimicrobial therapy and prophylaxis are recommended, where penicillin or ciprofloxacin are the available choices. However, the emergence of resistant isolates of N. meningitidis poses a challenge for antimicrobial therapy.

Objectives

To describe the clinical, epidemiological and biological characteristics of six penicillin- and ciprofloxacin-resistant, culture-confirmed IMD cases reported in El Salvador, Central America, between 2017 and 2019.

Methods

Following the detection of six patients presenting with IMD in El Salvador, clinical data were collected and epidemiological action plans conducted. Isolates were subjected to antimicrobial susceptibility testing by broth microdilution and WGS for genotyping and molecular characterization analysis, including phylogeny comparison with global sequences available from public databases.

Results

A total of six IMD cases caused by N. meningitidis serogroup Y, resistant to both penicillin (MIC >8.0 mg/L) and ciprofloxacin (MIC 0.125 mg/L), were detected from 2017 to 2019. Genomic analysis showed that penicillin resistance was mediated by the production of β-lactamase ROB-1. Ciprofloxacin resistance was attributed to an amino acid substitution in DNA gyrase (T91I). All isolates were classified as ST3587, clonal complex 23, and were genetically highly similar, based on core-genome SNP analysis.

Conclusions

To the best of our knowledge, we report the first cases of MDR N. meningitidis causing IMD in Latin America. Our findings highlight the emergence of this potential public health threat, with a profound impact on the efficacy of IMD treatment and prophylaxis protocols.
The case for ‘conservative pharmacotherapy’
Authors: Jorgensen Sarah C J , Stewart Jackson J , Dalton Bruce R
Published: January 2021

In the modern era of rapid advances in the field of antimicrobial ‘precision dosing’ through therapeutic drug monitoring (TDM), there is growing pressure to adopt new technologies and expand the number of antimicrobials managed with TDM and/or the complexity of TDM methods. For many clinicians, it may seem inevitable that TDM must improve patient outcomes. However, based on the evidence to date, this concept remains largely a hypothesis. Conversely, it is plausible that focusing on TDM may distract from careful clinical monitoring of the patient for efficacy and drug-related toxicities and shift finite resources from other valuable interventions. In this article we make the case for embracing critical appraisal of precision dosing, remaining skeptical until persuaded by compelling evidence, and adopting new technologies only when they have proven their value over competing priorities; that is, we make the case for using ‘conservative pharmacotherapy’.
Quanta prudentia et usus administrandæ reipublicæ: Quiccheberg and Mylaeus on the utility of techne
Authors: Meadow Mark A
Published: January 2021

Two mid-sixteenth-century treatises, by Samuel Quiccheberg (1565) and Christophorus Mylaeus (1551), provide important insights into how early modern collections were understood in their own day to be useful. This essay argues that both authors conceptualize utility in relation to the Aristotelian concept of prudence: the kind of practical wisdom required to govern effectively. Although the two texts were written on very different topics – respectively, how to create a Kunstkammer and how to write history – Quiccheberg and Mylaeus share an understanding of wisdom that posits ‘techne’, in the form of collected works of artistry, as a necessary aspect of prudential governance.
Clinical approach to re-irradiation for recurrent diffuse intrinsic pontine glioma
Authors: Krishnatry Rahul , Manjali Jifmi Jose , Chinnaswamy Girish , Chatterjee Abhishek , Goda Jayant Sastri , Janu Amit , Sahu Arpita , Jalali Rakesh , Gupta Tejpal
Published: January 2021

Background

We present our institutional approach for re-irradiation in diffuse intrinsic pontine glioma and their outcomes.

Methods

Consecutive patients of recurrent diffuse intrinsic pontine glioma treated with re-irradiation (January 2015–September 2019) were reviewed retrospectively to describe the clinical-response-based approach followed for the dose and volume decision. Outcomes were defined with clinical and steroid response criteria and survival endpoints included progression-free survival and overall survival as cumulative(c) overall survival and re-irradiation overall survival (re-irradiation starting to death). The Kaplan–Meier method and log-rank test were used for survival analysis.

Results

Twenty-patient cohort with a median (m) age of 7.5 years, m-progression-free survival of 8.4 months and m-Lansky performance score of 50 received re-irradiation of which 17 (85%) were called clinical responders. The median re-irradiation-overall survival with 39.6–41.4, 43.2 and 45 Gy were 5.8, 7 and 5.3 months, respectively. One-month post-re-irradiation steroid independent status was a significant predictor of better survival outcomes (overall survival, P≤0.004). No ≥ grade 3 toxicities were noticed. Two patients succumbed to intra-tumoral hemorrhage.

Conclusions

Higher doses of re-irradiation based on a clinical-response-based approach show improvement in survival and steroid dependence rates with acceptable toxicity. Steroid independent status at 1-month post-re-irradiation predicts better outcomes. Prospective studies may validate this with quality of life data.
Kidney injury molecule-1 is a potential receptor for SARS-CoV-2
Authors: Yang Chen , Zhang Yu , Zeng Xia , Chen Huijing , Chen Yuchen , Yang Dong , Shen Ziwei , Wang Xiaomu , Liu Xinran , Xiong Mingrui , Chen Hong , Huang Kun
Published: January 2021

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and mortality. The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2. However, whether there is a specific target of SARS-CoV-2 in the kidney remains unclear. Herein, by using in silico simulation, coimmunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labeling, and rational design of antagonist peptides, we demonstrate that kidney injury molecule-1 (KIM1), a molecule dramatically upregulated upon kidney injury, binds with the receptor-binding domain (RBD) of SARS-CoV-2 and facilitates its attachment to cell membrane, with the immunoglobulin variable Ig-like (Ig V) domain of KIM1 playing a key role in this recognition. The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2. In addition, our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV, pathogens of two severe infectious respiratory diseases. Together, these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses. We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target.
Developmental and water deficit-induced changes in hydraulic properties and xylem anatomy of tomato fruit and pedicels
Authors: Li Hao , Zhang Xianbo , Hou Xuemin , Du Taisheng
Published: January 2021

Xylem water transport from the parent plant plays a crucial role in fruit growth, development, and the determination of quality. Attempts have been made to partition the hydraulic resistance of the pathway over the course of development, but no consensus has been reached. Furthermore, the issue has not been addressed in the context of changing plant and fruit water status under water deficit conditions. In this study, we have conducted a rigorous investigation into the developmental changes that occur in the hydraulic properties of tomato fruits and their pedicels under well-irrigated and water deficit conditions, based on hydraulic measurements, fruit rehydration, dye-tracing, light and electron microscopy, and flow modeling. We found that a decline in water transport capacity during development did not occur in the xylem pathway leading up to the fruit, but within the fruit itself, where the effect might reside either inside or outside of the xylem pathway. The developmental pattern of the hydraulic resistance of the xylem pathway was not significantly influenced by water deficit. The changes in xylem flow between the fruit and the parent plant resulting from the reduced driving force under water deficit could explain the reduced accumulation of water in the fruit. This study provides new insights that aid our understanding of xylem water transport in fleshy fruits and its sensitivity to water deficit from a hydraulic perspective.
Winds from fast rotating stars
Authors: Bogovalov S V , Petrov M A , Timofeev V A
Published: January 2021

Numerical modelling of an isothermal wind from a fast rotating star is performed. Excitation of hydrodynamical turbulence and deviation of the shape of the stellar surface from a sphere are taken into account. Rotation and turbulence result in a dramatic increase of the mass flow rate from the star in comparison with a non-rotating one. The outflow occurs predominantly from a region on the stellar surface located at the equator. This flow expands rapidly due to thermal pressure. However, a disc-like flow at the equator is formed. The flow is more complicated near the pole. At large distances from the star a radially expanding wind is formed while close to the star some fraction of the outflow from the equatorial region falls down on to the stellar surface, producing a huge vortex. The dependence of the mass loss rate on the parameters of the star is presented.
Cross-correlating radio continuum surveys and CMB lensing: constraining redshift distributions, galaxy bias, and cosmology
Authors: Alonso David , Bellini Emilio , Hale Catherine , Jarvis Matt J , Schwarz Dominik J
Published: January 2021

We measure the harmonic-space auto-power spectrum of the galaxy overdensity in the LOFAR Two-metre Sky Survey (LoTSS) first data release and its cross-correlation with the map of the lensing convergence of the cosmic microwave background (CMB) from the Planck collaboration. We report a ∼5σ detection of the cross-correlation. We show that the combination of the clustering power spectrum and CMB lensing cross-correlation allows us to place constraints on the high-redshift tail of the redshift distribution, one of the largest sources of uncertainty in the use of continuum surveys for cosmology. Our analysis shows a preference for a broader redshift tail than that predicted by the photometric redshifts contained in the LoTSS value-added catalogue, as expected, and more compatible with predictions from simulations and spectroscopic data. Although the ability of CMB lensing to constrain the width and tail of the redshift distribution could also be valuable for the analysis of current and future photometric weak lensing surveys, we show that its performance relies strongly on the redshift evolution of the galaxy bias. Assuming the redshift distribution predicted by the Square Kilometre Array Design simulations, we use our measurements to place constraints on the linear bias of radio galaxies and the amplitude of matter inhomogeneities σ8, finding $\sigma _8=0.69^{+0.14}_{-0.21}$ assuming the galaxy bias scales with the inverse of the linear growth factor, and $\sigma _8=0.79^{+0.17}_{-0.32}$ assuming a constant bias.
Far and extreme ultraviolet radiation fields and consequent disc destruction in star-forming regions
Authors: Parker Richard J , Nicholson Rhana B , Alcock Hayley L
Published: January 2021

The first stages of planet formation usually occur when the host star is still in a (relatively) dense star-forming region, where the effects of the external environment may be important for understanding the outcome of the planet formation process. In particular, star-forming regions that contain massive stars have strong far-ultraviolet (FUV) and extreme ultraviolet (EUV) radiation fields, which can induce mass-loss from protoplanetary discs due to photoevaporation. In this paper, we present a parameter-space study of the expected FUV and EUV fields in N-body simulations of star-forming regions with a range of initial conditions. We then use recently published models to determine the mass-loss due to photoevaporation from protoplanetary discs. In particular, we focus on the effects of changing the initial degree of spatial structure and initial virial ratio in the star-forming regions, as well as the initial stellar density. We find that the FUV fields in star-forming regions are much higher than in the interstellar medium, even when the regions have stellar densities as low as in the Galactic field, due to the presence of intermediate-mass, and massive, stars (>5 M⊙). These strong radiation fields lead to the destruction of the gas component in protoplanetary discs within 1 Myr, implying that gas giant planets must either form extremely rapidly (<1 Myr), or that they exclusively form in star-forming regions like Taurus, which contain no intermediate-mass or massive stars. The latter scenario is in direct tension with meteoritic evidence from the Solar system that suggests the Sun and its protoplanetary disc was born in close proximity to massive stars.
Photoionized Herbig–Haro objects in the Orion Nebula through deep high-spectral resolution spectroscopy – I. HH 529 II and III
Authors: Méndez-Delgado J E , Esteban C , García-Rojas J , Henney W J , Mesa-Delgado A , Arellano-Córdova K Z
Published: January 2021

We present the analysis of physical conditions, chemical composition, and kinematic properties of two bow shocks – HH 529 II and HH 529 III – of the fully photoionized Herbig–Haro object HH 529 in the Orion Nebula. The data were obtained with the Ultraviolet and Visual Echelle Spectrograph at the 8.2m Very Large Telescope and 20 yr of Hubble Space Telescope imaging. We separate the emission of the high-velocity components of HH 529 II and III from the nebular one, determining ne and Te in all components through multiple diagnostics, including some based on recombination lines (RLs). We derive ionic abundances of several ions, based on collisionally excited lines and RLs. We find a good agreement between the predictions of the temperature fluctuation paradigm (t2) and the abundance discrepancy factor (ADF) in the main emission of the Orion Nebula. However, t2 cannot account for the higher ADF found in HH 529 II and III. We estimate 6 per cent of Fe in the gas phase of the Orion Nebula, while this value increases to 14 per cent in HH 529 II and between 10 and 25 per cent in HH 529 III. We find that such increase is probably due to the destruction of dust grains in the bow shocks. We find an overabundance of C, O, Ne, S, Cl, and Ar of about 0.1 dex in HH 529 II and III that might be related to the inclusion of H-deficient material from the source of the HH 529 flow. We determine the proper motions of HH 529 finding multiple discrete features. We estimate a flow angle with respect to the sky plane of 58° ± 4° for HH 529.
Dinucleotides as simple models of the base stacking-unstacking component of DNA ‘breathing’ mechanisms
Authors: Beyerle Eric R , Dinpajooh Mohammadhasan , Ji Huiying , von Hippel Peter H , Marcus Andrew H , Guenza Marina G
Published: January 2021

Regulatory protein access to the DNA duplex ‘interior’ depends on local DNA ‘breathing’ fluctuations, and the most fundamental of these are thermally-driven base stacking-unstacking interactions. The smallest DNA unit that can undergo such transitions is the dinucleotide, whose structural and dynamic properties are dominated by stacking, while the ion condensation, cooperative stacking and inter-base hydrogen-bonding present in duplex DNA are not involved. We use dApdA to study stacking-unstacking at the dinucleotide level because the fluctuations observed are likely to resemble those of larger DNA molecules, but in the absence of constraints introduced by cooperativity are likely to be more pronounced, and thus more accessible to measurement. We study these fluctuations with a combination of Molecular Dynamics simulations on the microsecond timescale and Markov State Model analyses, and validate our results by calculations of circular dichroism (CD) spectra, with results that agree well with the experimental spectra. Our analyses show that the CD spectrum of dApdA is defined by two distinct chiral conformations that correspond, respectively, to a Watson–Crick form and a hybrid form with one base in a Hoogsteen configuration. We find also that ionic structure and water orientation around dApdA play important roles in controlling its breathing fluctuations.
PTEN deficiency leads to proteasome addiction: a novel vulnerability in glioblastoma
Authors: Benitez Jorge A , Finlay Darren , Castanza Anthony , Parisian Alison D , Ma Jianhui , Longobardi Ciro , Campos Alex , Vadla Raghavendra , Izurieta Alejandro , Scerra Gianluca , Koga Tomoyuki , Long Tao , Chavez Lukas , Mesirov Jill P , Vuori Kristiina , Furnari Frank
Published: January 2021

Background

Glioblastoma (GBM) is the most common primary brain tumor in adults with a median survival of approximately 15 months; therefore, more effective treatment options for GBM are required. To identify new drugs targeting GBMs, we performed a high-throughput drug screen using patient-derived neurospheres cultured to preferentially retain their glioblastoma stem cell (GSC) phenotype.

Methods

High-throughput drug screening was performed on GSCs followed by a dose-response assay of the 5 identified original “hits.” A PI3K/mTOR dependency to a proteasome inhibitor (carfilzomib), was confirmed by genetic and pharmacologic experiments. Proteasome Inhibition Response Signatures were derived from proteomic and bioinformatic analysis. Molecular mechanism of action was determined using three-dimensional (3D) GBM-organoids and preclinical orthotopic models.

Results

We found that GSCs were highly sensitive to proteasome inhibition due to an underlying dependency on an increased protein synthesis rate, and loss of autophagy, associated with PTEN loss and activation of the PI3K/mTOR pathway. In contrast, combinatory inhibition of autophagy and the proteasome resulted in enhanced cytotoxicity specifically in GSCs that did express PTEN. Finally, proteasome inhibition specifically increased cell death markers in 3D GBM-organoids, suppressed tumor growth, and increased survival of mice orthotopically engrafted with GSCs. As perturbations of the PI3K/mTOR pathway occur in nearly 50% of GBMs, these findings suggest that a significant fraction of these tumors could be vulnerable to proteasome inhibition.

Conclusions

Proteasome inhibition is a potential synthetic lethal therapeutic strategy for GBM with proteasome addiction due to a high protein synthesis rate and autophagy deficiency.
Private Equity Buyouts and Workplace Safety
Authors: Cohn Jonathan , Nestoriak Nicole , Wardlaw Malcolm
Published: January 2021

This paper presents evidence of a large, persistent decline in establishment-level workplace injury rates after private equity (PE) buyouts of publicly traded U.S. firms. We find that firms experience fewer OSHA safety violations after buyouts and that a larger decline in injury rates is associated with an increased probability of exit via IPO. Employment reductions after buyouts are concentrated in relatively low-injury-risk establishments. Overall, our results suggest that buyouts improve workplace safety and that PE acquirers benefit from this improvement. We explore possible causes of these changes through interviews with executives of companies acquired in buyouts and through cross-sectional analysis.
Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus
Authors: Song Qin , Lei Yao , Shao Li , Li Weiyang , Kong Qingsheng , Lin Zhiming , Qin Xiao , Wei Wei , Hou Fei , Li Jian , Guo Xianghua , Mao Yujing , Cao Yujie , Liu Zhongyi , Zheng Lichuan , Liang Rui , Jiang Yuping , Liu Yan , Zhang Lili , Yang Jing , Lau Yu Lung , Zhang Yan , Ban Bo , Wang Yong-Fei , Yang Wanling
Published: January 2021

Objectives

To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility.

Methods

A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9310 SLE cases and 17 464 controls) were included in this study.

Results

Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE [rs2362475; odds ratio (OR) = 0.85, P=2.00E-09]. KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, P =0.58), with evidence of heterogeneity (P=0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR= 0.89, P=4.08E-08) and DOT1L (rs4807205; OR= 1.12, P=8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance.

Conclusions

We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically.
Temporal and Spatial Genetic Population Structure of Cryphonectria parasitica and Its Associated Hypovirus Across an Invasive Range of Chestnut Blight in Europe
Authors: Ježić Marin , Schwarz Janine Melanie , Prospero Simone , Sotirovski Kiril , Risteski Mihajlo , Ćurković-Perica Mirna , Nuskern Lucija , Krstin Ljiljana , Katanić Zorana , Maleničić Ema , Poljak Igor , Idžojtić Marilena , Rigling Daniel
Published: January 2021

Chestnut blight has spread throughout Europe since the introduction of its causal agent, Cryphonectria parasitica, >70 years ago. In our study, we analyzed the diversity of vegetative compatibility (vc) and microsatellite genotypes of C. parasitica, as well as sequence diversity of Cryphonectria hypovirus 1 (CHV1) in six populations from Switzerland, Croatia, and North Macedonia. Resampling of local populations that were already investigated more than a decade ago allowed us to analyze the spatial and temporal population structure across an invasive range of the pathogen in Europe. Regardless of which genetic marker was used, the >60-year-old Swiss and Croatian populations had high population diversity, whereas more recent North Macedonian populations were mostly clonal. These diversity differences between the investigated populations remained stable over time. A high diversity of CHV1 was observed in all three countries, with North Macedonian strains forming a separate cluster from strains obtained in other countries. No correlation between vc diversity and CHV1 prevalence was observed, suggesting a well-established and maintained natural hypovirulence in all countries, further corroborated by an observed increase in genetic diversity of Croatian C. parasitica populations over time, without collapse of CHV1 prevalence.
Diverse mosquito-specific flaviviruses in the Bolivian Amazon basin
Authors: Orba Yasuko , Matsuno Keita , Nakao Ryo , Kryukov Kirill , Saito Yumi , Kawamori Fumihiko , Loza Vega Ariel , Watanabe Tokiko , Maemura Tadashi , Sasaki Michihito , Hall William W. , Hall Roy A. , Pereira Juan Antonio , Nakagawa So , Sawa Hirofumi
Published: January 2021

The genusFlavivirusincludes a range of mosquito-specific viruses in addition to well-known medically important arboviruses. Isolation and comprehensive genomic analyses of viruses in mosquitoes collected in Bolivia resulted in the identification of three novel flavivirus species. Psorophora flavivirus (PSFV) was isolated fromPsorophora albigenu. The coding sequence of the PSFV polyprotein shares 60 % identity with that of theAedes-associated lineage II insect-specific flavivirus (ISF), Marisma virus. Isolated PSFV replicates in bothAedes albopictus- andAedes aegypti-derived cells, but not in mammalian Vero or BHK-21 cell lines. Two other flaviviruses, Ochlerotatus scapularis flavivirus (OSFV) and Mansonia flavivirus (MAFV), which were identified fromOchlerotatus scapularisandMansonia titillans,respectively, group with the classical lineage I ISFs. The protein coding sequences of these viruses share only 60 and 40 % identity with the most closely related of known lineage I ISFs, including Xishuangbanna aedes flavivirus and Sabethes flavivirus, respectively. Phylogenetic analysis suggests that MAFV is clearly distinct from the groups of the current knownCulicinae-associated lineage I ISFs. Interestingly, the predicted amino acid sequence of the MAFV capsid protein is approximately two times longer than that of any of the other known flaviviruses. Our results indicate that flaviviruses with distinct features can be found at the edge of the Bolivian Amazon basin at sites that are also home to dense populations of human-biting mosquitoes.
Assessment of inactivation procedures for SARS-CoV-2
Authors: Auerswald Heidi , Yann Sokhoun , Dul Sokha , In Saraden , Dussart Philippe , Martin Nicholas J. , Karlsson Erik A. , Garcia-Rivera Jose A.
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), presents a challenge to laboratorians and healthcare workers around the world. Handling of biological samples from individuals infected with the SARS-CoV-2 virus requires strict biosafety measures. Within the laboratory, non-propagative work with samples containing the virus requires, at minimum, Biosafety Level-2 (BSL-2) techniques and facilities. Therefore, handling of SARS-CoV-2 samples remains a major concern in areas and conditions where biosafety for specimen handling is difficult to maintain, such as in rural laboratories or austere field testing sites. Inactivation through physical or chemical means can reduce the risk of handling live virus and increase testing ability especially in low-resource settings due to easier and faster sample processing. Herein we assess several chemical and physical inactivation techniques employed against SARS-CoV-2 isolates from Cambodia. This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat-treatment (56 and 98 °C) methods tested completely inactivated viral loads of up to 5 log10.
Chios mastic gum inhibits influenza A virus replication and viral pathogenicity
Authors: Kim Dong-In , Cho Yong-Bin , Lim Younghyun , Hong So-Hee , Hahm Bumsuk , Lee Sang-Myeong , Kang Se Chan , Seo Young-Jin
Published: January 2021

Chios mastic gum (CMG), a resin of the mastic tree (Pistacia lentiscus var. chia), has been used to treat multiple disorders caused by gastrointestinal malfunctions and bacterial infections for more than 2500 years. However, little is known about CMG’s antiviral activity. CMG is known to influence multiple cellular processes such as cell proliferation, differentiation and apoptosis. As virus replication is largely dependent on the host cellular metabolism, it is conceivable that CMG regulates virus infectivity. Therefore, in this study, we evaluated CMG’s potential as an antiviral drug to treat influenza A virus (IAV) infection. CMG treatment dramatically reduced the cytopathogenic effect and production of RNAs, proteins and infectious particles of IAV. Interestingly, CMG interfered with the early stage of the virus life cycle after viral attachment. Importantly, the administration of CMG greatly ameliorated morbidity and mortality in IAV-infected mice. The results suggest that CMG displays a potent anti-IAV activity by blocking the early stage of viral replication. Thus, mastic gum could be exploited as a novel therapeutic agent against IAV infection.
A high prevalence of bla
OXA-48 in Klebsiella (Raoultella) ornithinolytica and related species in hospital wastewater in South West England
Authors: Gibbon Marjorie J. , Couto Natacha , David Sophia , Barden Ruth , Standerwick Richard , Jagadeesan Kishore , Birkwood Hollie , Dulyayangkul Punyawee , Avison Matthew B. , Kannan Andrew , Kibbey Dan , Craft Tim , Habib Samia , Thorpe Harry A. , Corander Jukka , Kasprzyk-Hordern Barbara , Feil Edward J.
Published: January 2021

Klebsiella

species occupy a wide range of environmental and animal niches, and occasionally cause opportunistic infections that are resistant to multiple antibiotics. In particular,

Klebsiella pneumoniae

(Kpne) has gained notoriety as a major nosocomial pathogen, due principally to the rise in non-susceptibility to carbapenems and other beta-lactam antibiotics. Whilst it has been proposed that the urban water cycle facilitates transmission of pathogens between clinical settings and the environment, the level of risk posed by resistant

Klebsiella

strains in hospital wastewater remains unclear. We used whole genome sequencing (WGS) to compare

Klebsiella

species in contemporaneous samples of wastewater from an English hospital and influent to the associated wastewater treatment plant (WWTP). As we aimed to characterize representative samples of

Klebsiella

communities, we did not actively select for antibiotic resistance (other than for ampicillin), nor for specific

Klebsiella

species. Two species, Kpne and K. (

Raoultella

) ornithinolytica (Korn), were of equal dominance in the hospital wastewater, and four other

Klebsiella

species were present in low abundance in this sample. In contrast, despite being the species most closely associated with healthcare settings, Kpne was the dominant species within the WWTP influent. In total, 29 % of all isolates harboured the bla
OXA-48 gene on a pOXA-48-like plasmid, and these isolates were almost exclusively recovered from the hospital wastewater. This gene was far more common in Korn (68 % of isolates) than in Kpne (3.4 % of isolates). In general plasmid-borne, but not chromosomal, resistance genes were significantly enriched in the hospital wastewater sample. These data implicate hospital wastewater as an important reservoir for antibiotic-resistant

Klebsiella

, and point to an unsuspected role of species within the

Raoultella

group in the maintenance and dissemination of plasmid-borne bla
OXA-48. This article contains data hosted by Microreact.
An epigenetic switch regulates the ontogeny of AXL-positive/EGFR-TKI resistant cells by modulating miR-335 expression
Authors: Pal Debjani , Tepes Polona Safaric , Lindsted Trine , Ibarra Ingrid , Lujambio Amaja , Sabinina Vilma Jimenez , Senturk Serif , Miller Madison , Korimerla Navya , Huang Jiahao , Glassman Larry , Lee Paul , Zeltsman David , Hyman Kevin , Esposito Michael , Hannon Gregory J. , Sordella Raffaella
Published: January 2021

Lung cancer remains the leading cause of cancer-related mortality worldwide, despite current advancements in research and therapeutics. Many patients diagnosed with lung cancer will develop resistance to chemotherapeutic agents. In the context of non-small cell lung cancers (NSCLC) harboring EGFR oncogenic mutations, augmented levels of AXL and GAS6 have been found to drive Erlotinib resistance in certain tumors with mesenchymal-like features. By studying the ontogeny of AXL-positive cells, we have identified a novel non-genetic mechanism of drug resistance based on cell-state transition. We demonstrate that AXL-positive cells are already present as a sub-population of cancer cells in Erlotinib-naïve tumors and tumor-derived cell lines, and that the expression of AXL is regulated through a stochastic mechanism centered on the epigenetic regulation of miR-335. The existence of a cell-intrinsic program through which AXL-positive/Erlotinib-resistant cells emerge infers the need of treating tumors harboring EGFR-oncogenic mutations upfront with combinatorial treatments targeting both AXL-negative and AXL-positive cancer cells.
Quantitative proteomics reveals extensive lysine ubiquitination in the Arabidopsis root proteome and uncovers novel transcription factor stability states
Authors: Song Gaoyuan , Olatunji Damilola , Montes Christian , Clark Natalie M , Pu Yunting , Kelley Dior R , Walley Justin W
Published: January 2021

Protein activity, abundance, and stability can be regulated by posttranslational modification including ubiquitination. Ubiquitination is conserved among eukaryotes and plays a central role in modulating cellular function and yet we lack comprehensive catalogs of proteins that are modified by ubiquitin in plants. In this study, we describe an antibody-based approach to enrich peptides containing the di-glycine (diGly) remnant of ubiquitin and coupled that with isobaric labeling to enable quantification, from up to 16-multiplexed samples, for plant tissues. Collectively, we identified 7,130 diGly-modified lysine residues sites arising from 3,178 proteins in Arabidopsis primary roots. These data include ubiquitin proteasome dependent ubiquitination events as well as ubiquitination events associated with auxin treatment. Gene Ontology analysis indicated that ubiquitinated proteins are associated with numerous biological processes including hormone signaling, plant defense, protein homeostasis, and root morphogenesis. We determined the ubiquitinated lysine residues that directly regulate the stability of the transcription factors CRYPTOCHROME-INTERACTING BASIC-HELIX-LOOP-HELIX 1 (CIB1), CIB1 LIKE PROTEIN 2 (CIL2), and SENSITIVE TO PROTON RHIZOTOXICITY (STOP1) using site directed mutagenesis andin vivodegradation assays. These comprehensive site-level ubiquitinome profiles provide a wealth of data for future studies related to modulation of biological processes mediated by this posttranslational modification in plants.
Crystal structure and Hirshfeld surface analysis of ethyl (4R,4aS)-2-methyl-5,8-dioxo-6-phenyl-4a,5,6,7,7a,8-hexahydro-4H-furo[2,3-f]isoindole-4-carboxylate
Authors: Zaytsev Vladimir P. , Chervyakova Lala V. , Sorokina Elena A. , Vasilyev Kirill A. , Çelikesir Sevim Türktekin , Akkurt Mehmet , Bhattarai Ajaya
Published: January 2021

In the title compound, C20H19NO5, the central six-membered ring has a slightly distorted half-chair conformation, with puckering parameters of Q
T = 0.3387 (11) Å, θ = 49.11 (19)° and φ = 167.3 (2)°. The conformation of the fused pyrrolidine ring is that of an envelope. Molecules are connected by intermolecular C—H...O hydrogen bonds, C—H...π interactions and π–π stacking interactions [centroid-to-centroid distance = 3.9536 (11) Å, with a slippage of 2.047 Å], forming a three-dimensional network. The most important contributions to the surface contacts are from H...H (46.3%), O...H/H...O (31.5%) and C...H/H...C (17.3%) interactions, as concluded from a Hirshfeld surface analysis.
Two coordination compounds of SnCl2 with 4-methylpyridine N-oxide
Authors: Henkel Felix , Reuter Hans
Published: January 2021

In the solid-state structures of catena-poly[[dichloridotin(II)]-μ2-(4-methylpyridine N-oxide)-κ2
O:O], [SnCl2(C6H7NO)]
n
, 1, and dichloridobis(4-methylpyridine N-oxide-κO)tin(II), [SnCl2(C6H7NO)2], 2, the bivalent tin atoms reveal a seesaw coordination with both chlorine atoms in equatorial and the Lewis base molecules in axial positions. While the Sn—Cl distances are almost identical, the Sn—O distances vary significantly as a result of the different bonding modes (μ2 for 1, μ1 for 2) of the 4-methylpyridin-N-oxide molecules, giving rise to a one-dimensional coordination polymer for the 1:1 adduct, 1, and a molecular structure for the 1:2 adduct, 2. The different coordination modes also influence the bonding parameters within the almost planar ligand molecules, mostly expressed in N—O-bond lengthening and endocyclic bond-angle widening at the nitrogen atoms. Additional supramolecular features are found in the crystal structure of 2 as two adjacent molecules form dimers via additional, weak O...Sn interactions.
Fertility care quality and experiential relationship marketing: a case study of mainland Chinese fertility tourists to Malaysia
Authors: Wu Hung-Che , Chen Xiaolian , Chang Ya-Yuan
Published: January 2021

Purpose

This study examines the relationship between the dimensions of fertility care quality and the dimensions of experiential relationship marketing in fertility tourism.

Design/methodology/approach

The data used in this study were based on a sample of 532 Mainland Chinese fertility tourists who received fertility care services in eight private fertility clinics in four Malaysian states, indicating that the proposed model fitted the data.

Findings

Findings show that the dimensions of fertility care quality (professional skills, patient orientation and physical comfort) and experiential value positively influence experiential satisfaction. Additionally, experiential trust is positively influenced by both experiential satisfaction and experiential value. Also, experiential commitment is positively influenced by experiential satisfaction, experiential trust and experiential value.

Practical implications

Fertility tourism service providers could focus on refining the dimensions of fertility care quality to improve experiential relationship marketing.

Originality/value

This paper provides the data that result in a better understanding of the relationship between the dimensions of fertility care quality and the dimensions of experiential relationship marketing in fertility tourism.
The effect of nWOM firestorms on South African retail banking
Authors: Lappeman James , Clark Robyn , Evans Jordan , Sierra-Rubia Lara
Published: January 2021

Purpose

This study analysed the effect of online negative word-of-mouth (nWOM) firestorms in the retail banking sector. By understanding negative sentiment and sentiment recovery across an entire retail banking sector, the research exposed a unique view of banking in South Africa.

Design/methodology/approach

The study made use of both a sentiment and topic analysis of over 1.7 million social media posts in South Africa. The methodology made use of both NLP and human validation techniques to measure changes in social media sentiment during online firestorms. This measurement included each of South Africa's major retail banks over a twelve month period.

Findings

From the analysis, key trigger characteristics for these firestorms (product failures, service failures, social failures and communication failures) were categorised. In addition, the average duration of a firestorm was calculated and factors that impact sentiment recovery were explored.

Originality/value

The study was located in South Africa and, unlike firm level studies, researched nWOM for the whole retail banking sector. A theoretical footprint depicting the typical anatomy of a firestorm was derived in order to aid stakeholders to be more vigilant and better equipped to provide correct intervention in such times of crisis.
Fluffy PR and ‘comms girls’: banter, social interactions and the office culture in public relations in England
Authors: Topić Martina
Published: January 2021

Purpose

The purpose of this paper was to explore social interactions, banter and the office culture in the public relations (PR) industry in England with the use of the difference approach and Bourdieu’s habitus theory. The paper explores whether PR organisations act as masculine habitus.

Design/methodology/approach

Qualitative interviews were conducted with 26 women practitioners, and thematic analysis was used to analyse data. Women were asked questions on social interactions, banter and the office culture, as well as questions on exclusion, from business decisions and having to work harder to succeed.

Findings

Findings show that two main themes dominate in responses from interviewees, “de-patriarchalisation” of PR with no personal appearance requirements and no business exclusions because of gender, and “gendered organisations” where interviewees reported dismissive stereotypes of women who work in PR, networking as a job requirement and differences between male-dominated and female-dominated offices, which includes differences between social interactions and banter among men and women.

Practical implications

Results indicate that women feel there are differences in social interactions and banter between men and women. Interviewees also report masculine domination as and harmful stereotypes of public PR professionals, most of whom are women. Organisations who have PR departments, as well as those who hire PR agencies to do the work externally, should design policies on the office culture to ensure equality and respectful work environment for everyone.

Social implications

In line with the difference approach, women report differences in social interactions and banter between them and men, thus signalling that social differences influence the office culture and work interactions, which tend to be gendered. Findings also indicate that organisations are functioning as a masculine world where women struggle to fit in and obtain recognition. Consciousness-raising is needed in the industry because many women do not recognise oppression in the form of social interactions, and its effect on the position of women or the fact that the most feminized industry is being trivialised by the men on top.

Originality/value

To the best of the author’s knowledge, this is the first paper analysing interactions in PR offices using the difference approach and Bourdieu’s habitus theory.