bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Duloxetine in Patients with Central Post-stroke Pain: A Randomized Double Blind Placebo Controlled Trial
Authors: Mahesh Bandari , Singh Varun Kumar , Pathak Abhishek , Kumar Anand , Mishra Vijaya Nath , Joshi Deepika , Chaurasia Rameshwar Nath
Published: November 2022

Objective

Central post-stroke pain (CPSP) refers to neuropathic pain in areas of the body corresponding to stroke lesions. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is safe and effective against neuropathic pain. In this randomized double-blind placebo-controlled study, we studied the effect of duloxetine in CPSP patients.

Methods

Consecutive patients satisfying the inclusion criteria were enrolled in the study and were randomized in a simple 1:1 randomization to duloxetine and placebo groups. Baseline demographic, clinical and imaging data were obtained. Prespecified primary outcome was comparison of change in pain intensity from baseline to 4 weeks, as assessed on Numeric Rating Scale (NRS) in both groups. Prespecified secondary outcomes were comparison of change in average pain severity from baseline to 4 weeks as measured on Short-form McGill Pain Questionnaire-2 (SFMPQ-2) score and Pain Disability Index (PDI) score and comparison of Patient Global Impression of Change (PGIC) score at the end of 4 weeks of treatment in both groups. Duloxetine at doses of 30 mg and similarly appearing placebo tablets were given and the dose was doubled if there was no response at the end of 2 weeks. Response to treatment was defined as ≥2 points reduction of NRS pain score.

Results

In total, 82 patients were enrolled in the study, 41 in each group. There was a significant difference in reduction in NRS score between duloxetine and placebo group from baseline (6.51 ± 1.03 vs 6.37 ± 1.41) to 4 weeks (3.02 ± 1.70 vs 4.40 ± 1.77, P = .02 for difference in reduction between groups). SFMPQ-2 score (P = .032) and Pain Disability Index score (P = .005) also differ significantly from baseline to 4 weeks between the two groups. PGIC score at the end of 4 weeks was significantly different between the two groups (5.15 ± 1.54 vs 3.89 ± 1.51; P < .001). Responder rate (defined as % of patients with ≥ 2 points reduction on NRS pain score from baseline to end of 4 weeks), on post hoc analysis was found to be significantly higher in duloxetine group (80.5%) than placebo group (43.9%) (P = .042).

Conclusions

Duloxetine can be an effective treatment option for patients with moderate to severe central post-stroke pain.
De-policing, police stops, and crime
Authors: Powell Zachary A
Published: November 2022

Contemporary discussions on policing focus on the impact of intense external scrutiny on proactive policing practices. Some commentators suggest negative feedback directed at law enforcement inhibits police willingness to engage in proactive police practices. This effect, known as ‘de-policing’, endangers communities due to officer disengagement in crime prevention techniques. To examine this effect, previous research relies on crime data to examine de-policing; few studies explore how officer-initiated actions, such as a stop, shift in the wake of a de-policing effect. Using data from the Stanford Open Policing Project, this paper examines how officer-initiated behaviour (vehicle and pedestrian stops) changes after a negative public scrutiny shock (in this case, the shooting of Michael Brown). Further, the study examines how crime rates changed after Brown’s death. The findings of this paper suggest police proactivity declined and crime increased after Michael Brown’s death in Ferguson, Missouri. Policy implications, future research avenues, and theoretical enhancements to de-policing are discussed.
Pistachio Male Inflorescences as an Alternative Substrate for the Application of Atoxigenic Strains of Aspergillus flavus
Authors: Garcia-Lopez M. Teresa , Gordon Ana , Puckett Ryan D. , Chevailler Coralie , Doster Mark , Michailides Themis J. , Moral Juan
Published: November 2022

Aflatoxins are carcinogens mainly produced by Aspergillus flavus and A. parasiticus in susceptible crops, including pistachio. The primary inoculum sources of these pathogens are plant debris in the orchard soils. In Californian fields, one approach to controlling aflatoxin contamination is based on releasing the atoxigenic strain of A. flavus AF36 in inoculated (coated) sorghum grains (AF36 Prevail). However, this control method can fail due to poor sporulation of the AF36 strain or sorghum grain losses due to predation. In 2008 and 2018, we showed that toxigenic and atoxigenic isolates of Aspergillus spp. frequently colonized fallen inflorescences of male pistachio trees. Under controlled conditions, strain AF36 profusely colonized pistachio male inflorescences when humidity was higher than 90%. However, there were significant differences between types of inflorescence (aerial > fallen). In 2016, we considerably (P = 0.015) increased the population of AF36 on the canopies of trees when fallen inflorescences were inoculated with AF36, compared with untreated trees. In 2017 and 2018, these differences were not detected (P > 0.05) due to cross-contamination of strain AF36 between seasons and neighboring plots. In any case, the density of AF36 spores on the canopy of the inflorescence-treated trees was similar (P > 0.05) to that on trees treated with the commercial product. Here, we present a new method for applying strain AF36 based on using a natural, abundant, and uniformly distributed substrate in pistachio fields, and we discuss how it can be improved. Furthermore, our results indicate that, in pistachio orchards where biocontrol practices are not conducted, eliminating this important source of toxigenic Aspergillus inoculum is recommended.
Phytophthora capsici, 100 Years Later: Research Mile Markers from 1922 to 2022
Authors: Sanogo Soum , Lamour Kurt , Kousik Chandrasekar S. , Lozada Dennis N. , Parada-Rojas Camilo H. , Quesada-Ocampo Lina M. , Wyenandt Christian A. , Babadoost Mohammad , Hausbeck Mary K. , Hansen Zachariah , Ali Emran , McGrath Margaret T. , Hu Jiahuai , Crosby Kevin , Miller Sally A.
Published: November 2022

In 1922, Phytophthora capsici was described by Leon Hatching Leonian as a new pathogen infecting pepper ( Capsicum annuum), with disease symptoms of root rot, stem and fruit blight, seed rot, and plant wilting and death. Extensive research has been conducted on P. capsici over the last 100 years. This review succinctly describes the salient mile markers of research on P. capsici with current perspectives on the pathogen's distribution, economic importance, epidemiology, genetics and genomics, fungicide resistance, host susceptibility, pathogenicity mechanisms, and management.
Running ahead of evolution - AI based simulation for predicting future high-risk SARS-CoV-2 variants
Authors: Chen Jie , Nie Zhiwei , Wang Yu , Wang Kai , Xu Fan , Hu Zhiheng , Zheng Bing , Wang Zhennan , Song Guoli , Zhang Jingyi , Fu Jie , Huang Xiansong , Wang Zhongqi , Ren Zhixiang , Wang Qiankun , Li Daixi , Wei Dongqing , Zhou Bin , Yang Chao , Tian Yonghong , Gao Wen
Published: November 2022

The never-ending emergence of SARS-CoV-2 variations of concern (VOCs) has challenged the whole world for pandemic control. In order to develop effective drugs and vaccines, one needs to efficiently simulate SARS-CoV-2 spike receptor binding domain (RBD) mutations and identify high-risk variants. We pretrain a large protein language model with approximately 408 million protein sequences and construct a high-throughput screening for the prediction of binding affinity and antibody escape. As the first work on SARS-CoV-2 RBD mutation simulation, we successfully identify mutations in the RBD regions of 5 VOCs and can screen millions of potential variants in seconds. Our workflow scales to 4096 NPUs with 96.5% scalability and 493.9× speedup in mixed precision computing, while achieving a peak performance of 366.8 PFLOPS (reaching 34.9% theoretical peak) on Pengcheng Cloudbrain-II. Our method paves the way for simulating coronavirus evolution in order to prepare for a future pandemic that will inevitably take place. Our models are released athttps://github.com/ZhiweiNiepku/SARS-CoV-2_mutation_simulationto facilitate future related work.

Justification

We develop a novel multi-constraint variation prediction framework to simulate SARS-CoV-2 RBD mutations, reaching a peak performance of 366.8 PFLOPS with 96.5% scalability and achieving 493.9× speedup. Our method facilitates the prediction and prioritization of future high-risk variants for the early deployment of drugs and vaccines.

Performance attributes

Overview of the problem

Coronavirus Disease 2019 (COVID-19) has spread rapidly to more than 200 countries or regions since December 2019. Due to its high infectivity, there have been over 645 million confirmed cases, including approximately 6.6 million deaths, reported by the World Health Organization (WHO) as of December 20221. In addition to being a serious threat to human health, COVID-19 has had a catastrophic impact on the global economy.
Mammary epithelium permeability during established lactation: Associations with cytokine levels in human milk
Authors: Kivlighan Katie T. , Schneider Sallie S. , Browne Eva P. , Pentecost Brian T. , Anderton Douglas L. , Arcaro Kathleen F.
Published: November 2022

Objective

The cytokine profile of human milk may be a key indicator of mammary gland health and has been linked to infant nutrition, growth, and immune system development. The current study examines the extent to which mammary epithelium permeability (MEP) is associated with cytokine profiles during established lactation among a diverse group of US mothers.

Methods

Participants were drawn from a previous study of human milk cytokines. The present analysis includes 162 participants (98 Black women, 64 White women) with infants ranging from 1-18 months of age. Levels of cytokines were determined previously. Here we measure milk sodium (Na) and potassium (K) levels with ion-selective probes.Elevated MEPwas defined and evaluated by both Na levels > 10 mmol/L and Na/K ratios greater than 0.6. Bivariate associations, principal components analysis, and multivariable logistic regression models were used to examine associations between maternal-infant characteristics, twelve cytokines (IL-6, IL8, TNFα, IL-1β, FASL, VEGFD, FLT1, bFGF, PLGF, EGF, leptin, adiponectin), and elevated MEP.

Results

Elevated MEP was observed in 12% and 15% of milk samples as defined by Na and Na/K cutoffs, respectively. The odds of experiencing elevated MEP (defined by Na > 10 mmol/L) were higher among Black participants and declined with older infant age. All cytokines, except leptin, were positively correlated with either Na or the Na/K ratio. A pro-inflammatory factor (IL-6, IL-8, TNFα, IL-1β, EGF) was more strongly correlated with the Na/K ratio, while a tissue remodeling factor (FASL, VEGFD, FLT1, bFGF, PLGF, adiponectin) was more strongly correlated with Na. The pro-inflammatory and tissue remodeling factors each contributed uniquely to raising the odds of elevated MEP as defined by either Na or the Na/K ratio.

Conclusion

This exploratory analysis of MEP and cytokine levels during established lactation indicates that elevated MEP among US women may be more common than previously appreciated and that Black women may have increased odds of experiencing elevated MEP based on current definitions. Research aimed at understanding the role of MEP in mammary gland health or infant growth and development should be prioritized.
A New Variant of Hepatitis A Virus Causing Transient Liver Enzyme Elevations in Mauritius-origin Laboratory-housed Cynomolgus macaques
Authors: Mecklenburg Lars , Ducore Rebecca , Boyle Molly , Newell Andrew , Boone Laura , Luft Joerg , Romeike Annette , Haverkamp Ann-Kathrin , Mansfield Keith , Baczenas JJ , Minor Nick , O’Connor Shelby L. , O’Connor David H.
Published: November 2022

Hepatitis A virus (HAV) infects humans and non-human primates causing an acute self-limited illness. Three HAV genotypes have been described for humans and three genotypes have been described for non-human primates. We observed transiently elevated liver enzymes in Mauritius-origin laboratory-housed macaques in Germany and were not able to demonstrate HAV by serology and PCR. Using deep sequencing, we have identified a new HAV genotype with 86% nucleotide sequence homology to HAV genotype IV capsid proteins and approximately 80% nucleotide homology to other HAV genotypes. In situ hybridization indicates persistence in the biliary epithelium up to 3 months after liver enzymes were elevated. Vaccination using a commercial vaccine against human HAV prevented reoccurrence of liver enzyme elevations. Since available assays for HAV did not detect this new variant, knowledge of its existence may ameliorate potential significant epidemiological and research implications in laboratories globally.

Article Summary Line

A new genotype of hepatitis A virus, that was not identifiable by available diagnostic assays, caused liver enzyme elevations in laboratory-housed Mauritius-origin Cynomolgus macaques.
Structural dynamics of E6AP E3 ligase HECT domain and involvement of flexible hinge loop in ubiquitin chain synthesis mechanism
Authors: Takeda Kazusa , Muro Ikumi , Kobayashi Fuminori , Flechsig Holger , Kodera Noriyuki , Ando Toshio , Konno Hiroki
Published: November 2022

Ubiquitin (Ub) ligases E3 are an important factor in selecting target proteins for ubiquitination and determining the type of polyubiquitin chains on the target proteins. In the HECT (homologous to E6AP C-terminus)-type E3 ligases, the HECT domain is composed of an N-lobe containing the E2-binding site and a C-lobe containing the catalytic Cys residue that forms a thioester bond with Ub. These two lobes are connected by a flexible hinge loop. The large conformational rearrangement of the HECT domain via the flexible hinge loop is essential for HECT-type E3-mediated Ub transfer from E2 to a target protein. However, detailed insights into the structural dynamics of this type of E3 ligases remain unclear. Here, we provide the first direct demonstration of structural dynamics of the E6AP HECT domain using high-speed atomic force microscopy. We also investigated structural dynamics of hinge loop flexibility restricted HECT domain, and we found that flexibility of the E6AP hinge loop has a great impact not only on its structural dynamics but also on the formation of free Ub chains mediated by E3-E3 interactions.
Hungry for compliments? Ghrelin is not associated with neural responses to social rewards or their pleasantness
Authors: Sailer Uta , Riva Federica , Lieberz Jana , Campbell-Meiklejohn Daniel , Scheele Dirk , Pfabigan Daniela M.
Published: November 2022

The stomach-derived hormone ghrelin motivates food search and stimulates food consumption, with highest plasma concentrations before a meal and lowest shortly after. However, ghrelin also appears to affect the value of non-food rewards such as interaction with rat conspecifics, and monetary rewards in humans. The present pre-registered study investigated how nutritional state and ghrelin concentrations are related to the subjective and neural responses to social and non-social rewards.

In a cross-over feed-and-fast design, 67 healthy volunteers (20 women) underwent functional magnetic resonance imaging (fMRI) in a hungry state and after a meal with repeated plasma ghrelin measurements. In task 1, participants received social rewards in the form of approving expert feedback, or non-social computer reward. In task 2, participants rated the pleasantness of compliments and neutral statements.

Nutritional state and ghrelin concentrations did not affect the response to social reward in task 1. In contrast, ventromedial prefrontal cortical activation to non-social rewards was reduced when the meal strongly suppressed ghrelin. In task 2, fasting increased activation in the right ventral striatum during all statements, but ghrelin concentrations were neither associated with brain activation nor with experienced pleasantness. Complementary Bayesian analyses provided moderate evidence for a lack of correlation between ghrelin concentrations and behavioral and neural responses to social rewards, but moderate evidence for an association between ghrelin and non-social rewards.

This suggests that ghrelin’s influence may be restricted to non-social rewards. Social rewards implemented via social recognition and affirmation may be too abstract and complex to be susceptible to ghrelin’s influence. In contrast, the non-social reward was associated with the expectation of a material object that was handed out after the experiment. This may indicate that ghrelin might be involved in anticipatory rather than consummatory phases of reward.
Repurposing of the multiciliation gene regulatory network in fate specification of Cajal-Retzius neurons
Authors: Moreau Matthieu X , Saillour Yoann , Elorriaga Vicente , Bouloudi Benoît , Delberghe Elodie , Guerrero Tanya Deutsch , Ochandorena-Saa Amaia , Maeso-Alonso Laura , Marques Margarita M , Marin Maria C , Spassky Nathalie , Pierani Alessandra , Causeret Frédéric
Published: November 2022

Cajal-Retzius (CR) neurons are key players of cortical development that display a very unique transcriptomic identity. However, little is known about the mechanisms involved in their fate specification. Here we use scRNAseq to reconstruct the differentiation trajectory of hem-derived CR cells (CRs) and unravel the transient expression of a complete gene module previously known to control the cellular process of multiciliogenesis. However, we find that CRs do not undergo centriole amplification or multiciliation. We show that upon genetic disruption ofGmnc, the master regulator of the multiciliation cascade, CRs are initially produced but fail to reach their normal identity and lean towards an aberrant fate resulting in their massive apoptosis. We further dissect the contribution of multiciliation effector genes and identifyTrp73as a key determinant. Finally, we usein uteroelectroporation to demonstrate that the intrinsic competence of hem progenitors as well as the heterochronic expression ofGmncprevent centriole amplification in the CR lineage. Our work exemplifies how the co-option of a complete gene module, repurposed to control a completely distinct process, may contribute to the emergence of novel cell identities.
Neuroprotective potential of anAyurvediccompound “Ras-Sindoor” onDrosophila melanogastermodel of Parkinson’s disease
Authors: Narwal Sonia , Rai Arushi , Iyer Shreyas , Tare Kirti , Tare Meghana
Published: November 2022

Parkinson’s Disease (PD) is the second most common neurodegenerative disease affecting 1-2% of the global population with no cure to date. PD is characterized by accumulation of Lewy Bodies (LBs), which are caused due to aggregation of incorrectly folded α-Synuclein, (SNCA). Another form of PD manifestation is characterized by loss of function ofparkin, which encodes an E3 ubiquitin ligase. Despite extensive research, the cause for onset and progression of PD remains unknown and current therapeutics mainly help manage the disease. An alternative line of treatment can be useful.

In this study, we have employed two different genetic models ofDrosophilato screen forAyurvediccompounds and found anAyurvedicmercury based organo-metallic drug Ras-Sindoor has neuroprotective function. Our data indicate that characteristic locomotory dysfunction phenotype of PD is restored upon administration of the compound. Interestingly, RS fed flies also exhibit reduced transcript levels of initiator caspasedronc, which possibly prevents cell death in dopaminergic neurons. Additionally, RS fed PD model flies exhibit an enhanced life span. Our studies emphasize beneficial use of traditionalAyurvediccompounds as a holistic cure for PD like multifactorial diseases.
Structural basis for Fc receptor recognition of immunoglobulin M
Authors: Chen Qu , Menon Rajesh , Tolar Pavel , Rosenthal Peter B.
Published: November 2022

FcμR is the IgM-specific Fc receptor involved in the survival and activation of B cells. Using cryo-EM, we reveal eight binding sites for the human FcμR Ig domain on the IgM pentamer, one of which overlaps with the receptor binding site for the transcytosis receptor pIgR, but a different mode of binding explains Ig isotype specificity. The complex explains engagement with polymeric serum IgM and the monomeric IgM B cell receptor.
Pyruvate-conjugation of PEGylated liposomes effectively enhances their uptake in retinal photoreceptors
Authors: Christensen Gustav , Chen Yiyi , Urimi Dileep , Schipper Nicolaas , Paquet-Durand François
Published: November 2022

Despite several promising candidates there is a paucity of drug treatments available for patients suffering from retinal diseases. An important reason for this is the lack of suitable delivery systems that can achieve sufficiently high drug uptake in the retina and its photoreceptors. A promising and versatile method for drug delivery to specific cell types involves liposomes, surface-coated with substrates for transporter proteins highly expressed on the target cell.

We identified strong lactate transporter (monocarboxylate transporter, MCT) expression on photoreceptors as a potential target for drug delivery vehicles. To evaluate MCT suitability for drug targeting, we used PEG-coated liposomes and conjugated these with different monocarboxylates, including lactate, pyruvate, and cysteine. Monocarboxylate-conjugated dye-loaded liposomes were tested on both human-derived cell-lines and murine retinal explant cultures. We found that liposomes conjugated with pyruvate consistently displayed higher cell uptake than unconjugated liposomes or liposomes conjugated with lactate or cysteine. Pharmacological inhibition of MCT1 and MCT2 reduced internalization, suggesting an MCT-mediated uptake mechanism. Pyruvate-conjugated liposomes loaded with the drug candidates CN03 and CN04 reduced photoreceptor cell death in murinerd1andrd10retinal degeneration models.

Overall, this study proposes pyruvate-conjugated liposomes as a vehicle for drug delivery specifically to photoreceptors. Notably, in retinal degeneration models, free drug solutions could not achieve the same therapeutic effect. Our study thus highlights pyruvate-conjugated liposomes as a promising system for drug delivery to retinal photoreceptors, as well as other neuronal cell types displaying high expression of MCT-type proteins.
Steroidogenesis and androgen/estrogen signaling pathways are altered inin vitromatured testicular tissues of prepubertal mice
Authors: Moutard Laura , Goudin Caroline , Jaeger Catherine , Duparc Céline , Louiset Estelle , Pereira Tony , Fraissinet François , Delessard Marion , Saulnier Justine , Rives-Feraille Aurélie , Delalande Christelle , Lefebvre Hervé , Rives Nathalie , Dumont Ludovic , Rondanino Christine
Published: November 2022

Children undergoing cancer treatments are at risk for impaired fertility. Cryopreserved prepubertal testicular biopsies could theoretically be later maturedin vitroto produce spermatozoa for assisted reproductive technology. A completein vitrospermatogenesis has been obtained from mouse prepubertal testicular tissue, although with low efficiency. Steroid hormones being essential for the progression of spermatogenesis, the aim of this study was to investigate steroidogenesis and steroid signaling in organotypic cultures. Histological, RT-qPCR, western blot analyses and steroid hormone measurements were performed onin vitrocultured mouse prepubertal testicular tissues and age-matchedin vivocontrols. Despite a conserved density of Leydig cells after 30 days of culture (D30), transcript levels of adult Leydig cell and steroidogenic markers were decreased. Increased amounts of progesterone and estradiol and reduced androstenedione levels were observed at D30, together with decreased transcript levels of steroid metabolizing genes and steroid target genes. hCG was insufficient to facilitate Leydig cell differentiation, restore steroidogenesis and improve sperm yield. In conclusion, this study reports the failure of adult Leydig cell development and altered steroid production and signaling in tissue cultures. The organotypic culture system will need to be further improved before it can be translated in clinics for childhood cancer survivors.
DNA bridging explains sub-diffusive movement of chromosomal loci in bacteria
Authors: Subramanian Srikanth , Murray Seán M.
Published: November 2022

Chromosomal loci in bacterial cells show a robust sub-diffusive scaling of the mean square displacement, MSD(τ) ∼τα, withα< 0.5. On the other hand, recent experiments have also shown that DNA-bridging Nucleoid Associated Proteins (NAPs) play an important role in chromosome organisation and compaction. Here, using polymer simulations we investigate the role of DNA bridging in determining the dynamics of chromosomal loci. We find that bridging compacts the polymer and reproduces the sub-diffusive elastic dynamics of monomers at timescales shorter than the bridge lifetime. Consistent with this prediction, we measure a higher exponent in a NAP mutant (ΔH-NS) compared to wild-typeE. coli. Furthermore, bridging can reproduce the rare but ubiquitous rapid movements of chromosomal loci that have been observed in experiments. In our model the scaling exponent defines a relationship between the abundance of bridges and their lifetime. Using this and the observed mobility of chromosomal loci, we predict a lower bound on the average bridge lifetime of around 5 seconds.

Significance Statement

The bacterial chromosome exhibits dynamics that cannot be explained by simple polymer models. In particular, the mean square displacement of individual chromosomal loci exhibits a power law scaling with an exponent less than that predicted by polymer theory. Here, we use polymer simulations and experiments to show that DNA bridging by Nucleoid Associated Proteins can explain these anomalous dynamics. Consistent with this, we show that in the absence of the bridging protein H-NS, the scaling exponent increases. Chromosomal loci also display rare rapid movements not explainable by polymer theory, even accounting for the viscoelasticity of the cytoplasm. Our simulations show that bridging can additionally explain this behaviour. Finally, we predict a lower bound on the average bridge lifetime within cells.
A stochastic compartmental model to simulate intra- and inter-species influenza transmission in an indoor swine farm
Authors: Kontowicz Eric , Moreno-Madriñan Max , Ragland Darryl , Beauvais Wendy
Published: November 2022

Common in swine production worldwide, influenza causes significant reductions in feed efficiency and potential transmission to the workforce. Swine vaccines are not universally used in swine production, partly due to their limited efficacy because of continuously evolving influenza viruses. We evaluated the effects of vaccination, quarantine of infected pigs, and changes to workforce routine (ensuring workers moved from younger pig batches to older pig batches). A Susceptible-Exposed-Infected-Recovered model was used to simulate stochastic influenza transmission during a single production cycle on an indoor hog growing unit containing 4000 pigs and two workers. The absence of control practices resulted in 3,958 pigs [1 – 3972] being infected and a 0.61 probability of workforce infection. Quarantine of infected pigs the same day they became infectious was the single effective control practice, reducing the number of infected pigs to 3 [1 - 3961] and the probability of workforce infection to 0.27. The second-best control practice was mass pig vaccination (80% effective vaccine), which reduced the number of infected pigs to 23.5 [1 - 635] and the probability of workforce infection to 0.07. The third-best control practice was changing the worker routine by starting with younger to older pig batches, which reduced the number of infected pigs to 997 [1 - 1984] and the probability of workforce infection (0.22). All other control practices, when considered alone, showed little improvement in reducing total infected pigs and the probability of workforce infection. Combining all control strategies reduced the total number of infected pigs to 1 or 2 with a minimal probability of workforce infection (0.03 – 0.01). These findings suggest that non-pharmaceutical interventions can reduce the impact of influenza on swine production and reduce the risk of interspecies transmission when efficacious vaccines are unavailable. Therefore, these results can help prevent the emergence of influenza strains with pandemic potential.
Finding Consensus miRNAs Silencing KLF1 Expression as A Promising Therapeutic Option of Sickle Cell Anemia
Authors: Al-Madhagi Haitham Ahmed
Published: November 2022

1

Sickle cell anemia (SCA) is the almost the severest hemoglobinopathy known with no cure till date. Patients with SCA has a shorter lifespan and suffer from painful crises and end-organ damages. The goal of this in silico work is to find the consensus miRNAs targeting KLF1 gene, responsible for HbF-to-HbA switching followed by generating the corresponding miRNA sponge for gene silencing purposes. 3 publicly available databases were searched, miRDB, miRWalk and TargetScan. Afterwards, the hybridization examination of the predicted miRNAs was evaluated. Finally, the design of miRNA sponge as a means to target miRNA was performed. In conclusion, hsa-miR-330-5p was the best miRNA targeting KLF1 gene in many aspects and its miRNA sponge sequence was provided.
Overexpression of PSR1 inChlamydomonas reinhardtiiinduces luxury phosphorus uptake
Authors: Slocombe Stephen P. , Zúñiga-Burgos Tatiana , Chu Lili , Mehrshahi Payam , Davey Matthew P. , Smith Alison G. , Camargo-Valero Miller Alonso , Baker Alison
Published: November 2022

Remediation using micro-algae offers an attractive solution to environmental phosphate (Pi) pollution. However, for maximum efficiency, pre-conditioning of algae to induce ‘luxury phosphorus (P) uptake’ is needed. Here we show that natural pre-conditioning can be mimicked through over-expression of a single gene, the global regulator PSR1 (Myb transcription factor: Phosphate Starvation Response 1), raising P levels to 8% dry cell weight from 2% in control. Complete removal of Pioccurred in log phase, unlike the control. This was associated with increases in PolyP granule size and uptake of Mg2+, the principal counterion. Hyper-accumulation of P depended on a feed-forward mechanism, where a small set of ‘Class I’ genes were activated despite abundant external Pilevels. This drove a reduction in external Pilevels, permitting more genes to be expressed (Class II), leading to more Pi-uptake. These discoveries enable a bio-circular approach of recycling nutrients from wastewater back to agriculture.

Teaser

Manipulating a single gene drove uptake of P and a Mg2+counter-ion for increased PolyP accumulation.
Anticipatory and evoked visual cortical dynamics of voluntary temporal attention
Authors: Denison Rachel N. , Tian Karen J. , Heeger David J. , Carrasco Marisa
Published: November 2022

We can often anticipate the precise moment when a stimulus will be relevant for our behavioral goals. Voluntary temporal attention, the prioritization of sensory information at task-relevant time points, enhances visual perception. However, the neural mechanisms of voluntary temporal attention have not been isolated from those of temporal expectation, which reflects timing predictability rather than relevance. Here we used time-resolved steady-state visual evoked responses (SSVER) to investigate how temporal attention dynamically modulates visual activity when temporal expectation is controlled. We recorded MEG while observers directed temporal attention to one of two sequential grating targets with predictable timing. Meanwhile, we used a co-localized SSVER probe to continuously track visual cortical modulations both before and after the target stimuli. In the pre-target period, the SSVER gradually ramped up as the targets approached, reflecting temporal expectation. Furthermore, we found a low-frequency modulation of the SSVER, which shifted approximately half a cycle in phase according to which target was attended. In the post-target period, temporal attention to the first target transiently modulated the SSVER shortly after target onset. Thus, temporal attention dynamically modulates visual cortical responses via both periodic pre-target and transient post-target mechanisms to prioritize sensory information at precise moments.
Predicting environmental stressor levels with machine learning: a comparison between amplicon sequencing, metagenomics, and total RNA sequencing based on taxonomically assigned data
Authors: Hempel Christopher A. , Buchner Dominik , Mack Leoni , Brasseur Marie V. , Tulpan Dan , Leese Florian , Steinke Dirk
Published: November 2022

Background

Microbes are increasingly (re)considered for environmental assessments because they are powerful indicators for the health of ecosystems. The complexity of microbial communities necessitates powerful novel tools to derive conclusions for environmental decision-makers, and machine learning is a promising option in that context. While amplicon sequencing is typically applied to assess microbial communities, metagenomics and total RNA sequencing (herein summarized as omics-based methods) can provide a more holistic picture of microbial biodiversity at sufficient sequencing depths. Despite this advantage, amplicon sequencing and omics-based methods have not yet been compared for taxonomy-based environmental assessments with machine learning. In this study, we applied 16S and ITS-2 sequencing, metagenomics, and total RNA sequencing to samples from a stream mesocosm experiment that investigated the impacts of two aquatic stressors, insecticide and increased fine sediment deposition, on stream biodiversity. We processed the data using similarity clustering and denoising (only applicable to amplicon sequencing) as well as multiple taxonomic levels, data types, feature selection, and machine learning algorithms and evaluated the stressor prediction performance of each generated model for a total of 1,536 evaluated combinations of taxonomic datasets and data-processing methods.

Results

Sequencing and data-processing methods had a substantial impact on stressor prediction. While omics-based methods detected much more taxa than amplicon sequencing, 16S sequencing outperformed all other sequencing methods in terms of stressor prediction based on the Matthews Correlation Coefficient. However, even the highest observed performance for 16S sequencing was still only moderate. Omics-based methods performed poorly overall, but this was likely due to insufficient sequencing depth. Data types had no impact on performance while feature selection significantly improved performance for omics-based methods but not for amplicon sequencing.

Conclusion

Amplicon sequencing might be a better candidate for machine-learning-based environmental stressor prediction than omics-based methods, but the latter require further research at higher sequencing depths to confirm this conclusion. More sampling could improve stressor prediction performance, and while this was not possible in the context of our study, thousands of sampling sites are monitored for routine environmental assessments, providing an ideal framework to further refine the approach for possible implementation in environmental diagnostics.
Robust identification of regulatory variants (eQTLs) using a differential expression framework developed for RNA-sequencing
Authors: Marrella Mackenzie A. , Biase Fernando H.
Published: November 2022

Background

A gap currently exists between genetic variants and the underlying cell and tissue biology of a trait, and expression quantitative trait loci (eQTL) studies provide important information to help close that gap. However, two concerns that arise with eQTL analyses using RNA-sequencing data are normalization of data across samples and the data not following a normal distribution. Multiple pipelines have been suggested to address this. For instance, the most recent analysis of the human and farm Genotype-Tissue Expression (GTEx) project proposes using trimmed means of M-values (TMM) to normalize the data followed by an inverse normal transformation.

Results

In this study, we reasoned that eQTL analysis could be carried out using the same framework used for differential gene expression (DGE), which uses a negative binomial model, a statistical test feasible for count data. Using the GTEx framework, we identified 38 significant eQTLs (P<5×10-8) following the ANOVA model and 15 significant eQTLs (P<5×10-8) following the additive model. Using a differential gene expression framework, we identified 2,471 and nine significant eQTLs (P<5×10-8) following an analytical framework equivalent to the ANOVA and additive model, respectively. When we compared the two approaches, there was no overlap of significant eQTLs between the two frameworks. Because we defined specific contrasts, we identified trans eQTLs that more closely resembled what we expect from genetic variants showing complete dominance between alleles. Yet, these were not identified by the GTEx framework.

Conclusions

Our results show that transforming RNA-sequencing data to fit a normal distribution prior to eQTL analysis is not required when the DGE framework is employed, thus this may be more suitable for finding genes whose expression are impacted by genetic variants. Our approach detected biologically relevant variants that otherwise would not have been identified due to data transformation to fit a normal distribution.
In-silicodocking platform with serine protease inhibitor (SERPIN) structures identifies host cysteine protease targets with significance for SARS-CoV-2
Authors: Rodriguez Galvan Joaquín J , de Vries Maren , Belblidia Shiraz , Fisher Ashley , Prescott Rachel A , Crosse Keaton M , Mangel Walter F. , Duerr Ralf , Dittmann Meike
Published: November 2022

Serine Protease Inhibitors (SERPINs) regulate protease activity in various physiological processes such as inflammation, cancer metastasis, angiogenesis, and neurodegenerative diseases. However, their potential in combating viral infections, where proteases are also crucial, remains underexplored. This is due to our limited understanding of SERPIN expression during viral-induced inflammation and of the SERPINs’ full spectrum of target proteases. Here, we demonstrate widespread expression of human SERPINs in response to respiratory virus infections, bothin vitroandin vivo, alongside classical antiviral effectors. Through comprehensivein-silicodocking with full-length SERPIN and protease 3D structures, we confirm known inhibitors of specific proteases; more importantly, the results predict novel SERPIN-protease interactions. Experimentally, we validate the direct inhibition of key proteases essential for viral life cycles, including the SERPIN PAI-1’s capability to inhibit select cysteine proteases such as cathepsin L, and the serine protease TMPRSS2. Consequently, PAI-1 suppresses spike maturation and multi-cycle SARS-CoV-2 replication. Our findings challenge conventional notions of SERPIN selectivity, underscore the power ofin-silicodocking for SERPIN target discovery, and offer potential therapeutic interventions targeting host proteolytic pathways to combat viruses with urgent unmet therapeutic needs.

SIGNIFICANCE

Serine protease inhibitors (SERPINs) play crucial roles in various physiological processes, including viral infections. However, our comprehension of the full array of proteases targeted by the SERPIN family has traditionally been limited, hindering a comprehensive understanding of their regulatory potential. We developed anin-silicodocking platform to identify new SERPIN target proteases expressed in the respiratory tract, a critical viral entry portal. The platform confirmed known and predicted new targets for every SERPIN examined, shedding light on previously unrecognized patterns in SERPIN selectivity. Notably, both key proteases for SARS-CoV-2 maturation were among the newly predicted targets, which we validated experimentally. This underscores the platform’s potential in uncovering targets with significance in viral infections, paving the way to define the full potential of the SERPIN family in infectious disease and beyond.
Streptomycesalleviate abiotic stress in plant by producing pteridic acids
Authors: Yang Zhijie , Strøbech Emil , Qiao Yijun , Konakall Naga Charan , Harris Pernille , Peschel Gundela , Agler-Rosenbaum Miriam , Weber Tilmann , Andreasson Erik , Ding Ling
Published: November 2022

Soil microbiota can confer fitness advantages to plants and increase crop resilience to drought and other abiotic stressors. However, there is little evidence on the mechanisms correlating a microbial trait with plant abiotic stress tolerance. Here, we report thatStreptomyceseffectively alleviates the drought and salinity stress by producing spiroketal polyketide pteridic acid H (1) and its isomer F (2), both of which promote root growth inArabidopsisat a concentration of 1.3 nM under abiotic stress. Pteridic acids induce stress response genes expression in salinity-stressedArabidopsisseedlings. The bifunctional biosynthetic gene cluster of pteridic acids and antimicrobial elaiophylin is confirmed in vivo and mainly disseminated by vertical transmission which is geographically distributed in various environments. This discovery reveals a perspective for understanding plant-Streptomycesinteractions and provides a promising approach for utilising beneficialStreptomycesand their secondary metabolites in agriculture to mitigate the detrimental effects of climate change.
Beyond technology in smart cities: a multivocal literature review on data governance
Authors: Kvalvik Petter , Sánchez-Gordón Mary , Colomo-Palacios Ricardo
Published: November 2022

Purpose

Smart cities require data governance to articulate data sharing and use among relevant stakeholders. Given the lack of a comprehensive examination of this research topic, this study aims to review data governance publications to detect and categorize endeavors backing up data sharing in smart cities.

Design/methodology/approach

A systematic literature review was conducted, and 568 academic and professional sources were identified, but finally, only 10 relevant papers were selected.

Findings

Results reveal that data governance must be based on well-defined mechanisms, procedures and roles to achieve accountability and responsibility in a multi-actor environment. Moreover, data governance should be adapted to address power imbalances among all interested parties.

Research limitations/implications

The main limitation is the list of sources considered for the literature review. However, this study provides a holistic overview for researchers and professionals willing to know more about smart city data sharing.

Originality/value

This review identifies the data governance approaches supporting data sharing in smart cities, analyzes their data dimension, enhances the state-of-the-art literature on this topic and suggests possible areas for future research.
Modeling of planning function management in Vietnam’s public construction works
Authors: Luong Hai Nguyen , Tuan Ngo Anh
Published: November 2022

Purpose

The planning function is a central component of management principles, enabling the success of construction project management. Many works have been highlighting the topic of critical success factors within construction organizations, yet the results have rarely covered planning behaviors within public construction work management; these less investigated areas were the aims of this study.

Design/methodology/approach

To fulfill this research aim, seven attributes of planning function were first derived through focus group studies, a focused literature review and focal interviews with industry practitioners. Then, a regression analysis design was employed with data collected from 139 professionals who are involved in public construction works management in Vietnam. The structural equation modeling technique with partial least-squares estimation was utilized to analyze the data.

Findings

The results revealed seven behavioral dimensions (i.e. Goals planning (PL1), Planning guidance (PL2), Strategic planning (PL3), Financial mobilization (PL4), Action plan (PL5), Expenditure planning (PL6) and Responsibility assignment (PL7)) to measure planning function management in terms of public construction works. The study also reveals that Goals planning (PL1), Financial mobilization (PL4), Expenditure planning (PL6) and Responsibility assignment (PL7) have significant effects on management effectiveness. At the same time, Goals planning (PL1) acts as the mediator of Planning guidance (PL2) and Strategic planning (PL3); while Action plan (PL5) specifies an indirect influence through the mediator of PL4, PL6 and PL7.

Originality/value

The success of this approach is expected to reinforce the contribution of the planning function and suggest a useful tool for supporting the professionals in managing public construction works.
Differences in financial inclusion by disability type
Authors: Wann Christi R. , Burke-Smalley Lisa
Published: November 2022

Purpose

The purpose of this study is to determine the nature of financial inclusion for individuals with various types of disabilities.

Design/methodology/approach

Data from 2015, 2017 and 2019 FDIC Survey of Household Use of Banking and Financial Services was pooled, and binary logistic regressions were used to investigate differences in barriers to financial inclusion (e.g. unbanked) between people with different types of disabilities (e.g. cognitive) and those without such disabilities.

Findings

Using five separate barrier measures, the authors found specific disability types face different barriers to financial inclusion. For example, respondents with cognitive, ambulatory or two or more disabilities were more likely to use nonbank transaction products and alternative financial services. And, those with vision or cognitive disabilities were more likely to be denied or receive reduced credit. When examining aggregate barriers to financial inclusion (total number of barriers faced) respondents with cognitive, ambulatory, hearing or two or more disabilities experienced the lowest degree of financial inclusion in the authors’ dataset.

Research limitations/implications

Causal inference cannot be made due to the cross-sectional nature of the data. The data only covers the US population, and the measurement of disability type could include those with short-term impairments. Further, there may be an omitted variable bias.

Practical implications

Best practices to maximize financial inclusion for those with different disability types should address accessibility issues, bank staff education, financial literacy education and poverty issues. Additional government policies and oversight are also needed to protect and enhance the overall financial inclusion of people with disabilities.

Originality/value

To the best of the authors’ knowledge, this paper is the first to examine the relationship between various barriers to financial inclusion and aggregate barriers to financial inclusion by disability type. Specific disability types are found to face different barriers to financial inclusion.