bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of inflammatory pain on CB1 receptor in the midbrain periaqueductal gray
Authors: Wilson-Poe Adrianne R. , Wiese Beth , Kibaly Cherkaouia , Lueptow Lindsay , Garcia Jeniffer , Anand Preeti , Cahill Catherine , Morón Jose A. 
Published: March 2021

Abstract

Introduction:
The periaqueductal gray (PAG) mediates the antinociceptive properties of analgesics, including opioids and cannabinoids. Administration of either opioids or cannabinoids into the PAG induces antinociception. However, most studies characterizing the antinociceptive properties of cannabinoids in the PAG have been conducted in naive animals. Few studies have reported on the role of CB1 receptors in the PAG during conditions which would prompt the administration of analgesics, namely, during pain states.

Objectives:
To examine inflammatory pain-induced changes in CB1 receptor expression and function in the midbrain periaqueductal gray.

Methods:
In this study, we used the Complete Freund Adjuvant model to characterize CB1 receptor expression and G-protein coupling during persistent inflammatory pain.

Results:
Inflammatory pain induced an upregulation in the expression of synaptic CB1 receptors in the PAG. Despite this pain-induced change in CB1 expression, there was no corresponding upregulation of CB1 mRNA after the induction of inflammatory pain, suggesting a pain-induced recruitment of CB1 receptors to the synaptic sites within PAG neurons or increased coupling efficiency between the receptor and effector systems. Inflammatory pain also enhanced ventrolateral PAG CB1 receptor activity, as there was an increase in CP55,940-stimulated G-protein activation compared with pain-naïve control animals.

Conclusion:
These findings complement a growing body of evidence which demonstrate pain-induced changes in brain regions that are responsible for both the analgesic and rewarding properties of analgesic pharmacotherapies. Because much of our understanding of the pharmacology of cannabinoids is based on studies which use largely pain-naïve male animals, this work fills in important gaps in the knowledge base by incorporating pain-induced adaptations and cannabinoid pharmacology in females.
ANTERIOR OR POSTERIOR ANKLE FOOT ORTHOSES FOR ANKLE SPASTICITY: WHICH ONE IS BETTER?
Authors: Suputtitada Areerat , Chatkungwanson Watchara , Seehaboot Kittikorn , Chen Carl PC 
Published: March 2021

AbstractBackgroudAnkle foot orthoses (AFOs) have been widely used in stroke patients to assist in safe, energy efficient walking. Since they provide mediolateral ankle stability during stance, adequate toes clearance during swing phase and also facilitation of heel strike.ObjectiveTo compare the efficacy of anterior or posterior plastic ankle foot orthoses (AFOs) for ankle spasticity.MethodsCrossover design with randomization for the interventions, blinded assessors was used. 20 patients with chronic stroke, Modified Ashworth scale (MAS) of ankle ≤ 2 and Tardieu angle ≥ 20 degrees. The participants were random to treat with anterior or posterior plastic AFOs and then were crossover to treat with the other one. Outcomes measurement was performed by using passive range of motion (PROM), MAS, walking velocity, stretch reflex surface EMG and walking surface EMG of medial gastrocnemius muscle. Patient satisfaction was evaluated at 1 month.ResultsTwenty stroke patients with ankle spasticity were recruited. Mean age was 46.60(38-60) years old.Mean duration. of times since stroke was 9.35 (6-15) months. Comparison between two types of orthoses revealed statistically significant improvement of walking surface EMG of medial gastrocnemius muscles when using anterior plastic AFO more than posterior plastic AFO at p=0.015. Patients satisfaction were statistically significant higher when using anterior plastic AFO more than posterior plastic AFO at p<0.05.ConclusionAnterior plastic AFO has more efficacy in reduced dynamic ankle spasticity during walking than posterior plastic AFO proven by comparison the dynamic electromyography changes in dynamic spasticity during walking.
Testing Black-White disparities in biological aging in older adults in the United States: analysis of DNA-methylation and blood-chemistry methods
Authors: Graf GH , Crowe CL , Kothari M , Kwon D , Manly JJ , Turney IC , Valeri L , Belsky DW 
Published: March 2021

ABSTRACTBiological aging is a proposed mechanism through which social determinants drive health disparities. We conducted proof-of-concept testing of eight DNA-methylation and blood-chemistry quantifications of biological aging as mediators of disparities in healthspan between Black and White participants in the United States Health and Retirement Study (HRS; n=9005). We quantified biological aging from four DNA-methylation “clocks” (Horvath, Hannum, PhenoAge, and GrimAge), a DNA-methylation Pace of Aging (DunedinPoAm), and three blood-chemistry measures (PhenoAge, Klemera-Doubal method Biological Age, and homeostatic dysregulation). We quantified Black-White disparities in healthspan from cross-sectional and longitudinal data on physical-performance tests, self-reported activities of daily living (ADL) limitations and physician-diagnosed chronic diseases, self-rated health, and survival. DNA-methylation and blood-chemistry quantifications of biological aging were moderately correlated (Pearson-r range 0.1-0.4). GrimAge, DunedinPoAm and all three blood-chemistry measures were associated with healthspan characteristics (e.g. mortality effect-size range 1.71-2.32) and showed evidence of more advanced/faster biological aging in Black compared with White participants (Cohen’s d=.4-.5). These measures accounted for 13-95% of Black-White differences in healthspan-related characteristics. Findings that Black Americans are biologically older and aging more rapidly than White Americans of the same chronological age suggest that eliminating disparities in the pace of aging can contribute building to aging health equity.
Redesigning SARS-CoV-2 clinical RT-qPCR assays for wastewater RT-ddPCR
Authors: Gonzalez Raul , Larson Allison , Thompson Hannah , Carter Errin , Cassi Xavier Fernandez 
Published: March 2021

AbstractCOVID-19 wastewater surveillance has gained widespread acceptance to monitor community infection trends. Wastewater samples primarily differ from clinical samples by having low viral concentrations due to dilution, and high levels of PCR inhibitors. Therefore, wastewater samples should be processed by appropriately designed and optimized molecular workflows to accurately quantify targets. Digital PCR has shown to be more sensitive and resilient to environmental matrix inhibition. However, most SARS-CoV-2 assays have been designed for clinical use on RT-qPCR instruments, then adopted to digital PCR platforms. But it is unknown whether clinical RT-qPCR assays are adequate to use on digital PCR platforms. Here we designed an N and E gene multiplex (ddCoV_N and ddCoV_E) specifically for RT-ddPCR and benchmarked them against the nCoV_N2 and E_Sarbeco assays. ddCoV_N and ddCoV_E have equivalent limits of detections and wastewater sample concentrations to NCoV_N2 and E_Sarbeco but showed improved signal-to-noise ratios that eased interpretation and ability to multiplex. From GISAID downloaded unique sequences analyzed, 2.12% and 0.83% present a mismatch or would not be detected by the used primer/probe combination for the ddCoV_N and ddCoV_E, respectively.
Characterizing all-cause excess mortality patterns during COVID-19 pandemic in Mexico
Authors: Dahal Sushma , Banda Juan M. , Bento Ana I. , Mizumoto Kenji , Chowell Gerardo 
Published: March 2021

AbstractBackgroundLow testing rates and delays in reporting hinder the estimation of the mortality burden associated with the COVID-19 pandemic. During a public health emergency, estimating all cause excess deaths above an expected level of death can provide a more reliable picture of the mortality burden. Here, we aim to estimate the absolute and relative mortality impact of COVID-19 pandemic in Mexico.MethodsWe obtained weekly mortality time series due to all causes for Mexico, and by gender, and geographic region from 2015 to 2020. We also compiled surveillance data on COVID-19 cases and deaths to assess the timing and intensity of the pandemic and assembled weekly series of the proportion of tweets about ‘death’ from Mexico to assess the correlation between people’s media interaction about ‘death’ and the rise in pandemic deaths. We estimated all-cause excess mortality rates and mortality rate ratio increase over baseline by fitting Serfling regression models and forecasted the total excess deaths for Mexico for the first four weeks of 2021 using the generalized logistic growth model.ResultsWe estimated the all-cause excess mortality rate associated with the COVID-19 pandemic in Mexico in 2020 at 26.10 per 10,000 population, which corresponds to 333,538 excess deaths. Males had about 2-fold higher excess mortality rate (33.99) compared to females (18.53). Mexico City reported the highest excess death rate (63.54) and RR (2.09) compared to rest of the country (excess rate=23.25, RR=1.62). While COVID-19 deaths accounted for only 38.64% of total excess deaths in Mexico, our forecast estimate that Mexico has accumulated a total of ∼61610 [95% PI: 60003, 63216] excess deaths in the first four weeks of 2021. Proportion of tweets was significantly correlated with the excess mortality (ρ=0.508 [95% CI: 0.245, 0.701], p-value=0.0004).ConclusionThe COVID-19 pandemic has heavily affected Mexico. The lab-confirmed COVID-19 deaths accounted for only 38.64% of total all cause excess deaths (333,538) in Mexico in 2020. This reflects either the effect of low testing rates in Mexico, or the surge in number of deaths due to other causes during the pandemic. A model-based forecast indicates that an average of 61,610 excess deaths have occurred in January 2021.
Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination
Authors: Müller Lisa , Andrée Marcel , Moskorz Wiebke , Drexler Ingo , Walotka Lara , Grothmann Ramona , Ptok Johannes , Hillebrandt Jonas , Ritchie Anastasia , Rabl Denise , Ostermann Philipp Niklas , Robitzsch Rebekka , Hauka Sandra , Walker Andreas , Menne Christopher , Grutza Ralf , Timm Jörg , Adams Ortwin , Schaal Heiner 
Published: March 2021

AbstractBackgroundThe SARS-CoV-2 pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees over 80 years old is still underrepresented despite the prioritization of the elderly in vaccination campaigns.MethodsWe conducted a cohort study with two age groups, young vaccinees below the age of 60 and elderly vaccinees over the age of 80, to compare their antibody responses to the first and second dose of the BNT162b2 COVID-19 vaccination.ResultsWhile the majority of participants in both groups produced specific IgG antibody titers against SARS-CoV-2 spike protein, titers were significantly lower in elderly participants. Although the increment of antibody levels after the second immunization was higher in elderly participants, the absolute mean titer of this group remained lower than the <60 group. After the second vaccination, 31.3 % of the elderly had no detectable neutralizing antibodies in contrast to the younger group, in which only 2.2% had no detectable neutralizing antibodies.ConclusionOur data suggests that lower frequencies of neutralizing antibodies after BNT162b2 vaccination in the elderly population may require earlier revaccination to ensure strong immunity and protection against infection.
Manipulating vector transmission reveals local processes in bacterial communities of bats
Authors: McKee Clifton D. , Webb Colleen T. , Kosoy Michael Y. , Bai Ying , Osikowicz Lynn M. , Suu-Ire Richard , Ntiamoa-Baidu Yaa , Cunningham Andrew A. , Wood James L. N. , Hayman David T. S. 
Published: March 2021

AbstractInfectious diseases result from multiple interactions among microbes and hosts, but community ecology approaches are rarely applied. Manipulation of vector populations provides a unique opportunity to test the importance of vectors in infection cycles while also observing changes in pathogen community diversity and species interactions. Yet for many vector-borne infections in wildlife, a biological vector has not been experimentally verified and few manipulative studies have been performed. Using a captive colony of fruit bats in Ghana, we observed changes in the community ofBartonellabacteria over time after the decline and subsequent reintroduction of bat flies. With reduced transmission, community changes were attributed to ecological drift and potential selection through interspecies competition mediated by host immunity. This work demonstrated that forces maintaining diversity in communities of free-living macroorganisms act in similar ways in communities of symbiotic microorganisms, both within and among hosts. Additionally, this study is the first to experimentally test the role of bat flies as vectors ofBartonellaspecies.
Insights into the susceptibility of rice to a floral disease
Authors: Li Guo-Bang , Fan Jing , Liu Jie , Wu Jin-Long , Hu Xiao-Hong , He Jia-Xue , Shen Shuai , Wang He , Zhu Yong , He Feng , Gao Han , Gishkori Zeeshan Ghulam Nabi , Zhao Jing-Hao , Li Yan , Huang Fu , Huang Yan-Yan , Zhao Zhi-Xue , Zhang Ji-Wei , Zhou Shi-Xin , Pu Mei , Chen Xuewei , Wang Jing , Li Weitao , Wu Xian-Jun , Ning Yuese , Sun Wenxian , Wang Wen-Ming 
Published: March 2021

ABSTRACTCrop floral diseases are economically important as they reduce grain yield and quality and even introduce food toxins. Rice false smut has emerged as a serious floral disease producing mycotoxins. However, very little is known on the interaction mechanisms between rice flower and the causal fungusUstilaginoidea virens. Here we show that a conserved anti-fungal immunity in rice flower is disarmed byU. virensvia a secreted protein UvChi1. UvChi1 functioned as an essential virulence factor and directly interacted with the chitin receptor CEBiP and co-receptor CERK1 in rice to disrupt their oligomerizations and subsequent immune responses. Moreover, intraspecific-conserved UvChi1 could target OsCEBiP/OsCERK1 receptor complex in at least 98.5% of 5232 surveyed rice accessions. These results demonstrate thatU. virensutilizes a crucial virulence factor to subvert chitin-triggered flower immunity in most rice varieties, providing new insights into the susceptibility of rice to false smut disease.One Sentence SummaryThe fungal pathogenUstilaginoidea virensdisarms chitin-triggered immunity in rice flower via a secreted chitinase.
Novel Paju Apodemus Paramyxovirus 1 and 2, Harbored byApodemus agrariusin The Republic of Korea
Authors: Lee Seung-Ho , No Jin Sun , Kim Kijin , Budhathoki Shailesh , Park Kyungmin , Lee Geum Young , Cho Seungchan , Choi Hyeok Sun , Kim Bong-Hyun , Cho Seunghee , Kim Jong Woo , Lee Jin Gyeong , Cho Seung Hye , Kim Heung-Chul , Klein Terry A. , Uhm Chang-Sub , Kim Won-Keun , Song Jin-Won 
Published: March 2021

AbstractParamyxoviruses, negative-sense single-stranded RNA viruses, pose a potential threat to public health. Currently, 78 species and 17 genera of paramyxoviruses are classified and harbored by multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish.Jeilongvirushas been proposed as a novel paramyxovirus genus containing J-, Beilong, and Tailam viruses, found in wild rodents. Using RT-PCR, 824Apodemus agrariusindividuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was detected in 108 (13.1%) rodents captured at 14 trapping sites in Korea. We first present two genetically distinct novel paramyxoviruses (genusJeilongvirus), Paju Apodemus paramyxoviruses 1 (PAPV-1) and 2 (PAPV-2), fromA. agrarius. Six PAPV strains were completely sequenced using next-generation and Sanger sequencing. PAPV-1 genome comprised 19,716 nucleotides, with eight genes (3′-N-P/V/C-M-F-SH-TM-G-L-5′), whereas PAPV-2 genome contained 17,475 nucleotides, with seven genes (3′-N-P/V/C-M-F-TM-G-L-5′). The disparity between PAPV-1 and -2 revealed the presence of theSHgene and length of theGgene in the genome organization. The phylogenies of PAPV-1 and -2 belong to distinct genetic lineages ofJeilongvirusdespite being from the same natural host. PAPV-1 clustered with Beilong and Tailam viruses, while PAPV-2 formed a genetic lineage with Mount Mabu Lophuromys virus-1. PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. Therefore, this study provides profound insights into the molecular epidemiology, virus-host interactions, and zoonotic potential of novel rodent-borne paramyxoviruses.ImportanceParamyxoviruses are a critical public health and socio-economic burden to humans. Rodents play a crucial role in transmitting pathogens to humans. In the last decade, novel paramyxoviruses have been discovered in different rodents. Here, we found thatApodemus agrariusharbored two distinct genotypes of the novel paramyxoviruses, Paju Apodemus paramyxovirues 1 (PAPV-1) and 2 (PAPV-2), possessing unique genome structures that are responsible for encoding TM and G proteins of different sizes. In addition, PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III IFNs, ISGs, and proinflammatory cytokines. Thus, this study provides significant insights into molecular prevalence, virus-host interactions of paramyxoviruses. These observations raise the awareness of physicians and scientists about the emergence of new rodent-borne paramyxoviruses.
Suppression of PIK3CA-driven epileptiform activity by acute pathway control
Authors: Roy Achira , Han Victor Z. , Bard Angela M. , Wehle Devin T. , Smith Stephen E. P. , Ramirez Jan-Marino , Kalume Franck , Millen Kathleen J. 
Published: March 2021

ABSTRACTPatients harboring mutations in the PI3K-AKT-MTOR signaling pathway often develop a spectrum of neurodevelopmental disorders including epilepsy. A significant proportion of them remain unresponsive to conventional anti-seizure medications. Understanding mutation-specific pathophysiology is thus critical for molecularly targeted therapies. We previously determined that mouse models expressing patient-related activating mutation inPIK3CAare epileptic and acutely treatable with PI3K inhibition, irrespective of dysmorphology (Roy et al. 2015). Using the same mutant model, we have now identified physiological mechanisms underlying the dysregulated neuronal excitability and its acute attenuation. We show that Pik3ca-driven hyperexcitability in hippocampal pyramidal neurons is mediated by changes in multiple non-synaptic, cell-intrinsic properties. These are distinct from mechanisms driving epilepsy in TSC/RHEB models. Further, we report that acute inhibition of PI3K or AKT, but not MTOR, suppresses the intrinsic epileptiform nature of the mutant neurons. These data represent an important step towards precision therapeutics against intractable epilepsy, using pathway drugs originally developed as anti-cancer agents.
Lipid production fromZygosaccharomyces siamensisAP1 using glycerol as a carbon source
Authors: Ilmi M , Siswantoro M 
Published: March 2021

AbstractYeasts are considered as potential lipid producer because they are easy to cultivate, able to grow in high cell densities and can produce high concentrations of lipids. Previously we had isolated a promising lipid producing yeast,Zygosaccharomyces siamensisAP1, from wild honey of Central Sulawesi, Indonesia. The strain was able to produce around 19% (w/w biomass) of lipid on glucose. However, its ability to produce lipid on other types of carbon source is still not studied. In this study, we compared the strain ability to produce lipid on glycerol and glucose using different C/N ratio. We also investigated optimum temperature, pH, and growth time for lipid production on glycerol. We found that growing the strain on glycerol with C/N ratio 120 gave the highest lipid content (29.7%). We also found that optimum growth temperature and pH are 30°C and 5, respectively. Maximum lipid biomass, 0.28 g/L, was produced when the strain was grown in the optimum conditions for 72 hours. In conclusion, our results suggest that glycerol is a potential cheap carbon source for lipid production fromZ. siamensisAP1. We suggest further study to increase lipid yield either by fermentation or strain improvement.
Stabilization of Brain Network Dynamics during Childhood and Adolescence is Associated with Gene Expressions
Authors: Lei Tianyuan , Liao Xuhong , Chen Xiaodan , Zhao Tengda , Xu Yuehua , Xia Mingrui , Zhang Jiaying , Sun Xiaochen , Wei Yongbin , Men Weiwei , Wang Yanpei , Hu Mingming , Zhao Gai , Du Bin , Wu Qian , Tan Shuping , Gao Jiahong , Qin Shaozheng , Tao Sha , Dong Qi , He Yong 
Published: March 2021

AbstractFunctional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.