bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Intrinsic Membrane Properties are Modulated in a Switch from Single to Dual-Network Activity
Authors: Snyder Ryan R. , Blitz Dawn M. 
Published: August 2022

AbstractNeural network flexibility extends to changes in neuronal participation between networks. This neuronal switching can include neurons moving between single- and dual-network activity. We previously identified an example in which bursting at a second frequency occurs due to modulation of intrinsic membrane properties instead of synaptic recruitment into a second network. However, the intrinsic properties that are modulated were not determined. Here, we use small networks in the Jonah crab (Cancer borealis) stomatogastric nervous system (STNS) to examine modulation of intrinsic properties underlying neuropeptide- (Gly1-SIFamide) elicited neuronal switching. The LPG neuron switches from exclusive participation in the fast pyloric (∼1 Hz) network, due to electrical coupling, to dual-network activity which includes periodic escapes from the fast rhythm via intrinsically-generated oscillations at the slower gastric mill network frequency (∼0.1 Hz). We isolated LPG from both networks using pharmacology and hyperpolarizing current injection. Gly1-SIFamide increased LPG intrinsic excitability and rebound from inhibition, and decreased spike frequency adaptation, which can all contribute to intrinsic bursting. Using ion substitution and channel blockers, we found that a hyperpolarization-activated current, a persistent sodium current, and a calcium or calcium-related current(s) appear to be primary contributors to Gly1-SIFamide-elicited LPG intrinsic bursting. However, this intrinsic bursting was more sensitive to blocking currents when LPG received rhythmic electrical coupling input from the fast network than in the isolated condition. Overall, a switch from single- to dual-network activity can involve modulation of multiple intrinsic properties, while synaptic input from a second network can shape the contributions of these properties.New and NoteworthyNeuropeptide-elicited intrinsic bursting was recently determined to switch a neuron from single to dual-network participation. Here we identified multiple intrinsic properties modulated in the dual-network state and candidate ion channels underlying the intrinsic bursting. Bursting at the second network frequency was more sensitive to blocking currents in the dual-network state than when neurons were synaptically isolated from their home network. Thus, synaptic input can shape the contributions of modulated intrinsic properties underlying dual-network activity.
V2b neurons act via multiple targets in spinal motor networks
Authors: Sengupta Mohini , Bagnall Martha W. 
Published: August 2022

AbstractWithin the spinal cord, interneurons shape motor neuron activity. These interneurons can project over long distances in the longitudinal axis, but systematic mapping of their connectivity has been limited. In this study, using larval zebrafish, we mapped local and long-range connectivity of a cardinal spinal population, the Gata3+ V2b class. V2b neurons are inhibitory and project ipsilateral, descending axons. We show that V2b neurons are active during fictive swimming, slightly leading the motor burst. Via optogenetic mapping of output in the rostrocaudal axis, we demonstrate that V2b neurons robustly inhibit motor neurons and other major spinal interneuron classes, including V2a, V1, commissural neurons and other V2b neurons. V2b inhibition is patterned along the rostrocaudal axis, providing long-range inhibition to motor and V2a neurons but more localized innervation of the V1 class. Furthermore, these results provide the first demonstration of reciprocal V1/V2b inhibition in axial circuits, potentially representing an ancestral motif of the limb control network.
USAG1 protein: An important drug target in teeth regeneration
Authors: Poorani R , Elakkiya E , Gupta Krishna Kant 
Published: August 2022

AbstractThe BMP antagonist and Wnt signaling modulator, USAG-1 (uterine sensitization associated gene-1) is mostly expressed in the kidneys and suppresses BMP7 bioactivity, which is crucial for tooth development. The homodimeric 35-kDa protein known as bone morphogenetic protein-7 is essential for the specification and patterning of the early embryo and controls apoptosis in a variety of developmental events. A single-gene knockout (KO) mouse model for Usag-1, also known as Sclerostin domain containing 1 (SOSTDC1), ectodin, Wnt modulator in surface ectoderm (WISE), CCAAT/enhancer-binding protein beta (CEBPB), Sprouty homolog 2 (SPRY2), Sprouty homolog 3 (SPRY3), or Epiprofin (EPFN), has demonstrated that Usag1 inhibition is important for teeth regeneration in mice. Anti Usag1 method was done by other scientists outside India. Tideglusib when placed at damaged teeth, it increases WNT signaling by inhibiting GSK-3.It results into teeth repair .Suginami et al proposed USAG-1 as a promising drug target for teeth regeneration .They proposed anti-USAG-1 approach to induce teeth regeneration but it has been associated with many sideaffects. This study aims to provide a natural lead molecule as a therapeutic drug for teeth regeneration.
Multiple pathways mediate chloroplast singlet oxygen stress signaling
Authors: Tano David W. , Kozlowska Marta A. , Easter Robert A. , Woodson Jesse D. 
Published: August 2022

AbstractChloroplasts can respond to stress and changes in the environment by producing reactive oxygen species (ROS). Aside from being cytotoxic, ROS also have signaling capabilities. For example, the ROS singlet oxygen (1O2) can initiate nuclear gene expression, chloroplast degradation, and cell death. To unveil the signaling mechanisms involved, researchers have used several 1O2-producing Arabidopsis thaliana mutants as genetic model systems, including plastid ferrochelatase two (fc2), fluorescent in blue light (flu), chlorina 1 (ch1), and accelerated cell death 2 (acd2). Here, we compare these 1O2-producing mutants to elucidate if they utilize one or more signaling pathways to control cell death and nuclear gene expression. Using publicly available transcriptomic data, we demonstrate fc2, flu, and ch1 share a core response to 1O2 accumulation, but maintain unique responses, potentially tailored to respond to their specific stresses. Subsequently, we used a genetic approach to determine if these mutants share 1O2 signaling pathways by testing the ability of genetic suppressors of one 1O2 producing mutant to suppress signaling in a different 1O2 producing mutant. Our genetic analyses revealed at least two different chloroplast 1O2 signaling pathways control cellular degradation: one specific to the flu mutant and one shared by fc2, ch1, and acd2 mutants, but with life-stage-specific (seedling vs. adult) features. Overall, this work reveals chloroplast stress signaling involving 1O2 is complex and may allow cells to finely tune their physiology to environmental inputs.
Cardiovascular measures from abdominal MRI provide insights into abdominal vessel genetic architecture
Authors: Basty Nicolas , Sorokin Elena P. , Thanaj Marjola , Whitcher Brandon , Liu Yi , Bell Jimmy D. , Thomas E. Louise , Cule Madeleine 
Published: August 2022

AbstractFeatures extracted from cardiac MRI (CMR) are correlated with cardiovascular disease outcomes such as aneurysm, and have a substantial heritable component. To determine whether disease-relevant measurements are feasible in non-cardiac specific MRI, and to explore their associations with disease outcomes, and genetic and environmental risk factors. We segmented the heart, aorta, and vena cava from abdominal MRI scans using deep learning, and generated six image-derived phenotypes (IDP): heart volume, four aortic and one vena cava cross-sectional areas (CSA), from 44,541 UK Biobank participants. We performed genome- and phenome-wide association studies, and constructed a polygenic risk score for each phenotype. We demonstrated concordance between our IDPs and related IDPs from CMR, the current gold standard. We replicated previous findings related to sex differences and age-related changes in heart and vessel dimensions. We identified a significant association between infrarenal descending aorta CSA and incident abdominal aortic aneurysm, and between heart volume and several cardiovascular disorders. In a GWAS, we identified 72 associations at 59 loci (15 novel). We derived a polygenic risk score for each trait and demonstrated an association with TAA diagnosis, pointing to a potential screening method for individuals at high-risk of this condition. We demonstrated substantial genetic correlation with cardiovascular traits including aneurysms, varicose veins, dysrhythmia, and cardiac failure. Finally, heritability enrichment analysis implicated vascular tissue in the heritability of these traits. Our work highlights the value of non-specific MRI for exploring cardiovascular disease risk in cohort studies.
Archi-Prevaleat project. A National cohort of color-Doppler ultrasonography of the epi-aortic vessels in Patients Living with HIV
Authors: Maggi P. , Ricci E.D. , Muccini C. , Galli L. , Celesia B.M. , Ferrara S. , Salameh Y. , Basile R. , Di Filippo G. , Taccari F. , Tartaglia A. , Castagna A. 
Published: August 2022

AbstractObjectivesTo evaluate the prevalence of carotid intima-media thickness and plaques in a cohort of persons living with HIV, the role of cardiovascular risk factors, the impact of the antiretroviral regimens, and the difference between naïve and experienced patients in the onset of carotid lesions.MethodsThis project was initiated in 2019 and involves eight Italian Centers. Carotid changes were detected using a power color-Doppler ultrasonography with 7.5 MHz probes. The following parameters are evaluated: intima-media thickness of both the right and left common and internal carotids: Data regarding risk factors for CVD, HIV viral load, CD4+ cell counts, serum lipids, glycaemia, and body mass index. The associations between pathological findings and potential risk factors were evaluated by logistical regression, with odds ratios (OR) and 95% confidence intervals (95% CI).ResultsAmong 1147 evaluated patients, aged 52 years on average, 347 (30.2%) had pathological findings (15.8% plaques and 14.5% IMT). Besides usual risk factors, such as older age, male sex, and dyslipidemia, CD4+ cell nadir <200 cells/mL (OR 1.51, 95% CI 1.14-1.99) and current use of raltegravir (OR 1.54, 95% CI 1.01-2.36) were associated with higher prevalence of pathological findings.ConclusionsOur data show that the overall percentage of carotid impairments nowadays remains high. Color-Doppler ultrasonography could play a pivotal role in identifying and quantifying atherosclerotic lesions among persons living with HIV, even at a very premature stage, and should be included in the algorithms of comorbidity management of these patients.
A comprehensive evaluation of minimally invasive Achilles tendon reconstruction with hamstring graft indicates satisfactory long-term outcomes
Authors: Kiedrowski Bartosz , Bąkowski Paweł , Cisowski Paweł , Stołowski Łukasz , Kaszyński Jakub , Małecka Magdalena , Piontek Tomasz 
Published: August 2022

AbstractGiven the relevance of the Achilles tendon in proper function of the foot and ankle, the primary goal of the present study was to use a holistic approach for a comprehensive evaluation of Achilles tendon reconstruction results on multiple levels. 30 patients with partial or total Achilles tendon tears were subjected to the minimally invasive Achilles tendon reconstruction. Patients were then subjected to the clinical, functional and isokinetic tests 12 and 24 months after the treatment. The overall results of this extensive evaluation are highly satisfactory and patients returned to their normal physical activity.
Keeping on target during a low-calorie diet: The experiences of participants in a type 2 diabetes reversal pilot
Authors: Bartholomew Latoya , Unwin Nigel , Guell Cornelia , Murphy Madhuvanti M. 
Published: August 2022

AbstractRapid weight loss using a very low-calorie diet (VLCD) for 2 to 3 months followed by weight maintenance has been shown to lead to the restoration of normal glucose and insulin metabolism in people recently diagnosed with type 2 diabetes. We explored the barriers and facilitators of adhering to a VLCD for remission in an Afro-Caribbean population. Twenty-five participants completed an eight-week VLCD followed by a six-month structured weight maintenance phase. Semi-structured interviews and focus groups were thematically analysed. Cravings for ‘usual foods’ consumed by friends and family, stigma of diabetes and resulting lack of disclosure and the participants’ busy schedules were noted as predominant challenges throughout the study. In turn, social support and the participants’ internal drive were considered as key facilitators for success. VLCD is a feasible approach for type 2 diabetes remission. Self-motivation and supportive environments are however crucial in meeting and maintaining the weight loss goals.
Assessment of Joint and Interactive Effects of Multimorbidity and Chronic Pain on ADRD Risk in the Elder Population
Authors: Khalid Sumaira , Innes Kim E. , Umer Amna , Lilly Christa , Gross Diane , Sambamoorthi Usha 
Published: August 2022

AbstractObjectiveMultimorbidity and non-cancer chronic pain conditions (NCPC) are independently linked to elevated risk for cognitive impairment and incident Alzheimer’s Disease and Related Dementias (ADRD)-both - We present the study of potential joint and interactive effects of these conditions on the risk of incident ADRD in older population.MethodsThis retrospective-cohort study drew baseline and 2-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey (MCBS). Baseline multimorbidity and NCPC were ascertained using claims data. ADRD was ascertained at baseline and follow-up.ResultsNCPC accompanied by multimorbidity (vs. absence of NCPC or multimorbidity) had a significant and upward association with incident ADRD (adjusted odds ratio (AOR): 1.72, 95% CI 1.38, 2.13, p<0.0001). Secondary analysis by number of comorbid conditions suggested that the joint effects of NCPC and multimorbidity on ADRD risk may increase with rising number contributing chronic conditions. Interaction analyses indicated significantly elevated excess risk for incident ADRD.
Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens
Authors: Hielscher Franziska , Schmidt Tina , Klemis Verena , Wilhelm Alexander , Marx Stefanie , Abu-Omar Amina , Ziegler Laura , Guckelmus Candida , Urschel Rebecca , Sester Urban , Widera Marek , Sester Martina 
Published: August 2022

AbstractThe NVX-CoV2373-vaccine has recently been licensed, although data on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to dual-dose mRNA-regimens are limited. In this observational study including 66 participants, we show that NVX-CoV2373-induced IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (n=22 each, p=0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. Interestingly, spike-specific CD8 T-cell levels after NVX-CoV2373-vaccination were significantly lower and were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals. However, CD4 T-cell levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFαα and IL-2 (p=0.0007) as compared to mRNA-vaccinated individuals. Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T cells cross-reacted to all tested VOCs from Alpha to Omicron, which may hold promise to protect from severe disease.
Adolescent binge drinking leads to long-lasting changes in cortical microcircuits in mice
Authors: Sicher Avery R. , Starnes William D. , Griffith Keith R. , Dao Nigel C. , Smith Grace C. , Brockway Dakota F. , Crowley Nicole A. 
Published: August 2022

ABSTRACTAdolescent drug consumption has increased risks to the individual compared to consumption in adulthood, due to the likelihood of long-term and permanent behavioral and neurological adaptations. However, little is known about how adolescent alcohol consumption influences the maturation and trajectory of cortical circuit development. Here, we explore the consequences of adolescent binge drinking on somatostatin (SST) neuronal function in superficial layers of the prelimbic (PL) cortex in male and female SST-Ai9 mice. We find that adolescent drinking-in-the-dark (DID) produces sex-dependent increases in intrinsic excitability of SST neurons, with no change in overall SST cell number, persisting well into adulthood. While we did not find evidence of altered GABA release from SST neurons onto other neurons within the circuit, we found a complementary reduction in layer II/III pyramidal neuron excitability immediately after binge drinking; however, this hypoexcitability rebounded towards increased pyramidal neuron activity in adulthood in females, suggesting long-term homeostatic adaptations in this circuit. Together, this suggests that binge drinking during key developmental timepoints leads to permanent changes in PL microcircuitry function, which may have broad behavioral implications.
HD-PTP/PTPN23 hypomorphic mice display lipodystrophy
Authors: Davies Brian A. , Payne Johanna A. , Martin Cole P. , Schultz Destiny , Childs Bennett G. , Zhang Cheng , Jeganathan Karthik , Sturmlechner Ines , White Thomas A. , de Bruin Alain , Chen Huiqin , Davies Michael A. , Jachim Sarah , LeBrasseur Nathan K. , Piper Robert C. , Li Hu , Baker Darren J. , van Deursen Jan , Katzmann David J. 
Published: August 2022

AbstractEndosomal Sorting Complexes Required for Transport (ESCRTs) drive reverse topology membrane remodeling events including the formation of intralumenal vesicles within multivesicular bodies, the budding of retroviruses from the plasma membrane, and the scission of the cytokinetic bridge. It has been difficult to study the physiological relevance of this machinery in mammals because many contributing components are essential for viability. To bypass this problem we used combinations of knockout (−), hypomorphic (H) and wildtype (+) alleles to generate a series of mice with a gradual reduction of HD-PTP (product ofPTPN23), an ESCRT-associated protein known to cause embryonic lethality when fully depleted. WhereasPTPN23-/Hmice died shortly after birth,PTPN23H/Hmice developed into adulthood but had reduced size, lipodystrophy, and shortened lifespan. Analysis of 14-day inguinal adipose tissue indicated reduced expression of adipogenesis markers, andPTPN23knockout preadipocytes similarly display reduced adipogenesisin vitro.Defects in insulin-stimulated signaling were apparent in differentiatedPTPN23knockout adipocytes andPTPN23H/Hinguinal adipose tissuein vitro, correlating with reduced levels of insulin signaling hallmarks observed in adultPTPN23H/Hinguinal adipose tissuein vivo.Whereas the ESCRT machinery have been suggested to downregulate signaling, these results indicate that HD-PTP promotes insulin-induced signaling in, as well as differentiation of, inguinal adipose tissue. These results revealed unexpected roles for HD-PTP in promoting fat accumulation in mammalian cells through supporting insulin signaling, adipogenesis, and lipid droplet formation.
Occurrence and Antimicrobial Resistance Pattern of E. coli O157:H7 Isolated from Foods of Bovine Origin in Dessie and Kombolcha Towns, Ethiopia
Authors: Abebe Engidaw , Gugsa Getachew , Ahmed Meselu , Awol Nesibu , Tefera Yalew , Abegaz Shimelis , Sisay Tesfaye 
Published: August 2022

ABSTRACTE. coli are frequently isolated food-borne pathogens from meat, milk, and their products. Moreover, there has been a significant rise in the antimicrobial resistance patterns of E. coli O157:H7 to commonly used antibiotics. A cross-sectional study was conducted from October, 2019 to July, 2021 to estimate prevalence and identify associated factors of E. coli and E. coli O157:H7 and to determine antibiotic resistance pattern of E. coli O157:H7 from foods of bovine origin in Dessie and Kombolcha towns. A total of 384 samples were collected. Systematic and simple random sampling techniques were employed for sampling carcasses and milking cows, respectively. E. coli and E. coli O157:H7 were detected according to recommended bacteriological protocols. E. coli O157:H7 strains were evaluated for in vitro antimicrobial susceptibility using agar disk diffusion method. Both descriptive and inferential statistical techniques were applied to analyze the data. Overall prevalence rates of E. coli and E. coli O157:H7 were 54.7% and 6.5%, respectively. Highest prevalence rates of E. coli (79.6%) and E. coli O157:H7 (16.7%) were obtained from carcass swab and milk tank samples, respectively. Unlike E. coli O157:H7, a statistically significant difference in the E. coli prevalence (P<0.05) was observed among the different sample types. Multidrug resistance was observed among all isolates of E. coli O157:H7. All E. coli O157:H7 isolates (100.0%) were susceptible to Ampicillin, Sulfamethoxazole-trimethoprim, and Norfloxacin. On the contrary, all of the isolates (100%) were resistant to Penicillin G, Vancomycin, and Oxacillin. The current study indicated that different foods of bovine origin in the study area were unsafe for human consumption. Hence, good hygienic production methods should be employed to ensure the safety of foods of bovine origin.
Single-cell transcriptomics defines an improved, validated monoculture protocol for differentiation of human iPSCs to microglia
Authors: Washer Sam J , Perez-Alcantara Marta , Chen Yixi , Steer Juliette , James William S , Bassett Andrew R , Cowley Sally A 
Published: August 2022

AbstractThere is increasing genetic evidence for the role of microglia in neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and motor neuron disease. Therefore, there is a need to generate authenticin vitromodels to study human microglial physiology. Various methods have been developed using human induced Pluripotent Stem Cells (iPSC) to generate microglia, however, systematic approaches to identify which media components are actually essential for functional microglia are mostly lacking. Here, we systematically assess medium components, coatings, and growth factors required for iPSC differentiation to microglia. Using single-cell RNA sequencing, qPCR, and functional assays, with validation across two labs, we have identified several medium components from previous protocols that are redundant and do not contribute to microglial identity. We provide an optimised, defined medium which produces both transcriptionally and functionally relevant microglia for modelling microglial physiology in neuroinflammation and for drug discovery.