bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLASTICITY OF RESPONSE PROPERTIES OF MOUSE VISUAL CORTEX NEURONS INDUCED BY OPTOGENETIC TETANIZATIONIN VIVO
Authors: Osipova A.A. , Smirnov I.V. , Smirnova M.P. , Borodinova A.A. , Volgushev M.A. , Malyshev A.Y. 
Published: October 2023

ABSTRACTHeterosynaptic plasticity, along with Hebbian homosynaptic plasticity, is an important mechanism ensuring stable operation of learning neuronal networks. However, whether heterosynaptic plasticity occurs in the whole brain in vivo, and what role(s) in brain function in vivo it could play, remains unclear. Here, we used an optogenetics approach to apply a model of intracellular tetanization, which was established and employed to study heterosynaptic plasticity in brain slices, to study plasticity of response properties of neurons in mouse visual cortex in vivo. We show that optogenetically evoked high-frequency bursts of action potentials (optogenetic tetanization) in principal neurons of the visual cortex induce long-term changes of responses to visual stimuli. Optogenetic tetanization had distinct effects on responses to different stimuli: responses to optimal and orthogonal orientations decreased, response to null direction did not change, and responses to oblique orientations increased. As a result, direction selectivity of the neurons decreased, and orientation tuning became broader. Since optogenetic tetanization was a purely postsynaptic protocol, applied in the absence of sensory stimulation, and thus without association of presynaptic activity with bursts of action potentials, the observed changes were mediated by mechanisms of heterosynaptic plasticity. We conclude that heterosynaptic plasticity can be induced in vivo and propose that it may play important homeostatic roles in operation of neural networks by helping to prevent runaway dynamics of responses to visual stimuli and to keep the tuning of neuronal responses within the range optimized for encoding of multiple features in population activity.
Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria
Authors: Martiniano Rui , Haber Marc , Almarri Mohamed A. , Mattiangeli Valeria , Kuijpers Mirte C. M. , Chamel Berenice , Breslin Emily M. , Littleton Judith , Almahari Salman , Aloraifi Fatima , Bradley Daniel G. , Lombard Pierre , Durbin Richard 
Published: October 2023

AbstractThe harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modelled as a mixture of sources from ancient Anatolia, Levant and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam. We identify the G6PD Mediterranean mutation associated with malaria-resistance in three out of four ancient Bahraini samples and estimate that it rose in frequency in Eastern Arabia from 5-6 kya onwards, around the time agriculture appeared in the region. Our study provides the first characterisation of the genetic composition of ancient Arabians, shedding light on the population history of Bahrain and demonstrating the feasibility of aDNA studies in the region.
RNA virus-mediated gene editing for tomato trait breeding
Authors: Uranga Mireia , Aragonés Verónica , García Arcadio , Mirabel Sophie , Gianoglio Silvia , Presa Silvia , Granell Antonio , Pasin Fabio , Daròs José-Antonio 
Published: October 2023

ABSTRACTVirus-induced genome editing (VIGE) is a flexible and robust technology that relies on viral vectors for the transient delivery of CRISPR-Cas components into plants. Tomato (Solanum lycopersicumL.) is a mayor horticultural crop grown worldwide; despite its economic importance, little is known about VIGE applicability in this species.This study presents the successful use of VIGE in tomato for fruit color breeding. We report (i) the generation of a transgenic Cas9-expressing line of tomato cv. Micro-Tom (MT-Cas9), (ii) the use of pLX-PVX, an enhanced RNA viral vector, for single-guide RNA (sgRNA) delivery into MT-Cas9 plants, (iii) heritable, proof-of-concept VIGE ofPHYTOENE DESATURASEand recovery of albino progeny, and (iv) the recovery of progeny with recoloredgreen-fleshfruits by VIGE ofSTAYGREEN 1, thus confirming the successful breeding of tomato fruit color.Altogether, our results indicate that the presented VIGE approach can be readily applied for accelerated functional genomics of tomato variation, as well as for precision breeding of tomato traits with horticultural interest.HIGHLIGHTSGeneration of a transgenic Cas9-expressing line of tomato cv. Micro-TomUse of PVX for sgRNA delivery into Micro-Tom Cas9 plantsHeritable proof-of-concept VIGE of tomatoPHYTOENE DESATURASE(PDS)Recovery of green-flesh fruits by VIGE of tomato STAYGREEN 1 (SGR1)
Bronze Age Northern Eurasian Genetics in the Context of Development of Metallurgy and Siberian Ancestry
Authors: Childebayeva Ainash , Fricke Fabian , Rohrlach Adam Benjamin , Huang Lei , Schiffels Stephan , Vesakoski Outi , Semerau Lena , Aron Franziska , Moiseyev Vyacheslav , Khartanovich Valery , Kovtun Igor , Krause Johannes , Kuzminykh Sergey , Haak Wolfgang 
Published: October 2023

AbstractThe Eurasian Bronze Age (BA) has been described as a period of substantial human migrations, the emergence of pastoralism, horse domestication, and development of metallurgy. This study focuses on individuals associated with BA metallurgical production, specifically the Seima-Turbino (ST) phenomenon (∼2,200-1,900 BCE) associated with elaborate metal objects found across Northern Eurasia. The genetic profiles of nine ST-associated individuals vary widely ranging between ancestries maximized in individuals from the Eastern Siberian Late Neolithic/BA, and those of the Western Steppe Middle Late BA. The genetic heterogeneity observed is consistent with the current understanding of the ST metallurgical network as a transcultural phenomenon. The new data also shed light on the temporal and spatial range of an ancient Siberian genetic ancestry component, which is shared across many Uralic-speaking populations, and which we explore further via demographic modeling using additional genome-wide (2 individuals) and whole genome data (5 individuals, including a ∼30x genome) from northwestern Russia.
Modeling Stereospecific Drug Interactions with Beta-Adrenergic Receptors
Authors: Dawson John R.D. , DeMarco Kevin R. , Han Yanxiao , Bekker Slava , Clancy Colleen E. , Yarov-Yarovoy Vladimir , Vorobyov Igor 
Published: October 2023

AbstractBeta adrenergic receptors (βARs) are G protein-coupled receptors that control processes as varied as heart rhythm and vascular tone by binding agonists such as norepinephrine to induce downstream signaling pathways. Beta blockers antagonize βARs to downregulate their activity, thus reducing heart rate and lowering vascular tone. We developed new Rosetta structural modeling protocol to develop state-specific models of β1AR, expressed in cardiac myocytes, as well as β2AR, expressed in the smooth muscle cells of vasculature and other tissues, and their atomistic-scale interactions with beta-blockers using RosettaLigand. We identified structural features of drug – receptor interactions, which may account for their receptor conformational state and drug stereospecific preferences. Furthermore, we estimated structural stabilities of our models using atomistic molecular dynamics (MD) simulations. In our recent study we validated our structural models of norepinephrine-bound β2AR and its complex with stimulatory G protein via multi-microsecond MD simulations. Thus, here we mostly focused on state-dependent and stereospecific β1AR interactions with beta-blocking drugs sotalol and propranolol. We observed expected inactive receptor state preferences and structural stabilities of our models in MD simulations, but neither those simulations nor RosettaLigand docking could clearly distinguish stereospecific preferences of those drugs. This warrants consideration of alternative hypotheses and enhanced sampling MD simulations, which we discussed as well. Nevertheless, our study provides basis for understanding conformational state selectivity and stereospecificity of beta-blockers for βARs, important pharmacological targets, and may be extended to other drug classes and receptor types.Graphical abstractNorepinephrine (NE) bound active-state beta-1 adrenergic receptor (β1AR) in complex with the stimulatory G protein (Gs) heterotrimer embedded in a lipid bilayer.When expressed at the plasma membrane, the β1AR is oriented such that the ligand binding pocket (*) is accessible to ligands from the extracellular side (Ex.) of the membrane. The Gsα (red), Gβ (blue), and Gγ (yellow) subunits comprise the Gs heterotrimer. Nucleotides GDP or GTP bind Gα at the P-loop (**).Inset:Representative image of NE bound within the orthosteric ligand binding pocket.
Spores of the fungal pathogenCryptococcusexhibit cell type-specific carbon source utilization during germination
Authors: Ortiz Sébastien C. , McKeon Megan C. , Botts Michael R. , Gage Hunter , Frerichs Anna , Hull Christina M. 
Published: October 2023

AbstractSpores are critical morphotypes required for long-term survival of most fungi. Under the right environmental conditions, spores can escape dormancy and differentiate into vegetatively growing cells through the process of germination. For fatal human fungal pathogens likeCryptococcus, germination is the key differentiation process required for spores to initiate vegetative growth and ultimately cause disease; however, relatively little is known about the molecular mechanisms that control germination. To this end, we performed an extensive characterization ofCryptococcusspore germination through the morphological assessment of germinating spores, the inhibition of key eukaryotic processes, and the detailed quantification of fungal spore germination kinetics under numerous nutrient conditions. We identified temporal associations between molecular and morphological events and determined that carbon metabolism pathways (both glycolysis and oxidative phosphorylation) were required from the beginning of germination. We further determined that carbon sources are primarily used as fuel rather than as simply triggers of germination ‘commitment,’ and identified spore-specific carbon source utilization that is absent in yeast. Finally, we discovered the first spore-specific enzyme, Nth2, a trehalase that is required for germination when trehalose is the primary available carbon source. Together this work provides an extensive characterization ofCryptococcusspore germination and suggests that germination is more than simply a ‘modified cell cycle’ but is rather a highly adapted differentiation process.
Controlling Genome Topology with Sequences that Trigger Post-replication Gap Formation During Replisome Passage: TheE. coliRRS Elements
Authors: Pham Phuong , Wood Elizabeth A. , Dunbar Emma L. , Cox Michael M. , Goodman Myron F. 
Published: October 2023

ABSTRACTWe report that theEscherichia colichromosome includes novel GC-rich genomic structural elements that trigger formation of post-replication gaps upon replisome passage. The two nearly perfect 222 bp repeats, designated Replication Risk Sequences or RRS, are each 650 kb from the terminus sequencedifand flank the Ter macrodomain. RRS sequence and positioning is highly conserved in enterobacteria. At least one RRS appears to be essential unless a 200 kb region encompassing one of them is amplified. The RRS contain a G-quadruplex on the lagging strand which impedes DNA polymerase extension producing lagging strand ssDNA gaps, ≤2000 bp long, upon replisome passage. Deletion of both RRS elements has substantial effects on global genome structure and topology. We hypothesize that RRS elements serve as topological relief valves during chromosome replication and segregation. There have been no screens for genomic sequences that trigger transient gap formation. Functional analogs of RRS could be widespread, possibly including some enigmatic G-quadruplexes in eukaryotes.
Brassinosteroid recruits FERONIA to safeguard cell expansion in Arabidopsis
Authors: Chaudhary Ajeet , Hsiao Yu-Chun , Yeh Fang-Ling Jessica , Wu Hen-Ming , Cheung Alice Y. , Xu Shou-Ling , Wang Zhi-Yong 
Published: October 2023

AbstractPlant cell expansion is driven by turgor pressure and regulated by hormones. How plant cells avoid cell wall rupture during hormone-induced cell expansion remains a mystery. Here we show that brassinosteroid (BR), while stimulating cell elongation, promotes the plasma membrane (PM) accumulation of the receptor kinase FERONIA (FER), which monitors cell wall damage and in turn attenuates BR-induced cell elongation to prevent cell rupture. The GSK3-like kinase BIN2 phosphorylates FER, resulting in reduced FER accumulation and translocation from endoplasmic reticulum to PM. By inactivating BIN2, BR signaling promotes dephosphorylation and increases PM accumulation of FER, thereby enhancing the surveillance of cell wall integrity. Our study reveals a vital signaling circuit that coordinates hormone signaling with mechanical sensing to prevent cell bursting during hormone-induced cell expansion.One-Sentence SummaryBrassinosteroid recruits a cell wall integrity monitor to prevent growth-induced cell wall damage.
Aberrant functional brain network organization is associated with relapse during 1‐year follow‐up in alcohol‐dependent patients
Authors: Böhmer Justin , Reinhardt Pablo , Garbusow Maria , Marxen Michael , Smolka Michael N. , Zimmermann Ulrich S. , Heinz Andreas , Bzdok Danilo , Friedel Eva , Kruschwitz Johann D. , Walter Henrik 
Published: October 2023

AbstractAlcohol dependence (AD) is a debilitating disease associated with high relapse rates even after long periods of abstinence. Thus, elucidating neurobiological substrates of relapse risk is fundamental for the development of novel targeted interventions that could promote long‐lasting abstinence. In the present study, we analysed resting‐state functional magnetic resonance imaging (rsfMRI) data from a sample of recently detoxified patients with AD (n = 93) who were followed up for 12 months after rsfMRI assessment. Specifically, we employed graph theoretic analyses to compare functional brain network topology and functional connectivity between future relapsers (REL, n = 59), future abstainers (ABS, n = 28) and age‐ and gender‐matched controls (CON, n = 83). Our results suggest increased whole‐brain network segregation, decreased global network integration and overall blunted connectivity strength in REL compared with CON. Conversely, we found evidence for a comparable network architecture in ABS relative to CON. At the nodal level, REL exhibited decreased integration and decoupling between multiple brain systems compared with CON, encompassing regions associated with higher‐order executive functions, sensory and reward processing. Among patients with AD, increased coupling between nodes implicated in reward valuation and salience attribution constitutes a particular risk factor for future relapse. Importantly, aberrant network organization in REL was consistently associated with shorter abstinence duration during follow‐up, portending to a putative neural signature of relapse risk in AD. Future research should further evaluate the potential diagnostic value of the identified changes in network topology and functional connectivity for relapse prediction at the individual subject level.
Milk as an indicator of dietary imbalance
Authors: Lean IJ , Golder HM 
Published: October 2023

BackgroundMilk provides a readily available diagnostic fluid collected daily or more frequently on an individual animal or herd basis. Milk, as an aggregated sample in bulk tank milk (BTM) represents the status of a herd instead of a single animal. In this review, we examine the potential for milk to predict risks to efficient production, reproductive success, and health on the individual cow and herd level.FindingsFor many conditions related to disorders of metabolism including hyperlipdaemia and ketonaemia, improved individual cow milk testing may allow a temporally useful detection of metabolic disorder that can target intervention. However, the extension of these tests to the BTM is made more difficult by the tight temporal clustering of disorder to early lactation and the consequent mixing of cows at even moderately different stages of lactation. Integrating herd recording demographic information with Fourier‐transformed mid‐infrared spectra (FT‐MIR) can provide tests that are useful to identify cows with metabolic disorders. The interpretation of BTM urea and protein content provides useful indications of herd nutrition. These may provide indicators that encourage further investigations of nutritional influences on herd fertility but are unlikely to provide strong diagnostic value. The fat‐to‐protein ratio has a high specificity, but poor sensitivity for detection of fibre insufficiency and acidosis on an individual cow basis. Selenium, zinc, β‐carotene, and vitamin E status of the herd can be determined using BTM.ConclusionsThere appears to be increasing potential for the use of milk as a diagnostic fluid as more in‐parlour tests become available for individual cows. However, the BTM appears to have under‐utilised potential for herd monitoring.
Tax compliance and firm response to electronic sales monitoring
Authors: Boyer M. Martin , d'Astous Philippe 
Published: October 2023

AbstractThis paper analyzes how firms respond to an Internet of Things technology that reduces significantly the tax authorities' marginal cost of monitoring firm activity. More precisely, we analyze how mandating every restaurant of a single Canadian province to have sales recording modules (SRMs) affects restaurant sales, expenses and profits. We estimate that SRMs increase reported sales by 5.8% to 9.8% on average and that this increase is almost completely offset by an equal increase in expenses, including wages. As a result, the firms' taxable income remains mostly unchanged. Our results suggest that sales tax remittance enforcement at the firm level spills over to other firm stakeholders, such as employees and suppliers. Overall, the one‐time cost of the device needed to monitor sales more efficiently is small compared with the recurring benefits for tax authorities.
Vaping among young people—Our best defence is self‐defence
Authors: Stockings Emily A. , Gardner Lauren A. , Newton Nicola C. 
Published: October 2023

AbstractUse of electronic cigarettes (e‐cigarettes or ‘vapes’) has risen rapidly among young Australians in recent years. To combat this, on 2 May 2023, the Albanese Government announced a suite of reforms to reduce the desirability and accessibility of e‐cigarettes to young people—including a ban on disposable e‐cigarettes, restricting flavours, colours and nicotine content and requiring pharmaceutical‐like packaging. While many have welcomed this announcement, the efficacy of such reforms in reducing the availability of e‐cigarettes to young people remain to be seen, particularly given the current prescription‐only model has done little to curb youth vaping. We argue that, in an uncertain landscape where e‐cigarettes will likely remain accessible and desirable to young people, it is critical that we also upskill, empower and arm our young people with the skills, resilience, resources and knowledge to make informed and positive health decisions so that: (i) fewer young people opt to take up vaping (primary prevention); and (ii) among those who already do vape, more seek help earlier on to reduce or cease their use before dependency develops (secondary prevention). Schools are an ideal setting for the delivery of these programs, where they can be delivered en masse, integrated into existing alcohol and other drug programs and aligned with school curricula. Skills‐based school prevention programs have demonstrated significant and sustained reductions in drug‐related harms up to 7 years post‐intervention. For as long as vapes remain widely available, desirable and purposefully marketed towards young people, we believe our best defence is self‐defence.
Diabetes and pancreatic cancer risk in a multiracial cohort
Authors: Conway Rebecca B. N. , Hudson Alana G. , Munro Heather , Fu David , McClain Donald A. , Blot William J. 
Published: October 2023

AbstractAimsTo determine the relationship of diabetes with pancreatic cancer incidence among African American and Whites of similar socio‐economic status.MethodsUsing the Southern Community Cohort Study, we conducted a follow‐up during 2002–2015 of pancreatic cancer incidence of 73,378 mostly low‐income participants aged 40–79 years; 15,913 reported diabetes at baseline. Multivariable Cox analysis controlling for sex, family history of pancreatic cancer, BMI, smoking status, alcohol consumption, education, income and other important covariates, and with age as the timescale was used.ResultsTotally, 265 incident pancreatic cancer cases were observed. Pancreatic cancer risk was increased among those with diabetes (HR 1.54, CI 1.16–2.05), with similar increases among African Americans (HR 1.51, CI 1.08–2.11) and Whites (HR 1.78, CI 1.00–3.16). No trend in risk was observed for diabetes duration among those with diabetes, with HRs of 1.39 (0.91–2.11), 2.31 (1.51–3.54) and 1.23 (0.80–1.89) for <5, 5–9 and 10+ years duration, respectively. African Americans were at increased risk of pancreatic cancer (HR = 1.40, 95% CI 1.05–1.87), which persisted after adjusting for diabetes (HR 1.36, CI 1.02–1.81). The effect sizes for other pancreatic cancer risk factors with pancreatic cancer were similar by diabetes status, although a stronger association with low BMI was evident among those with diabetes.ConclusionsDiabetes increases pancreatic cancer risk similarly among African Americans and Whites in this Southern U.S. cohort.