bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem cell-laden hydrogel bioink for generation of high resolution and fidelity engineered tissues with complex geometries
Authors: Jeon Oju , Lee Yu Bin , Lee Sang Jin , Guliyeva Nazilya , Lee Joanna , Alsberg Eben
Published: April 2021

Recently, 3D bioprinting has been explored as a promising technology for biomedical applications with the potential to create complex structures with precise features. Cell encapsulated hydrogels composed of materials such as gelatin, collagen, hyaluronic acid, alginate and polyethylene glycol have been widely used as bioinks for 3D bioprinting. However, since most hydrogel-based bioinks may not allow rapid stabilization immediately after 3D bioprinting, achieving high resolution and fidelity to the intended architecture is a common challenge in 3D bioprinting of hydrogels. In this study, we have utilized shear-thinning and self-healing ionically crosslinked oxidized and methacrylated alginates (OMAs) as a bioink, which can be rapidly gelled by its self-healing property after bioprinting and further stabilized via secondary crosslinking. It was successfully demonstrated that stem cell-laden calcium-crosslinked OMA hydrogels can be bioprinted into complicated 3D tissue structures with both high resolution and fidelity. Additional photocrosslinking enables long-term culture of 3D bioprinted constructs for formation of functional tissue by differentiation of encapsulated human mesenchymal stem cells.
Organization and priming of long-term memory representations with two-phase plasticity
Authors: Luboeinski Jannik , Tetzlaff Christian
Published: April 2021

Synaptic tagging and capture (STC) is a molecular mechanism that accounts for the consolidation of synaptic changes induced by plasticity. To link this mechanism to long-term memory and thereby to the level of behavior, its dynamics on the level of recurrent networks have to be understood. To this end, we employ a biologically detailed neural network model of spiking neurons featuring STC, which models the learning and consolidation of long-term memory representations. Using this model, we investigate the effects of different organizational paradigms of multiple memory representations, and demonstrate a proof of principle for priming on long timescales. We examine these effects considering the spontaneous activation of memory representations as the network is driven by background noise. Our first finding is that the order in which the memory representations are learned significantly biases the likelihood of spontaneous activation towards more recently learned memory representations. Secondly, we find that hub-like structures counter this learning order effect for representations with less overlaps. We show that long-term depression is the mechanism underlying these findings, and that intermediate consolidation in between learning the individual representations strongly alters the described effects. Finally, we employ STC to demonstrate the priming of a long-term memory representation on a timescale of minutes to hours. As shown by these findings, our model provides a mechanistic synaptic and neuronal basis for known behavioral effects.
Predicting synaptic connectivity for large-scale microcircuit simulations usingSnudda
Authors: Hjorth J J Johannes , Kotaleski Jeanette Hellgren , Kozlov Alexander
Published: April 2021

Simulation of large-scale networks of neurons is an important approach to understanding and interpreting experimental data from healthy and diseased brains. Owing to the rapid development of simulation software and the accumulation of quantitative data of different neuronal types, it is possible to predict both computational and dynamical properties of local microcircuits in a ‘bottom-up’ manner. Simulated data from these models can be compared with experiments and ‘top-down’ modelling approaches, successively bridging the scales. Here we describe an open source pipeline, using the software Snudda, for predicting microcircuit connectivity and for setting up simulations using the NEURON simulation environment in a reproducible way. We also illustrate how to further ‘curate’ data on single neuron morphologies acquired from public databases. This model building pipeline was used to set up a first version of a full-scale cellular level model of mouse dorsal striatum. Model components from that work are here used to illustrate the different steps that are needed when modelling subcortical nuclei, such as the basal ganglia.
Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation
Authors: Serra Angela , Fratello Michele , Federico Antonio , Ojha Ravi , Provenzani Riccardo , Tasnadi Ervin , Cattelani Luca , del Giudice Giusy , Kinaret Pia Anneli Sofia , Saarimäki Laura Aliisa , Pavel Alisa , Cerullo Vincenzo , Vapalahti Olli , Horvarth Peter , Di Lieto Antonio , Yli-Kauhaluoma Jari , Balistreri Giuseppe , Greco Dario
Published: April 2021

New affordable therapeutic protocols for COVID-19 are urgently needed despite the increasing number of effective vaccines and monoclonal antibodies. To this end, there is increasing attention towards computational methods for drug repositioning andde novodrug design.

Here, we systematically integrated multiple data-driven computational approaches to perform virtual screening and prioritize candidate drugs for the treatment of COVID-19. From the set of prioritized drugs, we selected a subset of representative candidates to test in human cells. Two compounds, 7-hydroxystaurosporine and bafetinib, showed synergistic antiviral effects in ourin vitroexperiments, and strongly inhibited viral-induced syncytia formation. Moreover, since existing drug repositioning methods provide limited usable information forde novodrug design, we extracted and prioritized the chemical substructures of the identified drugs, providing a chemical vocabulary that may help to design new effective drugs.
Genomic organization of the autonomous regulatory domain ofeyelesslocus inDrosophila melanogaster
Authors: Verma Shreekant , Pathak Rashmi U , Mishra Rakesh K
Published: April 2021

InDrosophila, expression ofeyeless(ey) gene is restricted to the developing eyes and central nervous system. However, the flanking genes,myoglianin(myo), and bent (bt) have different temporal and spatial expression patterns as compared to theey. How distinct regulation ofeyis maintained is mostly unknown. Earlier, we have identified a boundary element interveningmyoandeygenes (ME boundary) that prevents the crosstalk between thecis-regulatory elements ofmyoandeygenes. In the present study, we further searched for thecis-elements that define the domain ofeyand maintain its expression pattern. We identify another boundary element betweeneyandbt, the EB boundary. The EB boundary separates the regulatory landscapes ofeyandbtgenes. The two boundaries, ME and EB, show a long-range interaction as well as interact with the nuclear architecture. This suggests functional autonomy of theeylocus and its insulation from differentially regulated flanking regions. We also identify a new Polycomb Response Element, theey-PRE, within theeydomain. The expression state of theeygene, once established during early development is likely to be maintained with the help ofey- PRE. Our study proposes a general regulatory mechanism by which a gene can be maintained in a functionally independent chromatin domain in gene-rich euchromatin.
Effects of sexual dimorphism on pollinator behaviour in a dioecious species
Authors: Moquet L. , Jacquemart A-L , Dufay M. , De Cauwer I.
Published: April 2021

Floral traits often display sexual dimorphism in insect-pollinated dioecious plant species, with male individuals typically being showier than females. While this strategy is theorized to be optimal when pollinators are abundant, it might represent a risk when they become scarce, because the disproportionately high number of visits on the most attractive sex, males, might preclude efficient pollen transfer from males to females. Here, the effect of sexual dimorphism on pollination efficiency was assessed in experimental arrays of dioeciousSilene dioicathat were exposed to one frequent visitor of the species,Bombus terrestris, and that differed in the magnitude of sexual dimorphism for either flower number or flower size. While flower size dimorphism did not impact pollination efficiency, we found that flower number dimorphism negatively affected the number of visits on female plants, on female flowers and on the number of female flowers visited after a male flower. However, flower number dimorphism had no effect on the number of pollen grains deposited per stigma, presumably because the decrease in the number of visits to female flowers was compensated by a higher number of pollen grains deposited per visit.
Quantification and uncertainty of root growth stimulation by elevated CO2in mature temperate deciduous forest
Authors: Ziegler Clare , Kulawska Aleksandra , Kourmouli Angeliki , Hamilton Liz , Shi Zongbo , MacKenzie A. Rob , Dyson Rosemary J. , Johnston Iain G.
Published: April 2021

Increasing CO2levels are a major global challenge, and the extent to which increasing anthropogenic CO2emissions can be mitigated by natural carbon sinks remains poorly understood. The uptake of elevated CO2(eCO2) by the terrestrial biosphere, and subsequent sequestration as biomass in ecosystems, may act as a negative feedback in the carbon budget, but remains hard to quantify in natural ecosystems. Here, we combine large-scale field observations of fine root stocks and flows, derived from belowground imaging and soil cores, with image analysis, stochastic modelling, and statistical inference, to elucidate belowground root dynamics in a mature temperate deciduous forest under free-air CO2enrichment to 150ppm above ambient levels. Using over 67kframes of belowground observation, we observe that eCO2leads to relatively faster root production (a peak volume fold change of 4.52 ± 0.44 eCO2versus 2.58 ± 0.21 control). We identify an increase in existing root elongation relative to root mass decay as the likely causal mechanism for this acceleration. Direct physical analysis of biomass and width measurements from 552 root systems recovered from soil cores support this picture, with lengths and widths of fine roots significantly increasing under eCO2. We use dynamic measurements to estimate fine root contributions to net primary productivity, finding an increase under eCO2, with an estimated mean annual 204 ± 93 g dw m−2yr−1eCO2versus 140 ± 60 g dw m−2yr−1control. We also quantify and discuss the uncertainties in such productivity measurements. This multi-faceted approach thus sheds quantitative light on the challenging characterisation of the eCO2response of root biomass in mature temperate forests.
Design and application of a knowledge network for automatic prioritization of drug mechanisms
Authors: Mayers Michael , Tu Roger , Steinecke Dylan , Li Tong Shu , Queralt-Rosinach Núria , Su Andrew I.
Published: April 2021

Motivation

Drug repositioning is an attractive alternative to de novo drug discovery due to reduced time and costs to bring drugs to market. Computational repositioning methods, particularly non-black-box methods that can account for and predict a drug’s mechanism, may provide great benefit for directing future development. By tuning both data and algorithm to utilize relationships important to drug mechanisms, a computational repositioning algorithm can be trained to both predict and explain mechanistically novel indications.

Results

In this work, we examined the 123 curated drug mechanism paths found in the drug mechanism database (DrugMechDB) and after identifying the most important relationships, we integrated 18 data sources to produce a heterogeneous knowledge graph, MechRepoNet, capable of capturing the information in these paths. We applied the Rephetio repurposing algorithm to MechRepoNet using only a subset of relationships known to be mechanistic in nature and found adequate predictive ability on an evaluation set with AUROC value of 0.83. The resulting repurposing model allowed us to prioritize paths in our knowledge graph to produce a predicted treatment mechanism. We found that DrugMechDB paths, when present in the network were rated highly among predicted mechanisms. We then demonstrated MechRepoNet’s ability to use mechanistic insight to identify a drug’s mechanistic target, with a mean reciprocal rank of .525 on a test set of known drug-target interactions. Finally, we walked through a repurposing example of the anti-cancer drug imantinib for use in the treatment of asthma, to demonstrate this method’s utility in providing mechanistic insight into repurposing predictions it provides.

Availability and implementation

The Python code to reproduce the entirety of this analysis is available at:https://github.com/SuLab/MechRepoNet

Contact

asu@scripps.edu

Supplementary information

Supplemental information is available at Bioinformatics online.
Increased pattern similarity in two major olfactory cortices despite higher sparseness levels
Authors: Markind Chaviva , Kundu Prosenjit , Barak Mor , Haddad Rafi
Published: April 2021

Pattern separation is a fundamental process that enhances discrimination of similar stimuli and can be achieved by sparsening the neural activity and expanding the coding space. Odor stimuli evoke patterns of activity in the olfactory bulb (OB) and these activity patterns are projected to several cortical regions that contain larger numbers of neurons and show sparser activity levels. However, whether these projected patterns are better separated is still unclear. Here we compared odor responses in the OB, anterior piriform cortex (aPC) and anterior olfactory nucleus (AON) to the exact same odor stimuli. We found that odor representations are more similar, noisier and less distinctive in aPC and AON than in the OB. The increase in similarity was observed for both similar and dissimilar odors. Modeling odor transformation from the OB to the olfactory cortex using simulated as well as actual OB odor responses as inputs, demonstrates that the observed rise in odor representation similarity can be explained by assuming biologically plausible variation in the number of OB inputs each cortical neuron receives. We discuss the possible advantages of our findings to odor processing in the aPC and AON.

Highlights

Odor representations in the aPC and AON are more correlated despite increase in sparseness levels.

Odor identity is best represented in the OB.

Variance in the number of inputs from OB can explain the reduction in odor separation.
Early low-level developmental arsenic exposure impacts mouse hippocampal synaptic function
Authors: Foley Karl F.W. , Barnett Daniel , Cory-Slechta Deborah A. , Xia Houhui
Published: April 2021

Background

Arsenic is a well-established carcinogen known to increase all-cause mortality, but its effects on the central nervous system are less well understood. Recent epidemiological studies suggest that early life exposure to arsenic is associated with learning deficits and behavioral changes, and increased arsenic exposure continues to affect an estimated 200 million individuals worldwide. Previous studies on arsenic exposure and synaptic function have demonstrated a decrease in synaptic transmission and long-term potentiation in adult rodents, but have relied on in vitro or extended exposure in adulthood. Therefore, little is known about the effect of arsenic exposure in development.

Objective

Here, we studied the effects of gestational and early developmental arsenic exposure in juvenile mice. Specifically, our objective was to investigate the impact of arsenic exposure on synaptic transmission and plasticity in the hippocampus.

Methods

C57BL/6 females were exposed to arsenic (0, 50ppb, 36ppm) in their drinking water two weeks prior to mating and continued to be exposed to arsenic throughout gestation and after parturition. We then performed field recordings in acute hippocampal slices from the juvenile offspring prior to weaning (P17-P23). In this paradigm, the juvenile mice are only exposed to arsenic in utero and via the mother’s milk.

Results

High (36ppm) and relatively low (50ppb) arsenic exposure both lead to decreased basal synaptic transmission in the hippocampus of juvenile mice. There was a mild decrease in paired-pulse facilitation in juvenile mice exposed to high, but not low, arsenic, suggesting the alterations in synaptic transmission are primarily post-synaptic. Finally, high developmental arsenic exposure led to a significant increase in long-term potentiation.

Discussion

These results suggest that indirect, ecologically-relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.
Geobacter sulfurreducensinner membrane cytochrome CbcBA controls electron transfer and growth yield near the energetic limit of respiration
Authors: Joshi Komal , Chan Chi Ho , Bond Daniel R.
Published: April 2021

Geobacter sulfurreducensutilizes extracellular electron acceptors such as Mn(IV), Fe(III), syntrophic partners, and electrodes that vary from +0.4 to −0.3 Vvs.Standard Hydrogen Electrode (SHE), representing a potential energy span that should require a highly branched electron transfer chain. Here we describe CbcBA, abc-type cytochrome essential near the thermodynamic limit of respiration when acetate is the electron donor. Mutants lackingcbcBAceased Fe(III) reduction at −0.21 Vvs.SHE, could not transfer electrons to electrodes between −0.21 and −0.28 V, and could not reduce the final 10% – 35% of Fe(III) minerals. As redox potential decreased during Fe(III) reduction,cbcBAwas induced with the aid of the regulator BccR to become one of the most highly expressed genes inG. sulfurreducens. Growth yield (CFU/mM Fe(II)) was 112% of WT in ΔcbcBA, and deletion ofcbcL(a differentbc-cytochrome essential near −0.15 V) in ΔcbcBAincreased yield to 220%. Together with ImcH, which is required at high redox potentials, CbcBA represents a third cytoplasmic membrane oxidoreductase inG. sulfurreducens. This expanding list shows how these important metal-reducing bacteria may constantly sense redox potential to adjust growth efficiency in changing environments.
Collateral Responses to Classical Cytotoxic Chemotherapies are Heterogeneous and Sensitivities are Sparse
Authors: Dalin Simona , Lauffenburger Douglas A. , Hemann Michael T.
Published: April 2021

Chemotherapy resistance is a major obstacle to curing cancer patients. Combination drug regimens have shown promise as a method to overcome resistance; however, to date only some cancers have been cured with this method. Collateral sensitivity – the phenomenon whereby resistance to one drug is co-occurrent with sensitivity to a second drug – has been gaining traction as a promising new concept to guide rational design of combination regimens. Here we survey collateral responses to acquisition of resistance to four classical chemotherapy agents. Although collateral sensitivities have been documented for antibiotics and targeted cancer therapies, we did not observe collateral sensitivities to any of the cytotoxic agents we studied. Interestingly, we did observe heterogeneity in the phenotypic response to acquisition of resistance to each drug, suggesting the existence of multiple different states of resistance for each drug. Surprisingly, this phenotypic heterogeneity was unrelated to transcriptomic heterogeneity in the resistant cell lines. These features of phenotypic and transcriptomic heterogeneity must be taken into account in future studies of treated tumor subclones and in design of chemotherapy combinations.
Extensive transgressive gene expression in testis but not ovary in the homoploid hybrid Italian sparrow
Authors: Yazdi Homa Papoli , Ravinet Mark , Rowe Melissah , Sætre Glenn-Peter , Øien Guldvog Caroline , Eroukhmanoff Fabrice , Marzal Alfonso , Magallanes Sergio , Runemark Anna
Published: April 2021

Hybridization can result in novel allelic combinations which can impact the hybrid phenotype through changes in gene expression. While mis-expression in F1 hybrids is well documented, how gene expression evolves in stabilized hybrid taxa remains an open question. As gene expression evolves in a stabilizing manner, break-up of co-evolvedcis- andtrans-regulatory elements could lead to transgressive patterns of gene expression in hybrids. Here, we address to what extent gonad gene expression has evolved in an established and stable homoploid hybrid, the Italian sparrow (Passer italiae). Through comparison of gene expression in gonads from individuals of the two parental species (i.e., house and Spanish sparrow) to that of Italian sparrows, we find evidence for strongly transgressive expression in male Italian sparrows - 22% of testis genes exhibit expression patterns outside the range of both parent species. In contrast, Italian sparrow ovary expression was similar to that of one of the parent species, the house sparrow (Passer domesticus). Moreover, the Italian sparrow testis transcriptome is 26 times as diverged from those of the parent species as the parental transcriptomes are from each other, despite being genetically intermediate. This highlights the potential for regulation of gene expression to produce novel variation following hybridization. Genes involved in mitochondrial respiratory chain complexes and protein synthesis are enriched in the subset that is over-dominantly expressed in Italian sparrow testis, suggesting that selection on key functions have molded the hybrid Italian sparrow transcriptome.
A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory
Authors: Lopez-Rojas Jeffrey , de Solis Christopher A. , Leroy Felix , Kandel Eric R. , Siegelbaum Steven A.
Published: April 2021

The storage of information by the hippocampus in long-term memory is thought to involve two distinct but related processes. First, the hippocampus determines whether a given stimulus is novel or familiar; next, the hippocampus stores the novel information in long-term memory. To date, the neural circuits that detect novelty and their relation to the circuits that store information of a specific memory are poorly understood. Here we address this question by examining the circuits by which the CA2 region of the hippocampus, which is essential for social memory, both detects social novelty and stores social memory. CA2, like the more thoroughly studied CA1 region, receives its major excitatory input from the entorhinal cortex through both a direct monosynaptic and indirect trisynaptic pathway. We find that the direct inputs to CA2 from the lateral entorhinal cortex, but not the indirect trisynaptic inputs, provide social information that is required for social memory. However, these direct inputs fail to discriminate a novel from a familiar animal. Thus, social novelty and social identity signals are likely conveyed through separate pathways, with the entorhinal cortex providing specific multisensory information about an animal’s identity and novelty detection requiring a local computation within CA2.
Dynamics of absolute and relative disparity processing in human visual cortex
Authors: Kaestner Milena , Evans Marissa L. , Chen Yulan D. , Norcia Anthony M.
Published: April 2021

Cortical processing of binocular disparity is believed to begin in V1 where cells are sensitive to absolute disparity, followed by the extraction of relative disparity in higher visual areas. While much is known about the cortical distribution and spatial tuning of disparity-selective neurons, the relationship between their spatial and temporal properties is less well understood. Here, we use steady-state Visual Evoked Potentials and dynamic random dot stereograms to characterize the temporal dynamics of spatial mechanisms in human visual cortex that are primarily sensitive to either absolute or relative disparity. Stereograms alternated between disparate and non-disparate states at 2 Hz. By varying the spatial frequency content of the disparate fields from a planar surface to corrugated ones, we biased responses towards absolute vs. relative disparities. Reliable Components Analysis was used to derive two dominant sources from the 128 channel EEG records. The first component (RC1) was maximal over the occipital pole while the second component (RC2) was maximal over right lateral occipital electrodes. In RC1, first harmonic responses were sustained, tuned for corrugation frequency, and sensitive to the presence of disparity references, consistent with prior psychophysical sensitivity measurements. By contrast, the second harmonic, associated with transient processing, was not spatially tuned and was indifferent to references, consistent with it being generated by an absolute disparity mechanism. In RC2, the sustained response component showed similar tuning and sensitivity to references. However, sensitivity for absolute disparity dropped off, and transient signals were mainly driven by the lowest corrugation frequencies.

SIGNIFICANCE STATEMENT

Sustained and transient mechanisms have been demonstrated across sensory systems and may reflect a common coding strategy. This strategy may be useful for the analysis of the form and duration of complex events in the case of sustained signals, and the onset and location of events in the case of transient signals. Here, we provide direct neural correlates of sustained and transient disparity mechanisms in human visual cortex. Early visual cortex is sensitive to both relative and absolute disparity, with the former being processed in a sustained fashion and the latter in a more transient fashion. Outside of early visual cortex, sustained relative disparity responses are readily measurable, but transient responses and responses to absolute disparity are not.
Arabidopsis CALMODULIN-BINDING PROTEIN 60b plays dual roles in plant immunity
Authors: Huang Weijie , Wu Zhongshou , Tian Hainan , Li Xin , Zhang Yuelin
Published: April 2021

Arabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1) and CALMODULIN-BINDING PROTEIN 60g (CBP60g) are two master transcription factors that regulate many defense-related genes in plant immunity. They are required for immunity downstream of the receptor-like protein SUPPRESSOR OF NPR1-1, CONSTITUTIVE 2 (SNC2). Constitutive defense responses in the gain-of-function autoimmunesnc2-1Dmutant are modestly affected by eithersard1orcbp60gsingle mutants, but completely suppressed by thesard1 cbp60gdouble mutant. Here we report that CBP60b, another member of the CBP60 family, also functions as a positive regulator of SNC2-mediated immunity. Loss-of-function mutations ofCBP60bsuppress the constitutive expression ofSARD1and enhanced disease resistance incbp60g-1 snc2-1D, whereas over-expression ofCBP60bleads to elevatedSARD1expression and constitutive defense responses. In addition, transient expression ofCBP60binNicotiana benthamianaactivates the expression of thepSARD1::luciferasereporter gene. Chromatin immunoprecipitation assay further showed that CBP60b is recruited to the promoter region ofSARD1, suggesting that it directly regulatesSARD1expression. Interestingly, knocking outCBP60bin the wild type background leads to ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)-dependent autoimmunity, suggesting that CBP60b is required for the expression of a guardee/decoy or a negative regulator in immunity mediated by receptors carrying an N-terminal TIR (Toll-interleukin-1 receptor-like) domain.

Significance statement

Arabidopsis SARD1 serves as a master transcription factor in plant immunity. In this study, we showed that CBP60b positively regulatesSARD1expression, and TIR signaling is activated when CBP60b is inactivated.
Dopaminergic but not Cholinergic Neurodegeneration is Correlated with Gait Disturbances in PINK1 Knockout Rats
Authors: DeAngelo VM , Hilliard JD , McConnell GC
Published: April 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by gait dysfunction in later stages of the disease. PD hallmarks include a decrease in stride length, run speed, and swing time; an increase in stride time, stance time, and base of support; dopaminergic degeneration in the basal ganglia; and cholinergic degeneration in the pedunculopontine nucleus (PPN). A progressive animal model of PD is needed to identify treatments for gait dysfunction. The goal of this study was to quantify progressive gait degeneration in PTEN-induced putative kinase 1 knockout (P1KO) rats and investigate neurodegeneration as potential underlying mechanisms. Gait analysis was performed in male P1KO and wild-type rats at 5 and 8 months of age and immunohistochemical analysis at 8 months. Multiple parameters of volitional gait were measured using a runway system. P1KO rats exhibited significant gait deficits at 5 months, but not 8 months. Gait abnormalities improved over time suggesting compensation during behavioral testing. At 8 months a 15% loss of tyrosine hydroxylase (TH) in the striatum, a 27% loss of TH-positive cells in the substantia nigra pars compacta, and no significant loss of choline acetyltransferase-positive cells in the PPN was found. Dopaminergic cell loss may contribute to gait deficits in the P1KO model, but not cholinergic cell loss. The P1KO rat with the greatest dopamine loss exhibited the most pronounced PD-like gait deficits, highlighting variability within the model. Further analysis is required to determine the suitability of the P1KO rat as a progressive model of gait abnormalities in PD.
“The green peach aphid,Myzus persicae,transcriptome in response to a circulative, nonpropagative polerovirus,Potato leafroll virus”
Authors: Patton MacKenzie F. , Hansen Allison K. , Casteel Clare L.
Published: April 2021

Viruses in theLuteoviridaefamily, such asPotato leafroll virus(PLRV), are transmitted by aphids in a circulative and nonpropagative mode. This means the virions enter the aphid body through the gut when they feed from infected plants and then the virions circulate through the hemolymph to enter the salivary glands before being released into the saliva. Although these viruses do not replicate in their insect vectors, previous studies have demonstrated viruliferous aphid behavior is altered and the obligate symbiont of aphids,Buchnera aphidocola,may be involved in transmission. Here we provide the transcriptome of green peach aphids (Myzus persicae) carryingPLRVand virus-free control aphids using Illumina sequencing. Over 150 million paired-end reads were obtained through Illumina sequencing, with an average of 19 million reads per library. The comparative analysis identified 134 differentially expressed genes (DEGs) between theM. persicaetranscriptomes, including 64 and 70 genes that were down- and up-regulated in aphids carrying PLRV, respectively. Using functional classification in the GO databases, 80 of the DEGs were assigned to 391 functional subcategories at category level 2. The most highly up-regulated genes in aphids carrying PLRV were cytochrome p450s, genes related to cuticle production, and genes related to development, while genes related to histone and histone modification were the most down-regulated. PLRV aphids had reducedBuchneratiter and lower abundance of severalBuchneratranscripts related to stress responses and metabolism. These results suggest carrying PLRV may reduce both aphid andBuchneragenes in response to stress. This work provides valuable basis for further investigation into the complicated mechanisms of circulative and nonpropogative transmission.
Intranasal oxytocin modulates very early visual processing of emotional faces
Authors: Hugrass Laila , Labuschagne Izelle , Mu Eveline , Price Ariane , Crewther David P
Published: April 2021

Functional imaging and behavioural studies have shown that the neuropeptide oxytocin influences processing of emotional faces. However, it is not clear whether these effects reflect modulation at an early or late stage of affective processing. We investigated the effects of oxytocin administration on early and late visual evoked potentials (VEP) in response to faces with neutral, fearful and happy expressions. In addition, we measured multifocal VEP and its associated nonlinearities to ascertain whether any changes observed in electrophysiology were indicative of a generalised effect or of one tied strictly to emotional processing. In a randomized, double-blind, cross-over design, 27 healthy male participants self-administered a nasal spray of either oxytocin (24 IU) or placebo. At very early latencies (40-60ms), oxytocin reduced right-temporal responses to fearful faces (d= .51), and central responses to both fearful (d= .48) and neutral faces (d= .54). For left occipito-temporal electrode sites, oxytocin decreased P100 reactivity to fearful expressions (d= 0.72). Oxytocin also decreased the amplitudes of the vertex positive potential (140-180ms) and late positive potential (400-600ms), regardless of whether the faces had fearful, happy or neutral expressions. The mfVEP showed no signs of selective magno-or parvo-cellular peak modulation comparing OXT with placebo with either low or high contrast stimulation. These results suggest that at early stages of visual processing, nasal oxytocin modulates responses to facial emotions, whereas at later stages of visual processing, it appears to influence more general face processing mechanisms. In addition, the measurable effects of OXT appear to be not a result of generalized brain change, but systematically related to emotional processing.
Humoral and cellular immune responses against SARS-CoV-2 variants and human coronaviruses after single BNT162b2 vaccination
Authors: Stankov Metodi V. , Cossmann Anne , Bonifacius Agnes , Dopfer-Jablonka Alexandra , Ramos Gema Morillas , Gödecke Nina , Scharff Anna Zychlinsky , Happle Christine , Boeck Anna-Lena , Tran Anh Thu , Pink Isabell , Hoeper Marius M. , Blasczyk Rainer , Winkler Martin S. , Nehlmeier Inga , Kempf Amy , Hofmann-Winkler Heike , Hoffmann Markus , Eiz-Vesper Britta , Pöhlmann Stefan , Behrens Georg M.N.
Published: April 2021

Vaccine-induced neutralizing antibodies are key in combating the COVID-19 pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and disease for prolonged periods. The emergence of SARS-CoV-2 variants of concern (VOC), B.1.1.7 (United Kingdom), B.1.351 (South Africa) and P.1 (Brazil), may reinforce this issue with the latter two being able to evade control by antibodies. We assessed humoral and T cell responses against SARS-CoV-2 WT and VOC and endemic human coronaviruses (hCoV) that were induced after single and double vaccination with BNT162b2. Despite readily detectable IgG against the receptor-binding domain (RBD) of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T cell frequencies reactive for WT, B.1.1.7 and B.1.351 variants. These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.
Increased neurotoxicity due to activated immune-inflammatory and nitro-oxidative stress pathways in patients with suicide attempts: a systematic review and meta-analysis
Authors: Vasupanrajit Asara , Jirakarn Ketsupa , Tunvirachaisakul Chavit , Maes Michael
Published: April 2021

Background

Suicide attempts (SA) frequently occur in patients with mood disorders and schizophrenia, which are both accompanied by activated immune-inflammatory and nitro-oxidative (IO&NS) pathways.

Methods

We searched PubMed, Google Scholar, and Web of Science, for articles published from inception until February 1, 2021. We included studies that compared blood biomarkers in psychiatric patients with (SA+) and without SA (SA-) and heathy controls and we combined different IO&NS biomarkers into immune, inflammatory, and neurotoxic profiles and used meta-analysis (random-effect model with restricted maximum-likelihood) to delineate effect sizes with 95% confidence interval (CI).

Findings

Our search included 51 studies comprising 4.945 SA+ patients and 24.148 controls. We stratified the control group into healthy controls and SA-patients. SA+ patients showed significantly (p<0.001) increased immune activation (SMD: 1.044; CI: 0.599-1.489), inflammation (SMD: 1.109; CI: 0.505, 1.714), neurotoxicity (SMD: 0.879; CI: 0.465, 1.293), and lowered neuroprotection (SMD: 0.648; CI: 0.354, 0.941) as compared with healthy controls. When compared with SA-patients, those with SA+ showed significant (p<0.001) immune activation (SMD: 0.290; CI: 0.183, 0.397), inflammation (SMD: 0.311; CI: 0.191, 0.432), and neurotoxicity (SMD: 0.315; CI: 0.198, 0.432), and lowered neuroprotection (SMD: 0.341; CI: 0.167, 0.515). Patients with current, but not lifetime, SA showed significant (p<0.001) levels of inflammation and neurotoxicity as compared with controls.

Conclusions

Patients with immune activation are at a higher risk of SA which may be explained by increased neurotoxicity due to inflammation and nitro-oxidative stress. This meta-analysis discovered new biomarkers of SA and therapeutic targets to treat individuals with SA.
lamaGOET: an interface for quantum crystallography
Authors: Malaspina Lorraine A. , Genoni Alessandro , Grabowsky Simon
Published: April 2021

In quantum crystallography, theoretical calculations and crystallographic refinements are closely intertwined. This means that the employed software must be able to perform both quantum-mechanical calculations and crystallographic least-squares refinements. So far, the program Tonto is the only one able to do that. The lamaGOET interface described herein deals with this issue since it interfaces dedicated quantum-chemical software (the widely used Gaussian package and the specialized ELMOdb program) with the refinement capabilities of Tonto. Three different flavours of quantum-crystallographic refinements of the dipetide glycyl-L-threonine dihydrate are presented to showcase the capabilities of lamaGOET: Hirshfeld atom refinement (HAR), HAR-ELMO, namely HAR coupled with extremely localized molecular orbitals, and X-ray constrained wavefunction fitting.
Identification of climate policy knowledge needs: a stakeholders consultation approach
Authors: Karakosta Charikleia , Flamos Alexandros , Forouli Aikaterini
Published: April 2021

Purpose

The purpose of this paper is to identify knowledge gaps on insinuations of possible directions of European Union (EU) and international climate policies.

Design/methodology/approach

This study has used participatory approach of highly experienced stakeholders’ engagement, involved directly or indirectly in the process of policymaking. A range of priority issues has been initially identified through desk analysis and key stakeholders have been selected and invited to partake in the process. Preliminary results have been validated through interaction with stakeholders during a series of workshops.

Findings

The results show the identification of a series of sectors, where climate policy is expected to focus in the future and the definition of 11 specific topics upon which knowledge gaps are expected to appear. Results on the identified knowledge needs are analysed and categorized by each prioritized main topic and compared with literature findings. Emphasis is identified to be placed on the topics of renewable energy, EU climate policy and international climate negotiations, which are the most popular ones, followed by energy policy and energy efficiency.

Originality/value

A key element of the approach is the consideration of key experts’ feedback on their specific area of expertise, instead of general public engagement, therefore leading to accurate results. Despite the fact that our approach was applied to a specific problem, the overall analysis could provide a framework for supporting applications in various problems in the field of priorities’ identification and even expanding to decision-making problems.
Farmers’ perspectives
Authors: Chepkoech Winifred , Mungai Nancy W. , Stöber Silke , Bett Hillary K. , Lotze-Campen Hermann
Published: April 2021

Purpose

Understanding farmers’ perceptions of how the climate is changing is vital to anticipating its impacts. Farmers are known to take appropriate steps to adapt only when they perceive change to be taking place. This study aims to analyse how African indigenous vegetable (AIV) farmers perceive climate change in three different agro-climatic zones (ACZs) in Kenya, identify the main differences in historical seasonal and annual rainfall and temperature trends between the zones, discuss differences in farmers’ perceptions and historical trends and analyse the impact of these perceived changes and trends on yields, weeds, pests and disease infestation of AIVs.

Design/methodology/approach

Data collection was undertaken in focus group discussions (FGD) (N = 211) and during interviews with individual farmers (N = 269). The Mann–Kendall test and regression were applied for trend analysis of time series data (1980-2014). Analysis of variance and least significant difference were used to test for differences in mean rainfall data, while a chi-square test examined the association between farmer perceptions and ACZs. Coefficient of variation expressed as a percentage was used to show variability in mean annual and seasonal rainfall between the zones.

Findings

Farmers perceived that higher temperatures, decreased rainfall, late onset and early retreat of rain, erratic rainfall patterns and frequent dry spells were increasing the incidences of droughts and floods. The chi-square results showed a significant relationship between some of these perceptions and ACZs. Meteorological data provided some evidence to support farmers’ perceptions of changing rainfall. No trend was detected in mean annual rainfall, but a significant increase was recorded in the semi-humid zone. A decreasing maximum temperature was noted in the semi-humid zone, but otherwise, an overall increase was detected. There were highly significant differences in mean annual rainfall between the zones. Farmers perceived reduced yields and changes in pest infestation and diseases in some AIVs to be prevalent in the dry season. This study’s findings provide a basis for local and timely institutional changes, which could certainly help in reducing the adverse effects of climate change.

Originality/value

This is an original research paper and the historical trends, farmers’ perceptions and effects of climate change on AIV production documented in this paper may also be representative of other ACZs in Kenya.
Effectiveness and Efficiency of Strategic and Systemic Therapy in Naturalistic Settings: Preliminary Results from a Systemic Practice Research Network (SYPRENE)
Authors: Vitry Grégoire , Pakrosnis Rytis , Brosseau Olivier Gabriel , Duriez Nathalie
Published: April 2021

SYPRENE, an international digital systemic practice research network (PRN), was established in 2014 to fill the gap in practice‐based research on the effectiveness and efficiency of systemic therapies, starting with strategic therapies. This article reports initial outcome results. So far, twenty‐seven therapists from several countries using the MRI brief therapy strategic approach have collected data for a wide range of problem diagnoses. Data are reported here for 1,150 completed cases. The drop‐out rate was 19%. Significant improvement or complete problem resolution was reported by therapists in 80% and by patients in 90% of cases, with an average of 5.4 sessions and 5.3 months of treatment. Patients reported significant improvement on the GHQ‐12 with a large effect size, and 76% of cases were evaluated as reaching reliable and clinically significant change.

Practitioner points

SYPRENE is a digital practice research network

Outcome data have been collected on 1,079 cases.

Evidence supports the effectiveness of strategic therapy.
Resistance and fitness costs in diamondback moths after selection using broflanilide, a novel meta‐diamide insecticide
Authors: Sun Xi , Wei Rui , Li Linhong , Zhu Bin , Liang Pei , Gao Xiwu
Published: April 2021

The diamondback moth (DBM) Plutella xylostella (L.) (Lepidoptera: Plutellidae) is an insect pest found around the world that feeds on cruciferous crops. The DBM has become resistant to most insecticides in current use in the field. Broflanilide is a novel meta‐diamide insecticide that binds to a new site on the γ‐aminobutyric acid receptor and very efficiently protects against most pests in the order Lepidoptera, including DBM. In this study, the resistance of a laboratory‐bred susceptible strain of DBM to broflanilide and the fitness costs posed by broflanilide to the DBM were evaluated. The DBM had no obvious resistance to broflanilide after 10 generations of selection. The realized heritability h2 was 0.033, suggesting a low risk of resistance developing in this strain. The F10 generation had no cross‐resistance to the insecticides abamectin and endosulfan (which target the γ‐aminobutyric acid receptor) and chlorantraniliprole (which targets a non‐γ‐aminobutyric acid receptor). The specific activities of important detoxification enzymes (cytochrome P450 monooxygenase, esterase, and glutathione S‐transferase) were not obviously altered. However, the larval stage was prolonged and the adult stage was shortened significantly in F11 generation than the F0 generation. The total preoviposition period TPOP significantly prolonged 1.90 d in F11 generation. The fitness value Rf (0.93) was lower for the F11 generation than the F0 generation. The results indicated that long‐term exposure to broflanilide exerts clear fitness costs in the DBM. This information will be useful in identifying reasonable broflanilide application guidelines for managing broflanilide resistance in the DBM.
The development of leaving care law, policy, and practice in India
Authors: Modi Kiran , Wadhwa Aneesha , Prasad Leena
Published: April 2021

Adoption, kinship care, and foster care are the oldest known forms of alternative care in India. Whilst these are recognized as the most appropriate forms of care today, institutional care has become the most dominant form of care in India in the last 100 years, although it is meant to be ‘a measure of last resort’. As in most countries, childcare institutions in India cater for children up to 18 years old. The sudden withdrawal of support at 18 leaves these young people facing heightened challenges and poorer outcomes on the journey to independence, not only because of their fractured pasts but also due to a lack of planned interventions towards preparing them for life. This paper, based on an extensive desk review, chronologically examines the evolution of aftercare laws and practices in India along with the factors that contributed to the rise of institutional care. Reference is made to the influence of the criminal justice system on aftercare and the impact of India's ratification of United Nations Convention on Rights of the Child, the movement from a welfare to rights‐based approach. The paper concludes by discussing the current challenges and the possible way forward for care leavers in India.