bluuebunny/crossref_metadata_2025_split huggingface dataset:
BrainAGE: Revisited and reframed machine learning workflow
Authors: Kalc Polona , Dahnke Robert , Hoffstaedter Felix , Gaser Christian ,   Alzheimer’s Disease Neuroimaging Initiative
Published: November 2022

AbstractSince the introduction of the BrainAGE method (Franke et al., 2010), novel machine learning methods of brain age prediction have continued to emerge. The idea of estimating the chronological age from magnetic resonance images proved to be an interesting field of research due to the relative simplicity of its interpretation and its potential use as a biomarker of brain health. We revised our previous BrainAGE approach, originally utilising relevance vector regression (RVR), and substituted it with Gaussian process regression (GPR), which enables more stable processing of larger datasets, such as the UK Biobank (UKB). In addition, we extended the global BrainAGE approach to regional BrainAGE, providing spatially specific scores for 5 brain lobes per hemisphere. We tested the performance of the new algorithms under several different conditions and investigated their validity on the ADNI and schizophrenia samples, as well as on a synthetic dataset of neocortical thinning. The results show an improved performance of the reframed global model on the UKB sample with a mean absolute error (MAE) of less than 2 years and a significant difference in BrainAGE between healthy participants and patients with Alzheimer’s disease and schizophrenia. Moreover, the workings of the algorithm show meaningful effects for a simulated neocortical atrophy dataset. The regional BrainAGE model performed well on two clinical samples, showing disease-specific patterns for different levels of impairment. The results demonstrate that the new improved algorithms provide reliable and valid brain age estimations.
A method for generating user-defined circular single-stranded DNA from plasmid DNA using Golden Gate intramolecular ligation
Authors: Strawn Isabell K. , Steiner Paul J. , Newton Matilda S. , Whitehead Timothy A. 
Published: November 2022

AbstractConstruction of user-defined long circular single stranded DNA (cssDNA) and linear single stranded DNA (lssDNA) is important for various biotechnological applications. Many current methods for synthesis of these ssDNA molecules do not scale to multi-kilobase constructs. Here we present a robust methodology for generating user-defined cssDNA employing Golden Gate assembly, a nickase, and exonuclease degradation. Our technique is demonstrated for three plasmids with insert sizes ranging from 2.1-3.4 kb, requires no specialized equipment, and can be accomplished in five hours with a yield of 33-43 % of the theoretical. To produce lssDNA, we evaluated different CRISPR-Cas9 cleavage conditions and report a 52 ± 8% cleavage efficiency of cssDNA. Our method presented here can make ssDNA readily available to biotechnology researchers.
Single-molecule tracking reveals the functional allocation,in vivointeractions and spatial organization of universal transcription factor NusG
Authors: el Sayyed Hafez , Pambos Oliver J. , Stracy Mathew , Gottesman Max E. , Kapanidis Achillefs N. 
Published: November 2022

AbstractBacterial gene expression is highly regulated to allow cells to grow and adapt. Much regulation occurs during transcription elongation, where RNA polymerase (RNAP) extends nascent RNA transcripts aided by global and universally-conserved elongation factor NusG. NusG modulates transcription by inhibiting pausing and backtracking; promoting anti-termination on ribosomal RNA (rrn) operons; coupling transcription with translation on mRNA genes; and stimulating Rho-dependent termination on toxic genes. Despite extensive work on NusG, its functional allocation and spatial distributionin vivois unknown. Here, we addressed these long-standing questions using single-molecule tracking and super-resolution imaging of NusG in liveE. colicells. We found that, under conditions of moderate growth, NusG is mainly present as a population that associates indirectly with the chromosome via RNAP in transcription elongation complexes, and a slowly diffusing population we identified as a NusG complex with the 30S ribosomal subunit; this complex offers a “30S-guided” path for NusG to enter transcription elongation. Only ~10% of total NusG was fast-diffusing, with the mobility of this population suggesting that free NusG interacts non-specifically with DNA for >50% of the time. Using antibiotics and deletion mutants, we showed that most chromosome-associated NusG is involved inrrnanti-termination and in transcriptiontranslation coupling. NusG involvement inrrnanti-termination was mediated via its participation in phase-separated transcriptional condensates. Our work illuminates the diverse activities of a central regulator while offering a guide on how to dissect the roles of multi-functional machines using in vivo imaging.
Pisces: A multi-modal data augmentation approach for drug combination synergy prediction
Authors: Xu Hanwen , Lin Jiacheng , Woicik Addie , Liu Zixuan , Ma Jianzhu , Zhang Sheng , Poon Hoifung , Wang Liewei , Wang Sheng 
Published: November 2022

AbstractDrug combination therapy is promising for cancer treatment through simultaneously reducing resistance and improving efficacy. Machine learning approaches to drug combination response prediction can prioritize experiments and discover new combinations, but require lots of training data in order to fit the nonlinearity of synergistic effect. Here, we propose Pisces, a novel machine learning approach for drug combination synergy prediction. The key idea of Pisces is to augment the sparse drug combination dataset by creating multiple views for each drug combination based on its different modalities. We combined eight different modalities of a single drug to create 64 augmented views for a pair of drugs, effectively expanding the size of the original data 64 times. Pisces obtained state-of-the-art results on cell-line-based drug synergy prediction, xenograft-based drug synergy prediction, and drug-drug interaction prediction. By interpreting Pisces’s predictions using a genetic interaction network, we further identified a breast cancer drug-sensitive pathway from BRCA cell lines in GDSC. We validated this pathway on an independent TCGA-BRCA tumor dataset and found that patients with this pathway activated had substantially longer survival time. Collectively, Pisces effectively predicts drug synergy and drug-drug interactions through augmenting the original dataset 64 times, and can be broadly applied to various biological applications that involve a pair of drugs.
Haptoglobin buffers lipopolysaccharides to safeguard against aberrant NFκB activation
Authors: Zein Laura , Grossmann Josina , Swoboda Helena , Borgel Christina , Wilke Bernhard , Awe Stephan , Nist Andrea , Stiewe Thorsten , Stehling Oliver , Freibert Sven-Andreas , Adhikary Till , Chung Ho-Ryun 
Published: November 2022

AbstractIt has remained yet unclear which soluble factors regulate the anti-inflammatory macrophage phenotype observed in both homeostasis and tumourigenesis. We show here that haptoglobin, a major serum pro-tein with elusive immunoregulatory properties, binds and buffers serum-borne bacterial lipopolysaccharides to attenuate activation of NFκB in macrophages. Haptoglobin binds different lipopolysaccharides with low micromolar affinities. Given its abundance, haptoglobin constitutes a buffer for lipopolysaccharides, shielding them to safeguard against aberrant inflammatory reactions caused by small fluctuations. Concordantly, NFκB activation by haptoglobin-associated lipopolysaccharides was delayed relative to stimulation with pure lipopolysaccharide. Our findings warrant evaluation of therapeutic benefits of haptoglobin for inflammatory conditions and re-evaluation of purification strategies. Finally, they allow to elucidate mechanisms of enhanced immunosuppression by oncofetal haptoglobin.
Neurogenetic identification of mosquito sensory neurons
Authors: Konopka Joanna K. , Task Darya , Poinapen Danny , Potter Christopher J. 
Published: November 2022

SummaryAnophelesmosquitoes, as vectors for the malaria parasite, are a global threat to human health. To find and bite a human, they utilize neurons within their sensory appendages. However, the identity and quantification of sensory appendage neurons are lacking. Here we use a neurogenetic approach to label all neurons inAnopheles coluzziimosquitoes. We utilize the Homology Assisted CRISPR Knock-in (HACK) approach to generate aT2A-QF2wknock-in of the synaptic genebruchpilot. We use a membrane-targeted GFP reporter to visualize the neurons in the brain and to quantify neurons in all major chemosensory appendages (antenna, maxillary palp, labella, tarsi). By comparing labeling of brp>GFP and Orco>GFP mosquitoes, we predict the extent of neurons expressing Ionotropic Receptors or other chemosensory receptors. This work introduces a valuable genetic tool for the functional analysis ofAnophelesmosquito neurobiology and initiates characterization of the sensory neurons that guide mosquito behavior.Graphical Abstract
Whole-brain afferent input mapping to functionally distinct brainstem noradrenaline cell types
Authors: Sulkes Cuevas Jessica , Watanabe Mayumi , Uematsu Akira , Johansen Joshua P. 
Published: November 2022

AbstractThe locus coeruleus (LC) is a small region in the pons and the main source of noradrenaline (NA) to the forebrain. While traditional models suggested that all LC-NA neurons project indiscriminately throughout the brain, accumulating evidence indicates that these cells can be heterogeneous based on their anatomical connectivity and behavioral functionality and exhibit distinct coding modes. How LC-NA neuronal subpopulations are endowed with unique functional properties is unclear. Here, we used a viral-genetic approach for mapping anatomical connectivity at different levels of organization based on inputs and outputs of defined cell classes. Specifically, we studied the whole-brain afferent inputs onto two functionally distinct LC-NA neuronal subpopulations which project to amygdala or medial prefrontal cortex (mPFC). We found that the global input distribution is similar for both LC-NA neuronal subpopulations. However, finer analysis demonstrated important differences in inputs from specific brain regions. Moreover, sex related differences were apparent, but only in inputs to amygdala-projecting LC-NA neurons. These findings reveal a cell type and sex specific afferent input organization which could allow for context dependent and target specific control of NA outflow to forebrain structures involved in emotional control and decision making.
Supramodal Shape Representation in the Human Brain
Authors: Xu Yangwen , Vignali Lorenzo , Sigismondi Federica , Crepaldi Davide , Bottini Roberto , Collignon Olivier 
Published: November 2022

AbstractWe can sense an object’s shape by vision or touch. Previous studies suggested that the inferolateral occipitotemporal cortex (ILOTC) implements supramodal shape representations as it responds more to seeing or touching objects than shapeless textures. However, such activation in the anterior portion of the ventral visual pathway could be due to the conceptual representation of an object or visual imagery triggered by touching an object. We addressed these possibilities by directly comparing shape and conceptual representations in early blind (who lack visual experience/imagery) and sighted participants. We found that bilateral ILOTC in both groups showed stronger activation during a shape verification task than during a conceptual verification task made on the names of the same manmade objects. Moreover, the distributed activity in the ILOTC encoded shape similarity but not conceptual association among objects. Besides the ILOTC, we also found shape representation in both groups’ bilateral ventral premotor cortices and intraparietal sulcus, a frontoparietal circuit relating to object grasping and haptic processing. In contrast, the conceptual verification task activated both groups’ left perisylvian brain network relating to language processing, and, interestingly, the cuneus in early blind participants only. The ILOTC had stronger functional connectivity to frontoparietal circuit than to the left perisylvian network, forming a modular structure specialized in shape representation. Our results conclusively support that the ILOTC selectively implements shape representation independently of visual experience, and this unique functionality likely comes from its privileged connection to the frontoparietal haptic circuit.
The shadowing effect of initial expectation on learning asymmetry
Authors: Sun Jingwei , Ni Yinmei , Li Jian 
Published: November 2022

AbstractEvidence for positivity and optimism bias abounds in high-level belief updates. However, no consensus has been reached regarding whether learning asymmetries exists in more elementary forms of updates such as reinforcement learning (RL). In RL, the learning asymmetry concerns the sensitivity difference in incorporating positive and negative prediction errors (PE) into value estimation, namely the asymmetry of learning rates associated with positive and negative PEs. Although RL has been established as a canonical framework in interpreting agent and environment interactions, the direction of the learning rate asymmetry remains controversial. Here, we propose that part of the controversy stems from the fact that people may have different value expectations before entering the learning environment. Such default value expectation influences how PEs are calculated and consequently biases subjects’ choices. We test this hypothesis in two learning experiments with stable or varying reinforcement probabilities, across monetary gains, losses and gain-loss mixtures environments. Our results consistently support the model incorporating asymmetric learning rates and initial value expectation, highlighting the role of initial expectation in value update and choice preference. Further simulation and model parameter recovery analyses confirm the unique contribution of initial value expectation in accessing learning rate asymmetry.Author SummaryWhile RL model has long been applied in modeling learning behavior, where value update stands in the core of the learning process, it remains controversial whether and how learning is biased when updating from positive and negative PEs. Here, through model comparison, simulation and recovery analyses, we show that accurate identification of learning asymmetry is contingent on taking into account of subjects’ default value expectation in both monetary gain and loss environments. Our results stress the importance of initial expectation specification, especially in studies investigating learning asymmetry.
Multi-session tDCS paired with passive mobilisation increases thalamo-cortical coupling during command following
Authors: Aloi Davide , Jalali Roya , Calzolari Sara , Lafanechere Melanie , Miall R. Chris , Fernández-Espejo Davinia 
Published: November 2022

AbstractBackgroundTherapeutic options for patients with prolonged disorder of consciousness (PDOC) are limited. PDOC patients often exhibit a dissociation between their retained level of (covert) cognitive ability and their (overt) behavioural responses (cognitive-motor dissociation; CMD). This is linked to reduced coupling between thalamus and the primary motor cortex.ObjectiveTo assess whether pairing tDCS with a concurrent passive mobilisation protocol (designed to be feasible in PDOC) can influence thalamo-M1 dynamics and whether these changes are enhanced after multiple stimulation sessions.MethodsWe used Dynamic Causal Modelling (DCM) on functional magnetic resonance imaging (fMRI) data from 22 healthy participants to assess tDCS changes on effective connectivity within motor network areas during command-following.ResultsWe found that a single anodal tDCS session (paired with passive mobilisation of the thumb) decreased self-inhibition in the motor cortex, with five sessions further enhancing this effect. In addition, anodal tDCS increased thalamo-M1 excitation as compared to cathodal stimulation, with the effects maintained after 5 sessions. In turn, cathodal tDCS had opposing effects on these connections after one session but became more similar to anodal after 5.ConclusionsTogether, our results suggest that pairing anodal tDCS with passive mobilisation across multiple sessions may facilitate behavioural command-following in PDOC patients with CMD. More broadly, they offer a mechanistic window into the neural underpinnings of the cumulative effects of multi-session tDCS.
Prior movement of one arm facilitates motor adaptation in the other
Authors: Gippert M. , Leupold S. , Heed T. , Howard I. S. , Villringer A. , Nikulin V. V. , Sehm B. 
Published: November 2022

AbstractMany movements in daily life are embedded in motion sequences that involve more than one limb, demanding the motor system to monitor and control different body parts in quick succession. During such movements, systematic changes in the environment or the body might require motor adaptation of specific segments. However, previous motor adaptation research has focused primarily on motion sequences produced by a single limb, or on simultaneous movements of several limbs. For example, adaptation to opposing force fields is possible in unimanual reaching tasks when the direction of a prior or subsequent movement is predictive of force field direction. It is unclear, however, whether multi-limb sequences can support motor adaptation processes in a similar way. In the present study, we investigated whether reaches can be adapted to different force fields in a bimanual motor sequence when the information about the perturbation is associated with the prior movement direction of the other arm. In addition, we examined whether prior perceptual (visual or proprioceptive) feedback of the opposite arm contributes to force field-specific motor adaptation. Our key finding is that only active participation in the bimanual sequential task supports pronounced adaptation. This result suggests that active segments in bimanual motion sequences are linked across limbs. If there is a consistent association between movement kinematics of the linked and goal movement, the learning process of the goal movement can be facilitated. More generally, if motion sequences are repeated often, prior segments can evoke specific adjustments of subsequent movements.Significance statementMovements in a limb’s motion sequence can be adjusted based on linked movements. A prerequisite is that kinematics of the linked movements correctly predict which adjustments are needed. We show that use of kinematic information to improve performance is even possible when a prior linked movement is performed with a different limb. For example, a skilled juggler might have learned how to correctly adjust his catching movement of the left hand when the right hand performed a throwing action in a specific way. Linkage is possibly a key mechanism of the human motor system for learning complex bimanual skills. Our study emphasizes that learning of specific movements should not be studied in isolation but within their motor sequence context.
Quantitative assessment of association between noncoding variants and transcription factor binding
Authors: Ouyang Ningxin , Boyle Alan P. 
Published: November 2022

AbstractAssociation fine-mapping of molecular traits is an essential method for understanding the impact of genetic variation. Sequencing-based assays, including RNA-seq, DNase-seq and ChIP-seq, have been widely used to measure different cellular traits and enabled genome-wide mapping of quantitative trait loci (QTLs). The disruption of cis-regulatory sequence, often occurring through variation within transcription factor binding motifs, has been strongly associated with gene dysregulation and human disease. We recently developed a computational method, TRACE, for transcription factor binding footprint prediction. TRACE integrates chromatin accessibility and transcription factor binding motifs to produce quantitative scores that describe the binding affinity of a TF for a specific TFBS locus. Here we have extended this method to incorporate variant data for 57 Yoruban individuals. Using genome-wide chromatin-accessibility data and human TF binding motifs, we have generated precise, genome-wide predictions of individual-specific transcription factor binding footprints. Subsequent association mapping between these footprints and nearby regulatory variants yielded numerous footprint-variant pairs with significant evidence for correlation, which we call footprint-QTLs (fpQTLs). fpQTLs appear to affect TF binding in a distance-dependent manner and share significant overlap with known dsQTLs and eQTLs. fpQTLs provide a rich resource for the study of regulatory variants, both within and outside known TFBSs, leading to improved functional interpretation of noncoding variation.
Five-year plan and agricultural productivity in China
Authors: Han Yali , Paudel Krishna P. , Wan Junyi , He Qinying 
Published: November 2022

PurposeChina's economy has transformed from a high-speed growth phase to a high-quality development phase. The agriculture sector has grown substantially since the economic reform in 1978. Considering the five-year plan (FYP) as a collection of policies, this study explores the relationship between the FYP and agricultural total factor productivity (TFP).Design/methodology/approachThis study uses 31 provincial-level panel data of the five FYPs from 1996 to 2020. The data envelopment analysis (DEA) is used to compute Malmquist productivity indexes. The authors analyze the temporal and spatial changes and convergences of China's agricultural TFP, and investigate the impact of economic planning on China's agricultural TFP and its regional difference.FindingsThere is a slow but upward growth trend in China's agricultural TFP. The technical change has played a leading role in the growth of China's agricultural TFP. The agricultural TFP of all provinces has shown a “catch-up” effect and is developing toward their respective steady-state levels. The regional difference in productivity growth among the eastern, central and western regions exists. Test results show that the FYP has a positive effect on the agricultural TFP, and the effect has obvious regional heterogeneity. The FYP also plays a positive role in the gross value of agricultural output, and the impact effect is greater than that on the improvement of agricultural productivity.Originality/valueThere are many forms of industrial policy in China, among which the FYP is the guiding document of industrial policy, which makes a systematic plan for industrial development in the subsequent five years. The development objectives, guidelines and overall deployment for agriculture in the FYP not only describe the general context of China's agricultural development but also show the key ideas of agricultural development. Therefore, this study explores its impact on agricultural quality development from the perspective of FYP. The results provide evidence for examining the governance performance of the government and the objective evaluation and restraint of the FYP. As agriculture moves toward the stage of high-quality development, the Chinese government should strengthen the critical guiding role of the FYP and pay attention to quality indicators such as technical progress, efficiency improvement and regional coordination in the formulation of the FYP.