Biology subjects

Yao, S.

Publications and source records attributed to Yao, S..

11 recordsLinked to original sources

bioRxiv2018

Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Type 1 Estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvlEsr1) play a causal role in the control of social behaviors including aggression. Here we use six different viral-genetic tracing methods to map the connectional architecture of VMHvlEsr1 neurons. These data reveal a high level of input convergence and output divergence (\"fan-in/fan-out\") from and to over 30 distinct brain regions, with a high degree (~90%) of recurrence. Unlike GABAergic populations in other hypothalamic nuclei controlling feeding and parenting behavior, VMHvlEsr1 glutamatergic neurons collateralize to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization patterns. Surprisingly, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the \"brain-inspired\" feed-forward circuits used in certain types of artificial intelligence networks.\n\nSIGNIFICANCEHow the cellular heterogeneity of brain nuclei maps onto circuit connectivity, the relationship of this anatomical mapping to behavioral function, and whether there are general principles underlying this relationship, remains poorly understood. Here we systematically map the connectivity of estrogen receptor-1-expressing neurons in the ventromedial hypothalamus (VMHvlEsr1), which control aggression and other social behaviors. We find that a relatively sparse, anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. Further, the VMHvl contains at least two subpopulations of Esr1+ neurons with different cell body characteristics and locations, with distinct patterns of collateralization to downstream targets. Nevertheless, these projection-defined subpopulations receive similar inputs. This input-output organization appears distinct from those described in other hypothalamic nuclei.

neuroscience↗

bioRxiv2018

NetGO: Improving Large-scale Protein Function Prediction with Massive Network Information

Automated function prediction (AFP) of proteins is of great significance in biology. In essence, AFP is a large-scale multi-label classification over pairs of proteins and GO terms. Existing AFP approaches, however, have their limitations on both sides of proteins and GO terms. Using various sequence information and the robust learning to rank (LTR) framework, we have developed GOLabeler, a state-of-the-art approach of CAFA3, which overcomes the limitation of the GO term side, such as imbalanced GO terms. Unfortunately, for the protein side issue, available abundant protein information, except for sequences, have not been effectively used for large-scale AFP in CAFA. We propose NetGO that is able to improve large-scale AFP with massive network information. The novelties of NetGO have threefold in using network information: 1) the powerful LTR framework of NetGO efficiently and effectively integrates both sequence and network information, which can easily make large-scale AFP; 2) NetGO can use whole and massive network information of all species (>2000) in STRING (other than only high confidence links and/or some specific species); and 3) NetGO can still use network information to annotate a protein by homology transfer even if it is not covered in STRING. Under numerous experimental settings, we examined the performance of NetGO, such as general performance comparison, species-specific prediction, and prediction on difficult proteins, by using training and test data separated by time-delayed settings of CAFA. Experimental results have clearly demonstrated that NetGO outperforms GOLabeler, DeepGO, and other compared baseline methods significantly. In addition, several interesting findings from our experiments on NetGO would be useful for future AFP research.

bioinformatics↗

bioRxiv2018

Can pharmacological enhancement of the placebo effect be a novel therapy for working memory impairments?

Working memory is considered as a core aspect of cognitive function and its impairment in a wide range of mental disorders has resulted in it being considered as an important transdiagnostic feature. To date pharmacological and behavioural strategies for augmenting working memory have achieved only moderate success. Here we have taken a different approach by combining expectancy effects with intranasal oxytocin as an adjunct given previous evidence that it may enhance placebo effects. In a randomised controlled clinical trial we demonstrate that while working memory performance is not influenced by expectancy per se when it is given in conjunction with oxytocin performance in terms of accuracy can be significantly enhanced following positive expectancy induction (placebo effect) and impaired following negative expectancy induction (nocebo effect). Thus combining expectancy effects with intranasal oxytocin may represent a radical new approach for improving working memory function in mental disorders.

neuroscience↗

bioRxiv2018

Modeling circRNAs expression pattern with integrated sequence and epigenetic features identifies H3K79me2 as regulators for circRNAs expression

Circular RNAs (circRNAs) are an abundant class of noncoding RNAs with widespread, cell/tissue specific pattern. Because of their involvement in the pathogenesis of multiple disease, they are receiving increasing attention. Previous work suggested that epigenetic features might be related to circRNA expression. However, current algorithms for circRNAs prediction neglect these features, leading to constant results across different cells.\n\nHere we built a machine learning framework named CIRCScan, to predict expression status and expression levels of circRNAs in various cell lines based on sequence and epigenetic features. Both expression status and expression levels can be accurately predicted by different groups of features. For expression status, the top features were similar in different cells. However, the top features for predicting expression levels were different in different cells. Noteworthy, the importance of H3K79me2 ranked high in predicting both circRNAs expression status and levels across different cells, indicating its important role in regulating circRNAs expression. Further validation experiment in K562 confirmed that knock down of H3K79me2 did result in reduction of circRNA production.\n\nOur study offers new insights into the regulation of circRNAs by incorporating epigenetic features in prediction models in different cellular contexts.

bioinformatics↗

bioRxiv2018

Oxytocin modulates the intrinsic dynamics between attention-related large scale networks

Attention and salience processing have been linked to the intrinsic between- and within-network dynamics of large scale networks engaged in internal (default mode network, DN) and external attention allocation (dorsal attention, DAN, salience network, SN). The central oxytocin (OXT) system appears ideally organized to modulate widely distributed neural systems and to regulate the switch between internal attention and salient stimuli in the environment. The current randomized placebo (PLC) controlled between-subject pharmacological resting-state fMRI study in N = 187 (OXT, n = 94; n = 93; single-dose intranasal administration) healthy male and female participants employed an independent component analysis (ICA) approach to determine the modulatory effects of OXT on the within- and between-network dynamics of the DAN-SN-DN triple network system. OXT increased the functional integration between subsystems within SN and DN and increased functional segregation of the DN with the SN and DAN engaged in attentional control. Whereas no sex differences were observed, OXT effects on the DN-SN interaction were modulated by autism traits. Together, the findings suggest that OXT may facilitate efficient attentional allocation towards social cues by modulating the intrinsic functional dynamics between DN components engaged in social processing and large-scale networks involved in external attentional demands (SN, DAN).

neuroscience↗

bioRxiv2018

Oxytocin facilitates empathic- and self-embarrassment ratings by attenuating amygdala and anterior insula responses

The hypothalamic neuropeptide oxytocin has been reported to enhance emotional empathy in association with reduced amygdala activation, although to date studies have not investigated empathy for individuals expressing self-conscious, moral emotions which engage mentalizing as well as emotion processing networks. In the current randomized, double-blind placebo controlled functional MRI experiment on 70 male and female subjects we have therefore investigated the effects of intranasal oxytocin (40 IU) on behavioral and neural responses to embarrassment experienced by others or by self. Results showed that oxytocin significantly increased ratings of both empathic and self-embarrassment and concomitantly decreased skin conductance response and activation in the right amygdala and insula but not in the medial prefrontal cortex. The amygdala effects of oxytocin were associated with the magnitude of the skin conductance response and trait anxiety scores. Overall our results demonstrate that oxytocin increases ratings of self- and other embarrassment and that this is associated with reduced physiological arousal and activity in neural circuitry involved in emotional arousal. The neural effects of oxytocin are also stronger in individuals with high trait anxiety suggesting that it may particularly reduce their anxiety in embarrassing situations.

neuroscience↗

bioRxiv2018

Real-time functional connectivity-based neurofeedback of amygdala-frontal pathways reduces anxiety

Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising strategy to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. In a randomized within-subject sham-controlled design high anxious subjects (n = 26) underwent real-time fMRI-guided training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after three days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Training of the target, yet not the sham-control, pathway significantly increased amygdala-vlPFC connectivity and decreased subjective anxiety levels. On the individual level stronger connectivity increases were significantly associated with anxiety reduction. At follow-up, volitional control over the target pathway and decreased anxiety level were maintained in the absence of feedback. The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel strategy to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.

clinical trials↗

bioRxiv2018

Oxytocin enhancement of emotional empathy: generalization across cultures and effects on amygdala activity

Accumulating evidence suggests that the neuropeptide oxytocin can enhance empathy although it is unclear which specific behavioral and neural aspects are influenced, and whether the effects are modulated by culture, sex and trait autism. Based on previous findings in Caucasian men, we hypothesized that a single intranasal dose of oxytocin would specifically enhance emotional empathy via modulatory effects on the amygdala in an Asian (Chinese) population and explored the modulatory role of sex and trait autism on the effects. We first conducted a double-blind, randomized between-subject design experiment using a modified version of the multifaceted empathy task (MET) to determine whether oxytocins facilitation of emotional empathy can be replicated in Chinese men (n = 60). To further explore neural mechanisms behind and potential sex differences, functional MRI and skin conductance measures were acquired in an independent experiment incorporating men and women (n = 72). Oxytocin enhanced emotional empathy across experiments and sex, an effect that was accompanied by reduced amygdala activity and increased skin conductance responses. On the network level oxytocin enhanced functional coupling of the right amygdala with the insula and posterior cingulate cortex for positive valence stimuli but attenuated coupling for negative valence stimuli. The effect of oxytocin on amygdala functional connectivity with the insula was modulated by trait autism. Overall, our findings provide further support for the role of oxytocin in facilitating emotional empathy and demonstrate that effects are independent of culture and sex and involve modulatory effects on the amygdala and its interactions with other key empathy regions.

neuroscience↗

bioRxiv2018

Attentional set to safety recruits the medial prefrontal cortex

During threat assessment, the early detection of danger is highly adaptive, yet the fast orientation towards safety is also key to survival. The present study aimed to explore how the human brain searches for safety by manipulating subjects attentional set to cues associated with shock probability. Subjects were asked to judge random dots motion (RDM) direction and could be shocked for incorrect responses (RDM task) while keeping alert in detecting the shock probability cues (cue detection task). In contrast to the safe condition, where subjects searched for cues associated with no shock probability, incorrect responses to dangerous+ (D+) cues would increase the shock probability and correct responses to dangerous- (D-) cues would decrease shock probability. In the RDM task, results showed that relative to the D+, the safe attentional set resulted in stronger activation in the ventral medial prefrontal cortex (vmPFC), a core region involved in flexible threat assessment and safety signalling. The vmPFC was also recruited by the D-compared to the D + attentional set. In the cue detection task, shorter response times and greater accuracy were observed for D+ compared to D- and safe cues. Correspondingly, at the neural level D+ cues induced increased activity in the frontoparietal attention network including the inferior parietal lobule and intraparietal sulcus. Overall, our findings demonstrate that attentional set for searching safety recruits the vmPFC, while detection of threat elicits activity in the frontoparietal attention network, suggesting a new role for these regions in human defensive survival circuitry.\n\nSignificance StatementWhile early detection of threat is highly adaptive, the fast orientation towards safety is also key to survival. However, little is known about neural mechanisms underlying attentional set to safety. Using a novel dots motion paradigm combined with fMRI, we explored how human brain prepares for safety searching by manipulating subjects attentional set to cues associated with shock probability. Relative to the dangerous attentional set associated with increasing shock probability, the safe attentional set resulted in stronger activity in the ventral medial prefrontal cortex, a core region involved in flexible threat assessment and safety signalling, suggesting a new role for this region in human defensive survival system in encoding stimuli with survival significance.

neuroscience↗

bioRxiv2017

Oxytocin Signaling in the Medial Amygdala is required for Sex Discrimination of Social Cues

The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single unit recording in the MeA uncovered significant changes in the sensory representation of conspecific cues in the absence of oxytocin signaling. Finally, acute manipulation of oxytocin signaling in adults is sufficient to alter social interaction preferences in males as well as responses of MeA neurons to chemosensory cues. These results uncover the critical role of oxytocin signaling in a molecularly defined neuronal population in order to modulate the behavioral and physiological responses of male mice to females on a moment-to-moment basis.

neuroscience↗

bioRxiv2017

Traction force screening enabled by compliant PDMS elastomers

Acto-myosin contractility is an essential element of many aspects of cellular biology, and manifests as traction forces that cells exert on their surroundings. The central role of these forces makes them a novel principal therapeutic target in diverse diseases. This requires accurate and higher capacity measurements of traction forces; however, existing methods are largely low throughput, limiting their utility in broader applications. To address this need, we employ Fourier-transform traction force microscopy in a parallelized 96-well format, which we refer to as contractile force screening (CFS).Critically, rather than the frequently employed hydrogel polyacrylamide (PAA), we fabricate these plates using polydimethylsiloxane (PDMS) rubber. Key to this approach is that the PDMS used is very compliant, with a lower-bound Youngs modulus of approximately 0.7 kPa. We subdivide these monolithic substrates spatially into biochemically independent wells, creating a uniform multiwell platform for traction force screening. We demonstrate the utility and versatility of this platform by quantifying the compound and dose-dependent contractility responses of human airway smooth muscle cells and retinal pigment epithelial cells.

biophysics↗