Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of Stk11 in basolateral amygdalar projection neurons impairs taste aversion learning by altering the temporal pattern of taste response plasticity in gustatory cortex

Gustatory cortex (GC) responds to tastes on the tongue with dynamic ensemble activity that represents first the presence, then the identity, and finally the hedonic value (palatability) of tastes. This final state of the taste response is uniquely altered by conditioned taste aversion (CTA) – a powerful one-trial learning paradigm in which a taste becomes aversive after association with gastric malaise – a process requiring coordination between GC and basolateral amygdala (BLA). Previously, we found that one key requirement for learning in this circuit is expression of the serine/threonine kinase 11 (Stk11) gene (a tumor suppression gene which has only recently been associated with learning; Levitan et al., 2020). When Stk11 is knocked out in BLA projection neurons (BLApn), CTA learning fails to occur. Here we have examined how learning-related response plasticity in GC taste responses is impacted by the knockout of Stk11 in BLApn. Contrary to the commonly held assumption that a lack of learning means a lack of such plasticity, but consistent with the fact that Stk11KO has been shown to increase the excitability of BLApn, our data reveal that the knockout of Stk11 in BLApn does not eliminate plasticity; rather, it shifts the impact of CTA training on GC taste responses to an earlier, learning-inappropriate epoch. Even naïve taste representations are altered—specifically, the pattern of similarities and differences among the different taste responses are rendered abnormal by Stk11 KO, and these relationships fail to change with training. Finally, the latency of behavior-related dynamic ensemble features of the GC taste response, which is also abnormal in naïve KO mice, is rendered disorganized by CTA. Together, these results suggest that Stk11 plays a role in governing the coordination of GC activity by BLA, and demonstrate that alterations in the function of BLApn caused by Stk11KO inhibit learning not by inhibiting plasticity but by changing its temporal properties.
Early Disruption of Photoreceptor Cell Architecture and Loss of Vision in a Humanized Pig Model of Usher Syndrome

Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and, so far, there are no suitable animal models for testing therapeutic strategies. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Primary cells from those animals and USH1C patients showed significantly elongated primary cilia, compared to wild-type, confirming the nature of USH as a true and general ciliopathy and proving the therapeutic capacity of gene supplementation and gene repair approaches.
Center-surround interactions underlie bipolar cell motion sensing in the mouse retina

Motion is a critical aspect of vision. We studied the representation of motion in mouse retinal bipolar cells and found, surprisingly, that some bipolar cells possess motion-sensing capabilities that rely on their center-surround receptive fields. Using a glutamate sensor, we directly observed motion-sensitive bipolar cell synaptic output, which was strongest for local motion and dependent on the motion’s origin. We characterized bipolar cell receptive fields and found that there are motion and non-motion sensitive bipolar cell types, the majority being motion sensitive. Next, we used these bipolar cell receptive fields along with connectomics to design biophysical models of downstream cells. The models and experiments demonstrated that bipolar cells pass motion-sensitive excitation to starburst amacrine cells through direction-specific signals mediated by bipolar cells’ center-surround receptive field structure. As bipolar cells provide excitation to most amacrine and ganglion cells, their motion sensitivity may contribute to motion processing throughout the visual system.
One shot generalization in humans revealed through a drawing task

Humans have the striking ability to learn and generalize new visual concepts from just a single exemplar. We suggest that when presented with a novel object, observers identify its significant features and infer a generative model of its shape, allowing them to mentally synthesize plausible variants. To test this, we showed participants abstract 2D shapes (‘Exemplars’) and asked them to draw new objects (‘Variations’) belonging to the same class. We show that this procedure created genuine novel categories. In line with our hypothesis, particular features of each Exemplar were preserved in its Variations and there was striking agreement between participants about which shape features were most distinctive. Also, we show that strategies to create Variations were strongly driven by part structure: new objects typically modified individual parts (e.g., limbs) of the Exemplar, often preserving part order, sometimes altering it. Together, our findings suggest that sophisticated internal generative models are key to how humans analyze and generalize from single exemplars.
PIF7 controls leaf cell proliferation through an AN3 substitution-repression mechanism

Plants are agile, plastic organisms, able to adapt to ever-changing circumstances. Responding to far-red (FR) wavelengths from nearby vegetation, shade-intolerant species elicit the adaptive Shade Avoidance Syndrome (SAS), characterised by elongated petioles, leaf hyponasty and smaller leaves. We utilised end-of-day FR (EODFR) treatments to interrogate molecular processes that underlie the SAS leaf response. Genetic analysis establishes PHYTOCHROME INTERACTING FACTOR 7 (PIF7) is required for EODFR-mediated constraint of leaf blade cell division, while EODFR mRNAseq data identified ANGUSTIFOLIA3 (AN3) as a potential PIF7 target. We show PIF7 can suppress AN3 transcription through a sequestering mechanism that prevents AN3 activation of its own expression. We also establish PIF7 and AN3 impose antagonistic control of gene expression via common cis-acting promoter motifs in several cell cycle regulator genes. EODFR triggers the molecular substitution of AN3 to PIF7 at G-box/PBE-box promoter regions, and a switch from promotion to repression of gene expression.
Single-Cell Profiling Resolved Transcriptional Alterations and Lineage Dynamics of Subventricular Zone after Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) is the most common form of brain trauma caused by physical impact. The subventricular zone (SVZ) is a neurogenetic niche that contributes to homeostasis and repair after brain injury. It is particularly challenging to fully elucidate the molecular alterations in the SVZ occurring in response to injury due to its cell diversity and the complex network. In this study, we aimed to address this issue using a novel transcriptomic technique- unbiased single-cell RNA sequencing. We resolved previous unknown cell subpopulations harbored in the niche, and uncovered cell type-specific alterations in gene expression, enriched pathways, and cell-cell crosstalk following mTBI. Notably, we also report novel lineage trajectories and molecular hallmarks that govern neurogenesis. This study dissects the delicate transcriptome changes of individual cell types as well as the reprogramming process of cells in the SVZ niche after mTBI, and our findings are expected to facilitate the development of therapeutic interventions or diagnostic tests for mTBI.
Attempted Validation of Surface Enhanced Laser Desorption Ionization-Time of Flight Derived Kinesin Biomarkers in Malignant Mesothelioma

Surface-enhanced Laser Desorption/Ionization Time-of-flight (SELDI-TOF) mass spectrometry allows researchers to search proteomes for biomarkers of disease. Validating SELDI-TOF results using traditional methodologies has yielded mixed results. Real-time PCR, ELISA and Western blot assays were utilized in an attempt to confirm the link between asbestos related cancers and kinesin family proteins, KIF5A and KIF18A. These proteins had been identified using SELDI-TOF and Classification and Regression Tree Analysis (CART) in serum of patients with asbestos related cancers. When well-characterized asbestos fibers were used to challenge mesothelial cell lines, mixed results in KIF5A and KIF18A RNA expression were observed. Western blot analysis comparing protein levels in mesothelioma cell lines versus transformed mesothelial cells yielded inconclusive results, as did Western blot analyses of human mesothelioma and non-cancerous peritoneum that had been obtained from the same patients. These results suggest that kinesin family proteins detected by SELDI-TOF CART are unlikely to be of use as biomarkers for malignant mesothelioma.
Coke Deposition Influence Based on a Run Length Simulation of a 1,2-Dichloroethane Cracker

A full cycle of an industrial ethylene dichloride cracker is simulated. Given the intense heat coupling between the furnace and the reactor, the cracker is divided into two parts: the furnace model and the reactor model, with heat flux and flue gas temperature profiles connecting the two models. A radical mechanism with coke formation is adopted to describe the EDC cracking reactions with 24 reaction equations and 31 components. In the full cycle simulation, two important aspects, namely, CCl4 concentration and fuel gas allocation, are investigated to understand the overall benefits of the whole operation cycle. Addition of the promoter CCl4 to EDC raw material can improve EDC conversion. However, this process aggravates the coking reaction, which causes the sharp deterioration of the cracking performance and the shortening of the running cycle. On the other hand, the fuel gas allocation factor facilitates analysis of the fuel gas allocation strategies. Increasing the fuel gas amount at the furnace bottom.
Continuous Exposure to Non-Soluble β-Glucans Induces Trained Immunity in M-CSF-Differentiated Macrophages

Beta-glucans enable functional reprogramming of innate immune cells, a process defined as “trained immunity”, which results in enhanced host responsiveness against primary (training) and/or secondary infections (resilience). Trained immunity holds great promise for promoting immune responses in groups that are at risk (e.g. elderly and patients). In this study, we modified an existing in vitro model for trained immunity by actively inducing monocyte-to-macrophage differentiation using M-CSF and applying continuous exposure. This model reflects mucosal exposure to β-glucans and was used to study the training effects of a variety of soluble or non-soluble β-glucans derived from different sources including oat, mushrooms and yeast. In addition, trained immunity effects were related to pattern recognition receptor usage, to which end, we analyzed β-glucan-mediated Dectin-1 activation. We demonstrated that β-glucans, with different sources and solubilities, induced training and/or resilience effects. Notably, trained immunity significantly correlated with Dectin-1 receptor activation, yet Dectin-1 receptor activation did not perform as a sole predictor for β-glucan-mediated trained immunity. The model, as validated in this study, adds on to the existing in vitro model by specifically investigating macrophage responses and can be applied to select non-digestible dietary polysaccharides and other components for their potential to induce trained immunity.
Parenthood—Lost and Found: Exploring Parents’ Experiences of Receiving a Program in Emotion Focused Skills Training

Background Parents play a crucial role in the development, maintenance, and deterioration of child difficulties. Emotion focused skills training (EFST) targets parents’ capacity to provide their child with emotion-oriented skills in order to promote good child mental health. Few qualitative studies have specifically investigated parents’ experiences of receiving such programs. Objective This study aimed to explore how parents experience working with their own and their child’s emotions undergoing a short-term program in EFST; in particular, changes in their experience of being a parent and in everyday life are reported. Method Semi-structured in-depth qualitative interviews were conducted with 14 parents who had completed a short-term EFST program (2-day group training and 6 h of supervision). Interview transcripts were analyzed using a reflexive thematic analysis approach. Results A total of 14 parents (40% men, four couples, Mage = 39.5, SD = 4.4) participated in the study. Our analysis resulted in the following three themes: (1) “Coming home” as a parent, with the following subthemes: (a) New ways of being with their child and (b) Parents’ painful inner world; (2) Reclaiming parenthood—applying new tools and learning in challenging situations; and (3) This is us—changing the heart of the story. The first theme was related to the descriptions of the changes that emerged in parents’ inner lives, the second revolved around the employment of their skills intuitively and creatively based on what was required by the challenging situations, and the third theme referred to new discoveries on family dynamics. Conclusion Parents’ experiences of having wisdom and calmness inside them (being) and doing parenting differently, as well as the changed perspectives of the family (living), resonate with the theoretical ground of emotion-focused therapy (EFT). The findings also indicate that therapists should be aware of potential parental distress when working in view of changing unpleasant emotions in such skill-based programs.
Heterogeneity in Regional Damage Detected by Neuroimaging and Neuropathological Studies in Older Adults With COVID-19: A Cognitive-Neuroscience Systematic Review to Inform the Long-Term Impact of the Virus on Neurocognitive Trajectories

Background: Other than its direct impact on cardiopulmonary health, Coronavirus Disease 2019 (COVID-19) infection affects additional body systems, especially in older adults. Several studies have reported acute neurological symptoms that present at onset or develop during hospitalisation, with associated neural injuries. Whilst the acute neurological phase is widely documented, the long-term consequences of COVID-19 infection on neurocognitive functioning remain unknown. Although an evidence-based framework describing the disease chronic phase is premature, it is important to lay the foundations for future data-driven models. This systematic review aimed at summarising the literature on neuroimaging and neuropathological findings in older over-60 patients with COVID-19 following a cognitive neuroscientific perspective, to clarify the most vulnerable brain areas and speculate on the possible cognitive consequences. Methods: PubMed and Web of Science databases were searched to identify relevant manuscripts published between 1st March 2020 and 31th December 2020. Outputs were screened and selected by two assessors. Relevant studies not detected by literature search were added manually. Results: Ninety studies, mainly single cases and case series, were included. Several neuroimaging and neuropathological findings in older patients with COVID-19 emerged from these studies, with cerebrovascular damage having a prominent role. Abnormalities (hyperintensities, hypoperfusion, inflammation, and cellular damage) were reported in most brain areas. The most consistent cross-aetiology findings were in white matter, brainstem and fronto-temporal areas. Viral DNA was detected mainly in olfactory, orbitofrontal and brainstem areas. Conclusion: Studies on COVID-19 related neural damage are rich and diverse, but limited to description of hospitalised patients with fatal outcome (i.e., in neuropathological studies) or severe symptoms (i.e., in neuroimaging studies). The damage seen in this population indicates acute and largely irreversible dysfunction to neural regions involved in major functional networks that support normal cognitive and behavioural functioning. It is still unknown whether the long-term impact of the virus will be limited to chronic evolution of acute events, whether sub-clinical pathological processes will be exacerbated or whether novel mechanisms will emerge. Based on current literature, future theoretical frameworks describing the long-term impact of COVID-19 infection on mental abilities will have to factor in major trends of aetiological and topographic heterogeneity.
Striatal Synapse Degeneration and Dysfunction Are Reversed by Reactivation of Wnt Signaling

Synapse degeneration in the striatum has been associated with the early stages of Parkinson’s and Huntington’s diseases (PD and HD). However, the molecular mechanisms that trigger synaptic dysfunction and loss are not fully understood. Increasing evidence suggests that deficiency in Wnt signaling triggers synapse degeneration in the adult brain and that this pathway is affected in neurodegenerative diseases. Here, we demonstrate that endogenous Wnt signaling is essential for the integrity of a subset of inhibitory synapses on striatal medium spiny neurons (MSNs). We found that inducible expression of the specific Wnt antagonist Dickkopf-1 (Dkk1) in the adult striatum leads to the loss of inhibitory synapses on MSNs and affects the synaptic transmission of D2-MSNs. We also discovered that re-activation of the Wnt pathway by turning off Dkk1 expression after substantial loss of synapses resulted in the complete recovery of GABAergic and dopamine synapse number. Our results also show that re-activation of the Wnt pathway leads to a recovery of amphetamine response and motor function. Our studies identify the Wnt signaling pathway as a potential therapeutic target for restoring neuronal circuits after synapse degeneration.
Dysregulation of the Excitatory Renal Reflex in the Sympathetic Activation of Spontaneously Hypertensive Rat

Excessive sympathetic activation plays crucial roles in the pathogenesis of hypertension. Chemical stimulation of renal afferents increases the sympathetic activity and blood pressure in normal rats. This study investigated the excitatory renal reflex (ERR) in the development of hypertension in the spontaneously hypertensive rat (SHR). Experiments were performed in the Wistar-Kyoto rat (WKY) and SHR aged at 4, 12, and 24 weeks under anesthesia. Renal infusion of capsaicin was used to stimulate renal afferents, and thus, to induce ERR. The ERR was evaluated by the changes in the contralateral renal sympathetic nerve activity and mean arterial pressure. At the age of 4 weeks, the early stage with a slight or moderate hypertension, the ERR was more enhanced in SHR compared with WKY. The pressor response was greater than the sympathetic activation response in the SHR. At the age of 12 weeks, the development stage with severe hypertension, there was no significant difference in the ERR between the WKY and SHR. At the age of 24 weeks, the later stage of hypertension with long-term several hypertensions, the ERR was more attenuated in the SHR compared with the WKY. On the other hand, the pressor response to sympathetic activation due to the ERR was smaller at the age of 12 and 24 weeks than those at the age of 4 weeks. These results indicate that ERR is enhanced in the early stage of hypertension, and attenuated in the later stage of hypertension in the SHR. Abnormal ERR is involved in the sympathetic activation and the development of hypertension.
Bawei Chenxiang Wan Ameliorates Cardiac Hypertrophy by Activating AMPK/PPAR-α Signaling Pathway Improving Energy Metabolism

Bawei Chenxiang Wan (BCW), a well-known traditional Chinese Tibetan medicine formula, is effective for the treatment of acute and chronic cardiovascular diseases. In the present study, we investigated the effect of BCW in cardiac hypertrophy and underlying mechanisms. The dose of 0.2, 0.4, and 0.8 g/kg BCW treated cardiac hypertrophy in SD rat model induced by isoprenaline (ISO). Our results showed that BCW (0.4 g/kg) could repress cardiac hypertrophy, indicated by macro morphology, heart weight to body weight ratio (HW/BW), left ventricle heart weight to body weight ratio (LVW/BW), hypertrophy markers, heart function, pathological structure, cross-sectional area (CSA) of myocardial cells, and the myocardial enzymes. Furthermore, we declared the mechanism of BCW anti-hypertrophy effect was associated with activating adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/peroxisome proliferator–activated receptor-α (PPAR-α) signals, which regulate carnitine palmitoyltransferase1β (CPT-1β) and glucose transport-4 (GLUT-4) to ameliorate glycolipid metabolism. Moreover, BCW also elevated mitochondrial DNA-encoded genes of NADH dehydrogenase subunit 1(ND1), cytochrome b (Cytb), and mitochondrially encoded cytochrome coxidase I (mt-co1) expression, which was associated with mitochondria function and oxidative phosphorylation. Subsequently, knocking down AMPK by siRNA significantly can reverse the anti-hypertrophy effect of BCW indicated by hypertrophy markers and cell surface of cardiomyocytes. In conclusion, BCW prevents ISO-induced cardiomyocyte hypertrophy by activating AMPK/PPAR-α to alleviate the disturbance in energy metabolism. Therefore, BCW can be used as an alternative drug for the treatment of cardiac hypertrophy.
Autumn Warming Delays the Downregulation of Photosynthesis and Does Not Increase the Risk of Freezing Damage in Interior and Coastal Douglas-fir

During autumn, evergreen conifers utilize the decrease in daylength and temperature as environmental signals to trigger cold acclimation, a process that involves the downregulation of photosynthesis, upregulation of photoprotection, and development of cold hardiness. Global warming will delay the occurrence of autumn low temperatures while daylength remains unaffected. The impact of autumn warming on cold acclimation and the length of the carbon uptake period of species with ranges that encompass diverse climates, such as Douglas-fir (Pseudotsuga menziesii), remains unclear. Our study investigated intraspecific variation in the effects of autumn warming on photosynthetic activity, photosynthetic pigments, and freezing tolerance in two interior (var. glauca) and two coastal (var. menziesii) Douglas-fir provenances. Following growth under simulated summer conditions with long days (16 h photoperiod) and summer temperatures (22/13°C day/night), Douglas-fir seedlings were acclimated to simulated autumn conditions with short days (8 h photoperiod) and either low temperatures (cool autumn, CA; 4/−4°C day/night) or elevated temperatures (warm autumn, WA; 19/11°C day/night). Exposure to low temperatures in the CA treatment induced the downregulation of photosynthetic carbon assimilation and photosystem II efficiency, increased the size and de-epoxidation of the xanthophyll cycle pigment pool, and caused the development of sustained nonphotochemical quenching (NPQ). Seedlings in the WA treatment exhibited no downregulation of photosynthesis, no change in xanthophyll cycle pigment de-epoxidation, and no development of sustained NPQ. Albeit these changes, freezing tolerance was not impaired under WA conditions compared with CA conditions. Interior Douglas-fir seedlings developed greater freezing tolerance than coastal seedlings. Our findings suggest that autumn warming, i.e., short photoperiod alone, does not induce the downregulation of photosynthesis in Douglas-fir. Although autumn warming delays the downregulation of photosynthesis, the prolonged period of photosynthetic activity does not bear a trade-off of impaired freezing tolerance.