Miracle-dz/UniFAR-FTUs huggingface dataset:
Polybasic RKKR motif in the linker region of lipid droplet (LD)–associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids

Lipid droplets (LDs) are intracellular organelles and a central site for lipid synthesis, storage, and mobilization. The size of LDs reflects the dynamic regulation of lipid metabolism in cells. Previously, we found that cell death–inducing DFFA-like effector C (CIDEC) mediates LD fusion and growth by lipid transfer through LD–LD contact sites in adipocytes and hepatocytes. The CIDE-N domains of CIDEC molecules form homodimers, whereas the CIDE-C domain plays an important role in LD targeting and enrichment. Here, using targeted protein deletions and GFP expression coupled with fluorescence microscopy, we identified a polybasic RKKR motif in the linker region that connects the CIDE-N and CIDE-C domains of CIDEC and functions as a regulatory motif for LD fusion. We found that deletion of the linker region or mutation of the RKKR motif increases the formation of supersized LDs compared with LD formation in cells with WT CIDEC. This enhanced LD fusion activity required the interaction between CIDE-N domains. Mechanistically, we found that the RKKR motif interacts with acidic phospholipids via electrostatic attraction. Loss of this motif disrupted the protein–lipid interaction, resulting in enhanced lipid droplet fusion activity and thus formation of larger LDs. In summary, we have uncovered a CIDEC domain that regulates LD fusion activity, a finding that provides insights into the inhibitory regulation of LD fusion through CIDEC–lipid interactions.
Terahertz Microscopy Down to the Atomic Scale

In this talk I will review terahertz scanning probe microscopy with a focus on recent developments that have made experiments with simultaneous ultrafast temporal resolution and atomic spatial resolution possible. Specifically, I will discuss the underlying principle of coupling terahertz radiation to sharp metallic tips, the connection between scattering-type scanning near-field optical microscopy (SNOM) and terahertz lightwave-driven scanning tunneling microscopy (THz-STM), and the key aspects of THz-STM that enable atomic spatial resolution. Finally, as an illustrative example, I will present ultrafast THz-STM snapshots and pump-probe measurements of electron densities in selected molecular orbitals of single molecules with sub-Angstrom spatial resolution [1].
The problem with probabilistic DAG automata for semantic graphs

Semantic representations in the form of directed acyclic graphs (DAGs) have been introduced in recent years, and to model them, we need probabilistic models of DAGs. One model that has attracted some attention is the DAG automaton, but it has not been studied as a probabilistic model. We show that some DAG automata cannot be made into useful probabilistic models by the nearly universal strategy of assigning weights to transitions. The problem affects single-rooted, multi-rooted, and unbounded-degree variants of DAG automata, and appears to be pervasive. It does not affect planar variants, but these are problematic for other reasons.
Influence of prenatal alcohol and smoke exposure on neonatal vagal tone in response to head-up tilt

This paper investigates differences in the parasympathetically mediated heart rate response to head-up tilt in two populations of newborns. One group was unexposed to any drug during pregnancy, the other was exposed to both alcohol and smoking in utero. Four different estimates of vagal tone were calculated. These indexes quantify vagal tone magnitude in four different domains: time, frequency, complexity and phase. Control group (CG) results across all parameters show a consistent physiological response to an orthostatic tilt consistent with vagal withdrawal. On the other hand, infants in the exposed group (EG) did not express a decrease in vagal measures following tilt.
Frequency Band Variations Predict EEG Single-Trial Classification Performance in Disorder of Consciousness Patients

Single-trial classification of EEG data from Disorder of Consciousness patients (DoC) has proved particularly challenging. We present an approach that establishes a measure to relate the performance of single-trial classification of DoC patient EEG data with relational frequency bands and thus with their mental state. We evaluate our approach on 31 patient data sets from two studies, showing that our measure indicates for different data sets a particular likelihood for misclassifying either target or non-target class samples.
The distribution pattern of metastatic lymph nodes after non‐curative endoscopic resection in early gastric cancer

Additional surgery should be done after non‐curative endoscopic resection (ER) in early gastric cancer (EGC) due to the risk of lymph node metastasis (LNM). However, the distribution pattern of LNM in these patients is complicated and unpredictable. The aim of this study is to identify any different distribution patterns of LNM in patients with EGC who underwent additional surgery after non‐curative (ER) comparing to those without ER.
Impact of Dark Annealing on the Kinetics of Light- and Elevated-Temperature-Induced Degradation

Light- and elevated-temperature-induced degradation (LeTID) has been shown to have a significant detrimental impact on p-type multicrystalline silicon solar cells and, in particular, on passivated emitter and rear cells. Previous studies have shown that defect kinetics can be modulated for samples that are dark annealed prior to light soaking at elevated temperature. In this work, we show that while short annealing durations help accelerate both degradation and recovery rates to different extents, extended annealing instead instigates a retarding effect. Our results confirm that thermally induced degradation and regeneration mechanisms can be observed during dark annealing. The results also suggest that the response to this yet undetermined defect mechanism not only depends on the initial dark annealing temperature, but it is also highly dependent on the stage of the dark annealing degradation and regeneration cycle reached before beginning light soaking. Finally, we propose a refined model of three generalized modes to describe the changes in LeTID kinetics after dark annealing.
Identifying the novel inhibitors of lysine-specific demethylase 1 (LSD1) combining pharmacophore-based and structure-based virtual screening

Abstract Lysine-specific demethylase 1 (LSD1) has been reported to connect with a range of solid tumors. Thus, the exploration of LSD1 inhibitors has emerged as an effective strategy for cancer treatment. In this study, we constructed a pharmacophore model based on a series of flavin adenine dinucleotide (FAD)-competing inhibitors bearing triazole − dithiocarbamate scaffold combining docking, structure–activity relationship (SAR) study, and molecular dynamic (MD) simulation. Meanwhile, another pharmacophore model was also constructed manually, relying on several speculated substrate-competing inhibitors and reported putative vital interactions with LSD1. On the basis of the two pharmacophore models, multi-step virtual screenings (VSs) were performed against substrate-binding pocket and FAD-binding pocket, respectively, combining pharmacophore-based and structure-based strategy to exploit novel LSD1 inhibitors. After bioassay evaluation, four compounds among 21 hits with diverse and novel scaffolds exhibited inhibition activity at the range of 3.63–101.43 μM. Furthermore, substructure-based enrichment was performed, and four compounds with a more potent activity were identified. After that, the time-dependent assay proved that the most potent compound with IC50 2.21 μM inhibits LSD1 activity in a manner of time-independent. In addition, the compound exhibited a cellular inhibitory effect against LSD1 in MGC-803 cells and may inhibit cell migration and invasion by reversing EMT in cultured gastric cancer cells. Considering the binding mode and SAR of the series of compounds, we could roughly deem that these compounds containing 3-methylxanthine scaffold act through occupying substrate-binding pocket competitively. This study presented a new starting point to develop novel LSD1 inhibitors. Graphical Abstract
Evolutionary Computation for Modelling Social Traits in Realistic Looking Synthetic Faces

Human faces play a central role in our lives. Thanks to our behavioural capacity to perceive faces, how a face looks in a painting, a movie, or an advertisement can dramatically influence what we feel about them and what emotions are elicited. Facial information is processed by our brain in such a way that we immediately make judgements like attractiveness or masculinity or interpret personality traits or moods of other people. Due to the importance of appearance-driven judgements of faces, this has become a major focus not only for psychological research, but for neuroscientists, artists, engineers, and software developers. New technologies are now able to create realistic looking synthetic faces that are used in arts, online activities, advertisement, or movies. However, there is not a method to generate virtual faces that convey the desired sensations to the observers. In this work, we present a genetic algorithm based procedure to create realistic faces combining facial features in the adequate relative positions. A model of how observers will perceive a face based on its features’ appearances and relative positions was developed and used as the fitness function of the algorithm. The model is able to predict 15 facial social traits related to aesthetic, moods, and personality. The proposed procedure was validated comparing its results with the opinion of human observers. This procedure is useful not only for creating characters with artistic purposes, but also for online activities, advertising, surgery, or criminology.
Comparison of performance, health and welfare aspects between commercially housed hatchery-hatched and on-farm hatched broiler flocks.

On-farm hatching systems for broiler chicks are increasingly used in practice. We studied whether or not performance, health and welfare aspects differed between commercial flocks hatched on-farm or in a hatchery (control). In two successive production cycles on seven farms, a total of 16 on-farm hatched flocks were paired to 16 control flocks, housed at the same farm. Paired flocks originated from the same batch of eggs and were subjected to similar on-farm management. On-farm hatched and control flocks only differed with respect to hatching conditions, with on-farm hatched flocks not being exposed to, for example, chick handling, post-hatch feed and water deprivation and transport, in contrast to control flocks that were subjected to standard hatchery procedures, subsequently transported and placed in the poultry house. Day-old chick quality (navel and hock scores), 1st week mortality, total mortality, BW at day (d) 0, d7 and at depopulation, and (total) feed conversion ratio were determined. Prevalence of footpad dermatitis, hock burn, breast discoloration/blisters and cleanliness, litter quality and gait score were determined at d21 of age and around depopulation (d39 on average). Gross pathology and gut morphology were examined at depopulation age in a sample of birds of five flocks per treatment. On-farm hatching resulted in a higher BW at d0 (Δ=5.4 g) and d7 (Δ=11.5 g) (P<0.001), but day-old chick quality as measured by navel (P=0.003) and hock (P=0.01) quality was worse for on-farm hatched compared to control birds. Body weight, 1st week and total mortality, and feed conversion ratio at slaughter age were similar for both on-farm hatched and control flocks. On-farm hatched flocks had less footpad dermatitis (P=0.05), which indicated a better welfare. This was likely related to a tendency for better litter quality in on-farm hatched flocks at 21 days of age in comparison to control flocks (P=0.08). No major differences in gross pathology or in intestinal morphology at depopulation age were found between treatments. In conclusion, on-farm hatching resulted in better 1st week broiler performance and better welfare compared to conventional hatching in a hatchery.
Respiratory response to finger clamping in dogs under general anesthesia: A descriptive pilot study

Aim of the study The aim of this study was to assess the effects of a nociceptive stimulus on respiratory variables in anesthetized dogs. Material and method Eleven dogs received acepromazine administered intramuscularly (IM) at a dose of 0.04 mg kg−1 45 mins before induction of anesthesia. Loss of consciousness was obtained with midazolam at 0.2 mg kg−1 and propofol administered at a dose of 2 mg kg−1 intravenously (IV). Orotracheal intubation was performed and anesthesia was maintained with isoflurane in 100% oxygen. Inspired (VTi) and expired (VTe) tidal volume (VT), minute volume (VM), inspiratory and expiratory time (Ti; Te) were measured and recorded twice a second by a spirometer. The Drive (VT/Ti) and Timing [Ti/(Ti+ Te)] were calculated. After stabilizing the depth of anesthesia the variables measured by the spirometer were recorded for 5 mins [T0−5-T0]. Then (T0) interdigital clamping of the hind leg was performed until a withdrawal movement was observed. If no reaction occurred, the clamp was left in place for 60s. After removal of the clamp, respiratory variables were measured continuously for another 5 mins [T0-T0+5]. At T0+5 morphine (0.2 mg kg−1 IV) was administered. Five minutes later (T0+10), a second clamp test was performed, using the same procedure. At T0+15 the data recording was stopped. Result The results showed a large variation in the individual values of Drive and Timing and are presented in a descriptive manner. The observation of Drive values over time showed variations following nociceptive stimuli. Drive appears to have increased only for those dogs that did not move during the stimulus, and were therefore pinched for a full 60 s. In contrast, the study of the Timing values revealed no difference between the data before and after nociceptive stimulation. However Timing seems to increase after morphine administration. Conclusion Drive remains a parameter that needs to be studied in depth to determine its sensitivity and precocity to monitor acute nociception.
Following instructions in a dual-task paradigm: Evidence for a temporary motor store in working memory

Evidence from dual-task studies suggests that working memory supports the retention and implementation of verbal instructions. One key finding that is not readily accommodated by existing models of working memory is that participants are consistently more accurate at physically performing rather than verbally repeating a sequence of commands. This action advantage has no obvious source within the multi-component model of working memory and has been proposed to be driven by an as yet undetected limited-capacity store dedicated to the temporary maintenance of spatial, motoric, and temporal features of intended movements. To test this hypothesis, we sought to selectively disrupt the action advantage with concurrent motor suppression. In three dual-task experiments, young adults’ immediate memory for sequences of spoken instructions was assessed by both action-based and spoken recall. In addition to classic interference tasks known to tax the phonological loop and central executive, motor suppression tasks designed to impair the encoding and retention of motoric representations were included. These required participants to produce repetitive sequences of either fine motor gestures (Experiment 1, N = 16) or more basic ones (Experiments 2, N = 16, and 3, N = 16). The benefit of action-based recall was reduced following the production of basic gestures but remained intact under all other interference conditions. These results suggest that the mnemonic advantage of enacted recall depends on a cognitive system dedicated to the temporary maintenance of motoric representations of planned action sequences.
Professional Dancers Distinct Biomechanical Pattern during Multidirectional Landings

Purpose This study aimed to compare lower extremity (LE) biomechanics between professional dancers (PD) and nondancers (ND) during multidirectional single-leg landings. Methods Fifteen PD (27 ± 7 yr, 1.69 ± 0.1 m, 57.8 ± 9.3 kg) and 15 ND (25 ± 5 yr, 1.69 ± 0.1 m, 66 ± 10.2 kg) performed single-leg jumps in three directions: 1) lateral, 2) diagonal, and 3) forward. Dominant LE biomechanical data were collected using a motion capture system. Data were processed in Visual3D. LE kinematic (hip, knee, and ankle joint angles in sagittal and frontal planes, and range of motion [ROM]) and kinetics (hip and knee internal joint moments and vertical ground reaction force) variables were analyzed at initial contact (IC), peak vertical ground reaction force (PvGRF), and peak knee flexion (PKF). Repeated-measures ANOVA was conducted (P < 0.05). Results At IC, statistically significant interactions were found for ankle frontal and hip sagittal angles (P < 0.05). The main effects for groups and jump directions were attained (P < 0.05). PD at IC had lower hip and knee flexion and higher ankle plantarflexion than ND. PD had significantly higher knee (PD, 41 ± 6.1; ND, 33.8 ± 8.4) and ankle (PD, 53.7 ± 3.4; ND, 38.9 ± 8.9) ROM than ND. At IC, the lateral jump had higher hip abduction moment, hip abduction, and ankle inversion and lower hip flexion and ankle plantarflexion than the forward and diagonal jumps. The lateral jump (15.5 ± 7.7) had higher hip excursion than the forward jump (12.7 ± 5.4). Conclusion The higher extended posture of PD at IC promoted an efficient use of the knee and ankle ROM to dissipate the landing forces. Regardless of the group, jump directions also solicited different biomechanical responses, particularly between lateral and forward directions. These strategies should be considered for implementation in prevention programs, as it can foster adequate LE neuromuscular control.
PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia

Background: Glucose-sensing neurons are located in several parts of the brain, but are concentrated in the ventromedial nucleus of the hypothalamus (VMH). The importance of these VMH neurons in glucose homeostasis is well-established, however, little is known about their individual identity. In the present study, we identified a distinct glucose-sensing population in the VMH and explored its place in the glucose-regulatory network. Methods: Using patch-clamp electrophysiology on Pacap-cre::EYFP cells, we explored the glucose-sensing ability of the pituitary adenylate cyclase-activating peptide (PACAP) neurons both inside and outside the VMH. We also mapped the efferent projections of these neurons using anterograde and retrograde tracing techniques. Finally, to test the functionality of PACAPVMH in vivo, we used DREADD technology and measured systemic responses. Results: We demonstrate that PACAP neurons inside (PACAPVMH), but not outside the VMH are intrinsically glucose inhibited (GI). Anatomical tracing techniques show that PACAPVMH neurons project to several areas that can influence autonomic output. In vivo, chemogenetic stimulation of these neurons inhibits insulin secretion leading to reduced glucose tolerance, implicating their role in systemic glucose regulation. Conclusion: These findings are important as they identify, for the first time, a specific VMH neuronal population involved in glucose homeostasis. Identifying the different glucose-sensing populations in the VMH will help piece together the different arms of glucose regulation providing vital information regarding central responses to glucose metabolic disorders including hypoglycaemia.
PubChem 2019 update: improved access to chemical data

Abstract PubChem (https://pubchem.ncbi.nlm.nih.gov) is a key chemical information resource for the biomedical research community. Substantial improvements were made in the past few years. New data content was added, including spectral information, scientific articles mentioning chemicals, and information for food and agricultural chemicals. PubChem released new web interfaces, such as PubChem Target View page, Sources page, Bioactivity dyad pages and Patent View page. PubChem also released a major update to PubChem Widgets and introduced a new programmatic access interface, called PUG-View. This paper describes these new developments in PubChem.
Molecular Distance to Health Transcriptional Score and Disease Severity in Children Hospitalized With Community-Acquired Pneumonia

Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP. Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization. Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1–1.07] and 1.12 [1.04–1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01–1.22]). Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP.
Taking the 'A' Out of 'AR': Play Based Low Fidelity Contextual Prototyping of Mobile Augmented Reality

Taking the 'A' out of 'AR' means implementing the augmented elements of an interface and contextual elements of reality in a more controlled context to allow for proof of concept evaluations. This paper proposes a prototyping technique that bridges the gap between traditional paper prototyping methods used for interface design and evaluation, and the challenges associated with the development of visual, context-aware augmented reality (AR) applications. An initial evaluation of this technique was conducted through the examination of a small-scale case study of user evaluation sessions of a mobile application.