Miracle-dz/UniFAR-FTUs huggingface dataset:
Production of designer egg: Effects of various n-3 lipid sources on fatty acids composition and sensory characteristics of chicken egg

Layer biological experiment was conducted to study the effect of various n-3 lipid sources such as fish, linseed and rapeseed oils to enrich n-3 or omega -3-fatty acids in chicken egg from 20–70 weeks of age. The supplementation of n-3 lipid sources in layer ration significantly increase linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), total n-3 fatty acids, total n-6 fatty acids and total n-3/n-6 fatty acids ratio of egg yolk, and a significant reduction in palmitic and stearic acid concentrations. The total unsaturated fatty acids concentration in egg yolk showed an increase in all the treated groups due to incorporation of various n-3 lipid sources in feed. The inclusion of n-3 lipid sources (at 1, 2 and 3% levels) independently and simultaneously in feed had no adverse effect on sensory quality of egg. Feeding layers with 3% fish oil showed significant increase in EPA, DHA and total n3 fatty acids in egg yolk.
Weighted RSA: An Improved Framework on the Perception of Audio-visual Affective Speech in Left Insula and Superior Temporal Gyrus

Being able to accurately perceive the emotion expressed by the facial or verbal expression from others is critical to successful social interaction. However, only few studies examined the multimodal interactions on speech emotion, and there is no consistence in studies on the speech emotion perception. It remains unclear, how the speech emotion of different valence is perceived on the multimodal stimuli by our human brain. In this paper, we conducted a functional magnetic resonance imaging (fMRI) study with an event-related design, using dynamic facial expressions and emotional speech stimuli to express different emotions, in order to explore the perception mechanism of speech emotion in audio-visual modality. The representational similarity analysis (RSA), whole-brain searchlight analysis, and conjunction analysis of emotion were used to interpret the representation of speech emotion in different aspects. Significantly, a weighted RSA approach was creatively proposed to evaluate the contribution of each candidate model to the best fitted model. The results of weighted RSA indicated that the fitted models were superior to all candidate models and the weights could be used to explain the representation of ROIs. The bilateral amygdala has been shown to be associated with the processing of both positive and negative emotions except neutral emotion. It is indicated that the left posterior insula and the left anterior superior temporal gyrus (STG) play important roles in the perception of multimodal speech emotion.
Ensemble learning for robust knee cartilage segmentation: data from the osteoarthritis initiative

Purpose To evaluate the performance of an ensemble learning approach for fully automated cartilage segmentation on knee magnetic resonance images of patients with osteoarthritis. Materials and Methods This retrospective study of 88 participants with knee osteoarthritis involved the study of three-dimensional (3D) double echo steady state (DESS) MR imaging volumes with manual segmentations for 6 different compartments of cartilage (Data available from the Osteoarthritis Initiative). We propose ensemble learning to boost the sensitivity of our deep learning method by combining predictions from two models, a U-Net for the segmentation of two labels (cartilage vs background) and a multi-label U-Net for specific cartilage compartments. Segmentation accuracy is evaluated using Dice coefficient, while volumetric measures and Bland Altman plots provide complimentary information when assessing segmentation results. Results Our model showed excellent accuracy for all 6 cartilage locations: femoral 0.88, medial tibial 0.84, lateral tibial 0.88, patellar 0.85, medial meniscal 0.85 and lateral meniscal 0.90. The average volume correlation was 0.988, overestimating volume by 9% ± 14% over all compartments. Simple post processing creates a single 3D connected component per compartment resulting in higher anatomical face validity. Conclusion Our model produces automated segmentation with high Dice coefficients when compared to expert manual annotations and leads to the recovery of missing labels in the manual annotations, while also creating smoother, more realistic boundaries avoiding slice discontinuity artifacts present in the manual annotations. Key Results Combining a 2-label U-Net (cartilage vs background) with a multi-class U-Net for segmentation of cartilage compartment boosts the accuracy of our deep learning model leading to the recovery of missing annotations in the manual dataset. Automatically generated segmentations have high Dice coefficients (0.85-0.90) and reduce inter-slice discontinuity artefact caused by slice wise delineation. Model refinement yields more anatomically plausible segmentations where each cartilage label is composed of only a single 3D region of interest.
Antigen-specific competitive inhibition of CD4+ T cell recruitment into the primary immune response

Previous studies suggest that recruitment of naïve T cells into a program of cell division and differentiation is a highly synchronous process under tight regulation. However it is not known whether antigen availability is the major regulator of this process, or whether other factors such as ongoing responses to unrelated antigens can affect the size of the primary response. We have developed an adoptive transfer system to investigate the efficiency with which additional antigen specific cells are recruited into an ongoing primary immune response. Recruitment of additional cells is an inverse function of the size of the response and is progressively inhibited with time. Cells recruited late into the response proliferate less, and fewer secrete IL-2 and IFN-γ. Thus the size of the response changes very little as a result of late recruitment. The inhibition of recruitment, proliferation and differentiation affects only cells of the same specificity as the ongoing response, indicating that the size of an antigen specific response is independent of any shared factors such as access to APCs, costimulation or cytokines. Thus, during infection, the immune system retains the ability to respond as necessary to secondary infections or antigens not presented until later stages of the response.
Sensory stimulus evoked responses in layer 2/3 pyramidal neurons of the hind paw-related mouse primary somatosensory cortex

The mouse primary somatosensory cortex (S1) processes tactile sensory information and is the largest neocortex area emphasizing the importance of this sensory modality for rodent behavior. Most of our knowledge regarding information processing in S1 stems from studies of the whisker-related barrel cortex (S1–BC), yet the processing of tactile inputs from the hind-paws is poorly understood. We used in vivo whole-cell patch-clamp recordings from layer (L) 2/3 pyramidal neurons (PNs) of the S1 hind-paw (S1-HP) region of anaesthetized wild type (WT) mice to investigate their evoked sub- and supra-threshold activity, intrinsic properties, and spontaneous activity. Approximately 45% of these L2/3 PNs responded to brief contralateral HP stimulation in a subthreshold manner, ~5% fired action potentials, and ~50% of L2/3 PNs did not respond at all. The evoked subthreshold responses had long onset- (~23 ms) and peak-latencies (~61 ms). The majority (86%) of these L2/3 PNs responded to prolonged (stance-like) HP stimulation with both on- and off-responses. HP stimulation responsive L2/3 PNs had a greater intrinsic excitability compared to non-responsive ones, possibly reflecting differences in their physiological role. Similar to S1-BC, L2/3 PNs displayed up- and down-states, and low spontaneous firing rates (~0.1 Hz). Our findings support a sparse coding scheme of operation for S1–HP L2/3 PNs and highlight both differences and similarities with L2/3 PNs from other somatosensory cortex areas. KEY POINTS Responses of layer (L) 2/3 pyramidal neurons (PNs) of the primary somatosensory hind-paw cortex (S1-HP) to contralateral hind-paw stimulation reveal both differences and similarities compared to those of somatosensory neurons responding to other tactile (e.g. whiskers, forepaw, tongue) modalities. Similar to whisker-related barrel cortex (S1-BC) and forepaw cortex (S1-FP) S1-HP L2/3 PNs show a low spontaneous firing rate and a sparse action potential coding of evoked activity. In contrast to S1-BC, brief hind-paw stimulus evoked responses display a long latency in S1-HP neurons consistent with their different functional role. The great majority of L 2/3 PNs respond to prolonged hind-paw stimulation with both on- and off-responses. These results help us to better understand sensory information processing within layer 2/3 of the neocortex and the regional differences related to various tactile modalities.
Comparison of transcriptional responses of three multidrug resistant model microorganisms, Staphylococcus aureus ATCC BAA-39, Escherichia coli ATCC BAA-196 and Acinetobacter baumannii ATCC BAA-1790, on exposure to iodine-containing nano-micelle drug FS-1

Iodine is one of the oldest antimicrobial agents. Till now there have been no reports on development of resistance to iodine. Recent studies showed promising results on the application of iodine-containing nano-micelles, FS-1, against antibiotic resistant pathogens as a supplement to antibiotic therapy. The mechanisms of action, however, remain unclear. The aim of this study was to perform a systemic analysis of gene regulation and metabolic alterations in three phylogenetically distant reference strains from ATCC culture collection representing multidrug resistant pathogens associated with nosocomial infections: Escherichia coli BAA-196, Staphylococcus aureus BAA-39 and Acinetobacter baumannii BAA-1790. These cultures were treated in 5 min exposure to sublethal doses of the iodine-containing drug FS-1 applied in the late lagging and the mid of the logarithmic growth phases. Complete genome sequences of these strains were obtained in previous studies. Gene regulation was studied by total RNA extraction and Ion Torrent sequencing followed by mapping the RNA reads against the reference genome sequences and statistical processing of read counts using the DESeq2 algorithm. It was found that the treatment of bacteria with FS-1 profoundly affected the expression of many genes involved in central metabolic pathways; however, alterations of gene expression profiles were species-specific and depended on the growth phase when the drug was applied. Disruption of respiratory electron-transfer membrane complexes, increased penetrability of bacterial cell wall, osmotic and oxidative stresses leading to DNA damage were the major factors influencing the treated bacteria. IMPORTANCE Infections caused by antibiotic resistant bacteria threaten public health worldwide. Combinatorial therapy when antibiotics are administrated together with supplementary drugs improving susceptibility of pathogens to regular antibiotics is considered as a promising way to overcome this problem. An induction of antibiotic resistance reversion by the iodine-containing nano-micelle drug FS-1 was reported recently. This drug is currently under clinical trials in Kazakhstan against multidrug resistant tuberculosis. The effect of iodine solutes on metabolic and regulatory processes in bacterial cells remain unexplored that precludes the effective application of iodine-containing antimicrobials in medicine. The current work provides an insight into gene regulation in antibiotic resistant bacteria treated with iodine-containing nanoparticles. Our expectation is that this study will shed light on unexplored bioactivities of iodine and the mechanisms of its antibacterial effect when applied in low concentrations. This knowledge will aid in future design of new drugs against antibiotic resistant infections.
Virtual metabolic human dynamic model for pathological analysis and therapy design for diabetes

A virtual metabolic human model is a valuable complement to experimental biology and clinical studies, because in vivo research involves serious ethical and technical issues. A whole-body dynamic model is required not only to reproduce a variety of physiological and metabolic functions, but also to analyze pathology and design drugs. I first proposed a virtual metabolic human model, a multi-organ and multi-scale kinetic model of the whole-body metabolism that formulates the reactions of enzymes and transporters with the regulation of enzyme activities and hormonal actions under prandial and rest conditions. To accurately simulate metabolic changes and robustness, the model incorporates nucleotide cofactors that are critically responsible for global feedback regulations to adapt to metabolic changes. The model predicted a two-phase hepatic fatty acid production that consists of the synthesis of malonyl-CoA and the NADPH-dependent synthesis of fatty acid. The model performed pathological analysis of type 2 diabetes. I divided type 2 diabetes into specific disorders of steatosis, β cell dysfunction and insulin resistance for each organ, and analyzed the effect of the individual disorders on the dynamics of plasma glucose (hyperglycemia) and hepatic TG (steatosis). The model suggested that a chronic or irreversible change in hepatic TG accumulation plays a critical role in disease progression. The model predicted a glycerol kinase inhibitor to be a new medicine for type 2 diabetes, because it not only decreased hepatic TG but also reduced plasma glucose, unexpectedly. The model also enabled us to rationally design combination therapy.
Representational Content of Oscillatory Brain Activity during Object Recognition: Contrasting Cortical and Deep Neural Network Hierarchies

Abstract Numerous theories propose a key role for brain oscillations in visual perception. Most of these theories postulate that sensory information is encoded in specific oscillatory components (e.g., power or phase) of specific frequency bands. These theories are often tested with whole-brain recording methods of low spatial resolution (EEG or MEG), or depth recordings that provide a local, incomplete view of the brain. Opportunities to bridge the gap between local neural populations and whole-brain signals are rare. Here, using representational similarity analysis (RSA) in human participants we explore which MEG oscillatory components (power and phase, across various frequency bands) correspond to low or high-level visual object representations, using brain representations from fMRI, or layer-wise representations in seven recent deep neural networks (DNNs), as a template for low/high-level object representations. The results showed that around stimulus onset and offset, most transient oscillatory signals correlated with low-level brain patterns (V1). During stimulus presentation, sustained β (∼20 Hz) and γ (>60 Hz) power best correlated with V1, while oscillatory phase components correlated with IT representations. Surprisingly, this pattern of results did not always correspond to low-level or high-level DNN layer activity. In particular, sustained β band oscillatory power reflected high-level DNN layers, suggestive of a feed-back component. These results begin to bridge the gap between whole-brain oscillatory signals and object representations supported by local neuronal activations.
Enhanced Synaptic Transmission in the Extended Amygdala and Altered Excitability in an Extended Amygdala to Brainstem Circuit in a Dravet Syndrome Mouse Model

Visual Abstract Dravet syndrome (DS) is a developmental and epileptic encephalopathy with an increased incidence of sudden death. Evidence of interictal breathing deficits in DS suggests that alterations in subcortical projections to brainstem nuclei may exist, which might be driving comorbidities in DS. The aim of this study was to determine whether a subcortical structure, the bed nucleus of the stria terminalis (BNST) in the extended amygdala, is activated by seizures, exhibits changes in excitability, and expresses any alterations in neurons projecting to a brainstem nucleus associated with respiration, stress response, and homeostasis. Experiments were conducted using F1 mice generated by breeding 129.Scn1a+/− mice with wild-type C57BL/6J mice. Immunohistochemistry was performed to quantify neuronal c-fos activation in DS mice after observed spontaneous seizures. Whole-cell patch-clamp and current-clamp electrophysiology recordings were conducted to evaluate changes in intrinsic and synaptic excitability in the BNST. Spontaneous seizures in DS mice significantly enhanced neuronal c-fos expression in the BNST. Further, the BNST had altered AMPA/NMDA postsynaptic receptor composition and showed changes in spontaneous neurotransmission, with greater excitation and decreased inhibition. BNST to parabrachial nucleus (PBN) projection neurons exhibited intrinsic excitability in wild-type mice, while these projection neurons were hypoexcitable in DS mice. The findings suggest that there is altered excitability in neurons of the BNST, including BNST-to-PBN projection neurons, in DS mice. These alterations could potentially be driving comorbid aspects of DS outside of seizures, including respiratory dysfunction and sudden death.
Rabaptin5 targets autophagy to damaged early endosomes and Salmonella containing vacuoles by interaction with FIP200 and ATG16L1

Selective autophagy of damaged organelles is an important process for cellular homeostasis. The mechanisms how autophagy selects specific targets is often poorly understood. Rabaptin5 was previously known as a major regulator of early endosome identity and maturation. Here we identified two novel Rabaptin5 interactors: FIP200, a subunit of the ULK1 autophagy initiator complex, and ATG16L1, a central component of the E3-like enzyme in LC3 lipidation. Indeed, autophagy of early endosomes damaged by chloroquine or monensin treatment was found to require Rabaptin5 and particularly a specific short sequence motif binding to the WD domain of ATG16L1. Rabaptin5 and this interaction with ATG16L1 is further required for much of autophagic elimination of Salmonella enterica in phagosomes with early endosomal characteristics early after infection. Our results demonstrate a novel function of Rabaptin5 in quality control of early endosomes as a selective receptor to recruit autophagy to damaged early endosomes and phagosomes.
cFIT: Integration and transfer learning of single cell transcriptomes, illustrated by fetal brain cell development

Large, comprehensive collections of scRNA-seq data sets have been generated that allow for the full transcriptional characterization of cell types across a wide variety of biological and clinical conditions. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these data sets or transfer knowledge from one to the other to better understand cellular identity and functions. Here, we present a simple yet surprisingly effective method named cFIT for capturing various batch effects across experiments, technologies, subjects, and even species. The proposed method models the shared information between various data sets by a common factor space, while allowing for unique distortions and shifts in gene-wise expression in each batch. The model parameters are learned under an iterative non-negative matrix factorization (NMF) framework and then used for synchronized integration from across-domain assays. In addition, the model enables transferring via low-rank matrix from more informative data to allow for precise identification in data of lower quality. Compared to existing approaches, our method imposes weaker assumptions on the cell composition of each individual data set, however, is shown to be more reliable in preserving biological variations. We apply cFIT to multiple scRNA-seq data sets of developing brain from human and mouse, varying by technologies and developmental stages. The successful integration and transfer uncover the transcriptional resemblance across systems. The study helps establish a comprehensive landscape of brain cell type diversity and provides insights into brain development.
The Impact of Pf Bacteriophages on the Fitness of Pseudomonas aeruginosa; A Mathematical Modeling Approach

Pseudomonas aeruginosa (Pa) is a major bacterial pathogen responsible for chronic lung infections in cystic fibrosis patients. Recent work by ourselves and others has implicated Pf bacteriophages, non-lytic filamentous viruses produced by Pa, in the chronicity and severity of Pa infections. Pf phages act as structural elements in Pa biofilms and sequester aerosolized antibiotics, thereby contributing to antibiotic tolerance. Consistent with a selective advantage in this setting, the prevalence of Pf+ bacteria increases over time in these patients. However, the production of Pf phages comes at a metabolic cost to bacteria, such that Pf+ strains grow more slowly than Pf- strains in vitro. Here, we use a mathematical model to investigate how these competing pressures might influence the relative abundance of Pf+ versus Pf- strains in different settings. Our model predicts that Pf+ strains of Pa can only outcompete Pf- strains if the benefits of phage production falls solely onto Pf+ strains and not onto the overall bacterial community in the lung. Further, phage production only leads to a net positive gain in fitness at antibiotic concentrations slightly above the minimum inhibitory concentration (i.e., concentrations for which the benefits of antibiotic sequestration outweigh the metabolic cost of phage production), but which are not lethal for Pf+ strains. As a result, our model predicts that frequent administration of intermediate doses of antibiotics with low decay rates favors Pf+ over Pf- strains. These models inform our understanding of the ecology of Pf phages and suggest potential treatment strategies for Pf+ Pa infections. Importance Filamentous phages are a frontier in bacterial pathogenesis, but the impact of these phages on bacterial fitness is unclear. In particular, Pf phages produced by Pa promote antibiotic tolerance but are metabolically expensive to produce, suggesting that competing pressures may influence the prevalence of Pf+ versus Pf- strains of Pa in different settings. Our results identify conditions likely to favor Pf+ strains and thus antibiotic tolerance. This study contributes to a better understanding of the unique ecology of filamentous phages and may facilitate improved treatment strategies for combating antibiotic tolerance.
Oxycodone self-administration activates the mitogen-activated protein kinase/ mitogen- and stress-activated protein kinase (MAPK-MSK) signaling pathway in the rat dorsal striatum

To identify signaling pathways activated by oxycodone self-administration (SA), Sprague–Dawley rats self-administered oxycodone for 20 days using short—(ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized 2 h after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs, in the LgA-H rats. GluA3 , but not GluA2 , mRNA expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. These findings suggest that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation and increases in striatal gene expression. These observations offer potential avenues for interventions against oxycodone addiction.