Miracle-dz/UniFAR-FTUs huggingface dataset:
Trait Anxiety Mediated by Amygdala Serotonin Transporter in the Common Marmoset

High trait anxiety is associated with altered activity across emotion regulation circuitry and a higher risk of developing anxiety disorders and depression. This circuitry is extensively modulated by serotonin. Here, to understand why some people may be more vulnerable to developing affective disorders, we investigated whether serotonin-related gene expression across the brain's emotion regulation circuitry may underlie individual differences in trait anxiety using the common marmoset (Callithrix jacchus, mixed sexes) as a model. First, we assessed the association of region-specific expression of the serotonin transporter (SLC6A4) and serotonin receptor (HTR1A, HTR2A, HTR2C) genes with anxiety-like behavior; and second, we investigated their causal role in two key features of the high trait anxious phenotype: high responsivity to anxiety-provoking stimuli and an exaggerated conditioned threat response. While the expression of the serotonin receptors did not show a significant relationship with anxiety-like behavior in any of the targeted brain regions, serotonin transporter expression, specifically within the right ventrolateral prefrontal cortex (vlPFC) and most strongly in the right amygdala, was associated positively with anxiety-like behavior. The causal relationship between amygdala serotonin levels and an animal's sensitivity to threat was confirmed via direct amygdala infusions of a selective serotonin reuptake inhibitor (SSRI), citalopram. Both anxiety-like behaviors, and conditioned threat-induced responses were reduced by the blockade of serotonin reuptake in the amygdala. Together, these findings provide evidence that high amygdala serotonin transporter expression contributes to the high trait anxious phenotype and suggest that reduction of threat reactivity by SSRIs may be mediated by their actions in the amygdala. SIGNIFICANCE STATEMENT Findings here contribute to our understanding of how the serotonin system underlies an individual's expression of threat-elicited negative emotions such as anxiety and fear within nonhuman primates. Exploration of serotonergic gene expression across brain regions implicated in emotion regulation revealed that serotonin transporter gene expression in the ventrolateral prefrontal cortex (vlPFC) and most strongly in the amygdala, but none of the serotonin receptor genes, were predictive of interindividual differences in anxiety-like behavior. Targeting of amygdala serotonin reuptake with selective serotonin reuptake inhibitors (SSRIs) confirmed the causal relationship between amygdala serotonin transporter and an animal's sensitivity to threat by reversing expression of two key features of the high trait-like anxiety phenotype: high responsivity to anxiety-provoking uncertain threat and responsivity to certain conditioned threat.
Organization and evolution of higher plant nuclear genomes

The knowledge gained from studies on eukaryotic genome organization is important for understanding how genomes function and evolve, and it provides the basis for designing strategies for manipulating genomes. Hence, numerous studies on this subject have been conducted over the years, utilizing a variety of methods. In the recent decade, several techniques have been developed that allow the study of eukaryotic genome organization at different levels. Molecular techniques including molecular cloning, DNA sequencing, restriction fragment length polymorphism mapping, in situ hybridization, and pulsed field gel electrophoresis together provide a means of obtaining a comprehensive and detailed view of eukaryotic genomes. This paper summarizes recent findings on the organization and evolution of the nuclear genomes of higher plants, with emphasis on representative species with varying genome sizes, including Arabidopsis thaliana, tomato, maize, and wheat. Common, as well as unique, features in the organization o.
DNA Nanolithography Enables Highly Ordered Recognition Interface in Microfluidic Chip for Efficient Capture and Release of Circulating Tumor Cells.

Microfluidic chip with nano-scale structures has shown great potential, but the fabrication and cost issues restrict its application. Here, we propose a conceptually new "DNA nanolithography in microfluidic chip" by using sub-10 nm three-dimensional DNA structures (TDNs) as frameworks with a pendant aptamer at the top vertex (ApTDN-Chip). The nano-scale framework ensures the aptamer with a highly ordered upright orientation, avoiding the undesired orientation or crowding effects caused by conventional microfluidic interface fabrication processes. Compared with a monovalent aptamer modified chip, the capture efficiency of ApTDN-Chip was enhanced nearly 60% due to the highly precise dimension and rigid framework of TDNs. In addition, the confined tetrahedral nanostructure scaffolds make DNase I more accessible to aptamer with up to 83% release efficiency and 91% cell viability, which is fully compatible with downstream molecular analysis. Overall, "DNA nanolithography in microfluidic chip" provides a novel perspective to engineer nano-scaffolds to achieve a more ordered nano-topography of microfluidic chip.
Recent Advances in Co-Processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies.

Optimized physical properties (e.g. bulk, surface/interfacial and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining consistent drug product critical quality attributes. However, an appreciable number of APIs have physical properties that cannot be managed via routes such as form selection, adjustments to the crystallization process parameters or milling. Approaches to control physical properties in innovative ways offer the possibility of providing additional and unique opportunities to control API physical properties for both batch and continuous drug product manufacturing, ultimately resulting in simplified and more robust pharmaceutical manufacturing processes. Specifically, diverse opportunities to significantly enhance API physical properties are created if allowances are made for generating co-processed APIs by introducing non-active components (e.g. excipients, additives, carriers) during drug substance manufacturing. The addition of a non-active co-former during drug substance manufacturing is currently an accepted approach for co-crystals, and it would be beneficial if a similar allowance could be made for other non-active components with the ability to modify the physical properties of the API. In many cases, co-processed APIs could enable continuous direct compression for small molecules, and longer term, this approach could be leveraged to simplify continuous end-to-end drug substance processes to drug product manufacturing processes for both small and large molecules. As with any novel technology, the regulatory expectations for co-processed APIs are not yet clearly defined and this creates challenges for commercial implementation of these technologies, by the pharmaceutical industry. The intent of this paper is to highlight the opportunities and growing interest in realizing the benefits of co-processed APIs, exemplified by a body of academic research and industrial examples. This work will highlight reasons why co-processed APIs would best be considered as drug substances from a regulatory perspective and emphasize the areas where regulatory strategies need to be established, in order to allow for commercialization of innovative approaches in this area.
EDTA induced autolysis in Escherichia coli and isolation of resistant mutants

Autolysis of Escherichia coli induced by a shock treatment with 10−3M EDTA, pH 6.5 was investigated. Mutants presenting reduced rates of EDTA-induced autolysis were isolated. A remarkable feature of these mutants was their tolerance to penicillin G, cephaloridine and moenomycin. Furthermore, a reduced level of peptidoglycan endopeptidase or N-acetylmuramidase activity was observed. Penicillin-binding protein patterns were unaltered.
Wound- and mechano-stimulated electrical signals control hormone responses.

Plants in nature are constantly exposed to organisms that touch them and wound them. A highly conserved response to these stimuli is a rapid collapse of membrane potential (i.e. a decrease of electrical field strength across membranes). This can be coupled to the production and/or action of jasmonate or ethylene. Here, the various types of electrical signals in plants are discussed in the context of hormone responses. Genetic approaches are revealing genes involved in wound-induced electrical signalling. These include clade 3 GLUTAMATE RECEPTOR-LIKE (GLR) genes, Arabidopsis H+ -ATPases (AHAs), RESPIRATORY BURST OXIDASE HOMOLOGUEs (RBOHs), and genes that determine cell wall properties. We briefly review touch- and wound-induced increases in cytosolic Ca2+ levels and their temporal relationship to electrical activities. We then look at the questions that need addressing to link mechanostimulation and wound-induced electrical activity to hormone responses. Utilising recently published results, we also present a hypothesis for wound-response leaf-to-leaf electrical signalling. This model is based on rapid electro-osmotic coupling between the phloem and xylem. The model suggests that the depolarisation of membranes within the vascular matrix triggered by physical stimuli and/or chemical elicitors is linked to changes in phloem turgour and that this plays vital roles in electrical signal generation.
Azacitidine in patients older than 80 years with acute myeloid leukaemia or myelodysplastic syndromes: a report on 115 patients

tre, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Cancer Immunology Program, Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre, Melbourne, VIC, The University of Sydney, Department of Haematology, Royal North Shore Hospital, Sydney, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville and Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. E-mail: ilia.voskoboinik@petermac.org
Exploring EEG Spectral Patterns in Episodic and Chronic Migraine During the Interictal State: Determining Frequencies of Interest in the Resting State.

OBJECTIVE The analysis of particular (electroencephalographic) EEG frequency bands has revealed new insights relative to the neural dynamics that, when studying the EEG spectrum as a whole, would have remained hidden. This study is aimed at characterizing spectral resting state EEG patterns for assessing possible differences of episodic and chronic migraine during the interictal period. For that purpose, a novel methodology for analyzing specific frequencies of interest was performed. METHODS Eighty-seven patients with migraine (45 with episodic and 42 with chronic migraine) and 39 age- and sex-matched controls performed a resting-state EEG recording. Spectral measures were computed using conventional frequency bands. Additionally, particular frequency bands were determined to distinguish between controls and migraine patients, as well as between migraine subgroups. RESULTS Frequencies ranging from 11.6 Hz to 12.8 Hz characterized migraine as a whole, with differences evident in the central and left parietal regions (controlling for false discovery rate). An additional band between 24.1 Hz and 29.8 Hz was used to discriminate between migraine subgroups. Interestingly, the power in this band was positively correlated with time from onset in episodic migraine, but no correlation was found for chronic migraine. CONCLUSIONS Specific frequency bands were proposed to identify the spectral characteristics of the electrical brain activity in migraine during the interictal stage. Our findings support the importance of discriminating between migraine subgroups to avoid hiding relevant features in migraine.
The Homologous Components of Flagellar Type III Protein Apparatus Have Acquired a Novel Function to Control Twitching Motility in a Non-Flagellated Biocontrol Bacterium

The bacterial flagellum is one of the best-studied surface-attached appendages in bacteria. Flagellar assembly in vivo is promoted by its own protein export apparatus, a type III secretion system (T3SS) in pathogenic bacteria. Lysobacter enzymogenes OH11 is a non-flagellated soil bacterium that utilizes type IV pilus (T4P)-driven twitching motility to prey upon nearby fungi for food. Interestingly, the strain OH11 encodes components homologous to the flagellar type III protein apparatus (FT3SS) on its genome, but it remains unknown whether this FT3SS-like system is functional. Here, we report that, despite the absence of flagella, the FT3SS homologous genes are responsible not only for the export of the heterologous flagellin in strain OH11 but also for twitching motility. Blocking the FT3SS-like system by in-frame deletion mutations in either flhB or fliI abolished the secretion of heterologous flagellin molecules into the culture medium, indicating that the FT3SS is functional in strain OH11. A deletion of flhA, flhB, fliI, or fliR inhibited T4P-driven twitching motility, whereas neither that of fliP nor fliQ did, suggesting that FlhA, FlhB, FliI, and FliR may obtain a novel function to modulate the twitching motility. The flagellar FliI ATPase was required for the secretion of the major pilus subunit, PilA, suggesting that FliI would have evolved to act as a PilB-like pilus ATPase. These observations lead to a plausible hypothesis that the non-flagellated L. enzymogenes OH11 could preserve FT3SS-like genes for acquiring a distinct function to regulate twitching motility associated with its predatory behavior.
Diet of Cattle Egrets (Bubulcus ibis ibis) in the Flood Valley of the Paraná River, Northern Argentina

We analysed the feeding ecology of Cattle Egrets (Bubulcus ibis ibis) based on 30 individuals captured on the Carabajal island, Santa Fe, Argentina (31°39′S, 60°42′W), determining the minimum sample, index of relative importance (IRI), size of prey, feeding efficiency, dietary selectivity, amplitude of the trophic niche, standardisation, circadian rhythm of feeding activity and habitat preference. The trophic spectrum was made up of 17 taxonomic entities, mainly insects (IRI = 15,000), among which orthopterans were the most numerous followed by spiders and amphibians (IRI = 250). The highest percentage of prey size was found in the interval 21-30 mm. The amplitude of the trophic niche ranged between 1.98 and 3.45, and the feeding efficiency between 89 and 92%. In relation to dietary selectivity, the correlation between abundance of prey in stomachs and abundance of prey in the study area yielded no significant results (rs = 0.84, P.0:001). The rhythm of feeding activity responded to the bell-shaped model, which meant a peak in its feeding behaviour pattern at the noon hours. The pastures were the units of vegetation and environment selected more frequently.
Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922-mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BB-induced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.
ISOLATION AND CHARACTERIZATION OF ICE STRUCTURING PROTEINS FROM COLD‐ACCLIMATED WINTER WHEAT GRASS EXTRACT FOR RECRYSTALLIZATION INHIBITION IN FROZEN FOODS

Antifreeze proteins have shown a great potential in improving the quality of frozen foods, and the isolation of proteins from natural sources that are readily available is deemed to be important. The raw leaf apoplastic extract from cold-acclimated winter wheat grass (Triticum aestivum) containing recrystallization inhibition (RI) proteins was screened for proteolytic and lipolytic activity, and a heat-stable RI protein was isolated. The enzymes detected could be easily removed by heat treatment without any loss in the RI activity. The RI protein was isolated after heat treatment of the raw extract, alcohol precipitation and separation on a size exclusion chromatographic column. Circular dichroism indicated that the RI protein was mainly β-sheet and random coil, and these structures were preserved up to 75C. After trypsin digestion, mass fingerprinting and sequencing of the digests revealed that the protein belongs to the thaumatin-like protein group.
The inheritance of mitochondrial DNA in Douglas-fir (Pseudotsugamenziesii)

Restriction fragment length polymorphisms were used to determine the mode of inheritance of mitochondrial DNA in Douglas-fir (Pseudotsugamenziesii (Mirb.) Franco). Total DNA of foliage from both of the parents and from progeny of a single Douglas-fir cross was digested with restriction enzymes and hybridized to a Zeamays L. mitochondrial DNA radiolabeled probe. Mitochondrial DNA was maternally inherited in this cross. Previous research showed paternal inheritance of chloroplast DNA in Douglas-fir, thus it appears that each of the three genomes of Douglas-fir is inherited differently.
Local–Global Memory Neural Network for Medication Prediction

Electronic medical records (EMRs) play an important role in medical data mining and sequential data learning. In this article, we propose to use a sequential neural network with dynamic content-based memories to predict future medications, given EMRs. The local–global memory neural network contains two layers of memories: the local memory and the global memory. Particularly, our method learns the hidden knowledge within EMRs by locally remembering individual patterns of a patient (via local memory) and globally remembering group evidence of disease (via global memory). In addition, we show how our model can be modified to classify the hidden states of EMRs from different patients at each time step into different phases that indicate the progressions of medications in terms of a specific disease, in an unsupervised manner. Experimental results on real EMRs data sets show that, by learning EMRs with external local and global memories, with regard to a given disease, our model improves the prediction performance compared with several alternative methods.
Muscovite nanoparticles mitigate neuropathic pain by modulating the inflammatory response and neuroglial activation in the spinal cord

Despite numerous efforts to overcome neuropathic pain, various pharmacological drugs often fail to meet the needs and have many side effects. Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect, but the efficacy of muscovite for neuropathic pain has not been investigated. Here, we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain. The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain, in which one-third to one-half of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side. Muscovite nanoparticles (4 mg/100 μL) was given intramuscularly to evaluate its effects on neuropathic pain (3 days per week for 4 weeks). The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia. In the spinal cord, the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α, interleiukin-6 and monocyte chemoattractant protein-1, which were upregulated in the partial sciatic nerve ligation model. Moreover, the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3, a neuronal injury marker, in the sciatic nerve. These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines. We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain. All experimental protocols in this study were approved by the Institutional Animal Ethics Committee (IACUC) at Dongguk University, South Korea (approval No. 2017-022-1) on September 28, 2017.
Exploiting genetic variation to improve wheat composition for the prevention of chronic diseases

The increasing global population places a clear priority on increasing food production. However, the continued undernourishment of a significant proportion of the global population is accompanied by increases in developed and rapidly developing countries of over-consumption, particularly of highly refined processed foods which are rich in starch, sugars, and fats, including products made from white wheat flour. This diet combined with an increasingly sedentary lifestyle is associated with a cluster of symptoms which have been termed the metabolic syndrome and are associated with increased risk of type 2 diabetes, atherosclerosis, cardiovascular disease, and forms of cancer. There is clear evidence that the consumption of either wholegrain cereals or components present in these (notably dietary fiber) has beneficial effects in reducing the risk of the metabolic syndrome and associated diseases. This article therefore reviews the major groups of bioactive components present in the wheat grain and discusses strategies for manipulating their amounts and compositions to increase the health benefits of both wholegrain and white flour products.