Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrating Pharmacology and Gut Microbiota Analysis to Explore the Mechanism of Citri Reticulatae Pericarpium Against Reserpine-Induced Spleen Deficiency in Rats

Citri Reticulatae Pericarpium (CRP), dried peels of Citrus reticulata Blanco and its cultivars, is an important traditional Chinese medicine for the treatment of spleen deficiency-related diseases. To date, the mechanism of CRP alleviating spleen deficiency has not been well investigated. This study aimed to explore corresponding mechanisms with integrating pharmacology and gut microbiota analysis. Firstly, the therapeutic effects of CRP against spleen deficiency were evaluated in reserpine-treated rats. CRP was found to effectively relieve the typical symptoms of spleen deficiency, including poor digestion and absorption capacity, and disorder in gastrointestinal hormones, immune cytokines and oxidative stress. Secondly, high throughput 16S rRNA gene sequencing revealed that CRP could not only up-regulate some short-chain fatty acids producing and anti-inflammatory bacteria but also down-regulate certain spleen deficiency aggravated related bacteria, eventually led to the rebalance of gut microbiota in spleen deficiency rats. In addition, a total of 49 compounds derived from CRP were identified in rat urine using ultra-high performance liquid chromatography-quadrupole- time of flight tandem mass spectrometry. Network pharmacology analysis showed that apigenin, luteolin, naringenin, hesperidin, hesperetin, homoeriodictyol, dihydroxy-tetramethoxyflavone, and monohydroxy-tetramethoxyflavone were the core bioactive components for CRP against spleen deficiency. Further Gene Ontology analysis and pathway enrichment suggested that therapeutic effects of CRP against spleen deficiency involved multiple pathways such as tumor necrosis factor signaling, hypoxia-inducible factor-1 signaling and Toll-like receptor signaling pathway. These results would help to understand the mechanism of CRP alleviating spleen deficiency and provide a reference for further studies.
Invasion and succession change the functional traits of serpentine plant communities1,3

Abstract Human impacts, such as invasive species introductions and land use changes, have the potential to alter the functional composition and diversity of plant communities. We can make and test clear predictions of how these processes should affect community-level trait values, yet very few studies have done so. We examined how three invasive species and succession from savanna to woodland because of fire suppression may change functional composition and diversity in the State Line serpentine barrens on the Pennsylvania-Maryland border. We characterized native and invasive plants in eight key functional leaf traits and quantified trait overlap between natives and invasives. We compared plots in two successional stages—savannas and woodlands—in functional composition and diversity. The invasive species Elaeagnus umbellata Thunb. and Microstegium vimineum (Trin.) A. Camus had extreme trait values and low overlaps with native species. Invasive species and plant assemblages including invasive species had traits more characteristic of fast growth, competitiveness, and inefficient resource use. Assemblages with invasive plants had higher functional diversity. The conversion of savannas to woodlands also shifted communities toward more fast-growing, competitive, and inefficient traits as well as decreasing functional diversity. Both invasion and succession appear to reduce the distinctive stress tolerance of plant communities on serpentine soils, with the potential for strong ecosystem-level impacts and positive feedbacks.
Confocal and SEM imaging to demonstrate food pathogen- biofilm biocontrol by pyocyanin from Pseudomonas aeruginosa BTRY1

An assortment of redox-active phenazine compounds like pyocyanin with their characteristic blue-green colour are synthesized by Pseudomonas aeruginosa, Gram-negative opportunistic pathogens , which are also considered one of the most commercially valuable microorganisms. In this study, pyocyanin from Pseudomonas aeruginosa BTRY1 from food sample was assessed for its antibiofilm activity by micro titer plate assay against strong biofilm producers belonging to the genera Bacillus, Staphylococcus, Brevibacterium and Micrococcus. Pyocyanin inhibited biofilm activity in very minute concentrations. This was also confirmed by Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM). Both SEM and CLSM helped to visualize the biocontrol of biofilm formation by eight pathogens. The imaging and quantification by CLSM also established the impact of pyocyanin on biofilm-biocontrol mainly in the food industry.
Predator-induced shell plasticity in mussels hinders predation by drilling snails

Sessile invertebrate prey that detect waterborne predator cues often respond by strengthening their structural defenses. Experimental evidence of the functional significance of such modifications using field-raised organisms is lacking. This study addresses that gap using intertidal mussels and predatory dogwhelks from Atlantic Canada. During the spring and summer of 2016, we ran a field experiment that manipulated dogwhelk presence to test their nonconsumptive effects on mussel traits. Dogwhelk cues elicited thickening at the lip, centre, and base of mussel shells, although simultaneously limiting shell growth in length. As shell mass was unaffected by dogwhelk presence, a trade-off between shell thickening and elongation was revealed. Thickening was strongest at the thinnest parts of the shell. Using the field-raised organisms, a lab experiment found that dogwhelks took, on average, 55 % longer to drill and consume mussels previously exposed to dogwhelk cues than mussels grown without such a cue exposure. Dogwhelks drilled at the thinnest parts of the shell but, nonetheless, the consumed cue-exposed mussels had thicker shells at the borehole than the consumed mussels not exposed to cues, which likely explains the observed difference in handling time. As handling time normally decreases predation success, this study indicates that the plastic structural modifications in mussels triggered by dogwhelk cues in the field hinder predation by these drilling predators.
Allosteric Modulation of Conformational Dynamics in Human Hsp90α: A Computational Study

Central to Hsp90’s biological function is its ability to interconvert between various conformational states. Drug targeting of Hsp90’s regulatory mechanisms, including its modulation by co-chaperone association, presents as an attractive therapeutic strategy for Hsp90 associated pathologies. Here, we utilize homology modeling techniques to calculate full-length structures of human Hsp90α in closed and partially-open conformations. Atomistic simulations of these structures demonstrated that bound ATP stabilizes the dimer by ‘tensing’ each protomer, while ADP and apo configurations ‘relax’ the complex by increasing global flexibility. Dynamic residue network analysis revealed regions of the protein involved in intra-protein communication, and identified several overlapping key communication hubs that correlate with known functional sites. Perturbation response scanning analysis identified several potential residue sites capable of modulating conformational change in favour of interstate conversion. For the ATP-bound open conformation, these sites were found to overlap with known Aha1 and client binding sites, demonstrating how naturally occurring forces associated with co-factor binding could allosterically modulate conformational dynamics.
Database limitations for studying the human gut microbiome

Background In the last twenty years, new methodologies have made possible the gathering of large amounts of data concerning the genetic information and metabolic functions associated to the human gut microbiome. In spite of that, processing all this data available might not be the simplest of tasks, which could result in an excess of information awaiting proper annotation. This assessment intended on evaluating how well respected databases could describe a mock human gut microbiome. Methods In this work, we critically evaluate the output of the cross–reference between the Uniprot Knowledge Base (Uniprot KB) and the Kyoto Encyclopedia of Genes and Genomes Orthologs (KEGG Orthologs) or the evolutionary genealogy of genes: Non-supervised Orthologous groups (EggNOG) databases regarding a list of species that were previously found in the human gut microbiome. Results From a list which contemplates 131 species and 52 genera, 53 species and 40 genera had corresponding entries for KEGG Database and 82 species and 47 genera had corresponding entries for EggNOG Database. Moreover, we present the KEGG Orthologs (KOs) and EggNOG Orthologs (NOGs) entries associated to the search as their distribution over species and genera and lists of functions that appeared in many species or genera, the “core” functions of the human gut microbiome. We also present the relative abundance of KOs and NOGs throughout phyla and genera. Lastly, we expose a variance found between searches with different arguments on the database entries. Inferring functionality based on cross-referencing UniProt and KEGG or EggNOG can be lackluster due to the low number of annotated species in Uniprot and due to the lower number of functions affiliated to the majority of these species. Additionally, the EggNOG database showed greater performance for a cross-search with Uniprot about a mock human gut microbiome. Notwithstanding, efforts targeting cultivation, single-cell sequencing or the reconstruction of high-quality metagenome-assembled genomes (MAG) and their annotation are needed to allow the use of these databases for inferring functionality in human gut microbiome studies.
Cytogenetics of the skinks (Reptilia, Scincidae) from Thailand; III: the first karyological study of Sphenomorphus maculatus and Jarujinia bipedalis

Abstract This is a karyological study of male and female Sphenomorphus maculatus from Khon Kaen Province in Northeastern Thailand, and female Jarujinia bipedalis from Kanchanaburi Province in Central Thailand. Chromosomes of two species were prepared by the squash technique from the bone marrow and testis. Conventional staining and Ag-NOR banding techniques were applied to stain the chromosome with Giemsa’s solution and silver nitrate solution, respectively. The results showed that the diploid chromosome number of Sphenomorphus maculatus and Jarujinia bipedalis was 30 and the fundamental number (NF) was 44. There were eight large metacentric, two medium metacentric, four small metacentric and 16 microchromosomes in Sphenomorphus maculatus and eight large metacentric, six small metacentric, two small telocentric and 14 microchromosomes in Jarujinia bipedalis. There was no irregularly sized chromosome related to sex in either species. For Sphenomorphus maculatus, NORs are located at the telomere on the long arms of the second pair of the metacentric chromosome. The karyotype formulae were deduced as: 2n (30) = Lm8 + Mm2 + Sm4 + 16 microchromosomes and 2n (30) = Lm8 + Sm6 + St2 + 14 microchromosomes for Sphenomorphus maculatus and Jarujinia bipedalis, respectively.
The Anticoagulant and Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides From Tuna Cooking Juice Produced By Alcalase

Background: Tuna Cooking Juice (TCJ) is a by-product of canned tuna industry. It usually was either used as protein source of feed meal or directly discharged to wastewater treatment system. However, the soluble proteins in TCJ could be used for producing bioactive peptides by enzymatic hydrolysis. The aims of this study were to produce and purify the anticoagulant and ACE inhibitory peptides from TCJ. Methods: The bioactive peptides were prepared from tuna cooking juice by enzymatic hydrolysis. In this study, four commercial proteases including alcalase, flavourzyme, pancreatin and pepsin were used for enzymatic hydrolysis of tuna cooking juice. Six biological activities including angiotensin I-converting enzyme inhibitor, anticoagulant, calcium binding, hypocholesterolemic, antioxidant, and antidiabetes were determined. The hydrolysate was performed in an in vitro digestive system. The bioactive peptides were purified by size exclusion chromatography and then high performance liquid chromatography. Results: The alcalase hydrolysate at the hydrolysate time of 240 and 120 min showed the highest ACE inhibitory of 96.9±0.54% and anticoagulant activities of 92.0±0.75%, respectively. Both ACE inhibitory and anticoagulant peptides from tuna cooking juice hydrolysate were able to survive in an in vitro digestive tract and improve its activities. The molecular weight range of peptides exhibited highest ACE inhibitory and anticoagulant activities was 238-829 and 1355-1880 Da, respectively and these peptides still showed high activities. Conclusion: Therefore, tuna cooking juice is a potential source of bioactive peptides production used for functional food and neutraceutical ingredients.
Lipid Biomarkers in Estuary of Sungai Selangor, Selangor: Principal Component Analysis (PCA) of Sterols and Fatty Alcohols

A total of 34 surface sediment samples were taken from Sungai Selangor estuary to identify sources and variations of sterols and fatty alcohols. Samples were then extracted and the compounds were analyzed using gas chromatography-mass spectrometry (GC-MS). As a result, 10 sterol compounds and 18 fatty alcohol compounds were determined presence in the samples. Generally, the study area is dominated by phytosterols, long chain fatty alcohols (C21-C24) and phytol which is the indicator for terrestrial organic matter. Other than that, various type of sterols and fatty alcohols have been quantified which indicated input of marine organisms, bacterial and sewage. Principal component analysis (PCA) carried out with all compounds successfully characterized three main sources in the study area which were terrestrial, algae and a mixture of marine, bacterial and sewage. Thus, based on individual concentrations and the PCA, this study showed the presence of sterols and fatty alcohols in the study area are derived from various sources even more dominated by inputs from terrestrial sources
Desvendando a fauna do bioma pampa no Rio Grande do Sul : inventário da fauna de Drosophilidae (Insecta, Diptera)

In the last decades many faunal surveys of Drosophilidae have been done in 1 various environments in Brazil. But approximately 30 to 50% of the drosophilids in 2 Brazil have not yet been described and the degradation of some biomes causes a 3 profound loss of species diversity and information about community structure. This is 4 the situation with the Pampa, which covers southernmost Brazil, all of Uruguay, and the 5 central east region of Argentina. Seasonal collections were made in a natural area of 6 Pampa within the limits of the municipality of Bossoroca in the state of Rio Grande do 7 Sul, Brazil (28° 45’024‖S 54° 56’729‖W), from April 2011 to April 2012. The survey 8 of pampas Drosophilidae diversity was conducted via an intensive literature search of 9 species recorded in Brazil, Uruguay and Argentina, including not only taxonomic 10 studies, but also genetic, evolutionary and ecological ones. A total of 7,164 drosophilids 11 of 51 species were collected, being 36 species belonging to the genus Drosophila, two 12 to Amiota, ten to Rhinoleucophenga, one to Zaprionus and two to Zygothrica. Some 13 species were for the first time recorded in the Pampa biome: Drosophila briegeri, D. 14 fuscolineata, Rhinoleucophenga obesa, R. punctulata, R. subradiata and Zygothrica 15 orbitalis. Furthermore, three new species of genus Rhinoleucophenga were described: 16 R. pampeana sp. nov., R. missionera sp. nov. and R. sulina sp. nov. Despite Brazilian 17 pampa being the richest when compared with Uruguay and Argentina, the three 18 countries presented the same problem: huge areas totally unknown about the 19 Drosophilidae fauna. The combination of this information and the knowledge of the 20 current state of preservation of Pampa biome stress the necessity of a continuous study 21 to unveil the Drosophilidae diversity in this biome. 22
Glucocorticoid-Dependent Circadian Modulation of Prefrontal Cortex Molecular Clocks and Functioning

Elizabeth R. Woodruff (Ph.D., Neuroscience) Glucocorticoid-dependent circadian modulation of prefrontal cortex molecular clocks and functioning Thesis directed by Professor Robert L. Spencer Circadian rhythms are 24-hour fluctuations in physiology and behavior that are driven by the oscillatory expression of positive arm (Clock, Bmal1) and negative arm (Period, Per; Cryptochrome, Cry) core clock genes. Glucocorticoid hormone (CORT) circulation exhibits robust circadian rhythmicity, which stabilizes physiological and behavioral clocks during times of unanticipated environmental change. In Chapter 2 of this dissertation, I extend CORT’s stabilizing nature to the effect of constant light-induced disruption of circadian locomotor activity. In Chapter 3, I show that the presence and appropriate circadian phasing of CORT circulation is necessary for normal prefrontal cortex (PFC) Per1, Per2, and Bmal1 mRNA expression in rats. In Chapter 4, I describe circadian variation in PFC-dependent cued conditioned fear extinction learning (a behavior that is often disrupted in human psychopathology), as evidenced by enhanced extinction recall and attenuated fear renewal in rats when they are trained/tested during their active phase. In Chapter 5, I provide evidence that optimal extinction learning requires the presence of a functional PFC molecular clock, as evidenced by exaggerated fear behavior in rats after PFC Per1 knockdown through RNA interference. Furthermore, removal of CORT via adrenalectomy (ADX) impairs extinction learning in rats trained/tested during their active phase but has no effect on rats trained/tested during their inactive phase (described in Chapters 4 and 5). Complete normalization of this ADX effect requires an undisrupted history of circadian CORT circulation and acute CORT circulation at the time of extinction testing/training—neither is sufficient by itself. I submit that circadian CORT entrainment of PFC clock gene expression, which is necessary for optimal extinction learning, primes PFC neurons to respond to acute CORT during active phase extinction training/testing, thereby enabling learning-associated neuroplasticity. The research presented in this report provides evidence of heretofore uncharacterized CORT-dependent circadian entrainment of the PFC molecular clock and establishes the
Homeostatic compensation and neuromodulation maintain synchronized motor neuron activity in the crustacean cardiac ganglion

Motor neurons of the crustacean cardiac ganglion have variable intrinsic conductance magnitudes, yet produce virtually identical synchronized voltage activity. However, it is not known whether this variability makes cells vulnerable to desynchronization during neuromodulation. Previous work has investigated whether neuromodulation of variable networks can produce reliable responses in particular features of network output, but these studies have not examined this question as it relates to synchrony. To investigate this, we exposed the cardiac ganglion to the amine modulators serotonin and dopamine while recording from multiple motor neurons. Each amine had distinct excitatory effects, and serotonin caused desynchronized activity whereas dopamine did not. Dopamine was found to directly modify gap junctional conductance, and co-application of both modulators induced a serotonin-like response in network activity, but burst waveforms remained synchronized. Dopamine was also able to prevent desynchronization induced by the K channel blocker tetraethylammonium (TEA), suggesting that dopaminergic modulation of electrical coupling potentially plays
Evaluating insecticide spray regimes to manage cotton leafhopper, Amrasca devastans (Distant): their impact on natural enemies, yield and fiber characteristics of transgenic Bt cotton.

Cotton leafhopper Amrasca devastans (Dist.) is a major sucking insect pest of cotton and unfortunately natural enemies are not effective for its control. Insecticides are the only option for the management of this pest in Pakistan. On the introduction of transgenic cotton, insecticides are applied to manage sucking insect pests only. In the present study, nine combinations of conventional and new insecticides were evaluated against A. devastans and natural enemies for two years in transgenic cotton field. In every spray regime three insecticides were applied after an interval of 15 days. Spray regime of dimethoate, chlorfenapyr and acephate was the best in reducing A. devastans populations. However, the efficacy of insecticides against A. devastans was reduced when insecticides having same mode of action were applied in a spray regime. All the regimes proved toxic to varying degree to generalist predators like Orius spp. , Geocoris spp. , Chrysoperla carnea (Stephen), Coccinellids spp. and spiders. Spray regimes differed in their impact on growth and reproductive parameters of Bt cotton, which was directly related to A. devastans infestation. Overall higher root length (cm), shoot length (cm), number of leaves, yield (kg ha-1), ginning out turn (GOT %), micronare (μg inch-1), staple length (mm) and fiber strength were found in plants treated with spray regime. These results will help to manage A. devastans on transgenic cotton and will ultimately reduce the yield and fiber quality losses.
Amino-terminal transactivation subdomains of p53 contribute equally to p53-induced gene expression

The p53 tumour suppressor is mutated in over 50% of sporadic cancers. Its tumour suppressive functions arise in large part from transcriptional activation of target genes. Two adjacent regions within the transactivation domain of p53 are sufficient to support sequence-specific transactivation when fused to a heterologous DNA binding domain. It has been hypothesized that these two subdomains of p53 may contribute to the expression of distinct p53-responsive genes and regulate distinct biological pathways. In order to examine the subdomain requirements during transactivation, we used oligonucleotide microarrays to identify transcripts induced by variants of p53 with point mutations within subdomains 1, 2, or both (QS1, QS2, and QS1/QS2, respectively). Expression of wild type p53 (P53*) statistically induced 254 transcripts and apoptosis transcripts (GO#0006915) were the only statistically over represented group. Most of these transcripts were poorly induced by the p53 variants and there was a corresponding decrease in the ability of these variants to induce apoptosis. Strikingly, several well known p53-regulated transcripts including TNFRSF10B, BTG2, and POLH were increased to wild type levels by p53 and p53 but not p53, indicating that either subdomainl or 2 is sufficient for p53-dependent expression of a small subset of p53-responsive genes. Unexpectedly, there was no evidence for p53or p53specific gene expression. Taken together, these results demonstrated heterogeneity in the requirement for transactivation subdomains 1 and 2 of p53 without subdomain-specific contributions to p53-induced gene expression. The MafB transcript was identified as a pSS^-induced transcript that was not statistically increased in response to either p53 or p53 expression. Nonetheless, MafB expression increased more in response to the QS2 compared to the QS1 variant of p53 so MafB was studied further as a potential p53 target gene exhibiting a QS2-specific pattern of expression. Expression of p S S ^ increased MafB mRNA and protein levels and bound to a putative response element 2400bp upstream of the transcription start site. Expression of p53 consistently increased MafB expression more than p53, however this level did not approach the expression of MafB induced by $5? ^. Therefore, MafB represents a novel p53-regulated transcript that is poorly induced by both p53 and p53.