bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activated Carbon-Based Immunochromatographic Strip Test for the Rapid Qualitative Analysis of Swertiamarin and Sweroside
Authors: Nuntawong Poomraphie , Horikawa Taiki , Tanaka Hiroyuki , Morimoto Satoshi , Sakamoto Seiichi 
Published: May 2022

Abstract

Background
Swertia japonica (S. japonica) is a medicinal plant that belongs to the Gentianaceae family. Several reports confirm the biological effects of the S. japonica extract. This plant is used mainly as a digestive stimulant, appetite stimulant, and gastrointestinal disease remedy in Japan. Secoiridoid glycosides are a group of compounds related to the beneficial effects of this plant.

Objective
We developed an immunochromatographic strip test for major secoiridoid glycosides, such as swertiamarin (SM) and sweroside (SS) detection.

Methods
We fabricated an immunoprobe using activated carbon as a reporter molecule and a monoclonal antibody against SM and SS (MAb D2) as a detection molecule. The test and control zones of the strip test contained SM-cBSA and Goat pAb anti-mouse IgM HRP conjugate, respectively. The immunoprobe reacted competitively with free SM and/or SS and immobilized SM-cBSA. The results were read and interpreted by the black spot intensity in the test zone.

Results
We succeeded in developing a strip test system with a detection limit (LOD) of 12.5 µg/mL. The selectivity and reliability evaluation revealed that the strip test is suitable for detecting SM and SS in S. japonica. The result was ready to be read in 30 min.

Conclusions
This method can be a useful tool for the screening of biologically active S. japonica samples for further preparation of traditional medicine.

Highlights
To the best of our knowledge, this is the first immunochromatographic strip test developed for the detection of SM and SS in S. japonica samples.
Spatiotemporal variation of ringed seal blubber cortisol levels in the Canadian Arctic
Authors: Ogloff Wesley R , Anderson Randi A , Yurkowski David J , Debets Cassandra D , Anderson W Gary , Ferguson Steven H 
Published: May 2022

AbstractClimate change in the Arctic has widespread and complex effects on the health of animals and their populations. We used radioimmunoassay to measure blubber cortisol in ringed seals (Pusa hispida) sampled in Ulukhaktok, Inuvialuit Settlement Region, Northwest Territories, Canada (spring, 2002, 2004–2005, 2007–2012) and Arviat, Nunavut, Canada (autumn, 2003–2012) to examine chronic stress relative to biology (age, sex, length), body condition (blubber depth), and diet (δ13C, δ15N, and isotopic niche size). Ulukhaktok ringed seals had higher cortisol concentrations overall (0.46 ± 0.04 ng/g) than Arviat ringed seals (0.36 ± 0.03 ng/g), and these higher concentrations were associated with higher muscle δ15N and lower blubber thickness. In contrast, blubber cortisol concentrations for Arviat ringed seals decreased with blubber depth and increased with age, though testing of age effects individually suggests that age-related patterns are weak. Annual mean cortisol concentration increased from 2003 to 2012 in Arviat ringed seals, but low sample sizes precluded analysis of annual patterns for Ulukhaktok ringed seals. The trend of increased cortisol over time in Arviat ringed seals suggests that they might be experiencing greater chronic stress over time, which could have implications for numerous population health metrics including reproduction and pup recruitment.
Design and fabrication of an electrochemical chip for liquid-phase transmission electron microscopy
Authors: Sasaki Yuki , Mizushima Ayako , Mita Yoshio , Yoshida Kaname , Kuwabara Akihide , Ikuhara Yuichi 
Published: May 2022

Abstract
Liquid-phase transmission electron microscopy (LP-TEM) can be used with an electrochemical chip (e-chip) to observe electrochemical reactions in a liquid in situ. The design of electrodes on an e-chip fabricated using microelectromechanical system technology cannot be easily changed. Here, we report a newly designed e-chip and its fabrication process. Electrodes with a desired shape were fabricated with various metals via an additional step of vacuum deposition onto our e-chip with a shadow mask. For precise control of the electrochemical reactions in LP-TEM, optimization of the electrode shape and material is critical.
Evolution, Expression Patterns, and Distribution of Novel Ribbon Worm Predatory and Defensive Toxins
Authors: Verdes Aida , Taboada Sergi , Hamilton Brett R. , Undheim Eivind A.B. , Sonoda Gabriel G. , Andrade Sonia C.S. , Morato Esperanza , Marina Ana Isabel , Cárdenas César A. , Riesgo Ana 
Published: May 2022

Abstract
Ribbon worms are active predators that use an eversible proboscis to inject venom into their prey and defend themselves with toxic epidermal secretions. Previous work on nemertean venom has largely focused on just a few species and has not investigated the different predatory and defensive secretions in detail. Consequently, our understanding of the composition and evolution of ribbon worm venoms is still very limited. Here, we present a comparative study of nemertean venom combining RNA-seq differential gene expression analyses of venom-producing tissues, tandem mass spectrometry-based proteomics of toxic secretions, and mass spectrometry imaging of proboscis sections, to shed light onto the composition and evolution of predatory and defensive toxic secretions in Antarctonemertes valida. Our analyses reveal a wide diversity of putative defensive and predatory toxins with tissue-specific gene expression patterns and restricted distributions to the mucus and proboscis proteomes respectively, suggesting that ribbon worms produce distinct toxin cocktails for predation and defense. Our results also highlight the presence of numerous lineage-specific toxins, indicating that venom evolution is highly divergent across nemerteans, producing toxin cocktails that might be finely tuned to subdue different prey. Our data also suggest that the hoplonemertean proboscis is a highly specialized predatory organ that seems to be involved in a variety of biological functions besides predation, including secretion and sensory perception. Overall, our results advance our knowledge into the diversity and evolution of nemertean venoms and highlight the importance of combining different types of data to characterize toxin composition in understudied venomous organisms.
Dietary Diversity and Evolution of Cranial Adaptations in Turtles
Authors: Smith Heather F. 
Published: May 2022

The evolution of the turtle skull has involved a series of unique modifications resulting in increased bite force stemming from cranial elongation, rearrangement of jaw adductor musculature, and reduction of cranial kinesis. Loss of teeth, development of the keratinous rhamphotheca, and evolution of a highly flexible neck have also driven turtle cranial evolution. Dietary diversity across the clade has resulted in a diverse range of morphological variations of the turtle cranial Bauplan, including those associated with suction feeding and tongue‐dependent food uptake.The Cenomanian Arlington Archosaur Site (AAS) from the Woodbine Formation of Texas was home to numerous mid‐Cretaceous turtle taxa. This diverse faunal assemblage allows an evaluation of how dietary adaptations can facilitate partitioning of the available niche space among co‐occurring turtle species. Baenids, such as Trinitichelys maini at AAS, are typically reconstructed as being primarily carnivorous, although there is evidence that some taxa were molluscivorous. The AAS helochelydrid Naomichelys was likely a generalized omnivore, being more terrestrial than the other AAS turtle taxa. Bothremydids, such as the AAS species Pleurochayah appalachius, have a wide range of dietary specializations including durophagy and suction‐feeding. These adaptations are evidenced by the broad range of bothremydid cranial morphologies including expanded triturating surfaces and an inflated face. Highly aquatic trionychids are predominantly piscivorous, although they will also opportunistically hunt other small prey such crustaceans and amphibians. Many trionychid species must be fully submerged under water in order to properly swallow their food in contrast to some semi‐aquatic turtles. A newly identified protostegid turtle reveals a marine component to the AAS turtle fauna, suggesting the presence of an open ocean piscivore. Finally, an intriguing new lower jaw with well‐developed denticles indicates the presence of an obligate herbivore among the AAS turtle fauna. This diverse array of dietary proclivities and adaptations reveals how AAS turtle communities divided the available ecospace in order to avoid interspecific competition for available resources among turtle taxa and with the other AAS herpetofauna.
Comparison of the Safety and Efficacy of Tofacitinib and Fingolimod in TNBS‐Induced Colitis Model in Adult Zebrafish: The Role of Myd88/NF‐κB/TNF‐α Signaling Pathway
Authors: Mousavi Taraneh , Hassani Shokoufeh , Gholami Mahdi , Vakhshiteh Faezeh , Baeeri Maryam , Rahimifard Mahban , Ghafour‐Broujerdi Elmira , Abdollahi Mohammad 
Published: May 2022

Due to the inadequate response, side effects, parenteral route of administration, and immunogenicity, oral targeted small molecules seem to replace monoclonal antibodies in the future management of ulcerative colitis (UC). In order to pave the way for clinical translations of small molecules in UC, for the first time, we compared the efficacy of fingolimod and tofacitinib in preclinical model of colitis, and uncovered another mechanism of action that these medicines may act through.We implicated adult zebrafish to find out its pros/cons, investigated aquatic toxicity of the mentioned compounds, and designed a procedure to evaluate compound's efficacy in adult zebrafish colitis model; hence, facilitating screening of further agents.Tofacitinib and fingolimod were investigated to be in category 1 of Globally Harmonized System (GHS) aquatic toxicity classification with the LC50 of 0.9014 and 0.36 mg/L, respectively, based on the acute toxicity assessment within 96 h.Considering efficacy assessments, colitis was induced through intrarectal administration of 160 mM TNBS for 48 h. Then, animals were exposed to different concentrations of tofacitinib (0.25, 0.57, 0.72, 0.90 mg/L) and fingolimod (0.23, 0.28, 0.36, 0.45 mg/L) for 96 h. Subsequent analyses revealed that TNBS significantly reduced length of villi, number of goblet cells, level of TNF‐α, MyD88, and NF‐κB2, increased thickness of villi and necrosis, and induced histopathological changes, including intestinal edema, submucosal hemorrhage/hyperemia with the presence of inflammatory cells. All the aforementioned parameters were considerably enhanced almost dose‐dependently with both agents, wherein the effect of 0.45 mg/L fingolimod was superior to other groups. As well, there were no signs of hyperemia/hemorrhage in harvested intestinal samples. Resultantly, we revealed that these medications may suppress canonical and non‐canonical NF‐κB pathways through targeting toll‐like receptors and MyD88.Given the better efficacy and multi‐targeted action of fingolimod, it worth to focus on sphingosine‐1 phosphate receptor modulators in clinical trials of UC and compare them with other classes of medications; albeit, their ecotoxicity aspect should not be overlooked.
The effect of photoperiod on the serotoninergic system of the thymus and its role in implementing the effects of exogenous melatonin
Authors: Luzikova Elena M. , Sergeeva Valentina E. , Sergeev Pavel V. , Lukachev Ivan A. 
Published: May 2022

Serotonin‐containing cells of the thymus in Wistar rats were studied, which were kept during 4 weeks of the experiment under the conditions of a natural photoperiod, under the conditions of constant blackout, under the conditions of continuous illumination. The effect of melatonin (“Melaxen” Unipharm, Inc., USA) ad libitum at a concentration of 4 mg / liter with drinking for four weeks) on serotonin‐positive cells of the thymus was studied.ResultsThe absence of light does not affect serotonin synthesis in the amine‐producing cells of the diffuse endocrine system in the border of the cortical and medullary lobules, but it suppresses the amine‐absorbing properties in the cortical substance cells of the thymus lobules. Continuous illumination does not affect the amine‐absorbing properties of the cells of the diffuse endocrine system in the cortical lobular substance, but promotes serotonin accumulation in the amine‐producing cells at the border of the thymus cortical and medullary lobules. Regardless of the photoperiod, exogenous melatonin increases the content of serotonin in the cells of the thymic diffuse endocrine system, which is more pronounced in continuous light conditions.ConclusionsOur studies have shown that changes in the photoperiod stimulate the serotoninergic system of the thymus, and exogenous melatonin smooths out these effects.
Down‐expression of MiR30a‐5p promotes proliferation and migration of Non‐Small Cell Lung Cancer cells by targetting MTDH
Authors: Tapara Dramani Maman Souraka 
Published: May 2022

OBJECTIVEMTDH has been identified to play a critical role in many cancer types, but its potential mechanism in Non‐Small Cell Lung Cancer (NSCLC) still remains unclear. We investigated the role of miRNA30a‐5p in the regulation of MTDH expression, which is known as an essential biomarker for NSCLC initiation and progression.MATERIALS AND METHODSQuantitative real‐time PCR (qRT‐PCR) has been performed to evaluate the expression level of MTDH and miR30a‐5p. Then, we transfected miR30a‐5p mimic and inhibitor into H1299 and A549 cells to investigate their impact in cell proliferation, migration, and invasion by using CCK‐8 assay, wound‐healing assay, and transwell assay respectively. The evidence of miR30a‐5p as a specific target of the MTDH gene was explored through luciferase report assay. The expression level of MTDH was evaluated by its mRNA and protein level using a western blot assay.RESULTSResults revealed that miR30a‐5p was upregulated whereas MTDH was downregulated. Down‐expression of miR30a‐5p increases the expression level of MTDH and promotes NSCLC cell proliferation and invasion. Luciferase report assay confirmed the binding of miR30a‐5p on MTDH mRNA 3′UTR region.CONCLUSIONSThis funding highlights the silencing mechanism of MTDH in lung cancer and further revealed that MTDH can be used as a potential diagnostic and therapeutic biomarker.
Pyridoxal phosphate‐dependent reactions in natural products biosynthesis
Authors: Ryan Katherine 
Published: May 2022

Pyridoxal 5′‐phosphate (PLP)‐dependent enzymes are widespread in nature. Most reactions catalyzed by PLP‐dependent enzymes traverse through a carbanionic intermediate, which is stabilized by the PLP cofactor. Like all enzymes that deal with carbanions, PLP‐dependent enzymes can be subject to reaction with electrophiles like O2. However, the majority reactions of PLP‐dependent enzymes with O2 are paracatalytic.Recent studies have identified PLP‐dependent enzymes that employ O2 as a co‐substrate for oxidation of arginine. Such enzymes are part of biosynthetic pathways that convert arginine into heterocycle‐containing natural products. In this talk, I will discuss the discovery of these arginine oxidases, and I will describe what we have learned about their mechanisms. I will furthermore highlight how we characterized an O2‐, PLP‐dependent enzyme encoded by an unknown gene cluster and then used this discovery as a starting point to reconstitute the biosynthetic pathway to the antibiotic azomycin.
Proteome‐scale amino‐acid resolution footprinting of protein‐binding sites in the intrinsically disordered regions
Authors: Ivarsson Ylva 
Published: May 2022

Protein‐protein interactions are central to cell function. Numerous studies have provided large‐scale information on human protein‐protein interactions. However, many interactions remain to be discovered, and low affinity, conditional and cell type‐specific interactions disproportionately under‐represented. I will present our efforts towards finding the short linear motif (SLiM)‐based interactions of a variety of protein domains. I will present an optimized proteomic peptide‐phage display (ProP‐PD) library that tiles all disordered regions of the human proteome and allows the screening of ~1,000,000 overlapping peptides in a single binding assay, and the tools and guidelines we have defined for processing the data (1). Using the approach we identified >2,000 interaction pairs for 35 known SLiM‐binding domains and confirmed the quality of the produced data by complementary biophysical or cell‐based assays. The amino acid resolution binding site information can be used to pin‐point functionally important disease mutations and phosphorylation events in intrinsically disordered regions of the proteome. Finally, I will describe how we developed the approach for large‐scale discovery of coronavirus‐host factor protein interactions (2). We screened more than 130 protein domains for binding to viral peptides, and translated the high‐resolution information on direct virus‐host interactions to a specific peptide‐based antiviral inhibitor of an interaction between the G3BP1/2 proteins and an ΦxFG peptide motif in the SARS‐CoV‐2 nucleocapsid (N) protein. ProP‐PD may thus be used both to illuminate the motif‐based part of the interactome and to uncover leads for innovative inhibitor design.References
Benz et al., (2022) Proteome‐scale mapping of binding sites in the unstructured regions of the human proteome. Mol Syst Biol. 2022 Jan;18(1):e10584.
Kruse et al., (2021) Large scale discovery of coronavirus‐host factor protein interaction motifs reveals SARS‐CoV‐2 specific mechanisms and vulnerabilities. Nat Commun. 2021 Nov 19;12(1):6761.
What makes a competitive applicant? Assessing students for graduate/professional school applications
Authors: Sayer Erin M. 
Published: May 2022

Whether a faculty member is asked to write one letter or several dozen letters of recommendation/reference, the process can be reflective or challenging for the writer as we support our undergraduate students applying to graduate or professional schools. What makes us “qualified” to assess students for these important letters? What process do we use to be sure we provide the schools/programs with the information they need to make an informed decision? In addition, there are recent challenges we face as letter writers when we are asked by students we barely know due to COVID‐capped in person classes or faceless Zoom sessions required by synchronous learning requirements.This presentation will discuss the difference between a “good/strong” letter of reference and a balanced letter of evaluation. We will consider what content makes a good letter of reference, what a writer can and cannot discuss in the letter, and what process a writer can use to collect relevant information to write a well‐rounded, factual letter that presents an accurate reflection of the student.
Uncovering conditional vulnerabilities in human cancer cells
Authors: Cantor Jason R. 
Published: May 2022

Forward genetic screens based on either RNAi or CRISPR make it possible to systematically identify genes required for the survival and growth of mammalian cells, and thus offer a powerful approach to characterize protein function and identify potential cancer vulnerabilities. Nonetheless, fitness genes can be context‐dependent, and indeed, CRISPR screens across hundreds of human cell lines have revealed that genetic dependencies can vary with natural cell‐intrinsic diversity. However, while the impact of environmental factors on cell physiology has become better appreciated, there has been little investigation into how nutrient availability affects gene essentiality and, further, most forward genetic screens are performed in vitro using culture media with little relevance to human physiology. We previously developed Human Plasma‐Like Medium (HPLM) – the first systematically designed physiologic medium, which contains over 60 components at concentrations that reflect their average values in human blood. To test the hypothesis that medium composition influences gene essentiality, we performed CRISPR‐based loss‐of‐function screens of blood cancer lines HPLM versus traditional media. Analysis of these data revealed that sets of conditionally essential genes are involved in several biological processes and can vary with both cell‐intrinsic diversity and the combination of basal and serum components that comprise typical media. Moreover, our approach allows for the downstream identification of gene‐nutrient interactions that underlie conditional CRISPR phenotypes, which can in turn uncover conditionally essential protein roles.Additionally, most preclinical therapies fail to achieve translation – a major problem attributed in part to the limited physiologic relevance of existing models. Nonetheless, there has been similarly little systematic investigation into how the composition of culture media might affect drug efficacy. Further, virtually all drug screens, initial hit validation efforts, and studies of drug activity are performed in vitro using traditional media as well. Therefore, we with collaborators at NCATS used a library of approved and (pre)‐clinical drugs to screen blood cancer lines in HPLM versus conventional media. Remarkably, we identified many whose killing activity varied with medium composition, including drugs approved for non‐oncology indications. Indeed, neither the drug‐nutrient interaction nor the mechanism of drug activity in cancer cells is immediately apparent in many such cases.