bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PK/PD Integration and Resistance of Tilmicosin AgainstMycoplasma hyopneumoniae
Authors: Huang Zilong , Hu Zixuan , Xia Xirui , Zheng Haorui , Gu Xiaoyan , Shen Xiangguang , Yang Hong , Ding Huanzhong 
Published: March 2020

AbstractMycoplasma hyopneumoniaeis the major pathogen causing enzootic pneumonia in pigs.M. hyopneumoniaeinfection can lead to considerable economic losses in the pig-breeding industry. Here, this study established a first-order absorption, one-compartment model to study the relationship between the pharmacokinetics/pharmacodynamics (PK/PD) index of tilmicosin againstM. hyopneumoniae in vitro. We simulated the drug concentration of timicosin in the fluid lining the lung epithelia of pigs. The minimum inhibitory concentration (MIC) of tilmicosin againstM. hyopneumoniaewith an inoculum of 106CFU/mL was 1.6 μg/mL using the microdilution method. Static time–kill curves showed that, if the drug concentration >1 MIC, the antibacterial effect showed different degrees of inhibition. At 32 MIC, the amount of bacteria decreased by 3.16 log10CFU/mL, thereby achieving a mycoplasmacidal effect. TheM. hyopneumoniaecount was reduced from 3.61 to 5.11 log10CFU/mL upon incubation for 96 h in a dynamic model with a dose of 40–200 mg, thereby achieving mycoplasmacidal activity. The peak concentration by MIC (Cmax/MIC) and the area under the concentration-time curve over 96 h divided by the MIC (AUC0–96 h/MIC) were the best-fit PK/PD parameters for predicting the antibacterial activity of tilmicosin againstM. hyopneumoniae(R2= 0.99), suggesting that tilmicosin had concentration-dependent activity. The estimated value for Cmax/MIC and AUC0–96 h/MIC for 2log10(CFU/mL) reduction and 3log10(CFU/mL) reduction from baseline was 1.44 and 1.91, and 70.55 h and 96.72 h, respectively. FourM. hyopneumoniaestrains (M1–M4) with reduced sensitivity to tilmicosin were isolated from the four dose groups. The susceptibility of these strains to tylosin, erythromycin and lincomycin was also reduced significantly. For sequencing analyses of 23S rRNA, an acquired A2058G transition in region V was found only in resistantM. hyopneumoniaestrains (M3, M4). In conclusion, in anin vitromodel, the effect of tilmicosin againstM. hyopneumoniaewas concentration-dependent and had a therapeutic effect. These results will help to design the optimal dosing regimen for tilmicosin inM. hyopneumoniaeinfection, and minimize the emergence of resistant bacteria.
No Relationship Between Perceived Health Anomalies and Perceived Experimental Success in Retired Breeder Male Hartley Albino Guinea Pigs
Authors: Bain Chandra B. , Settlage Julie M. , Blair Grace A. , Poelzing Steven 
Published: March 2020

ABSTRACTGuinea pigs used in our laboratory for cardiac research sometimes exhibit physical abnormalities. These issues may abate or intensify during the time they are housed in our facility. After using a guinea pig for research, experimentalists note the apparent health of an animal based on visible features and/or abnormal electrophysiology of the heart. There was an existing anecdotal observation that the health of the Guinea Pigs, and subsequently the experimental success rate, had a seasonal variation; therefore we sought to determine if there is a time of year in which our guinea pigs are more likely to be perceived as unhealthy, and whether any determined monthly pattern correlates with an experimentalist’s ability to complete an experimental protocol. An electronic log was created to record the perceived health of the animal and the ability to complete the experiment successfully. Irregular symptoms included, but were not limited to, severe weight or hair loss and irregularities with the heart found post thoracotomy or during baseline electrophysiological recordings of whole-heart preparations. Animals that did not exhibit significant weight or hair loss, or other ailments were considered “healthy”. Overall, our results indicate that there are no monthly variations in perceived Hartley Albino guinea pig health or correlations with experimental completion rates, suggesting mild hair or weight loss that is common when shipping animals may not significantly affect the ability to conductex vivowhole-heart electrophysiological studies.
Antibacterial efficacy of Jackfruit rag extract against clinically important pathogens and validation of its antimicrobial activity inShigella dysenteriaeinfectedDrosophila melanogasterinfection model
Authors: Dhwani NV , Raju Gayathri , Mathew Sumi E , Baranwal Gaurav , Shivaram Shivakumar B , Katiyar Neeraj , Pramanik Nilkamal , Jhunjhunwala Siddharth , Shilpashree H.B. , Nagegowda Dinesh A. , Kumar Ritesh , Shasany Ajit K. , Biswas Raja , Shankarappa Sahadev A 
Published: March 2020

AbstractThe aim of this study was to determine the antibacterial property of extract derived from a part of the Jackfruit called ‘rag’, that is generally considered as fruit waste. Morpho-physical characterization of the Jackfruit rag extract (JFRE) was performed using gas-chromatography, where peaks indicative of furfural; pentanoic acid; and hexadecanoic acid were observed.In vitrobiocompatibility of JFRE was performed using the MTT assay, which showed comparable cellular viability between extract-treated and untreated mouse fibroblast cells. Agar well disc diffusion assay exhibited JFRE induced zones of inhibition for a wide variety of laboratory and clinical strains of gram-positive and gram-negative bacteria. Analysis of electron microscope images of bacterial cells suggests that JFRE induces cell death by disintegration of the bacterial cell wall and precipitating intracytoplasmic clumping. The antibacterial activity of the JFREs was further validatedin vivousingShigella dysenteriaeinfected fly model, where JFRE pre-fed flies infected withS. dysenteriaehad significantly reduced mortality compared to controls. JFRE demonstrates broad antibacterial property, bothin vitroandin vivo, possibly by its activity on bacterial cell wall. This study highlights the importance of exploring alternative sources of antibacterial compounds, especially from plant-derived waste, that could provide economical and effective solutions to current challenges in antimicrobial therapy.
Metaplasticity in the ventral pallidum as a potential marker for the development of diet-induced obesity
Authors: Gendelis Shani , Inbar Dorrit , Inbar Kineret , Mesner Shanee , Kupchik Yonatan M. 
Published: March 2020

AbstractA major driver of obesity is the increasing palatability of processed foods. Although reward circuits promote the consumption of palatable food their involvement in obesity remains unclear. The ventral pallidum (VP) is a key hub in the reward system that encodes the hedonic aspects of palatable food consumption and participates in various proposed feeding circuits. However, there is still no evidence for its involvement in developing diet-induced obesity. Here we examine, using male C57bl6/J mice and patch-clamp electrophysiology, how chronic high-fat-high-sugar (HFHS) diet changes the physiology of the VP and whether mice that gain the most weight differ in their VP physiology from others. We found that 10-12 weeks of HFHS diet hyperpolarized and decreased the firing rate of VP neurons without a major change in synaptic inhibitory input. Within the HFHS group, obesity-prone (OP, top 33% weight gainers) mice had a more hyperpolarized VP with longer latency to fire action potentials upon depolarization compared to obesity-resistant (OR, bottom 33% weight gainers) mice. OP mice also showed synaptic potentiation of inhibitory inputs both at the millisecond and minute ranges. Moreover, we found that the tendency to potentiate the inhibitory inputs to the VP might exist in overeating mice even before exposure to HFHS, thus making it a potential property of being an overeater. These data point to the VP as a critical player in obesity and suggest that hyperpolarized membrane potential of, and potentiated inhibitory inputs to, VP neurons may play a significant role in promoting overeating of palatable food.Significance statementIn modern world, where highly-palatable food is readily available, overeating is often driven by motivational, rather than metabolic, needs. It is thus conceivable that reward circuits differ between obese and normal-weight individuals. But is such difference, if it exists, innate or develops with overeating? Here we reveal synaptic properties in the ventral pallidum, a central hub of reward circuits, that differ between mice that gain the most and the least weight when given unlimited access to highly-palatable food. We show that these synaptic differences exist also without exposure to palatable food, potentially making them innate properties that render some more susceptible than others to overeat. Thus, the propensity to overeat may have a strong innate component embedded in reward circuits.
Multiple-biological matrices metabolomics identified new metabolite biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis
Authors: Luo Xialin , Liu Jingjing , Wang Huaizhi , Lu Haitao 
Published: March 2020

AbstractPurposeTo improve clinical diagnosis and enhance therapeutic outcome, we figure out to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can easily, sensitively and efficiently diagnose the onsite progression, and metastasis of the disease.Experimental DesignWe employed the newly developed precision-targeted metabolomics method to validate that many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer from healthy controls. To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance.ResultsWe eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); Moreover, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages.ConclusionsTaken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficiently therapeutic interventions, which could largely improve the five-year survival rate of PC patients.
Three-dimensional contact point determination and contour reconstruction during active whisking behavior of the awake rat
Authors: Huet Lucie A. , Emnett Hannah M. , Hartmann Mitra J. Z. 
Published: March 2020

AbstractThe rodent vibrissal (whisker) system has been studied for decades as a model of active touch sensing. There are no sensors along the length of a whisker; all sensing occurs at the whisker base. Therefore, a large open question in many neuroscience studies is how an animal could estimate the three-dimensional location at which a whisker makes contact with an object. In the present work we simulated the exact shape of a real rat whisker to demonstrate the existence of a unique mapping from triplets of mechanical signals at the whisker base to the three-dimensional whisker-object contact point. We then used high speed video to record whisker deflections as an awake rat whisked against a peg and used the mechanics resulting from those deflections to extract the contact points along the peg surface. A video shows the contour of the peg gradually emerging during active whisking behavior.
Assessing the impact of introductory programming workshops on the computational reproducibility of biomedical workflows
Authors: Deardorff Ariel 
Published: March 2020

AbstractIntroductionAs biomedical research becomes more data-intensive, computational reproducibility is a growing area of importance. Unfortunately, many biomedical researchers have not received formal computational training and often struggle to produce results that can be reproduced using the same data, code, and methods. Programming workshops can be a tool to teach new computational methods, but it is not always clear whether researchers are able to use their new skills to make their work more computationally reproducible.MethodsThis mixed methods study consisted of in-depth interviews with 14 biomedical researchers before and after participation in an introductory programming workshop. During the interviews, participants described their research workflows and responded to a quantitative checklist measuring reproducible behaviors. The interview data was analyzed using a thematic analysis approach, and the pre and post workshop checklist scores were compared to assess the impact of the workshop on computational reproducibility of the researchers’ workflows.ResultsPre and post scores on a checklist of reproducible behaviors did not increase in a statistically significant manner. The qualitative interviews revealed that several participants had made small changes to their workflows including switching to open source programming languages for their data cleaning, analysis, and visualization. Overall many of the participants indicated higher levels of programming literacy and an interest in further training. Factors that enabled change included supportive environments and an immediate research need, while barriers included collaborators that were resistant to new tools and a lack of time.ConclusionWhile none of the participants completely changed their workflows, many of them did incorporate new practices, tools, or methods that helped make their work more reproducible and transparent to other researchers. This indicate that programming workshops now offered by libraries and other organizations contribute to computational reproducibility training for researchers
Mutagenic effectiveness and efficiency of gamma rays and sodium azide in M2generation of Cowpea [Vigna unguiculata(L.) Walp.]
Authors: Raina Aamir , Khan Samiullah 
Published: March 2020

AbstractLegumes play a pivotal role in combating the chronic hunger and malnutrition in the developing nations and are also ideal crops to achieve global food and nutrition security. In the era of climate change, erratic rainfalls, depleting arable land and water resource, feeding the rapidly growing population is a challenging task. Like most other pulses, cowpea is a self pollinated, nutritious, versatile and widely adapted grain legume, but harbor a little accessible genetic variability. Lack of sufficient genetic variability and small size of flowers, traditional plant breeding methods are not enough to meet the demands of improvement of cowpea. Hence, induced mutagenesis was employed to induce significant genetic variability across a range of agro-economical traits in two cowpea varieties Gomati VU-89 and Pusa- 578 from M1 to M4 generations. The success of induced mutagenesis largely depends on the selection of appropriate mutagen, its dose, effectiveness and efficiency. Hence present study was conduct to assess the effectiveness and efficiency of single and combined doses of sodium azide and gamma rays to set an appropriate protocol for induced mutagenesis experimentation in cowpea.
Schistosoma Japonicuminfection in Treg-specific USP21 knock-out mice
Authors: Zhang Youxiang , Xu Guina , Zhang Baoxin , Zhang Shan , Li Yangyang , Huang Qing , Chen Simin , Zeng Fansheng , Li Bin , Qin Zhiqiang , Zhang Zuping 
Published: March 2020

AbstractUSP21, an E3 de-ubiquitin enzyme playing vital roles in physiological activities, is important for Treg cells to maintain immune homeostasis and control immune tolerance. To understand its diverse functions and potential mechanism is essential for disease development. We, using the USP21 gene-conditional knock-out mice model ofSchistosoma Japonicuminfection, found more cercariae developed into adults, and more eggs deposited in the liver in KO mice. However, immunohistochemistry showed the degree and the area of egg granuloma and liver fibrosis were both reduced. This suggested knock-out USP21 did affect the immunoregulation between schistosomes and the host. In KO mice the content of IFN-gamma and IL-4, and the expression of anti-SEA IgG and anti-SWAP IgG both increased in the liver, spleen and blood by flow cytometry, while the content of IL-10, lL-17A, IL-23, IL-9 and the expression of USP21 and anti-SEA IgM decreased. This indicated USP21-knockout-Tregs promoted both Th1-type and Th2-type immunity and inhibited other immunities during schistosomes infection, which disordered the host immunity. This study revealed the immunomodulatory of USP21 and preliminarily suggests it might be essential to regulate the complex immune network between the host and schistosomes. USP21 provides a new possible target for schistosomiasis treatment in the future.Author summarySchistosomiasis is a common neglected tropical disease that affects more than 230 million people worldwide. Therefore, the study on the mechanism of immune interaction between schistosomas and the host is not only helpful for the understanding of immune homeostasis, but also helpful for the further development of the treatment of schistosomiasis. Ubiquitin Specific Protease 21(USP21) has been shown to be involved in the regulation of many biological processes, such as maintaining immune homeostasis and regulating cell growth. Here, we observed that the specific deletion of USP21 led to the decrease of mice’s ability to resist schistosomes infection and promoted the survival of schistosomes. It was also proved that unstable regulatory T cells would produce polarization phenomenon and promote differentiation to helper T cells, which would lead to disorder of immune response in mice. However, this process reduced the serious immune pathological damage caused by egg granuloma. Our findings reveal that USP21 may be an important molecule regulating immune interaction betweenSchistosoma japonicumand the host.
Identification of X-chromosomal genes that drive global X-dosage effects in mouse embryonic stem cells
Authors: Genolet Oriana , Monaco Anna A. , Dunkel Ilona , Boettcher Michael , Schulz Edda G. 
Published: March 2020

AbstractX-chromosomal genes contribute to sex differences, in particular during early development, when both X chromosomes are active in females. Here, double X-dosage shifts female pluripotent cells towards the naive stem cell state by increasing pluripotency factor expression, inhibiting the differentiation-promoting MAP kinase (MAPK) signalling pathway and delaying differentiation. To identify the genetic basis of these sex differences, we have performed a series of CRISPR knockout screens in murine embryonic stem cells to comprehensively identify X-linked genes that cause the female pluripotency phenotype. We found multiple genes that act in concert, among which Klhl13 plays a central role. We show that this E3 ubiquitin ligase substrate adaptor protein promotes pluripotency factor expression, delays differentiation and represses MAPK target genes, and we identify putative substrates. We thus elucidate the mechanisms that drive sex-induced differences in pluripotent cells with implications for gender medicine in the context of induced pluripotent stem cell based therapies.
Dynamic dot displays reveal material motion network in the human brain
Authors: Schmid Alexandra C. , Boyaci Huseyin , Doerschner Katja 
Published: March 2020

ABSTRACTThere is growing research interest in the neural mechanisms underlying the recognition of material categories and properties. This research field, however, is relatively more recent and limited compared to investigations of the neural mechanisms underlying object and scene category recognition. Motion is particularly important for the perception of non-rigid materials, but the neural basis of non-rigid material motion remains unexplored. Using fMRI, we investigated which brain regions respond preferentially to material motion versus other types of motion. We introduce a new database of stimuli – dynamic dot materials – that are animations of moving dots that induce vivid percepts of various materials in motion, e.g. flapping cloth, liquid waves, wobbling jelly. Control stimuli were scrambled versions of these same animations and rigid three-dimensional rotating dots. Results showed that isolating material motion properties with dynamic dots (in contrast with other kinds of motion) activates a network of cortical regions in both ventral and dorsal visual pathways, including areas normally associated with the processing of surface properties and shape, and extending to somatosensory and premotor cortices. We suggest that such a widespread preference for material motion is due to strong associations between stimulus properties. For example viewing dots moving in a specific pattern not only elicits percepts of material motion; one perceives a flexible, non-rigid shape, identifies the object as a cloth flapping in the wind, infers the object’s weight under gravity, and anticipates how it would feel to reach out and touch the material. These results are a first important step in mapping out the cortical architecture and dynamics in material-related motion processing.
Genetic sex determination and sex-specific lifespan in tetrapods – evidence of a toxic Y effect
Authors: Sultanova Zahida , Downing Philip A. , Carazo Pau 
Published: March 2020

ABSTRACTSex-specific lifespans are ubiquitous across the tree of life and exhibit broad taxonomic patterns that remain a puzzle, such as males living longer than females in birds and vice versa in mammals. The prevailing “unguarded-X” hypothesis (UXh) explains this by differential expression of recessive mutations in the X/Z chromosome of the heterogametic sex (e.g., females in birds and males in mammals), but has only received indirect support to date. An alternative hypothesis is that the accumulation of deleterious mutations and repetitive elements on the Y/W chromosome might lower the survival of the heterogametic sex (“toxic Y” hypothesis). Here, we report lower survival of the heterogametic relative to the homogametic sex across 138 species of birds, mammals, reptiles and amphibians, as expected if sex chromosomes shape sex-specific lifespans. We then analysed bird and mammal karyotypes and found that the relative sizes of the X and Z chromosomes are not associated with sex-specific lifespans, contrary to UXh predictions. In contrast, we found that Y size correlates negatively with male survival in mammals, where toxic Y effects are expected to be particularly strong. This suggests that small Y chromosomes benefit male lifespans. Our results confirm the role of sex chromosomes in explaining sex differences in lifespan, but indicate that, at least in mammals, this is better explained by “toxic Y” rather than UXh effects.