bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibacterial and immunomodulatory activities of insect defensins-DLP2 and DLP4 against multidrug-resistant Staphylococcus aureus
Authors: Li Zhanzhan , Mao Ruoyu , Teng Da , Hao Ya , Chen Huixian , Wang Xiumin , Wang Xiao , Yang Na , Wang Jianhua 
Published: September 2017

AbstractMethicillin-resistant Staphylococcus aureus (MRSA), are the most frequent cause of sepsis, which urgently demanding new drugs for treating infection. Two homologous insect CSαβ peptides-DLP2 and DLP4 from Hermetia illucens were firstly expressed in Pichia pastoris, with the yields of 873.5 and 801.3 mg/l, respectively. DLP2 and DLP4 displayed potent antimicrobial activity against Gram-positive bacteria especially MRSA and had greater potency, faster killing, and a longer postantibiotic effect than vancomycin. A 30-d serial passage of MRSA in the presence of DLP2/DLP4 failed to produce resistant mutants. Macromolecular synthesis showed that DLP2/DLP4 inhibited multi-macromolecular synthesis especially for RNA. Flow cytometry and electron microscopy results showed that the cell cycle was arrested at R-phase; the cytoplasmic membrane and cell wall were broken by DLP2/DLP4; mesosome-like structures were observed in MRSA. At the doses of 3‒7.5 mg/kg DLP2 or DLP4, the survival of mice challenged with MRSA were 80‒100%. DLP2 and DLP4 reduced the bacterial translocation burden over 95% in spleen and kidneys; reduced serum pro-inflammatory cytokines levels; promoted anti-inflammatory cytokines levels; and ameliorated lung and spleen injury. These data suggest that DLP2 and DLP4 may be excellent candidates for novel antimicrobial peptides against staphylococcal infections.
Silent Sentence Completion Shows Superiority Localizing Wernicke’s Area and Activation Patterns of Distinct Language Paradigms Correlate with Genomics: Prospective Study
Authors: Salek Kamel El , Hassan Islam S. , Kotrotsou Aikaterini , Abrol Srishti , Faro Scott H. , Mohamed Feroze B. , Zinn Pascal O. , Wei Wei , Li Nan , Kumar Ashok J. , Weinberg Jeffrey S. , Wefel Jeffrey S. , Kesler Shelli R. , Liu Ho-Ling Anthony , Hou Ping , Stafford R. Jason , Prabhu Sujit , Sawaya Raymond , Colen Rivka R. 
Published: September 2017

AbstractPreoperative mapping of language areas using fMRI greatly depends on the paradigms used, as different tasks harness distinct capabilities to activate speech processing areas. In this study, we compared the ability of 3 covert speech paradigms: Silent Sentence Completion (SSC), category naming (CAT) and verbal fluency (FAS), in localizing the Wernicke’s area and studied the association between genomic markers and functional activation. Fifteen right-handed healthy volunteers and 35 mixed-handed patients were included. We focused on the anatomical areas of posterosuperior, middle temporal and angular gyri corresponding to Wernicke’s area. Activity was deemed significant in a region of interest if P < 0.05. Association between fMRI activation and genomic mutation status was obtained. Results demonstrated SSC’s superiority at localizing Wernicke’s area. SSC demonstrated functional activity in 100% of cancer patients and healthy volunteers; which was significantly higher than those for FAS and CAT. Patients with 1p/19q non-co-deleted had higher extent of activation on SSC (P < 0.02). Those with IDH-1 wild-type were more likely to show no activity on CAT (P < 0.05). SSC is a robust paradigm for localizing Wernicke’s area, making it an important clinical tool for function-preserving surgeries. We also found a correlation between tumor genomics and functional activation, which deserves more comprehensive study.
Interference of stress with the somatotropic axis in pigs – lights on new biomarkers
Authors: Wirthgen Elisa , Kunze Martin , Goumon Sébastien , Walz Christina , Höflich Christine , Spitschak Marion , Brenmoehl Julia , Kanitz Ellen , Tuchscherer Margret , Otten Winfried , Gimsa Ulrike , Schön Peter , Manteuffel Christian , Tuchscherer Armin , Pfuhl Ralf , Metges Cornelia C. , Stabenow Bernd , Erdmann Sandra , Schluricke Kathleen , Faucitano Luigi , Hoeflich Andreas 
Published: September 2017

AbstractThe acceptance of animal products is increasingly associated with standardized animal welfare, which relates to appropriate animal husbandry from birth to slaughter. In particular, shipment to the slaughterhouse is considered as a critical process exposing the animals to a number of, in part severe, stressors. New biomarkers may be useful for the assessment of animal welfare. The IGF-system has been assessed in a commercial pig transport in conjunction with established markers of stress response. Furthermore, the effect of repeated restraint as an experimental model for repeated acute stress was investigated. During shipment from farm to slaughterhouse, plasma concentrations of IGFBP-3 and IGFBP-2 were significantly reduced (p < 0.01). After shipment, the plasma concentrations of IGFBP-5, glucocorticoids and IL-2 increased but decreased after lairage (p < 0.05) whereas IGF-1 decreased after shipment (p < 0.01). Repeated acute stress increased concentrations of IGFBP-3 and IGF-1 in exsanguination blood (p < 0.05). Differential IGF- signatures can indicate altered endocrine or metabolic control and thus contain complex animal-related information. The somatotropic axis may be of particular interest when established biomarkers such as cortisol, glucose, or lactate cannot be used for the assessment of animal stress or welfare.
Impact of mitochondrial nitrite reductase on hemodynamics and myocardial contractility
Authors: Dungel Peter , Penzenstadler Carina , Ashmwe Mostafa , Dumitrescu Sergiu , Stoegerer Tanja , Redl Heinz , Bahrami Soheyl , Kozlov Andrey V. 
Published: September 2017

AbstractInorganic nitrite (NO2−) can be reduced back to nitric oxide (NO) by several heme proteins called nitrite reductases (NR) which affect both the vascular tonus and hemodynamics. The objective of this study was to clarify the impact of several NRs on the regulation of hemodynamics, for which hemodynamic parameters such as heart rate, blood pressure, arterial stiffness, peripheral resistance and myocardial contractility were characterized by pulse wave analysis. We have demonstrated that NO2− reduced to NO in RBCs predominantly influences the heart rate, while myoglobin (Mb) and mitochondria-derived NO regulates arterial stiffness, peripheral resistance and myocardial contractility. Using ex vivo on-line NO-detection, we showed that Mb is the strongest NR occurring in heart, which operates sufficiently only at very low oxygen levels. In contrast, mitochondrial NR operates under both hypoxia and normoxia. Additional experiments with cardiomyocytes suggested that only mitochondria-derived generation of NO regulates cGMP levels mediating the contractility of cardiomyocytes. Our data suggest that a network of NRs is involved in NO2− mediated regulation of hemodynamics. Oxygen tension and hematocrit define the activity of specific NRs.
Demonstration and Analysis of the Suction Effect for Pumping Lymph from Tissue Beds at Subatmospheric Pressure
Authors: Jamalian Samira , Jafarnejad Mohammad , Zawieja Scott D. , Bertram Christopher D. , Gashev Anatoliy A. , Zawieja David C. , Davis Michael J. , Moore James E. 
Published: September 2017

AbstractMany tissues exhibit subatmospheric interstitial pressures under normal physiologic conditions. The mechanisms by which the lymphatic system extracts fluid from these tissues against the overall pressure gradient are unknown. We address this important physiologic issue by combining experimental measurements of contractile function and pressure generation with a previously validated mathematical model. We provide definitive evidence for the existence of ‘suction pressure’ in collecting lymphatic vessels, which manifests as a transient drop in pressure downstream of the inlet valve following contraction. This suction opens the inlet valve and is required for filling in the presence of low upstream pressure. Positive transmural pressure is required for this suction, providing the energy required to reopen the vessel. Alternatively, external vessel tethering can serve the same purpose when the transmural pressure is negative. Suction is transmitted upstream, allowing fluid to be drawn in through initial lymphatics. Because suction plays a major role in fluid entry to the lymphatics and is affected by interstitial pressure, our results introduce the phenomenon as another important factor to consider in the study of lymphoedema and its treatment.
Correlation profiling of brain sub-cellular proteomes reveals co-assembly of synaptic proteins and subcellular distribution
Authors: Pandya Nikhil J. , Koopmans Frank , Slotman Johan A. , Paliukhovich Iryna , Houtsmuller Adriaan B. , Smit August B. , Li Ka Wan 
Published: September 2017

AbstractProtein correlation profiling might assist in defining co-assembled proteins and subcellular distribution. Here, we quantified the proteomes of five biochemically isolated mouse brain cellular sub-fractions, with emphasis on synaptic compartments, from three brain regions, hippocampus, cortex and cerebellum. We demonstrated the expected co-fractionation of canonical synaptic proteins belonging to the same functional groups. The enrichment profiles also suggested the presence of many novel pre- and post-synaptic proteins. Using super-resolution microscopy on primary neuronal culture we confirmed the postsynaptic localization of PLEKHA5 and ADGRA1. We further detected profound brain region specific differences in the extent of enrichment for some functionally associated proteins. This is exemplified by different AMPA receptor subunits and substantial differences in sub-fraction distribution of their potential interactors, which implicated the differences of AMPA receptor complex compositions. This resource aids the identification of proteins partners and subcellular distribution of synaptic proteins.
Formalin Fixation and Cryosectioning Cause Only Minimal Changes in Shape or Size of Ocular Tissues
Authors: Tran Huong , Jan Ning-Jiun , Hu Danielle , Voorhees Andrew , Schuman Joel S. , Smith Matthew A. , Wollstein Gadi , Sigal Ian A. 
Published: September 2017

AbstractAdvances in imaging have made it increasingly common to study soft tissues without first embedding them in plastic or paraffin and without using labels or stains. The process, however, usually still involves fixation and cryosectioning, which could deform the tissues. Our goal was to quantify the morphological changes of ocular tissues caused by formalin fixation and cryosectioning. From each of 6 porcine eyes, 4 regions were obtained: cornea, equatorial and posterior sclera, and posterior pole containing the optic nerve head. Samples were imaged using visible light microscopy fresh, 1-minute and 24-hours post-fixation, and post-cryosectioning. Effects were assessed by 14 parameters representing sample size and shape. Overall, formalin fixation and sectioning caused only minimal changes to the ocular tissues, with average percentage parameter differences of 0.1%, 1%, and 1.2% between fresh and post-fixing by 1 minute, 24 hours, and post-cryosectioning, respectively. Parameter changes were not directional, and were only weakly dependent on the duration of fixation and the region of the eye. These results demonstrate that formalin fixation and cryosectioning are good choices for studying ocular tissue morphology and structure, as they do not cause the large tissue shrinkage or distortions typically associated with other, more complicated, techniques.
Serum Uric Acid to Creatinine Ratio and Risk of Metabolic Syndrome in Saudi Type 2 Diabetic Patients
Authors: Al-Daghri Nasser M. , Al-Attas Omar S. , Wani Kaiser , Sabico Shaun , Alokail Majed S. 
Published: September 2017

AbstractThis study aimed to investigate whether uric acid to creatinine (UA/Cr) ratio is associated with higher risk of metabolic syndrome (MetS) and its components. 332 adult Saudi type 2 diabetes mellitus (T2DM) patients were divided into UA/Cr tertiles. Risk for full MetS was significantly highest in individuals that constitutes the uppermost serum UA/Cr tertile [Odds ratio (OR): 1.80, 95% confidence interval (CI): 1.0–3.3; p < 0.001) after adjustment for age, gender and BMI. Similarly, risk for individual components of MetS like central obesity, hypertriglyceridemia, low HDL-cholesterol and hypertension was significantly highest in this tertile with OR’s of 2.61 (1.2–5.6), 1.42 (0.7–2.3), 1.45 (0.7–2.8) and 1.16 (0.6–2.2) respectively (all p-values < 0.001) after adjustment for age, gender, BMI and other components of MetS. Furthermore, serum UA/Cr levels increased with increasing number of MetS components (mean values of 4.44, 4.49, 4.64, 4.89 and 4.91 respectively for 1,2,3,4 and 5 MetS components, p-values < 0.001 after adjusting for age, gender and BMI). Our data suggest that serum UA/Cr in T2DM patients is strongly associated with full MetS as well as its individual components. These findings are of considerable clinical importance as serum UA/Cr may be used as a marker in the pathogenesis of MetS.
Membrane particles generated from mesenchymal stromal cells modulate immune responses by selective targeting of pro-inflammatory monocytes
Authors: Gonçalves Fabiany da C. , Luk Franka , Korevaar Sander S. , Bouzid Rachid , Paz Ana H. , López-Iglesias Carmen , Baan Carla C. , Merino Ana , Hoogduijn Martin J. 
Published: September 2017

AbstractMesenchymal stromal cells (MSC) are a promising therapy for immunological disorders. However, culture expanded MSC are large and get trapped in the capillary networks of the lungs after intravenous infusion, where they have a short survival time. Hypothetically, living cells are a risk for tumor formation. To reduce risks associated with MSC infusion and improve the distribution in the body, we generated membrane particles (MP) of MSC and MSC stimulated with IFN-γ (MPγ). Tracking analysis and electron microscopy indicated that the average size of MP was 120 nm, and they showed a round shape. MP exhibited ATPase, nucleotidase and esterase activity, indicating they are enzymatically active. MP and MPγ did not physically interact with T cells and had no effect on CD4+ and CD8+ T cells proliferation. However, MP and MPγ selectively bound to monocytes and decreased the frequency of pro-inflammatory CD14+CD16+ monocytes by induction of selective apoptosis. MP and MPγ increased the percentage of CD90 positive monocytes, and MPγ but not MP increased the percentage of anti-inflammatory PD-L1 monocytes. MPγ increased mRNA expression of PD-L1 in monocytes. These data demonstrate that MP have immunomodulatory properties and have potential as a novel cell-free therapy for treatment of immunological disorders.
Evidence of auditory insensitivity to vocalization frequencies in two frogs
Authors: Goutte Sandra , Mason Matthew J. , Christensen-Dalsgaard Jakob , Montealegre-Z Fernando , Chivers Benedict D. , Sarria-S Fabio A. , Antoniazzi Marta M. , Jared Carlos , Almeida Sato Luciana , Felipe Toledo Luís 
Published: September 2017

AbstractThe emergence and maintenance of animal communication systems requires the co-evolution of signal and receiver. Frogs and toads rely heavily on acoustic communication for coordinating reproduction and typically have ears tuned to the dominant frequency of their vocalizations, allowing discrimination from background noise and heterospecific calls. However, we present here evidence that two anurans, Brachycephalus ephippium and B. pitanga, are insensitive to the sound of their own calls. Both species produce advertisement calls outside their hearing sensitivity range and their inner ears are partly undeveloped, which accounts for their lack of high-frequency sensitivity. If unheard by the intended receivers, calls are not beneficial to the emitter and should be selected against because of the costs associated with signal production. We suggest that protection against predators conferred by their high toxicity might help to explain why calling has not yet disappeared, and that visual communication may have replaced auditory in these colourful, diurnal frogs.
Mucin 5B in saliva and serum of patients with oral lichen planus
Authors: Agha-Hosseini Farzaneh , Imanpour Mojtaba , Mirzaii-Dizgah Iraj , Moosavi Mahdieh-Sadat 
Published: September 2017

AbstractOral lichen planus (OLP) is among the most common oral diseases. Its etiopathogenesis has yet to be clearly identified. OLP patients complain of mouth dryness. This study aimed to assess the level of Mucin 5B in OLP patients with xerostomia. This study was conducted on 30 OLP patients and 30 healthy individuals. In addition to patient complaint of mouth dryness, xerostomia was assessed by tongue blade and lipstick tests. Stimulated and unstimulated saliva were collected in plastic vials by spitting method. Level of Mucin 5B was measured by ELISA. Unstimulated saliva flow was significantly lower in OLP patients (P = 0.0001). Stimulated saliva flow was not significantly different between the two groups (P > 0.05). Level of Mucin 5B in unstimulated saliva was significantly lower in OLP group (P = 0.0001) while it was not significantly different in stimulated saliva of the two groups (P > 0.05). Level of Mucin 5B was significantly higher in serum of OLP patients (P = 0.016). Both saliva flow and level of Mucin 5B decrease in OLP patients. Since Mucin 5B is effective for wetting and lubrication of the oral cavity, this result can suggest a possible reason for mouth dryness in OLP patients.
Novel scaffolds for inhibition of Cruzipain identified from high-throughput screening of anti-kinetoplastid chemical boxes
Authors: Salas-Sarduy Emir , Landaburu Lionel Urán , Karpiak Joel , Madauss Kevin P. , Cazzulo Juan José , Agüero Fernán , Alvarez Vanina Eder 
Published: September 2017

AbstractAmerican Trypanosomiasis or Chagas disease is a prevalent, neglected and serious debilitating illness caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The current chemotherapy is limited only to nifurtimox and benznidazole, two drugs that have poor efficacy in the chronic phase and are rather toxic. In this scenario, more efficacious and safer drugs, preferentially acting through a different mechanism of action and directed against novel targets, are particularly welcome. Cruzipain, the main papain-like cysteine peptidase of T. cruzi, is an important virulence factor and a chemotherapeutic target with excellent pre-clinical validation evidence. Here, we present the identification of new Cruzipain inhibitory scaffolds within the GlaxoSmithKline HAT (Human African Trypanosomiasis) and Chagas chemical boxes, two collections grouping 404 non-cytotoxic compounds with high antiparasitic potency, drug-likeness, structural diversity and scientific novelty. We have adapted a continuous enzymatic assay to a medium-throughput format and carried out a primary screening of both collections, followed by construction and analysis of dose-response curves of the most promising hits. Using the identified compounds as a starting point a substructure directed search against CHEMBL Database revealed plausible common scaffolds while docking experiments predicted binding poses and specific interactions between Cruzipain and the novel inhibitors.
Differential regulation of Effector and Regulatory T cell function by Blimp1
Authors: Bankoti Rashmi , Ogawa Chihiro , Nguyen Truc , Emadi Lena , Couse Michael , Salehi Soofia , Fan Xuemo , Dhall Deepti , Wang Yizhou , Brown Jordan , Funari Vincent , Tang Jie , Martins Gislâine A. 
Published: September 2017

AbstractThe transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated. Using mice with Foxp3+ Treg-cell specific deletion of Blimp1 and other approaches, here we show that Foxp3+ Treg cell-intrinsic expression of Blimp1 is required to control Treg and Teff cells homeostasis but, unexpectedly, it is dispensable to prevent development of severe spontaneous intestinal inflammation. In addition, we show that Blimp1 controls common and unique aspects of Treg and Teff cell function by differentially regulating gene expression in these T cell subsets. These findings document previously unappreciated aspects of Blimp1’s role in T cell biology and shed light on the intricate mechanisms regulating Treg and Teff cell function.
Effects of ticagrelor in a mouse model of ischemic stroke
Authors: Yamauchi Keita , Imai Takahiko , Shimazawa Masamitsu , Iwama Toru , Hara Hideaki 
Published: September 2017

AbstractTicagrelor is a direct acting and reversibly binding P2Y12 antagonist approved for the prevention of thromboembolic events. Its potential benefits in ischemic stroke have not been investigated sufficiently. Mice were subjected to 2 hours of transient middle cerebral artery occlusion (MCAO). Mice were orally treated with ticagrelor (10 or 30 mg/kg), aspirin (60 mg/kg), or vehicle at 3 and 24 hours before MCAO and 0 and 6 hours after reperfusion. The infarct volume and neurological deficits 22 hours after reperfusion were evaluated. Cerebral blood flow (CBF) within 24 hours after MCAO was monitored. We performed western blotting and in vitro analysis using oxygen-glucose deprivation (OGD) stress in human brain microvessel endothelial cells (HBMVECs) to investigate the protective effects of ticagrelor. Ticagrelor (30 mg/kg) improved neurological deficits, reduced the infarct volume, and improved CBF. It promoted the phosphorylation of endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase 1/2 (ERK1/2) during the early phase after reperfusion. Increased phosphorylation of eNOS and ERK1/2 were also observed in HBMVECs after OGD stress. Ticagrelor attenuate ischemia reperfusion injury possibly via phosphorylation of eNOS and ERK1/2 in endothelial cells. This suggests that ticagrelor has neuroprotective effects via mechanisms other than its antiplatelet action.
Toward the identification of a type I toxin-antitoxin system in the plasmid DNA of dairy Lactobacillus rhamnosus
Authors: Folli Claudia , Levante Alessia , Percudani Riccardo , Amidani Davide , Bottazzi Stefania , Ferrari Alberto , Rivetti Claudio , Neviani Erasmo , Lazzi Camilla 
Published: September 2017

AbstractPlasmids carry genes that give bacteria beneficial traits and allow them to survive in competitive environments. In many cases, they also harbor toxin-antitoxin (TA) systems necessary for plasmid maintenance. TA systems are generally characterized by a stable “toxin”, a protein or peptide capable of killing the cell upon plasmid loss and by an unstable “antitoxin”, a protein or a non-coding RNA that inhibits toxin activity. Here we report data toward the identification of a RNA-regulated TA system in the plasmid DNA of L. rhamnosus isolated from cheese. The proposed TA system comprises two convergently transcribed RNAs: a toxin RNA encoding a 29 amino acid peptide named Lpt and an antitoxin non-coding RNA. Both toxin and antitoxin RNAs resulted upregulated under conditions mimicking cheese ripening. The toxicity of the Lpt peptide was demonstrated in E. coli by cloning the Lpt ORF under the control of an inducible promoter. Bioinformatics screening of the bacterial nucleotide database, shows that regions homologous to the Lpt TA locus are widely distributed in the Lactobacillus genus, particularly within the L. casei group, suggesting a relevant role of TA systems in plasmid maintenance of cheese microbiota.