Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacteria in an intense competition for iron: Key component of the Campylobacter jejuni iron uptake system scavenges enterobactin hydrolysis product

Significance Almost all bacteria require Fe(III) for survival and growth. To compete successfully for this essential nutrient, bacteria developed very efficient Fe(III) uptake mechanisms based on high-affinity Fe(III) chelators, so-called siderophores. To gain a competitive advantage, many bacteria have evolved to scavenge and effectively poach siderophores from other species. Enterobactin, one of the strongest Fe(III) chelators known, is produced and secreted by many enteric bacteria. We show that a key protein involved in Fe(III) uptake in the foodborne pathogen Campylobacter jejuni is adapted to scavenge enterobactin hydrolysis products, a strategy that may enable the pathogen to more efficiently exploit siderophores produced by other bacteria and hence their resources. To acquire essential Fe(III), bacteria produce and secrete siderophores with high affinity and selectivity for Fe(III) to mediate its uptake into the cell. Here, we show that the periplasmic binding protein CeuE of Campylobacter jejuni, which was previously thought to bind the Fe(III) complex of the hexadentate siderophore enterobactin (Kd ∼ 0.4 ± 0.1 µM), preferentially binds the Fe(III) complex of the tetradentate enterobactin hydrolysis product bis(2,3-dihydroxybenzoyl-l-Ser) (H5-bisDHBS) (Kd = 10.1 ± 3.8 nM). The protein selects Λ-configured [Fe(bisDHBS)]2− from a pool of diastereomeric Fe(III)-bisDHBS species that includes complexes with metal-to-ligand ratios of 1:1 and 2:3. Cocrystal structures show that, in addition to electrostatic interactions and hydrogen bonding, [Fe(bisDHBS)]2− binds through coordination of His227 and Tyr288 to the iron center. Similar binding is observed for the Fe(III) complex of the bidentate hydrolysis product 2,3-dihydroxybenzoyl-l-Ser, [Fe(monoDHBS)2]3−. The mutation of His227 and Tyr288 to noncoordinating residues (H227L/Y288F) resulted in a substantial loss of affinity for [Fe(bisDHBS)]2− (Kd ∼ 0.5 ± 0.2 µM). These results suggest a previously unidentified role for CeuE within the Fe(III) uptake system of C. jejuni, provide a molecular-level understanding of the underlying binding pocket adaptations, and rationalize reports on the use of enterobactin hydrolysis products by C. jejuni, Vibrio cholerae, and other bacteria with homologous periplasmic binding proteins.
The Memory Assessment Scales and lateralized temporal lobe epilepsy.

We report Memory Assessment Scales (MAS) performance in 101 patients with unilateral temporal lobe epilepsy (TLE; left, n = 51; right, n = 50) with left cerebral language dominance. A significant multivariate group effect was present for the major summary indices (Verbal Memory, Visual Memory, and Global Memory, p < .04). Univariate analyses revealed no significant differences for either the Global Memory or Verbal Memory summary scores, although a significant group difference was present for Visual Memory (p < .04). The Verbal Memory-Visual Memory discrepancy score was significantly different between right and left TLE groups (p < .004). Verbal Memory scores were at least 14 points lower than Visual Memory scores in 34 patients (left = 20, 59%; right = 14, 41%). Visual Memory scores were at least 14 points lower than Verbal Memory performance in 20 patients (left = 5, 25%; right = 15, 75%). Diagnostic efficiency statistics show higher sensitivity but lower specificity in group classification for left TLE patients. These data suggest that the MAS is sensitive to material-specific memory deficits associated with a unilateral temporal lobe seizure focus. However, over one-third of the patients (19/54) with at least a 14-point Verbal Memory-Visual Memory discrepancy were classified incorrectly. The MAS, like other material-specific memory measures, should be interpreted within the context of other clinical findings.
Cdc37 Interacts with the Glycine-Rich Loop of Hsp90 Client Kinases

ABSTRACT Recently, we identified a client-binding site of Cdc37 that is required for its association with protein kinases. Phage display technology and liquid chromatography-tandem mass spectrometry (which identifies a total of 33 proteins) consistently identify a unique sequence, GXFG, as a Cdc37-interacting motif that occurs in the canonical glycine-rich loop (GXGXXG) of protein kinases, regardless of their dependence on Hsp90 or Cdc37. The glycine-rich motif of Raf-1 (GSGSFG) is necessary for its association with Cdc37; nevertheless, the N lobe of Raf-1 (which includes the GSGSFG motif) on its own cannot interact with Cdc37. Chimeric mutants of Cdk2 and Cdk4, which differ sharply in their affinities toward Cdc37, show that their C-terminal portions may determine this difference. In addition, a nonclient kinase, the catalytic subunit of cyclic AMP-dependent protein kinase, interacts with Cdc37 but only when a threonine residue in the activation segment of its C lobe is unphosphorylated. Thus, although a region in the C termini of protein kinases may be crucial for accomplishing and maintaining their interaction with Cdc37, we conclude that the N-terminal glycine-rich loop of protein kinases is essential for physically associating with Cdc37.
Alcohol and Substance Abuse in Solid-Organ Transplant Recipients

This review focuses on alcohol and substance abuse in the context of solid-organ transplantation. Alcohol and substance abuse are common and may lead to a need for solid-organ transplantation and may also contribute to significant physical and psychologic problems that impact upon the recipient. Damaging levels of alcohol intake can occur in the absence of dependence. Alcohol or substance abuse after transplantation is associated with poor medication compliance and this may increase risk of graft loss. Intravenous drug use is associated with increased risk of infections (especially secondary to opportunistic organisms—bacterial, viral, protozoal, and others—and such infections may be more severe in the immunosuppressed), but there is only anecdotal evidence that such behavior has a worse outcome in transplant recipients. Whereas previous alcohol excess and drug use in kidney recipients are both associated with a small but statistically significantly increased risk of adverse outcomes (hazard ratio, 1.16–1.56), alcohol use within recommended guidelines after transplantation appears safe and possibly beneficial. Robust data are lacking for other organs, but those available suggest that heart transplantation is safe in individuals with a history of alcohol or substance abuse. Health specialists in drug or alcohol addiction should carefully screen all potential transplant candidates for these conditions, and where there is evidence of dependency or abuse, effective psychologic and physical treatment should be offered. Studies have shown that interventions such as psychologic intervention have improved alcohol behavior in the context of liver transplantation. Although there are no comparable studies with other solid-organ recipients, it is reasonable to expect transferable outcomes.
Combined Therapy of Pegylated G-CSF and Alxn4100TPO Improves Survival and Mitigates Acute Radiation Syndrome after Whole-Body Ionizing Irradiation Alone and Followed by Wound Trauma

Exposure to ionizing radiation alone or combined with traumatic tissue injury is a crucial life-threatening factor in nuclear and radiological incidents. Radiation injuries occur at the molecular, cellular, tissue and systemic levels; their mechanisms, however, remain largely unclear. Exposure to radiation combined with skin wounding, bacterial infection or burns results in greater mortality than radiation exposure alone in dogs, pigs, rats, guinea pigs and mice. In the current study we observed that B6D2F1/J female mice exposed to 60Co gamma-photon radiation followed by 15% total-body-surface-area skin wounds experienced an increment of 25% higher mortality over a 30-day observation period compared to those subjected to radiation alone. Radiation exposure delayed wound healing by approximately 14 days. On day 30 post-injury, bone marrow and ileum in animals from both groups (radiation alone or combined injury) still displayed low cellularity and structural damage. White blood cell counts, e.g., neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets, still remained very low in surviving irradiated alone animals, whereas only the lymphocyte count was low in surviving combined injury animals. Likewise, in surviving animals from radiation alone and combined injury groups, the RBCs, hemoglobin, hematocrit and platelets remained low. We observed, that animals treated with both pegylated G-CSF (a cytokine for neutrophil maturation and mobilization) and Alxn4100TPO (a thrombopoietin receptor agonist) at 4 h postirradiation, a 95% survival (vehicle: 60%) over the 30-day period, along with mitigated body-weight loss and significantly reduced acute radiation syndrome. In animals that received combined treatment of radiation and injury that received pegylated G-CSF and Alxn4100TPO, survival was increased from 35% to 55%, but did not accelerate wound healing. Hematopoiesis and ileum showed significant improvement in animals from both groups (irradiation alone and combined injury) when treated with pegylated G-CSF and Alxn4100TPO. Treatment with pegylated G-CSF alone increased survival after irradiation alone and combined injury by 33% and 15%, respectively, and further delayed wound healing, but increased WBC, RBC and platelet counts after irradiation alone, and only RBCs and platelets after combined injury. Treatment with Alxn4100TPO alone increased survival after both irradiation alone and combined injury by 4 and 23%, respectively, and delayed wound healing after combined injury, but increased RBCs, hemoglobin concentrations, hematocrit values and platelets after irradiation alone and only platelets after combined injury. Taken together, the results suggest that combined treatment with pegylated G-CSF and Alxn4100TPO is effective for mitigating effects of both radiation alone and in combination with injury.
Improving the quality of care for patients with cystic fibrosis

Purpose of review Improvement in cystic fibrosis (CF) outcomes over the past 50 years has been dramatic. This article describes the factors that have contributed to the recent acceleration in this improvement and the important role of the Cystic Fibrosis Foundation. Recent findings Initiatives to improve CF care over the past decade include the refinement of a sophisticated patient registry that allows a comparison of center processes and outcomes; development of evidence-based and consensus-based guidelines regarding standards of care; cultural transformation, including the training of care center teams in a systems-oriented approach to quality improvement; data transparency; and encouragement of a patient-centered and family-centered orientation. Cystic Fibrosis Foundation initiatives have promoted an increase in the consistent provision of evidence-based care and the promulgation of innovative, proactive therapeutic approaches. Unfortunately, so far most of these accomplishments have not been documented in peer-reviewed research articles, but rather in platform presentations at national meetings, meeting abstracts, data reports to center directors, and published reports from individual centers. Summary While several new medications for CF lung disease have been introduced in the last decade, improvements in outcomes have been largely due to refinements in the delivery of care. At this point, the most efficient and reliably effective technique for promoting further improvement still needs to be identified. Recent discussions have centered on attempts at new innovative approaches that utilize more selective teaching of relevant systems-based quality improvement methods in the specific CF environment.
The Knowledge of Eye Physicians on Local Anesthetic Toxicity and Intravenous Lipid Treatment: Questionnaire Study

Objectives: To evaluate the knowledge of ophthalmologists regarding local anesthesia toxicity syndrome (LATS) and intravenous lipid emulsion used in treatment, and to raise awareness of this issue. Materials and Methods: A questionnaire comprising 14 questions about demographics, local anesthesia (LA) use, toxicity, and treatment methods was administered to ophthalmologists at different hospitals. Results: The study included 104 ophthalmologists (25% residents, 67.3% specialists, 7.7% faculty members) with a mean age of 35.71±6.53 years. The highest number of participants was from state hospitals (65.4%), and 34.6% of the physicians had been working in ophthalmology for more than 10 years. Seventy-six percent of the participants reported using LA every day or more than twice a week, but 56.7% had received no specific training on this subject. No statistically significant difference was observed between different education levels and the rates of training (p=0.419). Bupivacaine was the most preferred LA and the majority of respondents (97.1%) did not use a test dose. Allergy (76%) and hypotension (68.3%) were the most common responses for early findings of LATS, while cardiac arrest (57.4%) and hepatotoxicity (56.4%) were given for late findings. The most common responses concerning the prevention of LATS included monitorization (72.4%) and use of appropriate doses (58.2%). Symptomatic treatment was selected by 72.4% of respondents and cardiopulmonary resuscitation and antihistamine treatment by 58.8%. Of the ophthalmologists in the study, 62.5% had never encountered LATS. The use of 20% intravenous lipid emulsion therapy for toxicity was known by 65% of the physicians, but only 1 participant stated having used it previously. Conclusion: The importance of using 20% lipid emulsion in LATS treatment and having it available where LA is administered must be emphasized, and there should be compulsory training programs for ophthalmologists on this subject.
Isolation of RNA from Polysaccharide‐Rich Seeds

Abstract Commonly, RNA isolation is the initial step in the study of gene expression analysis and also in the utilization of genes for genetic improvement. However, the recovery of large amounts of RNA with high quality is a difficult process, especially in tissues containing enhanced levels of polysaccharides and other secondary metabolites. Since several procedures for RNA isolation from polysaccharides rich plant tissues have been resulting in poor yields, an effective new protocol is essential for RNA isolation and further analysis. Here, we describe a novel modified technique for isolating total RNA from maturing grains. As a model, we utilized little finger millets, important food staples, which correspond to short duration crops cultivated in varied agro climatic conditions. After isolation, the total RNA was resolved on a denaturing agarose gel, showing more sharp bands of 28S, 18S, and 5S with no degradation. Therefore, the RNA concentration (higher than 1.80) was calculated by spectrophotometry, indicating that RNA is concentrated. Finally, RT‐PCR and Northern hybridization confirmed high RNA quality.
Isolation, identification and antimicrobial activity of propolis-associated fungi

Propolis is a natural product widely known for its medicinal properties. In this work, fungi present on propolis samples were isolated, identified and tested for the production of antimicrobial metabolites. Twenty-two fungal isolates were obtained, some of which were identified as Alternaria alternata, Aspergillus flavus, Bipolaris hawaiiensis, Fusarium merismoides, Lasiodiplodia theobromae, Penicillium citrinum, Penicillium crustosum, Penicillium janthinellum, Penicillium purpurogenum, Pestalotiopsis palustris, Tetracoccosporium paxianum and Trichoderma koningii. These fungi were grown in liquid media to obtain crude extracts that were evaluated for their antibiotic activity against pathogenic bacteria, yeast and Cladosporium cladosporioides and A. flavus. The most active extract was obtained from L. theobromae (minimum inhibitory concentration = 64 μg/mL against Listeria monocitogenes). Some extracts showed to be more active than the positive control in the inhibition of Staphylococcus aureus and L. monocitogenes. Therefore, propolis is a promising source of fungi, which produces active agents against relevant food poisoning bacteria and crop-associated fungi.
Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293‐hP2X3 cells and their inhibition by ethanol and trichloroethanol

Membrane currents and changes in the intracellular Ca2+ concentration ([Ca2+]i) were measured in HEK293 cells transfected with the human P2X3 receptor (HEK293‐hP2X3). RT‐PCR and immunocytochemistry indicated the additional presence of endogenous P2Y1 and to some extent P2Y4 receptors. P2 receptor agonists induced inward currents in HEK293‐hP2X3 cells with the rank order of potency α,β‐meATP ≈ ATP > ADP‐β‐S > UTP. A comparable rise in [Ca2+]i was observed after the slow superfusion of ATP, ADP‐β‐S and UTP; α,β‐meATP was ineffective. These data, in conjunction with results obtained by using the P2 receptor antagonists TNP‐ATP, PPADS and MRS2179 indicate that the current response to α,β‐meATP is due to P2X3 receptor activation, while the ATP‐induced rise in [Ca2+]i is evoked by P2Y1 and P2Y4 receptor activation. TCE depressed the α,β‐meATP current in a manner compatible with a non‐competitive antagonism. The ATP‐induced increase of [Ca2+]i was much less sensitive to the inhibitory effect of TCE than the current response to α,β‐meATP. The present study indicates that in HEK293‐hP2X3 cells, TCE, but not ethanol, potently inhibits ligand‐gated P2X3 receptors and, in addition, moderately interferes with G protein‐coupled P2Y1 and P2Y4 receptors. Such an effect may be relevant for the interruption of pain transmission in dorsal root ganglion neurons following ingestion of chloral hydrate or trichloroethylene.
Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification

Objective: The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification (HO). Background: HO is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is upregulated during incidents of trauma, thereby coincident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation. Methods: Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury (burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO. Results: Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% vs 0.8%, P < 0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% vs 3.3%, P < 0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2-/CD45-/CD90-/BP1-) were also significantly decreased after lymph node excision (10.2% vs 0.5%, P < 0.05). A significant decrease was noted in the volume of de novo HO present within the soft tissues (0.12 mm3 vs 0.02 mm3). Conclusion: These findings suggest that lymphatic vessels are intimately linked with the de novo formation bone within soft tissues following trauma, and their presence may facilitate bone formation.
Animal models of headache: from bedside to bench and back to bedside

In recent years bench-based studies have greatly enhanced our understanding of headache pathophysiology, while facilitating the development of new headache medicines. At present, established animal models of headache utilize activation of pain-producing cranial structures, which for a complex syndrome, such as migraine, leaves many dimensions of the syndrome unstudied. The focus on modeling the central nociceptive mechanisms and the complexity of sensory phenomena that accompany migraine may offer new approaches for the development of new therapeutics. Given the complexity of the primary headaches, multiple approaches and techniques need to be employed. As an example, recently a model for trigeminal autonomic cephalalgias has been tested successfully, while by contrast, a satisfactory model of tension-type headache has been elusive. Moreover, although useful in many regards, migraine models are yet to provide a more complete picture of the disorder.
Terrein reduces age‐related inflammation induced by oxidative stress through Nrf2/ERK1/2/HO‐1 signalling in aged HDF cells

This study investigated whether multiple bioactivity of terrein such as anti‐inflammatory and anti‐oxidant inhibits age‐related inflammation by promoting an antioxidant response in aged human diploid fibroblast (HDF) cells. HDF cells were cultured serially for in vitro replicative senescence. To create the ageing cell phenotype, intermediate stage (PD31) HDF cells were brought to stress‐induced premature senescence (SIPS) using hydrogen peroxide (H2O2). Terrein increased cell viability even with H2O2 stress and reduced inflammatory molecules such as intracellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), interleukin‐1beta (IL‐1β) and tumour necrosis factor‐alpha (TNF‐α). Terrein reduced also phospho‐extracellular kinase receptor1/2 (p‐EKR1/2) signalling in aged HDF cells. SIPS cells were attenuated for age‐related biological markers including reactive oxygen species (ROS), senescence associated beta‐galactosidase (SA β‐gal.) and the aforementioned inflammatory molecules. Terrein induced the induction of anti‐oxidant molecules, copper/zinc‐superoxide defence (Cu/ZnSOD), manganese superoxide dismutase (MnSOD) and heme oxygenase‐1 (HO‐1) in SIPS cells. Terrein also alleviated reactive oxygen species formation through the Nrf2/HO‐1/p‐ERK1/2 pathway in aged cells. The results indicate that terrein has an alleviative function of age‐related inflammation characterized as an anti‐oxidant. Terrein might be a useful nutraceutical compound for anti‐ageing. Copyright © 2015 John Wiley & Sons, Ltd.
Groceries for Votes: The Electoral Returns of Vote Buying

Despite the prevalence of vote buying in many developing democracies, the evidence of its persuasive effects is very limited. This article proposes a way to evaluate the electoral impact of vote buying by using data from the 2012 presidential election in Mexico, where one of the parties distributed gift cards in exchange for support on election day. I evaluate the effect on citizens’ electoral behavior by considering voters’ proximity to the closest store where they could redeem the cards. The empirical analysis provides evidence of a persuasive effect of the gift cards, whose magnitude was positively related to precincts’ proximity to the store. The analysis also shows the local scope of this vote-buying incident on the electoral outcome, whose effect was focused on a defined group of voters. This study expands on recent theoretical accounts of parties’ targeting strategies and addresses some potential limitations in measuring the electoral consequences of vote buying.