bluuebunny/crossref_metadata_2025 huggingface dataset:
Faster Blood Flow Rate Does Not Improve Circuit Life in Continuous Renal Replacement Therapy: A Randomized Controlled Trial
Authors: Fealy Nigel , Aitken Leanne , du Toit Eugene , Lo Serigne , Baldwin Ian
Published: June 2017

Objectives:

To determine whether blood flow rate influences circuit life in continuous renal replacement therapy.

Design:

Prospective randomized controlled trial.

Setting:

Single center tertiary level ICU.

Patients:

Critically ill adults requiring continuous renal replacement therapy.

Interventions:

Patients were randomized to receive one of two blood flow rates: 150 or 250 mL/min.

Measurements and Main Results:

The primary outcome was circuit life measured in hours. Circuit and patient data were collected until each circuit clotted or was ceased electively for nonclotting reasons. Data for clotted circuits are presented as median (interquartile range) and compared using the Mann-Whitney U test. Survival probability for clotted circuits was compared using log-rank test. Circuit clotting data were analyzed for repeated events using hazards ratio. One hundred patients were randomized with 96 completing the study (150 mL/min, n = 49; 250 mL/min, n = 47) using 462 circuits (245 run at 150 mL/min and 217 run at 250 mL/min). Median circuit life for first circuit (clotted) was similar for both groups (150 mL/min: 9.1 hr [5.5–26 hr] vs 10 hr [4.2–17 hr]; p = 0.37). Continuous renal replacement therapy using blood flow rate set at 250 mL/min was not more likely to cause clotting compared with 150 mL/min (hazards ratio, 1.00 [0.60–1.69]; p = 0.68). Gender, body mass index, weight, vascular access type, length, site, and mode of continuous renal replacement therapy or international normalized ratio had no effect on clotting risk. Continuous renal replacement therapy without anticoagulation was more likely to cause clotting compared with use of heparin strategies (hazards ratio, 1.62; p = 0.003). Longer activated partial thromboplastin time (hazards ratio, 0.98; p = 0.002) and decreased platelet count (hazards ratio, 1.19; p = 0.03) were associated with a reduced likelihood of circuit clotting.

Conclusions:

There was no difference in circuit life whether using blood flow rates of 250 or 150 mL/min during continuous renal replacement therapy.
Post-Malaria Neurologic Syndrome: A Rare Pediatric Case Report
Authors: Siriez Jean-Yves , Prendki Virginie , Dauger Stéphane , Michel Jean-François , Blondé Renaud , Faye Albert , Houzé Sandrine , Mercier Jean-Christophe
Published: June 2017

Post-malaria neurologic syndrome (PMNS) is a rare complication following a Plasmodium falciparum infection and its pathophysiology remains unclear. This is the first report of a pediatric PMNS following an infection acquired in Africa and the fourth description of pediatric PMNS overall. Neither intrathecal synthesis of Immunoglobin G nor specific P. falciparum antibodies were found in the cerebrospinal fluid.
Management of chronic pruritus: from the dermatological office to the specialized itch center: a review
Authors: Pereira Manuel P. , Steinke Sabine , Bruland Philipp , Ständer Hartmut F. , Dugas Martin , Augustin Matthias , Ständer Sonja
Published: June 2017

Patient care for those affected by chronic pruritus is remarkably complex due to its high prevalence and multifactorial nature. It requires a comprehensive assessment of the patient’s medical history, extensive diagnostic procedures, and long treatment duration, including management of possible accompanying disorders such as sleep disturbances and mental distress. It is important to prioritize patient’s needs when developing a therapeutic treatment plan. Standardized questionnaires and scales should be used to better analyze the patient history, quality of life, symptom intensity, and course of treatment. These can be distributed via digital platforms, allowing for more effective communication between the treating agents and gathering of large volumes of data in central databases. In today’s health care system, it is essential for physicians with itch-related specializations and specialized itch centers to cooperate. It is thus crucial to focus efforts on the further development of specialized treatment centers and training courses for medical practitioners. There are, however, various regulatory and economic barriers to overcome in the modern health care system before patients with chronic pruritus can be offered the best possible care. Accordingly, health care authorities should be made aware of the difficulties associated with the management of chronic pruritus and of the high individual and societal burden it represents.
Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer
Authors: Kuroki Lindsay M. , Frolova Antonina I. , Wu Ningying , Liu Jingxia , Powell Matthew , Thaker Premal H. , Massad L. Stewart
Published: June 2017

Objectives

The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer.

Materials and Methods

We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer.

Results

Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50–7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76–9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29–5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26–10.83).

Conclusions

Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.
The ins and outs of endocytic trafficking in platelet functions
Authors: Banerjee Meenakshi , Whiteheart Sidney W.
Published: June 2017

Purpose of review

Although platelet endocytosis has been recognized in granule cargo loading and the trafficking of several platelet surface receptors, its acute physiological relevance is poorly understood as is its mechanism. The present review discusses the current understanding of platelet endocytosis and its implications for platelet function.

Recent findings

Recent studies are beginning to identify and define the proteins that mediate platelet endocytosis. These studies have shown that platelets contain different endosomal compartments and may use multiple endocytic routes to take in circulating molecules and surface proteins. The studies have also shown that platelet endocytosis is involved in several aspects of platelet function such as signaling, spreading, and granule cargo loading.

Mechanistic studies of platelet endocytosis have shown it to be not only involved in granule cargo loading but also in various other platelet functions important for hemostasis and beyond.
Hodgkin Lymphoma in a Patient With IFAP Syndrome: A Case Report and Review of Literature
Authors: Shakibazad Nader , Shahriari Mahdi , Inaloo Soroor
Published: June 2017

The IFAP syndrome is a rare X-linked recessive inheritance disorder with defect of the MBTPS2 gene defined by the triad of follicular ichthyosis, alopecia, and photophobia. A total of 40 cases has been reported, but no correlation with Hodgkin lymphoma has been reported yet. A 3.5-year-old boy was diagnosed with IFAP syndrome confirmed by Next Generation Sequencing. He was on regular follow-up when he developed prolonged fever and lymphadenopathy. His lymph node biopsy showed Hodgkin lymphoma with mixed cellularity subtype. This case is the first report on IFAP syndrome associated with malignancy. IFAP syndrome could be a risk factor in developing malignancy.
Residual Pure Intralymphatic Breast Carcinoma Following Neoadjuvant Chemotherapy Is Indicative of Poor Clinical Outcome, Even in Node-Negative Patients
Authors: Cheng Esther , Ko David , Nguyen Michaela , Moo Tracy-Ann , Andreopoulou Eleni , Hoda Syed A. , D’Alfonso Timothy M.
Published: June 2017

Residual carcinoma confined to lymphovascular spaces following neoadjuvant chemotherapy (NAC) for invasive breast carcinoma is an uncommon finding. We studied pathologic features and outcome for patients with pure intralymphatic carcinoma (PIC) following NAC, a pattern of residual disease reported to have a poor outcome in the only previously published series of this entity. Six of 284 (2.1%) patients treated with NAC were studied. All 6 patients had axillary lymph node involvement before NAC. Tumors were triple-negative (n=3) and HER2+ (n=3: 2 ER+, 1 ER−). Two patients presented with clinical findings of inflammatory carcinoma. Three of 5 pre-NAC core biopsies showed lymphovascular invasion. Three patients showed complete clinical response to NAC, and 3 showed partial response. Post-NAC surgical specimens showed foci of intralymphatic carcinoma in the breast spanning an extent of 0.5 mm to 0.5 cm. Residual ductal carcinoma in situ was present in 2 cases. Four of 6 patients converted to node-negative following NAC. One patient had distant metastasis at presentation and 1 patient died of pulmonary embolism 2 months after surgery. Three of the 4 remaining patients developed distant metastasis, of which 2 first recurred locally (in mean follow-up of 46.5 mo). Patients with PIC had significant greater risk for relapse (hazard ratio, 10.18 [1.97, 52.58]; P=0.006) compared with other NAC-treated patients, after controlling for residual lymph node involvement, tumor size, tumor subtype, histologic grade, and age. Residual PIC following NAC is associated with poor outcome, including in patients that are node-negative following NAC.
Overweight and Obesity in Children: More Than Just the Kilos
Authors: van Mil Edgar , Struik Arianne
Published: June 2017

A new model of diagnostics and treatment for overweight in children is used for implementation of a new approach toward childhood obesity. Although based in a hospital setting, it is part of a cure and care network with other professionals. By psycho-education about the body at a 6-year-old level, parents and children become informed and competent partners. This knowledge increases their autonomy and ability to make choices. Collaboration with the family's support group or network reduces isolation and increases the feeling of being connected and supported. Together with their support network, they can maintain this healthier lifestyle or adjust it where needed. Family workbooks and worksheets support the child and parents and increase their autonomy, self management skills, and motivation to take part in the cure and care network. The approach is a based on the three basic needs that determine motivation, namely autonomy, competence, and connectedness.
Virtual Reality and Serious Games in Neurorehabilitation of Children and Adults: Prevention, Plasticity, and Participation
Authors: Deutsch Judith E. , Westcott McCoy Sarah
Published: June 2017

Use of virtual reality (VR) and serious games (SGs) interventions within rehabilitation as motivating tools for task specific training for individuals with neurological conditions are fast-developing. Within this perspective paper we use the framework of the IV STEP conference to summarize the literature on VR and SG for children and adults by three topics: Prevention; Outcomes: Body-Function-Structure, Activity and Participation; and Plasticity. Overall the literature in this area offers support for use of VR and SGs to improve body functions and to some extent activity domain outcomes. Critical analysis of clients' goals and selective evaluation of VR and SGs are necessary to appropriately take advantage of these tools within intervention. Further research on prevention, participation, and plasticity is warranted. We offer suggestions for bridging the gap between research and practice integrating VR and SGs into physical therapist education and practice.
How Accurately Do Both Parents and Health Professionals Assess Overweight in Children?
Authors: Hong Ickpyo , Dodds Cynthia Brown , Coker-Bolt Patty , Simpson Annie N. , Velozo Craig A.
Published: June 2017

Background:

An accurate perception of weight status is important to prevent childhood obesity.

Objective:

We investigated whether parents and health professionals accurately identify children's weight status.

Methods:

On the 2012 National Health and Nutrition Examination Survey: National Youth Fitness Survey, parents and health professionals rated the same child's weight status as overweight or healthy. The sensitivity and specificity of their answers were computed by comparing parents' and health professionals' ratings to the age growth chart from the US Centers for Disease Control and Prevention.

Results:

Participants were 1571 children. Parents' sensitivity and specificity were 0.386 and 0.992, respectively. Health professionals' sensitivity and specificity were 0.343 and 0.981, respectively.

Conclusions:

Parents and health professionals demonstrate low sensitivity in identifying children's weight status. Health professionals should use the Centers for Disease Control and Prevention categories to more accurately identify children who are overweight.
A Range of Service Delivery Modes for Children With Developmental Coordination Disorder Are Effective: A Randomized Controlled Trial
Authors: Ward Emily J. , Hillier Susan , Raynor Annette , Petkov John
Published: June 2017

Purpose:

To investigate whether the environment and personnel providing intervention to children with developmental coordination disorder make a difference in motor outcomes and perceived competency.

Methods:

Ninety-three children (66 males), aged 5 years 1 month to 8 years 11 months, with developmental coordination disorder were randomized to receive a 13-week group-based task-oriented intervention, either at school by a school assistant or physical therapist, or in a health clinic by a physical therapist. The Movement Assessment Battery for Children (MABC) assessed motor skills pre- and postintervention. Self-perception and cost-effectiveness were also assessed.

Results:

Participants demonstrated a significant improvement in motor skills following intervention for all modes of delivery up to 6 months postintervention, MABC mean difference 7.20 (95% confidence interval, 5.89-8.81), effect size = 0.98.

Conclusion:

Group intervention programs for developmental coordination disorder can be run by either a health professional or a school assistant (supported by physical therapist) in either the school or clinic environment and provide successful outcomes.
Percutaneous Vascular Interventions Versus Bypass Surgeries in Patients With Critical Limb Ischemia
Authors: Wang Jiarong , Shu Chi , Wu Zhoupeng , Zhao Jichun , Ma Yukui , Huang Bin , Yuan Ding , Yang Yi , Bian He , He Yazhou , Wang Ziqiang
Published: June 2017

Objective:

The aim of our study was to compare percutaneous vascular interventions (PVI) versus bypass surgeries (BSX) in patients with critical limb ischemia (CLI).

Background:

Previous relevant reviews with limited numbers of included studies did not strictly confine the inclusion criteria to CLI, also involving patients with severe claudication, which may introduce bias in the decision-making of CLI revascularization. Current treatment strategies for CLI still remain controversial.

Methods:

We performed a meta-analysis of all available randomized controlled trials and observational clinical studies comparing PVI with BSX in CLI patients. Primary endpoints included overall survival, amputation-free survival, 30-day mortality, and major adverse cardiovascular and cerebrovascular events.

Results:

We identified 45 cohorts and 1 RCT in over 20,903 patients. In overall population, PVI reduced the risks of 30-day mortality [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.51–0.95), major adverse cardiovascular and cerebrovascular events (OR 0.42, 95% CI 0.29–0.61), and surgical site infection (OR 0.31, 95% CI 0.19–0.51), but increased the risks of long-term all-cause mortality [hazard ratio (HR) 1.16, 95% CI 1.05–1.27) and primary patency failure (HR 1.31, 95% CI 1.08–1.58). When compared with autogenous BSX, PVI was also associated with additional increased risks of long-term death or amputation (HR 1.41, 95% CI 1.02–1.94) and secondary patency failure (HR 1.51, 95% CI 1.17–1.95). In patients with infrapopliteal lesions, we found PVI had inferior primary patency (HR 1.39, 95% CI 1.10–1.75) compared with BSX.

Conclusion:

For patients in good physical condition with long life-expectancy, BSX may represent a better choice compared with PVI, particularly when autogenous bypass is available. While enhanced perioperative care for cardiovascular events and surgical site should be considered in patients underwent BSX to achieve comparable short-term outcomes provided by PVI.
The Effect of Resident Involvement in Pelvic Prolapse Surgery: A Retrospective Study From a Nationwide Inpatient Sample
Authors: Caveney Maxx , Matthews Catherine , Mirzazadeh Majid
Published: June 2017

Objective

The primary aim of this study was to assess the effect of resident involvement on perioperative complication rates in pelvic organ prolapse surgery using the National Surgical Quality Improvement database.

Methods

All pelvic organ prolapse operations from 2006 to 2012 were identified and dichotomized by resident participation. Preoperative characteristics and 30-day perioperative outcomes were compared using χ2 and Student t test. To control for nonrandomization of cases, propensity scores representing the probability of resident involvement as a function of a case's comorbidities were calculated. They were then divided into quartiles, and because of equal probabilities for the first and second quartiles, 3 groups were created (Q1/2, Q3, and Q4), followed by substratification and analysis. As a control, complications of transurethral resection of prostate and nephrectomy were dichotomized by resident involvement.

Results

We identified 2637 cases. Resident involvement was associated with increased postoperative urinary tract infections, perioperative complications, and procedure length. After stratification by propensity scoring, the following unique findings occurred in each group: in the first group, resident involvement was associated with increased rates of readmission, pulmonary embolism, and sepsis; in the second and third groups, resident involvement was associated with increased rates of superficial surgical site infection. Resident involvement in nephrectomy observed increased perioperative complications and procedural length. In prostate resection, increased procedure lengths and decreased postoperative length of stay were observed.

Conclusions

Resident involvement in pelvic organ prolapse surgery was associated with an increased risk of adverse outcomes. A similar effect was seen with nephrectomy but not with a more simple endoscopic urologic procedure.
Suppression of drug resistance reveals a genetic mechanism of metabolic plasticity in malaria parasites
Authors: Guggisberg Ann M. , Frasse Philip M. , Jezewski Andrew J. , Kafai Natasha M. , Gandhi Aakash Y. , Erlinger Samuel J. , Odom John Audrey R.
Published: June 2017

In the malaria parasitePlasmodium falciparum, synthesis of isoprenoids from glycolytic intermediates is essential for survival. The antimalarial fosmidomycin (FSM) inhibits isoprenoid synthesis. InP. falciparum, we identify a loss-of-function mutation inHAD2(PF3D7_1226300) as necessary for FSM resistance. Enzymatic characterization reveals that HAD2, a member of the haloacid dehalogenase-like hydrolase (HAD) superfamily, is a phosphatase. Harnessing a growth defect in resistant parasites, we select for suppression of HAD2-mediated FSM resistance and uncover hypomorphic suppressor mutations in the locus encoding the glycolytic enzyme phosphofructokinase (PFK9). Metabolic profiling demonstrates that FSM resistance is achieved via increased steady-state levels of MEP pathway and glycolytic intermediates and confirms reduced PFK9 function in the suppressed strains. We identify HAD2 as a novel regulator of malaria parasite metabolism and drug sensitivity and uncover PFK9 as a novel site of genetic metabolic plasticity in the parasite. Our study informs the biological functions of an evolutionarily conserved family of metabolic regulators and reveals a previously undescribed strategy by which malaria parasites adapt to cellular metabolic dysregulation.

IMPORTANCE

Unique and essential aspects of parasite metabolism are excellent targets for development of new antimalarials. An improved understanding of parasite metabolism and drug resistance mechanisms are urgently needed. The antibiotic fosmidomycin targets the synthesis of essential isoprenoid compounds from glucose and is a candidate for antimalarial development. Our study identifies a novel mechanism of drug resistance and further describes a family of metabolic regulators in the parasite. Using a novel forward genetic approach, we also uncover mutations that suppress drug resistance in the glycolytic enzyme PFK9. Thus, we identify an unexpected genetic mechanism of adaptation to metabolic insult that influences parasite fitness and tolerance to antimalarials.
Combining Semantic Similarity and GO Enrichment for Computation of Functional Similarity
Authors: Liu Wenting , Liu Jianjun , Rajapakse Jagath C.
Published: June 2017

Functional similarity between genes is widely used in many bioinformatics applications including detecting molecular pathways, finding co-expressed genes, predicting protein-protein interactions, and prioritization of candidate genes. Methods evaluating functional similarity of genes are mostly based on semantic similarity of gene ontology (GO) terms. Though there are hundreds of functional similarity measures available in the literature, none of them considers the enrichment of the GO terms by the querying gene pair. We propose a novel method to incorporate GO enrichment into the existing functional similarity measures. Our experiments show that the inclusion of gene enrichment significantly improves the performance of 44 widely used functional similarity measures, especially in the prediction of sequence homologies, gene expression correlations, and protein-protein interactions.

Software availability

The software (python code) and all the benchmark datasets evaluation (R script) are available athttps://gitlab.com/liuwt/EnrichFunSim.
Comparative transcriptomics of THP-1 monocytes in response to different pathogens
Authors: Thuer Ernst , Gabaldón Toni
Published: June 2017

Undifferentiated human monocytes encounter various pathogens while present in the bloodstream. They are considered a primary responder and regulator for human immune reactions. As such, experiments investigating responses to pathogens are often reliant on monocyte cell cultures. For reproducibility reasons, immortalized cell lines are used. One of the most important cell lines used to model pathogen interactions is THP-1, which has been used in a variety of high throughput transcriptomics experiments. Yet as a cancer derived cell line it may no longer maintain its orignial functionality in detecting and responding to pathogens. Using available large scale transcriptomics datasets, we compare the response of THP-1 to a variety of human pathogens; viruses, bacteria, protozoa and fungi. Our approach focuses on the behavior of THP1 in its response to the different pathogens. Our aim is to provide comparative insights into the cell lines, which may serve to potentially improve future experimental design.
Rap1, AF6 and Pak4 cooperate with Par3 to promoteZAassembly and remodeling in the fly photoreceptor
Authors: Walther Rhian F. , Burki Mubarik , Pinal Noelia , Rogerson Clare , Pichaud Franck
Published: June 2017

The epithelialZonula adherens (ZA)is a main adhesion compartment that enables organogenesis by allowing epithelial cells to assemble into sheets. HowZAassembly is regulated during epithelial cell morphogenesis is not fully understood. We show that duringZAmorphogenesis, the function of the small GTPase Rap1 and the F-actin binding protein AF6/Cno are both linked to that of the P21-activated kinase Pak4/Mbt. We find that Rap1 and Mbt regulate each other’s localization at theZAand cooperate in promoting ECadherin stabilization. During this process Cno regulates the recruitment of Baz at theZA,a process that is also regulated by Arm phosphorylation by Mbt. Altogether, we propose that Rap1, Cno and Mbt regulateZAmorphogenesis by coordinating ECadherin stabilization and Baz recruitment and retention. In addition, our work uncovers a new link between two main oncogenes, Rap1 and Pak4/Mbt, in a model developing epithelial cell.
A transgenic toolkit for visualizing and perturbing microtubules in mice reveals unexpected functions for non-centrosomal arrays in epidermal morphogenesis
Authors: Muroyama Andrew , Lechler Terry
Published: June 2017

Differentiation induces reorganization of microtubules (MTs) into non-centrosomal arrays in a variety of tissues. The physiological functions of these microtubule arrays are just beginning to be understood as few tools currently exist to genetically perturb microtubule organizationin vivo, particularly in mammals. We developed a genetic toolkit that can be broadly applied to the study of microtubule dynamics and function in many cell types. Using a TRE-EB1-GFP mouse we demonstrate that distinct differentiation transitions in the epidermis cause a decrease in microtubule growth rates and microtubule growth lifetimes, resulting in strong suppression of dynamics. To understand the physiological functions of these stable, non-centrosomal microtubules, we generated a TRE-spastin mouse, which can be used to perturb microtubule organization in a wide-variety of tissuesin vivo.Unexpectedly, microtubule perturbation exclusively in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled novel cell-autonomous roles for MTs in differentiation-driven cell flattening from non-cell autonomous functions in regulating proliferation, differentiation, and tissue architecture. Taken together, we have created tools that will be broadly useful for the study of microtubule dynamics and function in mammalian tissue physiology and have used them to uncover previously unknown functions for non-centrosomal microtubules during mammalian epidermal development.
Variation in the oxidative burst in response to wounding and bacterial infection among native and invading genotypes of yellow starthistle(Centaurea solstitialis)
Authors: Kaczowka Angela M. , Lu-Irving Patricia , Baltrus David A , Dlugosch Katrina M.
Published: June 2017

Premise of the study:Invasive plants may leave enemies behind when they colonize a new habitat, allowing selection to favor increased investment in growth and/or reproduction over defensive traits. Previous studies have identified reduced diversity of potential bacterial pathogens and evolutionary increases in growth and reproduction in invading populations of yellow starthistle (Centaurea solstitialis). This study leverages a recently developed high-throughput assay of immune function to test for evidence of a trade-off between increased growth and defense against bacterial pathogens in yellow starthistle’s invasion of California (USA).

Methods:Seven bacterial strains were cultured from infected leaf tissue in the native range. Healthy leaf tissue from five native European collections and six invading collections were exposed to these native bacterial strains. A standardized assay of peroxidase activity was used measure the oxidative burst immune response to pathogen recognition by the leaf. Immune responses were compared to plant growth within and between ranges to assess evidence for a trade-off.

Key Results:Plant genotypes from the native range demonstrated a higher immune response to bacterial strains than did invading genotypes, consistent with a trade-off with plant growth across regions. The same trade-off was also apparent across genotypes from the native range, but not across genotypes from the invaded range.

Conclusions:Our results provide evidence that increased growth in a highly invasive plant species may come at a cost to immune function, consistent with the hypothesis that escape from enemies can provide opportunities for shifts in resource allocation that favor the proliferation of non-native species.
Intestine-to-neuronal signaling alters risk-taking behaviors in food-deprivedCaenorhabditis elegans
Authors: Matty Molly A. , Lau Hiu E. , Singh Anupama , Haley Jessica A. , Chakraborty Ahana , Kono Karina , Reddy Kirthi C. , Hansen Malene , Chalasani Sreekanth H.
Published: June 2017

Animals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. We use the nematodeC. elegansto decode how changes in internal nutritional status affects chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (Mondo A) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm upon food deprivation. Next, we identify insulin-like peptides INS-23 and INS-31 as candidate ligands relaying food-status signals from the intestine to other tissues. Furthermore, we show that ASI chemosensory neurons use the DAF-2 insulin receptor, PI-3 Kinase, and the mTOR complex to integrate these intestine-released peptides. Together, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors.

Author Summary

We have all experienced behavioral changes when we are hungry - the pang in our stomach can cause us to behave erratically. In particular, hungry animals, including humans, are known to pursue behaviors that involve higher risk compared to when they are well-fed. Here we explore the molecular details of this behavior in the invertebrate animal model C. elegans. This behavior, termed sensory integration, shows that C. elegans display reduced copper sensitivity when hungry. Copper is toxic and repellant to C. elegans; reduced avoidance indicates that these animals use riskier food search behaviors when they are hungry. Luckily, like us, this behavioral change is reversible upon re-feeding. This hunger-induced behavioral change is not due to increased attraction to food or depletion of fat stores, but rather insulin signaling between the intestine and specific neurons. We use genetic tools, microscopy, and behavioral tests to determine that this risky behavior involves sensation of “lack of food” in the intestine, release of signaling molecules, and engagement with sensory neurons. Our work highlights new and potentially evolutionarily conserved ways in which intestinal cells and neurons communicate leading to largescale behavioral change, providing further support for the importance of the gut-brain-axis.
Competition of Charge-Mediated and Specific Binding by Peptide-Tagged Cationic Liposome–DNA NanoparticlesIn VitroandIn Vivo
Authors: Wonder Emily , Simón-Gracia Lorena , Scodeller Pablo , Majzoub Ramsey N. , Kotamraju Venkata Ramana , Ewert Kai K. , Teesalu Tambet , Safinya Cyrus R.
Published: June 2017

Cationic liposome–nucleic acid (CL–NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly(ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells. Such guidelines are desirable to accelerate the optimization of formulations with novel peptides. Using PEG-lipids functionalized with a library of prototypical tumor-homing peptides, we varied the peptide density and other parameters (binding motif, peptide charge, CL/DNA charge ratio) to study their effect on the binding and uptake of the corresponding NPs. We used flow cytometry to quantitatively assess binding as well as internalization of NPs by cultured cancer cells. Surprisingly, full peptide coverage resulted in less binding and internalization than intermediate coverage, with the optimum coverage varying between cell lines. In, addition, our data revealed that great care must be taken to prevent nonspecific electrostatic interactions from interfering with the desired specific binding and internalization. Importantly, such considerations must take into account the charge of the peptide ligand as well as the membrane charge density and the CL/DNA charge ratio. To test our guidelines, we evaluated thein vivotumor selectivity of selected NP formulations in a mouse model of peritoneally disseminated human gastric cancer. Intraperitoneally administered peptide-tagged CL–DNA NPs showed tumor binding, minimal accumulation in healthy control tissues, and preferential penetration of smaller tumor nodules, a highly clinically relevant target known to drive recurrence of the peritoneal cancer.

Graphical Abstract
48-spot single-molecule FRET setup with periodic acceptor excitation
Authors: Ingargiola Antonino , Segal Maya , Gulinatti Angelo , Rech Ivan , Labanca Ivan , Maccagnani Piera , Ghioni Massimo , Weiss Shimon , Michalet Xavier
Published: June 2017

Single-molecule FRET (smFRET) allows measuring distances between donor and acceptor fluorophores on the 3-10 nm range. Solution-based smFRET allows measurement of binding-unbinding events or conformational changes of dye-labeled biomolecules without ensemble averaging and free from surface perturbations. When employing dual (or multi) laser exci-tation, smFRET allows resolving the number of fluorescent labels on each molecule, greatly enhancing the ability to study heterogeneous samples. A major drawback to solution-based smFRET is the low throughput, which renders repetitive measurements expensive and hin-ders the ability to study kinetic phenomena in real-time.

Here we demonstrate a high-throughput smFRET system which multiplexes acquisition by using 48 excitation spots and two 48-pixel SPAD array detectors. The system employs two excitation lasers allowing separation of species with one or two active fluorophores. The performance of the system is demonstrated on a set of doubly-labeled double-stranded DNA oligonucleotides with different distances between donor and acceptor dyes along the DNA duplex. We show that the acquisition time for accurate subpopulation identification is reduced from several minutes to seconds, opening the way to high-throughput screening applications and real-time kinetics studies of enzymatic reactions such as DNA transcription by bacterial RNA polymerase.
Widespread translational remodeling during human neuronal differentiation
Authors: Blair John D. , Hockemeyer Dirk , Doudna Jennifer A. , Bateup Helen S. , Floor Stephen N.
Published: June 2017

Faithful cellular differentiation requires precise coordination of changes in gene expression. However, the relative contributions of transcriptional and translational regulation during human cellular differentiation are unclear. Here, we induced forebrain neuronal differentiation of human embryonic stem cells (hESCs) and characterized genomewide RNA and translation levels during neurogenesis. We find that thousands of genes change at the translation level across differentiation without a corresponding change in RNA level. Specifically, we identify mTOR complex 1 signaling as a key driver for elevated translation of translation-related genes in hESCs. In contrast, translational repression in active neurons is mediated by transcript 3′ UTRs, through regulatory sequences. Together, our findings identify a functional role for the dramatic 3′ UTR extensions that occur during brain development, and provide insights to interpret genetic variants in post-transcriptional control factors that influence neurodevelopmental disorders and diseases.
Characterization of SID-1-dependent and independent intergenerational RNA transport pathways inCaenorhabditis elegans
Authors: Wang Eddie , Hunter Craig P.
Published: June 2017

Systemic RNA interference (RNAi) inC. elegansis dependent onsid-1(Winstonet al.2002),sid-3(Joseet al.2012) andsid-5(Hinaset al.2012). After injection, expression, or ingestion, double-stranded RNA (dsRNA) is transported between cells throughout the animal to enable RNAi in most tissues, including the germline and progeny. Here, we characterize the role of the Sid genes in transport of dsRNA to progeny. We previously reported that dsRNA injected directly in the germline unexpectedly requiressid-1activity in the progeny to initiate RNAi (Winstonet al.2002). We now show that germline injected dsRNA can travel by three independent pathways to silence gene expression in embryos. First, germline injected dsRNA is delivered, presumably by bulk flow, into oocytes and embryos. This means of delivery, which does not requiresid-1,is limited by the amount and location of injected dsRNA. Second, maternalsid-1transports extracellular dsRNA into the germline where it can silence maternal deposited mRNAs and segregate to embryos to silence embryonically expressed mRNAs. Third, extracellular dsRNA is also endocytosed into oocytes by the low-density lipoprotein (LDL) receptor superfamily homolog RME-2. The endocytosed dsRNA then requiressid-1andsid-5in embryos to silence embryonically expressed genes. Extracellular fluorescent dsRNA, once endocytosed into oocytes, does not co-localize with VIT2::GFP and it does not requiresid-1activity to segregate from the late endocytosis marker GFP::RAB-7 in early embryos. In conclusion, we identify genes and pathways that function redundantly for intergenerational RNA transfer that may represent mechanisms for transgenerational epigenetic inheritance.
Cell-type selective deletion of RSK2 reveals insights into altered signaling in Coffin-Lowry Syndrome
Authors: Zhu Hu , Strachan Ryan T. , Urban Daniel J. , Farrell Martilias S. , Kroeze Wesley K. , English Justin G. , Olsen Reid H.J. , Roth Bryan L.
Published: June 2017

Coffin-Lowry syndrome (CLS) is an X-linked syndromic form of mental retardation characterized by various skeletal dysmorphisms, moderate to severe mental retardation, and in some cases, psychosis. CLS is caused by loss-of-function mutations of the p90 ribosomal S6 kinase 2 (RPS6KA3) gene encoding a growth factor-regulated serine/threonine kinase, ribosomal S6 kinase 2 (RSK2). We previously identified RSK2 as a novel interacting protein that tonically inhibits 5-HT2Areceptor signaling by phosphorylating Ser-314 within the third intracellular loop. To determine if RSK2 inhibits 5-HT2Areceptor signalingin vivoand whether disruption of RSK2 could lead to schizophrenia-like behaviors - as is seen in some CLS patients - we genetically disrupted the function of RSK2 either globally or selectively in forebrain pyramidal neurons in mice. Both global and forebrain-selective RSK2 deletion augmented the locomotor responses to the psychotomimetic drugs phencyclidine (PCP) and amphetamine (AMPH). Significantly, forebrain-selective deletion of RSK2 augmented 5-HT2Areceptor signaling as exemplified by enhanced 5-HT2A-mediated c-fos activation and head-twitch response without altering the levels or distribution of 5-HT2Areceptor protein. Thus, RSK2 modulates 5HT2Areceptor functionin vivo,and disruption of RSK2 leads to augmented psychostimulant-induced responses reminiscent of those seen in many animal models of schizophrenia. These findings strengthen the association between 5-HT2Areceptor dysfunction and psychosis, and provide a potential mechanism underlying the schizophrenia-like symptoms present in some CLS patients.

Highlights

Global and cell-type-specific RSK2 knock-out mice were assessed behaviorally and pharmacologically

Augmentation of amphetamine and PCP locomotor responses were seen in both global and forebrain-specific RSK2 KO mice

Augmentation of 5-HT2A serotonin receptor function but not number was also observed

These alterations reveal insights into mechanisms potentially responsible for behavioral sequlae of Coffin-Lowry Syndrome
Exceptional durable response to everolimus in a patient with biphenotypic breast cancer harboring an STK11 variant
Authors: Parachoniak Christine A. , Rankin Andrew , Gaffney Bernadette , Hartmaier Ryan , Spritz Dan , Erlich Rachel L. , Miller Vincent A. , Morosini Deborah , Stephens Phil , Ross Jeffrey S. , Keech John , Chmielecki Juliann
Published: June 2017

Metastatic triple-negative breast cancer comprises 12%–17% of breast cancers and carries a poor prognosis relative to other breast cancer subtypes. Treatment options in this disease are largely limited to systemic chemotherapy. A majority of clinical studies assessing efficacy of targeted therapeutics (e.g., the mammalian target of rapamycin [mTOR] inhibitor everolimus) in advanced breast cancer patients have not utilized predictive genomic biomarker-based selection and have reported only modest improvement in the clinical outcome relative to standard of care. However, recent reports have highlighted significant clinical responses of breast malignancies harboring alterations in genes involved in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway to mTOR-inhibitor-involving regimens, underscoring the potential clinical benefit of treating subsets of breast cancer patients with molecularly matched targeted therapies. As the paradigm of cancer treatment shifts from chemotherapeutic regimens to more personalized approaches, the identification of additional reliable biomarkers is essential for identifying patients likely to derive maximum benefit from targeted therapies. Herein, we report a near-complete and ongoing 14-mo response to everolimus therapy of a heavily pretreated patient with biphenotypic, metastatic breast cancer. Genomic profiling of the metastatic triple-negative liver specimen identified a single reportable point mutation, STK11 F354L, that appears to have undergone loss of heterozygosity. No other alterations within the PI3K/mTOR pathway were observed. Published functional biochemical data on this variant are conflicting, and germline data, albeit with unclear zygosity status, are suggestive of a benign polymorphism role. Together with the preclinical data, this case suggests further investigation of this variant is warranted to better understand its role as a potential biomarker for mTOR inhibitor sensitivity in the appropriate clinical context.
Tris(N-{bis[methyl(phenyl)amino]phosphoryl}benzenesulfonamidato-κ2O,O′)(1,10-phenanthroline-κ2N,N′)lanthanum(III)
Authors: Prytula-Kurkunova Angelina Yu. , Trush Victor A. , Dyakonenko Viktoriya V. , Sliva Tetyana Yu. , Amirkhanov Vladimir M.
Published: June 2017

The asymmetric unit of [La(C20H21N3O3PS)3(C12H8N2)] is created by one LaIIIion, three deprotonatedN-{bis[methyl(phenyl)amino]phosphoryl}benzenesulfonamidate (L−) ligands and one 1,10-phenanthroline (Phen) molecule. Each LaIIIion is eight-coordinated (6O+2N) by three phosphoryl O atoms, three sulfonyl O atoms of threeL−ligands and two N atoms of the chelating Phen ligand, leading to the formation of six- and five-membered metallacycles, respectively. The lanthanum coordination polyhedron has a bicapped trigonal–prismatic geometry. `Sandwich-like' intramolecular π–π stacking interactions are observed between the 1,10-phenanthroline ligand and two benzene rings of two differentL−ligands. The phenyl rings ofL−that are not involved in the stacking interactions show minor positional disorder. Molecules form layers parallel to the (010) plane due to weak C—H...O intermolecular hydrogen bonds. Unidentified highly disordered solvate molecules that occupyca400 Å3large voids have been omitted from the refinement model.
(Z)-2-(2-Chlorobenzylidene)-4-(prop-2-ynyl)-2H-1,4-benzothiazin-3(4H)-one
Authors: Sebbar Nada Kheira , Ellouz Mohamed , Ouzidan Younes , Kaur Manpreet , Essassi El Mokhtar , Jasinski Jerry P.
Published: June 2017

In the title compound, C18H12ClNOS, the thiazine-3-one ring of the 1,4-thiazin-3-one moiety adopts a slightly distorted twist-boat conformation. The dihedral angle between the benzene rings is 86.2 (1)°. In the crystal, the crystal packing features a single weak C—H...O interaction and weak π–π stacking interactions.
(2,2′-Bipyrazine-κ2N1,N1′)[1,2-bis(diphenylphosphanyl)methane-κP]tricarbonylrhenium(I) trifluoromethanesulfonate monohydrate
Authors: Rillema D. Paul , Komreddy Venugopal , Senaratne Nilmini K. , Eichhorn David M.
Published: June 2017

The title compound, [Re(C8H6N4)(C25H22P2)(CO)3]CF3SO3·H2O, crystallizes with one [Re(C8N4H6){P(Ph)2CH2P(Ph)2}(CO)3]+cation, where Ph is a phenyl group, one CF3SO3−anion and one water molecule of hydration. The three C atoms of thefacialoriented carbonyl groups, two N atoms from the bipyrazine ligand and one P atom from the (bis)diphenylphosphanylmethane ligand define a distorted octahedral coordination environment about the central ReIatom. The Re—Ccarbonylbond lengthtransto the P atom is longer than the the two Re—Ccarbonylbond lengths in the plane with the bipyrazine ligand. Hydrogen-bonding interactions between the solvent water molecule and the cation, as well as weak C—H...O interactions, consolidate a three-dimensional network structure.
Profit
Authors: Cowton Chris
Published: June 2017

Purpose

The purpose of this poem is to allow the reader to contemplate the substitution and to decide whether it works.

Design/methodology/approach

A short “poem” based on the idea of replacing “love” with “profit” in St Paul’s famous passage in 1 Corinthians 13, and often read at weddings. The word “charity” would appear instead of “love” if the old King James Version of the Bible were used instead.

Findings

An inference might be drawn that love is better than profit.

Originality/value

The poem encourages a comparison between profit and love.