bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of 4 New Mutations in the CYBB Gene in 10 Iranian Families With X-linked Chronic Granulomatous Disease
Authors: Teimourian Shahram , Sazgara Faezeh , de Boer Martin , van Leeuwen Karin , Roos Dirk , Lashkary Sharzad , Chavoshzadeh Zahra , Nabavi Mohammad , Bemanian Mohammad Hassan , Isaian Anna
Published: April 2018

Chronic granulomatous disease (CGD) is an inherited disease of the innate immune system that results from defects in 1 of the 5 subunits of nicotinamide adenine dinucleotide phosphate oxidase complex and leads to life-threatening infections with granuloma formation. During 3 years of study, we recognized 10 male patients with X-linked CGD from a tertiary referral center for immune deficiencies in Iran. The CGD patients were diagnosed according to clinical features and biochemical tests, including nitroblue tetrazolium and dihydrorhodamine-1, 2, 3 tests, performed on patients and their mothers. In all patients, Western blot analysis showed a gp910 phenotype. Mutation screening by single strand conformation polymorphism and multiplex ligation-dependent probe amplification analysis of the CYBB gene encoding gp91phox, followed by sequencing, showed 9 different mutations, 4 of them novel as far as we know.
Postpartum Depression Screening for New Mothers at Well Child Visits
Authors: Emerson Margaret R. , Mathews Therese L. , Struwe Leeza
Published: April 2018

Background:

Postpartum depression (PPD) is a debilitating emotional experience that can affect mothers and their infants. Screening for PPD is encouraged during pediatric well-child visits (WCVs); however, the frequency, referral process, and documentation relative to screening in clinical practice require further study.

Objectives:

There were three purposes to this study: 1) determine prevalence of mothers who scored in the at-risk range using the Edinburgh Postnatal Depression Scale (EPDS) at each of the 2-, 4-, and 6-month WCVs in a pediatric outpatient practice; 2) examine feasibility factors relative to extending the current standard of care for PPD screening; and 3) examine visit documentation for at-risk mothers.

Design:

A prospective cohort study design was used to screen mothers during their infants' 6-month WCV for PPD using the EPDS. Feasibility in adding the 6-month time frame was assessed using an investigator-designed clinical team survey. Visit documentation content was obtained through medical record review.

Results:

Forty-three postpartum women were included in the study. Prevalence rates among participants were 10%, 12.5%, and 14% for 2-month, 4-month, and 6-month WCVs, respectively. The clinical team found the additional screening at the 6-month visit to be feasible. Documentation for mothers identified to be at-risk varied greatly.Conclusions: Prevalence of PPD among participants is consistent with previously reported rates. Areas identified for improved clinical practice include the content of the visit that is documented in the medical record and reviewed with mothers identified to be at-risk, time allotted for the clinical team to screen new mothers, and appropriate referral to outside sources.
Use of Tranexamic Acid to Reduce Blood Loss in Liposuction
Authors: Cansancao Alvaro Luiz , Condé-Green Alexandra , David Joshua A. , Cansancao Bethania , Vidigal Rafael A.
Published: April 2018

Background:

The use of tranexamic acid for blood loss prevention has gained popularity in many specialties, including plastic surgery. However, its use in liposuction has not been studied. The authors present a prospective, double-blind, nonrandomized study evaluating the efficacy of tranexamic acid in reducing perioperative blood loss during liposuction.

Methods:

Twenty women undergoing liposuction were divided into two cohorts. Group 1 (n = 10) received a standard dose of 10 mg/kg of tranexamic acid intravenously in the preoperative and postoperative periods, whereas group 2 (n = 10) received a placebo. Patient hematocrit levels were evaluated preoperatively and postoperatively. Blood volume in the infranatant of the lipoaspirate was also measured; t tests were used for statistical analysis.

Results:

Age, body mass index, and volume of lipoaspirate were comparable between the two cohorts. The volume of blood loss for every liter of lipoaspirate was 56.2 percent less in the tranexamic group compared with the control group (p < 0.001). Hematocrit levels at day 7 postoperatively were 48 percent less in group 1 compared with group 2 (p = 0.001). Furthermore, a 1 percent drop in the hematocrit level was found after liposuction of 812 ± 432 ml in group 1 and 379 ± 204 ml in group 2. Thus, the use of tranexamic acid could allow for aspiration of 114 percent more fat, with comparable variation in hematocrit levels.

Conclusions:

Tranexamic acid has been shown to be effective for minimizing perioperative blood loss in liposuction. Further large randomized controlled studies are required to corroborate this effect.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Addressing the Opioid Epidemic: A Review of the Role of Plastic Surgery
Authors: Wang Annie M. Q. , Retrouvey Helene , Wanzel Kyle R.
Published: April 2018

The opioid epidemic has been a growing public health threat in the United States and Canada for the past 30 years, with alarming and steadily increasing opioid-related mortality rates. Originating with well-intentioned efforts by physicians to relieve pain and suffering in their patients, the source of the opioid epidemic and much of its ammunition continues to be the sales of legally produced pharmaceutical opioids. Although surgeons are increasingly recognizing the important role they can play in mitigating this crisis, the recognition and evaluation of the opioid epidemic in plastic surgery has been lacking. The authors identified several aspects of plastic surgery that make judicious prescription of opioids in this field uniquely complex, including high variability of cases managed, large volume of ambulatory procedures, and frequent involvement in collaborative care with other surgical specialties. Additional research in plastic surgery is needed to both increase current knowledge of opioid prescribing practices and provide evidence for recommendations that can successfully combat the opioid epidemic.
Predictive Value of Soluble Programmed Death-1 for Severe Sepsis and Septic Shock During the First Week in an Intensive Care Unit
Authors: Zhao Yongzhen , Jia Yumei , Li Chunsheng , Shao Rui , Fang Yingying
Published: April 2018

Objective:

Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) exists in both membrane-bound and soluble forms. In this study, we evaluated the predictive value of soluble PD-1 (sPD-1) for severity and 28-day mortality in patients with severe sepsis and septic shock during the first week in an intensive care unit (ICU).

Methods:

In this prospective cohort study, patients were classified into the severe sepsis group or the septic shock group according to the severity of their condition on ICU admission. All patients were also separated into the survivor or nonsurvivor groups according to their 28-day outcomes. Peripheral blood sPD-1 and soluble PD-L1 (sPD-L1) levels, PD-1 expression on CD4+ and CD8+ T cells, and PD-L1 expression on monocytes were measured and compared between the groups on days 1 and 7 after ICU admission.

Results:

In all, 45 healthy volunteers and 112 patients were recruited. Serum sPD-1 levels were positively correlated with the severity of sepsis, sPD-L1 levels, PD-1 expression on CD4+ or CD8+ T cells, and PD-L1 expression on monocytes. The sPD-1 was an independent predictive factor for 28-day mortality both on day 1 and day 7. The area under the curve (AUC) of the sPD-1 on day 7 (0.871) was higher than that on day 1 (0.785) (P < 0.05), and better than the AUC of the percentages of PD-L1 on monocytes (0.770) on day 7 (P < 0.05).

Conclusion:

Serum sPD-1 shows valuable predictive ability for the severity and 28-day mortality of severe sepsis and septic shock during the first week of ICU treatment.
Single Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression
Authors: Bernard Vincent , Semaan Alexander , Huang Jonathan , Lucas F. Anthony San , Mulu Feven C , Stephens Bret M , Guerrero Paola A. , Huang Yanqing , Zhao Jun , Kamyabi Nabiollah , Sen Subrata , Scheet Paul A , Taniguchi Cullen M , Kim Michael P , Tzeng Ching-Wei , Katz Matthew H , Singhi Aatur D , Maitra Anirban , Alvarez Hector A
Published: April 2018

Background

Early detection of pancreatic ductal adenocarcinoma (PDAC) remains elusive. Precursor lesions of PDAC, specifically, intraductal papillary mucinous neoplasms (IPMNs) represent abona fidepathway to invasive neoplasia, although the molecular correlates of progression remain to be fully elucidated. Single cell transcriptomics provides a unique avenue for dissecting both the epithelial and microenvironmental heterogeneity that accompany multistep progression from non-invasive IPMNs to PDAC.

Methods

Single cell RNA-sequencing was performed through droplet-based sequencing on 5,403 cells from two low-grade IPMNs (LGD-IPMN), two high-grade IPMNs (HGD-IPMN), and two PDACs (all surgically resected).

Results

Analysis of single cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of non-invasive dysplasia to invasive cancer. While HGD-IPMNs expressed many core-signaling pathways described in PDAC, LGD-IPMNs harbored subsets of single cells with a transcriptomic profile that overlapped with invasive cancer. Notably, a pro-inflammatory immune component was readily seen in low-grade IPMNs, comprised of cytotoxic T-cells, activated T-helper cells, and dendritic cells, which was progressively depleted during neoplastic progression, accompanied by infiltration of myeloid-derived suppressor cells. Finally, stromal myofibroblast populations were heterogeneous, and acquired a previously described tumor-promoting and immune-evading phenotype during invasive carcinogenesis.

Conclusions

This study demonstrates the ability to perform high resolution profiling of the transcriptomic changes that occur during multistep progression of cystic PDAC precursors to cancer. Notably, single cell analysis provides an unparalleled insight into both the epithelial and microenvironmental heterogeneity that accompany early cancer pathogenesis, and might be a useful substrate to identify targets for cancer interception.
Frequency shifts and depth dependence of premotor beta band activity during perceptual decision-making
Authors: Chandrasekaran Chandramouli , Bray Iliana E. , Shenoy Krishna V.
Published: April 2018

Neural activity in the premotor and motor cortex shows prominent structure in the beta frequency range (13-30 Hz). Currently, the behavioral relevance of beta band activity (BBA) in premotor and motor regions is not well understood. The underlying source of motor BBA and how it changes as a function of cortical depth is also unknown. Here, we addressed these unresolved questions by investigating BBA recorded using laminar electrodes in the dorsal premotor cortex (PMd) of two male rhesus macaques performing a visual reaction time (RT) reach discrimination task. We observed robust BBA before and after the onset of the visual stimulus but not during the arm movement. While post-stimulus BBA was positively correlated with RT throughout the beta frequency range, pre-stimulus correlation varied by frequency. Low beta frequencies (~15 to 20 Hz) were positively correlated with RT and high beta frequencies (~25 to 30 Hz) were negatively correlated with RT. Simulations suggested that these frequency-dependent correlations could be due to a shift in the component frequencies of the pre-stimulus BBA as a function of RT, such that faster RTs are accompanied by greater power in high beta frequencies. We also observed a laminar dependence of BBA, with deeper electrodes demonstrating stronger power in low beta frequencies both pre- and post-stimulus. The heterogeneous nature of BBA and the changing relationship between BBA and RT in different task epochs may be a sign of the differential network dynamics involved in expectation, decision-making, and motor preparation.
Characterization of the apicomplexan amino acid transporter (ApiAT) family inToxoplasma gondii
Authors: Parker Kathryn E. R. , Fairweather Stephen J. , Rajendran Esther , Blume Martin , McConville Malcolm J. , Bröer Stefan , Kirk Kiaran , van Dooren Giel G.
Published: April 2018

Apicomplexan parasites are auxotrophic for a range of amino acids which must be salvaged from their host cells, either through direct uptake or degradation of host proteins. Here, we describe a family of plasma membrane-localized amino acid transporters, termed the Apicomplexan Amino acid Transporters (ApiATs), that are ubiquitous in apicomplexan parasites. Functional characterization of the ApiATs ofToxoplasma gondiiindicate that several of these transporters are important for intracellular growth of the tachyzoite stage of the parasite, which is responsible for acute infections. We demonstrate that the ApiAT proteinTgApiAT5-3 is an exchanger for aromatic and large neutral amino acids, with particular importance for L-tyrosine scavenging and amino acid homeostasis, and thatTgApiAT5-3 is critical for parasite virulence. Our data indicate thatT. gondiiexpresses additional proteins involved in the uptake of aromatic amino acids, and we present a model for the uptake and homeostasis of these amino acids. Our findings identify a family of amino acid transporters in apicomplexans, and highlight the importance of amino acid scavenging for the biology of this important phylum of intracellular parasites.

Author Summary

The Apicomplexa comprise a large number of parasitic protozoa that have obligate intracellular lifestyles and cause significant human and animal diseases, including malaria, cryptosporidiosis, toxoplasmosis, coccidiosis in poultry, and various cattle fevers. Apicomplexans must scavenge essential nutrients from their hosts in order to proliferate and cause disease, including a range of amino acids. The direct uptake of these nutrients is presumed to be mediated by transporter proteins located in the plasma membrane of intracellular stages, although the identities of these proteins are poorly defined. Using a combination of bioinformatic, genetic, cell biological, and physiological approaches, we have characterized a family of plasma membrane-localized transporter proteins that we have called the Apicomplexan Amino acid Transporters (ApiATs). The family is found in apicomplexans and their closest free-living relatives. We show thatTgApiAT5-3, a member of the family in the apicomplexanToxoplasma gondii, is an exchanger for aromatic and large neutral amino acids. In particular, it is critical for uptake of tyrosine, and for parasite virulence in a mouse infection model. We conclude that ApiATs are a family of plasma membrane transporters that play crucial roles in amino acid scavenging by apicomplexan parasites.
Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis
Authors: Levanov Lev , Iheozor-Ejiofor Rommel Paneth , Lundkvist Åke , Vapalahti Olli , Plyusnin Alexander
Published: April 2018

Earlier four Monoclonal antibodies (MAbs) against surface glycoproteins Gn and Gc of Puumala virus (PUUV, genus Orthohantavirus, family Hantaviridae, order Bunyavirales) were generated and for three MAbs with neutralizing capacity the localization of binding epitopes was predicted using pepscan and phage-display techniques. In this work, we produced vesicular stomatitis virus (VSV) particles pseudotyped with the Gn and Gc glycoproteins of PUUV and applied site-directed mutagenesis to dissect the structure of neutralizing epitopes. Replacement of cysteine amino acid (aa) residues with alanines resulted in pseudotype particles with diminished (16 to 18%) neut-titers; double Cys→Ala mutants, as well as mutants with bulky aromatic and charged residues replaced with alanines, have shown even stronger reduction in neut-titers (from 25% to the escape phenotype). In silico modelling of the neut-epitopes supported the hypothesis that these critical residues are located on the surface of viral glycoprotein molecules and thus can be recognized by the antibodies indeed. Similar pattern was observed in experiments with mutant pseudotypes and sera collected from patients suggesting that these neut-epitopes are utilized in a course of human PUUV infection.

IMPORTANCE

Neutralization of viruses by antibodies is one of the key events in infection. We identified a set of mutations in the surface proteins of PUUV that reduced the virus-neutralizing activity of MAbs. Moreover, we found three mutants with escaped phenotype. These data will help understanding the mechanisms of hantavirus neutralization and assist construction of vaccine candidates.
Transcranial photoacoustic imaging of NMDA-evoked focal circuit dynamics in rat hippocampus
Authors: Kang Jeeun , Kadam Shilpa D. , Elmore Joshua S. , Sullivan Brennan J. , Valentine Heather , Malla Adarsha P. , Harraz Maged M. , Rahmim Arman , Kang Jin U. , Loew Leslie M. , Baumann Michael , Grace Anthony A. , Gjedde Albert , Boctor Emad M. , Wong Dean F.
Published: April 2018

Transcranial functional photoacoustic (fPA) voltage-sensitive dye (VSD) imaging promises to overcome current temporal and spatial limitations of current neuroimaging modalities. The technique previously distinguished global seizure activity from control neural activity in groups of rats. To validate the focal specificity of transcranial fPA neuroimaging in vivo, we now present proofs-of-concept that the results differentiate between low- and high-dose N-methyl-D-aspartate (NMDA) evoked neural activity in rat hippocampus. Concurrent quantitative EEG (qEEG) and microdialysis recorded real-time circuit dynamics and glutamate concentration change, respectively. We hypothesized that location-specific fPA VSD contrast would identify the neural dynamics in hippocampus with the correlation to NMDA evoked focal glutamate release and time-specific EEG signals. To test the hypothesis, we infused 0.3 to 3.0 mM NMDA at 2 μl/min over 60 min via an implanted microdialysis probe. The dialysate samples collected every 20 min during the infusion were analyzed for focal changes in extracellular glutamate release. Transcranial fPA VSD imaging provided NMDA-evoked VSD responses with positive correlation to extracellular glutamate concentration change at the contralateral side of the microdialysis probe. The graded response represents the all-or-none gating system of the dentate gyrus (DG) in hippocampus. Quantitative EEG (qEEG) successfully confirmed induction of focal seizure activity during NMDA infusion. We conclude that transcranial fPA VSD imaging distinguished graded DG gatekeeping functions, based on the VSD redistribution mechanism sensitive to electrophysiologic membrane potential. The results suggest the potential future use of this emerging technology in clinics and science as an innovative and significant functional neuroimaging modality.
A synthetic bacterial information transfer system functions in the mammalian gut
Authors: Kim Suhyun , Kerns S. Jordan , Ziesack Marika , Bry Lynn , Gerber Georg K. , Way Jeffrey C. , Silver Pamela A.
Published: April 2018

The gut microbiome is intricately involved with establishing and maintaining the health of the host. Engineering of gut microbes aims to add new functions and expand the scope of control over the gut microbiome. To create systems that can perform increasingly complex tasks in the gut with multiple engineered strains it is necessary to program communication among these bacteria in the gut. Towards this goal, we engineered an information transfer system for inter-cellular communication, using native gutEscherichia coliand attenuatedSalmonella entericaserovar Typhimurium. Specifically, we have taken two genetic circuits-one for signaling from the quorum sensing system and the other for memory from the bacteriophage genetic switch–and integrated them into a robust system that can report on successful communication in the mammalian gut. Our system provides a basis for the construction of a programmable gut consortia as well as a basis for further understanding of bacterial interactions in an otherwise hard-to-study environment.
Fungal Bioaerosols at Five Dairy Farms: A Novel Approach to Describe Workers’ Exposure
Authors: Mbareche Hamza , Veillette Marc , Bilodeau Guillaume J , Duchaine Caroline
Published: April 2018

Occupational exposure to harmful bioaerosols in industrial environments is a real treat to the workers. In particular, dairy-farm workers are exposed to high levels of fungal bioaerosols on a daily basis. Associating bioaerosol exposure and health problems is challenging and adequate exposure monitoring is a top priority for aerosol scientists. Using only culture-based tools do not express the overall microbial diversity and underestimate the large spectrum of microbes in bioaerosols and therefore the identification of new airborne etiological agents. The aim of this study was to provide an in-depth characterization of fungal exposure at Eastern Canadian dairy farms using qPCR and next-generation sequencing methods. Concentrations ofPenicillium/Aspergillusranged from 4.6 × 106to 9.4 × 106gene copies/m3and from 1 × 104gene copies/m3to 4.8 × 105gene copies/m3forAspergillus fumigatus. Differences in the diversity profiles of the five dairy farms support the idea that the novel approach identifies a large number of fungal taxa. These variations may be explained by the presence of different and multiple sources of fungal bioaerosols at dairy farms. The presence of a diverse portrait of fungi in air may represent a health risk for workers who are exposed on a daily basis. In some cases, the allergen/infective activity of the fungi may not be known and can increase the risks to workers. The broad spectrum of fungi detected in this study includes many known pathogens and proves that adequate monitoring of bioaerosol exposure is necessary to evaluate and minimize risks.

Importance

While bioaerosols are a major concern for public health, accurately assessing human exposure is challenging. Highly contaminated environments, such as agricultural facilities, contain a broad diversity of aerosolized fungi that may impact human health. Effective bioaerosol monitoring is increasingly recognized as a strategic approach for achieving occupational exposure description. Workers exposure to diverse fungal communities is certain, as fungi are ubiquitous in the environments and the presence of potential sources increase their presence in the air. Applying new molecular approaches to describe occupational exposure is a necessary work around the traditional culture approaches and the biases they introduce to such studies. The importance of the newly developed approach can help to prevent worker’s health problems.
Regulation of transcription factor SP1 by β-catenin destruction complex modulates Wnt response
Authors: Mir Rafeeq , Sharma Ankita , Pradhan Saurabh J. , Galande Sanjeev
Published: April 2018

The ubiquitous transcription factor Specificity protein 1 (SP1) is heavily modified post-translationally. These modifications are critical for switching its functions and modulation of its transcriptional activity, DNA-binding and stability. However the mechanism governing the stability of SP1 by cellular signaling pathways is not well understood. Here, we provide biochemical and functional evidences that SP1 is an integral part of the Wnt signaling pathway. We identified a phosphodegron motif in SP1 that is specific to mammals. In absence of Wnt signaling, GSK3β kinase mediated phosphorylation and β-TrCP E3 ubiquitin ligase mediated ubiquitination is required to induce SP1 degradation. When Wnt signaling is on, SP1 is stabilized in β-catenin-dependent manner. SP1 directly interacts with β-catenin and Wnt signaling induces the stabilization of SP1 by impeding its interaction with β-TrCP and AXIN1, components of the destruction complex. Wnt signaling suppresses ubiquitination and subsequent proteosomal degradation of SP1. Furthermore, SP1 regulates Wnt-dependent stability of β-catenin and their mutual stabilization is critical for target gene expression, suggesting a feedback mechanism. Upon stabilization SP1 and β-catenin co-occupy the promoters of TCFL2/β-catenin target genes. Collectively, this study uncovers a direct link between SP1 and β-catenin in Wnt signaling pathway.
Interruption of signaling pathways in lung epithelial cell byMycobacterium tuberculosis
Authors: Hadifar Shima , Behrouzi Ava , Fateh Abolfazl , Khatami Shohreh , Jamnani Fatemeh Rahimi , Siadat Seyed Davar , Vaziri Farzam
Published: April 2018

Alveolar epithelial cell (AEC) provides a replication niche forMycobacterium tuberculosis (M.tb). Based on the role of AEC inM.tbpathogenesis and existence of genetic diversity within this bacterium, we investigated interactions between AEC II and two differentM.tblineages. We have compared the transcriptome and cytokines/chemokines levels of A549 infected byM.tblineage 3 and 4 using qRT-PCR and ELISA arrays, respectively. We showed differentM.tbstrains induced changes in different effectors that involved in TLRs and NF-κB signalling pathways. We observed different reaction of the studied lineages specifically in pathogenesis, immune evasion mechanism, IL-12/IFN-γ axis and autophagy. Similar behaviour was detected in regarding to apoptosis, necroptosis, anti-inflammatory responses and canonical inflammasome. Our findings contribute to elucidate more details in pathogenesis, immune evasion strategies, novel target and druggable pathway for therapeutic intervention and host directed therapy in TB infection. Also, differentM.tblineages-dependent host–pathogen interactions suggested using only one standard strain (e.g. H37Rv) for this kind of research will be controversial.
Genome-wide CRISPR-dCas9 screens inE. coliidentify essential genes and phage host factors
Authors: Rousset François , Cui Lun , Siouve Elise , Depardieu Florence , Bikard David
Published: April 2018

High-throughput genetic screens are powerful methods to identify genes linked to a given phenotype. The catalytic null mutant of the Cas9 RNA-guided nuclease (dCas9) can be conveniently used to silence genes of interest in a method also known as CRISPRi. Here, we report a genome-wide CRISPR-dCas9 screen using a pool of ~ 92,000 sgRNAs which target random positions in the chromosome ofE. coli. We first investigate the utility of this method for the prediction of essential genes and various unusual features in the genome ofE. coli. We then apply the screen to discoverE. coligenes required by phages λ, T4 and 186 to kill their host. In particular, we show that colanic acid capsule is a barrier to all three phages. Finally, cloning the library on a plasmid that can be packaged by λ enables to identify genes required for the formation of functional λ capsids. This study demonstrates the usefulness and convenience of pooled genome-wide CRISPR-dCas9 screens in bacteria in order to identify genes linked to a given phenotype.
TMS orientation and pulse waveform manipulation activates different neural populations: direct evidence from TMS-EEG
Authors: Pisoni Alberto , Vergallito Alessandra , Mattavelli Giulia , Varoli Erica , Fecchio Matteo , Rosanova Mario , Casali Adenauer G. , Romero Lauro Leonor J.
Published: April 2018

Monophasic and biphasic TMS pulses and coil orientations produce different responses in terms of motor output and sensory perception. Those differences have been attributed to the activation of specific neural populations. However, up to date, direct evidence supporting this hypothesis is still missing since studies were mostly based on indirect measures of cortical activation, i.e., motor evoked potentials or phosphenes. Here, we investigated for the first time the impact of different coil orientations and waveforms on a non-primary cortical area, namely the premotor cortex, by measuring TMS evoked EEG potentials (TEPs). We aimed at determining whether TEPs produced by differently oriented biphasic and monophasic TMS pulses diverge and whether these differences are underpinned by the activation of specific neural populations. To do so, we applied TMS over the right premotor cortex with monophasic or biphasic waveforms oriented perpendicularly (in the anterior-posterior direction and vice-versa) or parallel (latero-medial or medio-laterally) to the target gyrus. EEG was concurrently recorded from 60 electrodes. We analyzed TEPs at the level of EEG sensors and cortical sources both in time and time-frequency domain. Biphasic pulses evoked larger early TEP components, which reflect cortical excitability properties of the underlying cortex, in both parallel directions when compared to the perpendicular conditions. Conversely, monophasic pulses, when oriented perpendicularly to the stimulated gyrus, elicited a greater N100, which is a reliable TEP component linked to GABAb-mediated inhibitory processes, than when parallel to the gyrus. Our results provide direct evidence supporting the hypothesis that TMS pulse waveform and TMS coil orientations affect which neural population is engaged.
Cascaded Processing of Amplitude Modulation for Natural Sound Recognition
Authors: Koumura Takuya , Terashima Hiroki , Furukawa Shigeto
Published: April 2018

Temporal variation of sound envelope, or amplitude modulation (AM), is essential for auditory perception of natural sounds. Neural representation of stimulus AM is successively transformed while processed by a cascade of brain regions in the auditory system. Here we sought the functional significance of such cascaded transformation of AM representation. We modelled the function of the auditory system with a deep neural network (DNN) optimized for natural sound recognition. Neurophysiological analysis of the DNN revealed that AM representation similar to the auditory system emerged during the optimization. The better-recognizing DNNs exhibited larger similarity to the auditory system. The control experiments suggest that the cascading architecture, the data structure, and the optimization objective may be essential factors for the lower, middle and higher regions, respectively. The results were consistently observed across independent datasets. These results suggest the emergence of AM representation in the auditory system during optimization for natural sound recognition.
Oscillatory cortical forces promote three dimensional cell intercalations that shape the mandibular arch
Authors: Tao Hirotaka , Zhu Min , Lau Kimberly , Whitley Owen K.W. , Samani Mohammad , Xiao Xiao , Chen Xiao Xiao , Hahn Noah A. , Liu Weifan , Valencia Megan , Wu Min , Wang Xian , Fenelon Kelli D. , Pasiliao Clarissa C. , Hu Di , Wu Jinchun , Spring Shoshana , Ferguson James , Karuna Edith P. , Henkelman R. Mark , Dunn Alexander , Huang Huaxiong , Ho Hsin-Yi Henry , Atit Radhika , Goyal Sidhartha , Sun Yu , Hopyan Sevan
Published: April 2018

Multiple vertebrate embryonic structures such as organ primordia are composed of a volume of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show 3D mesenchymal cell intercalations, rather than cell divisions and biophysical tissue properties, are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor, we show that cortical force oscillations promote these intercalations. Genetic loss and gain of function approaches show thatWnt5afunctions as a spatial cue to coordinate cell polarity with cytoskeletal oscillation. YAP/TAZ and PIEZO1 serve as downstream effectors ofWnt5a-mediated actomyosin bias and cytosolic calcium transients, respectively, to ensure appropriate tissue form during growth. Our data support oriented 3D cell neighbour exchange as a conserved mechanism driving volumetric morphogenesis.
Transcriptome Analysis of FourArabidopsis thalianaMediator Tail Mutants Reveals Overlapping and Unique Functions in Gene Regulation
Authors: Dolan Whitney L. , Chapple Clint
Published: April 2018

The Mediator complex is a central component of transcriptional regulation in Eukaryotes. The complex is structurally divided into four modules known as the head, middle, tail and kinase modules, and inArabidopsis thaliana, comprises 28-34 subunits. Here, we explore the functions of four Arabidopsis Mediator tail subunits, MED2, MED5a/b, MED16, and MED23, by comparing the impact of mutations in each on the Arabidopsis transcriptome. We find that these subunits affect both unique and overlapping sets of genes, providing insight into the functional and structural relationships between them. The mutants primarily exhibit changes in the expression of genes related to biotic and abiotic stress. We find evidence for a tissue specific role for MED23, as well as in the production of alternative transcripts. Together, our data help disentangle the individual contributions of these MED subunits to global gene expression and suggest new avenues for future research into their functions.
Structural insight into industrially relevant glucoamylases: flexible positions of starch-binding domains
Authors: Roth Christian , Moroz Olga V. , Ariza Antonio , Skov Lars K. , Ayabe Keiichi , Davies Gideon J. , Wilson Keith S.
Published: April 2018

Glucoamylases are one of the most important classes of enzymes in the industrial degradation of starch biomass. They consist of a catalytic domain and a carbohydrate-binding domain (CBM), with the latter being important for the interaction with the polymeric substrate. Whereas the catalytic mechanisms and structures of the individual domains are well known, the spatial arrangement of the domains with respect to each other and its influence on activity are not fully understood. Here, the structures of three industrially used fungal glucoamylases, two of which are full length, have been crystallized and determined. It is shown for the first time that the relative orientation between the CBM and the catalytic domain is flexible, as they can adopt different orientations independently of ligand binding, suggesting a role as an anchor to increase the contact time and the relative concentration of substrate near the active site. The flexibility in the orientations of the two domains presented a considerable challenge for the crystallization of the enzymes.
Poems and pancakes for alcohol harm reduction
Authors: Misell Andrew
Published: April 2018

Purpose

Programmes to promote alcohol awareness and harm reduction in the general population often take an atomised approach, encouraging individual drinkers to understand their unit intake and adjust it accordingly. Although many public health practitioners harbour doubts about the value of this approach, few clear alternatives have emerged. The purpose of this paper is to provide such an alternative.

Design/methodology/approach

Alcohol Concern’s Communities Together project was rooted in the idea that drinking patterns can only be understood in their social context. It was an attempt to take seriously Harold Holder’s injunction to “cease to focus narrowly on the individual and begin to adopt broader community perspectives on alcohol problems”. The project applied Asset-Based Community Development methods, handing a large degree of control over to the participants, drawing on their own talents and enthusiasms, and recognising their autonomy and their authority as experts in their own lives.

Findings

The project outputs have been described as “community development with an alcohol twist”. They included a range of activities and events that created inclusive and non-judgemental spaces for people to think about alcohol and draw their own conclusions. It was also a lesson in humility for those of us who like to consider ourselves as the experts in public health: we had to learn that we did not have all the answers to questions about other people’s lives.

Practical implications

The project indicates that community development may be a valid alternative to more traditional and more didactic approaches to alcohol harm reduction.

Originality/value

The project may provide an innovative and flexible model that could be applied in various communities in order to address alcohol misuse in an engaging and undogmatic fashion that helps people take more control of their own lives.
Policy analysis and implications of establishing the Caribbean Cannabis Economy (CCE): lessons from Jamaica
Authors: Emanuel Machel Anthony , Haughton Andre Yone , K’nife K’adamawe
Published: April 2018

Purpose

The purpose of this paper is to explore the effects of legislative amendments to the Dangerous Drugs Act in 2015 and the establishment of a Cannabis Licensing Authority (CLA) in Jamaica as the first Caribbean country to decriminalize cannabis and attempt to establish a medical cannabis industry. The research also attempts to understand the perception of key industry players and interest groups to the existing regulatory framework in Jamaica.

Design/methodology/approach

The research reviews local and global trends, the developments in cannabis legislation and conducts questionnaires as well as semi-structured interviews to get feedback from key industry stakeholders and interest groups.

Findings

The findings suggest that there is a lack of confidence in the CLA in Jamaica, who are faced with the task of balancing the emerging medical cannabis industry and formalizing the existing illegal cannabis trade. There appears to be inconsistencies and lack of coordination between the associated ministries, departments and agencies. The CLA in Jamaica has established two separate cannabis models that appear to be incoherent in their approach to policy. On the one hand they are regulating cultivation, processing and supply, and on the other hand, the law remains unclear about the purchase or consumption of cannabis and its by-products.

Practical implications

Countries must learn from Jamaica’s experience if they wish to effectively establish a medical cannabis industry and legitimize existing illegal cannabis economic activities. These countries must ensure they tailor fit the approach of their CLAs to minimize any negative perception from industry players. Laws established to facilitate linkages from the cultivation to processing to packaging to transportation to retail must also include clear laws surrounding the purchase and consumption of cannabis. Jamaica has a far way to go and must continue to learn from other countries and states, for example, Holland, Spain and Uruguay, while at the same time learning from itself.

Originality/value

This paper is novel as it addresses the transition of the legislative process in Jamaica. It also serves as lesson for other countries that seek to engage in the development of their cannabis industries.
Iron deficiency and obesity in pre-school children
Authors: Ibrahim Loay , Allehdan Sabika , Alassaf Abeer , Tayyem Reema
Published: April 2018

Purpose

The purpose of this review was to highlight the association between ID and obesity in toddlers and preschool children.

Design/methodology/approach

This review aimed to review and evaluate literature of the published research discussing the relationship between ID and overweight and obesity in children under the age of 5 years. Conflicting results of iron status in overweight and obese children under the age of 5 years had been found. However, most articles concluded that ID is associated significantly with overweight and obesity in children because of the systemic inflammatory reaction which is considered the major cause of ID; hepcidin with its resultant effect in decreasing duodenal absorption of iron; in addition to other causes including dietary and genetic factors.

Findings

Conflicting results of iron status in overweight and obese children under the age of 5 years had been found, but most articles concluded that ID is associated significantly with overweight and obesity in children, with systemic inflammatory reaction being the major cause through hepcidin with its resultant effect in decreased duodenal absorption of iron, in addition to other causes including dietary and genetic factors.

Originality/value

Many nutrients have been associated with weight gain and ID development. Unbalanced diet either in excess or shortage may affect weight status and serum iron profile. Future research is needed to study more in depth the association between ID and obesity in toddlers and preschool children and to further explore the various factors involved in pathogenesis of ID.
Consumption of plantain suppresses pain and enhances social behavior in mice
Authors: Erigbali Peter Perebiri , Okon Udemeobong Edet , Ofem Ofem Effiong , Osim Eme Efiom
Published: April 2018

Purpose

Plantain (Musa paradisiaca), a staple food source for many people especially in the tropics, contains the neurotransmitter, serotonin which has analgesic and antidepressant effects. Therefore, this study aims to investigate the effects of chronic consumption of plantain diet on pain perception and social behavior in mice.

Design/methodology/approach

In the first set of experiments, three groups of mice were either fed rodent chow (control) or 50 or 100 per cent plantain diet, while in a second set of experiments, another three groups of mice were fed either rodent chow (control) or 100 per cent plantain or plantain + ritanserin (serotonin antagonist) for 30 days. Response to pain stimuli was studied by hot plate and formalin tests. Also, the ability of the mice to fluff up suitable beds to build nestle from nesting material was used as an index for social behavior. Serotonin concentration in mice brain was measured using high performance liquid chromatography.

Findings

The results showed that plantain diet-fed mice consumed less food but gained more body weight than control mice. Pain perception was significantly reduced in the plantain diet-fed mice compared to the control. Social behavior was enhanced in the plantain diet-fed mice when compared to control (p < 0.05). There was significant increase in serotonin concentration in the brains of 100 per cent diet-fed mice. Administration of serotonin blocker, ritanserin reversed the effects observed in pain and social behavior tests.

Originality/value

Chronic consumption of plantain diet increases serotonin concentration in the brain, suppresses spontaneous perception of pain and improves social behavior in mice. These actions may involve serotonergic pathway.
Systematic review: resilience enablers to combat
counterfeit medicines
Authors: Lima Flávia Renata Pinho de , Da Silva Andrea Lago , Godinho Filho Moacir , Dias Eduardo Mario
Published: April 2018

Purpose

The purpose of this paper is to understand the role of resilience enablers in
combating counterfeits in the medicine supply chain based on a Systematic
Literature Review (SLR). The objective is also to help practitioners and
scholars as the review revealed that little research has been conducted on
selecting and implementing practices to improve resilience to
counterfeiting.

Design/methodology/approach

Based on the literature review, a content analysis was performed for 84
selected papers to explore the potential relationship among resilience
enablers and counterfeit anti-measures.

Findings

This paper contributes to Supply Chain Resilience (SCR) research by
summarizing the highly fragmented literature concerning how to combat
counterfeiting. The SLR indicated reengineering, collaboration, visibility,
innovation, SCR culture and trust as six key enablers to combat counterfeit
medicines and identified literature gaps. Moreover, the paper discusses
other resilience enablers which have been less studied in the literature and
shows new avenues of research.

Research
limitations/implications

This paper is limited in that it is an exploratory literature review and
focuses only on three databases over the past 15 years. Furthermore,
counterfeit is a rapidly evolving issue and anti-measure studies require
frequent surveillance concerning new discoveries.

Originality/value

The main contribution of this paper is to provide a better understanding of
enablers most often associated with counterfeit anti-measures, which,
therefore, might help to increase resilience to counterfeit medicines.
Moreover, research gaps involving enablers less associated with
anti-measures are presented.
Making it stick on borrowed time: the role of internal consultants in public sector lean transformations
Authors: Holmemo Marte Daae-Qvale , Powell Daryl John , Ingvaldsen Jonas A.
Published: April 2018

Purpose

The purpose of this paper is to explore the roles of internal lean consultants in western organizations during lean transformation processes and how these roles affect the outcomes of the changes.

Design/methodology/approach

Findings are based on a qualitative study of four Norwegian public organizations.

Findings

Characteristics of western organizations put internal lean consultants in important roles during the project initiation and change phases. However, consultants have less impact in the last phase of the transformation process while transferring the responsibilities over to line management. The organizations struggle to “make lean stick” due to the distribution of responsibilities between managers and internal consultants.

Practical implications

The distribution of responsibilities between managers and consultants should be carefully considered in lean transformation processes. Internal lean consultants should serve the managers as teachers and coaches, rather than doing their jobs for them.

Originality/value

The paper contributes with in-depth knowledge of the roles of internal consultants in lean transformation processes, a topic that the literature has left unexplored and undebated.
Spermidine prevents high glucose‐induced senescence in HT‐22 cells by upregulation of CB1 receptor
Authors: Zhu Wei‐Wen , Xiao Fan , Tang Yi‐Yun , Zou Wei , Li Xiang , Zhang Ping , Wang Ai‐Ping , Tang Xiao‐Qing
Published: April 2018

Hyperglycaemia‐induced neurotoxicity involved in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglyceamic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti‐aging function in many tissues. However, the role of Spd in hyperglyceamia‐induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)‐treated HT‐22 cell as vitro model to investigate whether Spd protects neurons against hyperglyceamia‐induced senescence and the mediatory role of CB1 receptor. The HT‐22 cells were cultured in HG condition in the presence of different dose of Spd. Then, the viability of cells was measured by Cell Counting Kit‐8 (CCK‐8) assay. The senescence of cells was detected by Senescence‐associated β‐galactosidase (SA‐β‐Gal) staining. The expressions of p16INK4a, p21CIP1 and CB1 receptor were measured by western blot. We found that Spd inhibited HG‐induced neurotoxicity (the loss of cell viability) and senescence (the increase of SA‐β‐Gal positive cells, the upregulation of p16INK4a and p21CIP1) in HT‐22 cells. Also, Spd prevented HG‐induced downregulation of CB1 receptor in HT‐22 cells. Furthermore, we demonstrated that AM251 (a specific inhibitor of the CB1 receptor) reversed the protective effects of Spd on HG‐induced neurotoxicity and senescence. These results indicated that Spd prevents HG‐induced neurotoxicity and senescence via the upregulation of CB1 receptor. Our findings provide a promising future of Spd‐based preventions and therapies for diabetic encephalopathy.