bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleoid openness profiling links bacterial genome structure to phenotype
Authors: Al-Bassam Mahmoud M , Moyne Oriane , Chapin Nate , Zengler Karsten 
Published: May 2020

ABSTRACTGene expression requires specific structural alternations in the nucleoid structure to enable the access of the transcription machinery into the genomic DNA. In prokaryotes, DNA binding proteins, including nucleoid-associated proteins (NAPs) and transcription factors (TFs), drive the change in structure and gene expression. Currently, studies of global NAP and TF binding are often hindered by the lack of appropriate epigenomic tools. Here, we present POP-seq, a method that providesin vivogenome-wide openness profiles of the bacterial nucleoid. We demonstrate that POP-seq can be used to map the globalin vivoprotein-DNA binding events. Our results highlight a negative correlation between genome openness, compaction and transcription, suggesting that regions that are not accessible to Tn5 transposase are either too compacted or occupied by RNA polymerase. Importantly, we also show that the least open regions are enriched in housekeeping genes, while the most open regions are significantly enriched in genes important for fast adaptation to changing environment. Finally, we demonstrated that the genome openness profile is growth condition specific. Together, those results suggest a model where one can distinguish two types of epigenetic control: one stable, long-term silencing of highly compacted regions, and a second, highly responsive regulation through the dynamic competition between NAPs and RNA polymerase binding. Overall, POP-seq captures structural changes in the prokaryotic chromatin and provides condition-specific maps of global protein-DNA binding events, thus linking overall transcriptional and epigenetic regulation directly to phenotype.
Conjugated activation of myocardial-specific transcription ofGja5by a pair of Nkx2-5-Shox2 co-responsive elements
Authors: Yang Tianfang , Huang Zhen , Li Hua , Wang Linyan , Chen YiPing 
Published: May 2020

AbstractThe sinoatrial node (SAN) is the primary pacemaker in the heart. During cardiogenesis,Shox2andNkx2-5are co-expressed in the junction domain of the SAN and regulate pacemaker cell fate through a Shox2-Nkx2-5 antagonism. Cx40 is a marker of working myocardium and an Nkx2-5 transcriptional output antagonized by Shox2, but the underlying regulatory mechanisms remain elusive. Here we characterized a bona fide myocardial-specificGja5(coding gene of Cx40) distal enhancer consisting of a pair of Nkx2-5 and Shox2 co-bound elements in the regulatory region ofGja5. Transgenic reporter assays revealed that neither element alone, but the conjugation of both elements together, drives myocardial-specific transcription. Genetic analyses confirmed that the activation of this enhancer depends on Nkx2-5 but is inhibited by Shox2in vivo, and its presence is essential forGja5expression in the myocardium but not the endothelial cells of the heart. Furthermore, chromatin conformation analysis showed an Nkx2-5-dependent loop formation between these two elements and theGja5promoterin vivo, indicating that Nkx2-5 bridges the conjugated activation of this enhancer by pairing the two elements to theGja5promoter.
A 5-min RNA preparation method for COVID-19 detection with RT-qPCR
Authors: Ladha Alim , Joung Julia , Abudayyeh Omar O. , Gootenberg Jonathan S. , Zhang Feng 
Published: May 2020

AbstractRNA extraction has become a bottleneck for detection of COVID-19, in part because of reagent shortages. We present here a rapid protocol that circumvents the need for RNA extraction that is compatible with RT-qPCR-based detection methods.
The actin-modulating protein Synaptopodin mediates long-term survival of dendritic spines
Authors: Yap Kenrick , Drakew Alexander , Smilovic Dinko , Rietsche Michael , Vuksic Mario , Turco Domenico Del , Deller Thomas 
Published: May 2020

AbstractLarge spines are stable and important for memory trace formation. The majority of large spines also contains Synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using time-lapse 2-photon-imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP-positive (SP+) spines followed conditional two-phase decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single exponential decays. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines and the presence of SP indicates spines of high stability.
SGT1 is not required for bacterial PAMP-triggered immunity
Authors: Yu Gang , Xian Liu , Zhuang Haiyan , Macho Alberto P. 
Published: May 2020

SummaryPlant immune signaling activated by the perception of pathogen-associated molecular patterns (PAMPs) or effector proteins is mediated by PRRs and NLRs, respectively, and often share cellular components and downstream responses. The suppressor of the G2 allele of skp1 (SGT1) is a core immune regulator required for the activation of NLR-mediated immunity. In this work, we examined the requirement of SGT1 for PRR-mediated immune responses in bothNicotiana benthamianaand Arabidopsis. Using complementary genetic approaches, we found that SGT1 is not limiting for early PRR-dependent responses or anti-bacterial immunity. Therefore, we conclude that SGT1 does not play a significant role in bacterial PAMP-triggered immunity.
Efficacy and safety of a combination regimen of phenothrin and ivermectin lotion in patients with head lice in Okinawa, Japan
Authors: Komoda Masayo , Yamaguchi Sayaka , Takahashi Kenzo , Yanase Kazuko , Umezawa Masakazu , Miyajima Atsushi , Yoshimasu Takashi , Sato Eiji , Ozeki Rie , Ishii Norihisa 
Published: May 2020

AbstractIn Japan, pyrethroid‐resistant head lice have been increasing; however, only 0.4% phenothrin, a pyrethroid drug, is available as an over the counter formulation. In recent years, Sumithrin® Lotion containing 5% phenothrin (PHT) was approved for scabies. In the USA, Sklice® Lotion containing 0.5% ivermectin (IVM) is used for the treatment of pyrethroid‐resistant head lice. Therefore, to enhance the treatment of head lice in Japan, we conducted a clinical study to confirm the efficacy and safety of a combination regimen of PHT and IVM (PI regimen). Twelve cases were enrolled and PHT was applied to all patients on day 1. On day 8, five patients (41.7%) were lice free, and PHT was applied again. Notably, seven patients were not lice free and were switched to IVM. The rate of patients who were lice free on the PI regimen, which was the primary end‐point, was 75.0% on day 15 and 91.7% on day 22. No adverse events were reported. A genetic analysis of the head lice collected at each visit revealed a kdr mutation in all patients. These results suggest that the PI regimen is safe and effective for the treatment of pyrethroid‐resistant head lice in Japan.
Altered protein levels in bone marrow lesions of hip osteoarthritis: Analysis by proteomics and multiplex immunoassays
Authors: Shabestari Maziar , Shabestari Yashar R. , Landin Maria A. , Pepaj Milaim , Cleland Timothy P. , Reseland Janne E. , Eriksen Erik F. 
Published: May 2020

AbstractAimTo assess tissue level changes of proteome and cytokine profiles of subchondral bone in hip osteoarthritis (OA) affected by bone marrow lesions (BMLs). We compared significant protein level differences in osteoarthritic bone with BMLs to control bone without bone marrow lesions.MethodsSubchondral bone biopsies were taken from femoral heads of end‐stage osteoarthritis patients with (BML, n = 21) and without (CON, n = 9) BMLs. Proteins were extracted through a standardized Trizol protocol and used in the subsequent analyses. Angiogenesis and bone markers were assessed using multiplex immunoassays (Luminex). Liquid chromatography tandem mass spectrometry (LC‐MS/MS) was performed to detect significant differences in proteome and peptide profiles between BML and CON.ResultsMultiplex immunoassays revealed increased tissue contents of vascular endothelial growth factors (VEGF‐A/C/D), endothelin‐1, angiopoietin‐2 and interleukin‐6 (IL‐6) in bone with BMLs compared to control bone, whereas osteoprotegerin levels were reduced. Mass spectrometry demonstrated pronounced increase in the levels of hemoglobin (73‐fold), serum albumin (30‐fold), alpha‐1‐antitrypsin (9‐fold), apolipoprotein A1 (4.7‐fold), pre‐laminin‐A/C (3.7‐fold) and collagen‐alpha1‐XII (3‐fold) in BMLs, while aggrecan core protein (ACAN) and hyaluronan and proteoglycan link protein 1 (HAPL1) decreased 37‐ and 29‐fold respectively.ConclusionReduced osteoprotegerin, ACAN and HAPL1 are consistent with osteoclastic activation and high remodeling activity in BMLs. The pronounced increase in angiogenesis markers, hemoglobin and serum albumin support the presence of increased vascularity in subchondral bone affected by BMLs in OA. VEGFs and IL‐6 are known nociceptive modulators, and increased levels are in keeping with pain being a clinical feature frequently associated with BMLs.
Unraveling the complexity of human–tiger conflicts in the Leuser Ecosystem, Sumatra
Authors: Lubis M. I. , Pusparini W. , Prabowo S. A. , Marthy W. , Tarmizi  , Andayani N. , Linkie M. 
Published: May 2020

AbstractConserving large carnivores that live in close proximity to people depends on a variety of socio‐economic, political and biological factors. These include local tolerance toward potentially dangerous animals, efficacy of human–carnivore conflict mitigation schemes, and identifying and then addressing the underlying causes of conflict. The Leuser Ecosystem is the largest contiguous forest habitat for the critically endangered Sumatran tiger. Its extensive forest edge is abutted by farming communities and we predict that spatial variation in human–tiger conflict (HTC) would be a function of habitat conversion, livestock abundance, and poaching of tiger and its wild prey. To investigate which of these potential drivers of conflict, as well as other biophysical factors, best explain the observed patterns, we used resource selection function (RSF) technique to develop a predictive spatially explicit model of HTC. From 148 conflict incidences recorded from 2008 to 2018 across the Leuser Ecosystem, the areas that were closer to villages and with lower occurrence of wild prey were most susceptible to tiger attacks. From 18 districts monitored, 6 stood out for having disproportionately high levels of HTC. We recommend that these areas be prioritized with increased support from conflict mitigation teams to prevent further injuries to people, livestock or tigers; district governments address one underlying cause of HTC by supporting improved animal husbandry practices, such as tiger‐proof livestock pen construction; and, an increase in ranger patrol effort to recover wild prey populations. This type of priority setting approach has wide application for better determining the required management response to reduce conflicts between people and large carnivores in both tropical and temporal landscapes.
Effects of a selective long‐acting amylin receptor agonist on alcohol consumption, food intake and body weight in male and female rats
Authors: Kalafateli Aimilia Lydia , Vestlund Jesper , Raun Kirsten , Egecioglu Emil , Jerlhag Elisabet 
Published: May 2020

AbstractAlcohol use disorder is a complex neuropsychiatric disorder affecting both males and females worldwide; however, the efficacy of current pharmacotherapies varies. Recent advances show that gut‐brain peptides, like amylin, regulate alcohol behavioural responses by acting on brain areas involved in alcohol reward processes. Thus, the activation of amylin receptors (AMYRs) by salmon calcitonin (sCT) decreases alcohol behaviours in male rodents. Given that sCT also activates the sole calcitonin receptor (CTR), studies of more selective AMYR agonists in both male and female rodents are needed to explore amylinergic modulation of alcohol behaviours. Therefore, we investigated the effects of repeated administration of a selective long‐acting AMYR agonist, NNC0174‐1213 (AM1213), on alcohol, water and food intake, as well as body weight in male and female rats chronically exposed to alcohol. We confirm our previous studies with sCT in male rats, as repeated AM1213 administration for 2 weeks initially decreased alcohol intake in both male and female rats. However, this reduction ceases in both sexes on later sessions, accompanied by an increase in males. AM1213 reduced food intake and body weight in both male and female rats, with sustained body weight loss in males after discontinuation of the treatment. Moreover, AM1213 administration for 3 or 7 days, differentially altered dopamine, serotonin and their metabolites in the reward‐related areas in males and females, providing tentative, but different, downstream mechanism through which selective activation of AMYR may alter alcohol intake. Our data provide clarified insight into the importance of AMYRs for alcohol intake regulation in both sexes.
10 kHz spinal cord stimulation for the treatment of non‐surgical refractory back pain: subanalysis of pooled data from two prospective studies
Authors: Al‐Kaisy A. , Van Buyten J. P. , Kapural L. , Amirdelfan K. , Gliner B. , Caraway D. , Subbaroyan J. , Edgar D. , Rotte A. 
Published: May 2020

SummarySpinal cord stimulation at 10 kHz is a promising therapy for non‐surgical refractory back pain; however, published data are currently limited. We present a subanalysis of prospectively collected clinical outcome data for non‐surgical refractory back pain patients treated with 10 kHz spinal cord stimulation, from the independent cohorts of two previous studies (SENZA‐RCT and SENZA‐EU). Clinical outcomes were evaluated at pre‐implantation (baseline), 3 months, 6 months and 12 months following 10 kHz spinal cord stimulator implantation. These included: pain relief; responder rate (≥ 50% pain relief from baseline); remission rate (VAS ≤ 3.0 cm); disability (Oswestry Disability Index(ODI)); and opioid use. At 3 months, average back pain decreased by 70% in the combined cohort (60% in the SENZA‐RCT and 78% in the SENZA‐EU cohorts). This was sustained at 12 months, with a 73% back pain responder rate and 68% remission rate in the combined cohort. Leg pain relief results were generally comparable to those for back pain relief. At 12 months, the combined cohort had an average decrease in ODI scores of 15.7% points from baseline and opioid use more than halved. In conclusion, 10 kHz spinal cord stimulation reduced pain, disability and opioid consumption in non‐surgical refractory back pain subjects. Application of this therapy may improve the care of non‐surgical refractory back pain patients and reduce their opioid consumption.
p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome
Authors: Lobo João , Alzamora Maria Ana , Guimarães Rita , Cantante Mariana , Lopes Paula , Braga Isaac , Maurício Joaquina , Jerónimo Carmen , Henrique Rui 
Published: May 2020

AbstractBackgroundTesticular germ cell tumors (TGCTs) are highly sensitive to platinum‐based chemotherapy, and wild‐type p53 seems to play a pivotal role in this susceptibility. On the other hand, overexpression of MDM2 seems to entail treatment resistance and unfavorable prognosis.ObjectivesWe aimed to describe p53 and MDM2 immunoexpression in a well‐characterized cohort of primary and metastatic TGCTs and evaluate associations with clinicopathological and prognostic variables, including survival.Materials and methods237 primary tumor samples and 12 metastases were evaluated for p53 and MDM2 immunoexpression using digital image analysis. Clinical records of all patients were reviewed for baseline clinical/pathologic characteristics and follow‐up.ResultsA significant positive correlation between p53 and MDM2 H‐scores was found (rs = 0.590, P < .0001). Non‐seminomas showed significantly higher expression levels of both p53 and MDM2 (P = .0002, P < .0001), which peaked in embryonal carcinomas and choriocarcinomas. Percentage of immunoexpressing cells and H‐score were significantly higher in chemo‐treated metastases compared with chemo‐naïve primary tumors for MDM2 (P ≤ .0001 for both), but not for p53 (P = .919 and P = .703, respectively). Cases with higher MDM2 immunoexpression showed a statistically significant trend for association with poorer prognosis (P = .043). Relapse/progression‐free survival at 12 months post‐diagnosis was lower in the “MDM2‐high” (≥P50) vs. the “MDM2‐low” (<P50) expression groups.Discussion and ConclusionIn TGCTs, MDM2 overexpression may indicate a more aggressive tumor phenotype, with propensity for therapy resistance and recurrence. If validated in larger multi‐institutional studies with precise quantification, it may be envisioned as a useful predictive biomarker of poor response to cisplatin.
Device‐associated multidrug‐resistant bacteria surveillance in critically ill children: 10 years of experience
Authors: Girona‐Alarcón Mònica , Fresán Elena , Garcia‐Garcia Ana , Bobillo‐Perez Sara , Balaguer Monica , Felipe Aida , Esteban Maria Esther , Jordan Iolanda 
Published: May 2020

AbstractAimMultidrug‐resistant bacterial infections are a public health problem worldwide. However, most of the information available refers to adults. The main objectives were to determine the incidence, risk factors, and outcomes for device‐associated infections, especially those involving multidrug‐resistant bacteria.MethodsThis is a prospective, observational study. Children aged ≥1 month and <18 years admitted to the paediatric intensive care unit from 2008 to 2017, with a device‐associated infection microbiologically confirmed were included. Patients infected with resistant bacteria were compared with those who had a drug‐susceptible infection.ResultsThe study included 213 patients. Out of all the device‐associated infections, 22% (48 patients) were caused by multidrug‐resistant bacteria. The most frequent were extended‐spectrum beta‐lactamase (ESBL)‐producing enterobacteria. Cardiovascular diseases, age under 1year, comorbidity, prolonged use of invasive device, and length of stay until infection were risk factors for resistant bacteria, but not specifically for ESBL‐producing bacteria. Length of stay and mortality was increased in patients with multidrug‐resistant bacteria.ConclusionBeing under 1‐year‐old and having a cardiovascular disease were the two major risk factors for resistant bacterial infection. ESBL‐producing bacteria were the most frequent multidrug‐resistant agents. However, patients with ESBL‐producing bacteria did not have any additional risk factors, so they may have been colonised in the community.
Identifying food provenience using Sr/Ca ratio in human enamel
Authors: Sołtysiak Arkadiusz 
Published: May 2020

The strontium (Sr) concentration in bioapatite of human bone and teeth reflects the Sr concentration in food that is differentiated by two major factors: an abundance of Sr in local soils and the biopurification effect along the trophic levels. Eastern Syria is an area with a relatively high concentration of Sr within the Euphrates valley and a low concentration of Sr beyond the valley. For this reason, the strontium/calcium (Sr/Ca) ratio in human enamel retrieved from skeletons buried in cemeteries within the Euphrates valley may be used as a proxy for food provenience in a local population. A sample of human teeth (N = 72) from Tell Ashara and Tell Masaikh was divided into seven temporal subsets covering periods between c.2200 bce and the early 20th century ce. A significant difference in Sr/Ca values between temporal subsets is observed. The Sr/Ca values in later subsets are negatively correlated with δ13C values, indicating the wider exploitation of steppe areas outside the valley with more wild C4 grasses and a low Sr concentration. For periods with lower Sr/Ca values (c.2200–1900 bce and 19th–20th centuries ce) there is additional textual and isotopic evidence for food transportation from outside the river valley, supporting the interpretation of Sr/Ca values as a proxy for food provenience in this specific area.
Effectiveness of a multicomponent pharmacist intervention at hospital discharge for drug‐related problems: A cluster randomised cross‐over trial
Authors: Pourrat Xavier , Leyrat Clémence , Allenet Benoît , Bouzige Brigitte , Develay Armelle , Fraysse Martial , Garnier Valérie , Halimi Jean‐Michel , Roux‐Marson Clarisse , Giraudeau Bruno 
Published: May 2020

AimsThe aim of this study was to assess whether a pharmacist intervention associating medication reconciliation at discharge with a link to the community pharmacist reduces drug‐related problems (DRP) in adult patients during the 7 days after hospital discharge in 22 university or general hospitals in France.MethodsWe conducted a cluster randomised cross‐over superiority trial with hospital units as the cluster unit. The primary outcome was a composite of any kind of DRP (prescription/dispensation, patient error or gap due to no medication available) during the 7 days after discharge, assessed by phone with the patient and community pharmacist. Among secondary outcomes, we studied self‐reported unplanned hospitalisations at day 35 after discharge and severe iatrogenic problems.ResultsA total of 1092 patients were enrolled in 48 units (538 in the experimental periods and 554 in the control periods). Three patients refused to have their data analysed and were excluded from the analyses. As compared with usual care, the pharmacist intervention led to a lower proportion of patients with at least one DRP (44.0% vs 50.6%; odds ratio [OR] 0.77, 95% confidence interval [CI] 0.61–0.98) and severe iatrogenic problems (5.2% vs 8.7%; OR 0.57, 95% CI 0.35–0.93) but no significant difference in unplanned hospitalisations at day 35 (5.8% vs 4.5%; OR 1.46, 95% CI 0.91–2.35).ConclusionMedication reconciliation associated with communication between the hospital and community pharmacist may decrease patient exposure to DRP and severe iatrogenic problems but not unplanned hospitalisation. However, this intervention could be recommended in health policies to improve drug management.