bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the hospital built environment on treatment satisfaction of psychiatric in-patients
Authors: Jovanović Nikolina , Miglietta Elisabetta , Podlesek Anja , Malekzadeh Adam , Lasalvia Antonio , Campbell Justin , Priebe Stefan
Published: October 2020

Background

A hospital built environment can affect patients’ treatment satisfaction, which is, in turn, associated with crucial clinical outcomes. However, little research has explored which elements are specifically important for psychiatric in-patients. This study aims to identify which elements of the hospital environment are associated with higher patient satisfaction with psychiatric in-patient care.

Methods

The study was conducted in Italy and the United Kingdom. Data was collected through hospital visits and patient interviews. All hospitals were assessed for general characteristics, aspects specific to psychiatry (patient safety, mixed/single-sex wards, smoking on/off wards), and quality of hospital environment. Patients’ treatment satisfaction was assessed using the Client Assessment of Treatment Scale (CAT). Multi-level modelling was used to explore the role of environment in predicting the CAT scores adjusted for age, gender, education, diagnosis, and formal status.

Results

The study included 18 psychiatric hospitals (7 in Italy and 11 in the United Kingdom) and 2130 patients. Healthcare systems in these countries share key characteristics (e.g. National Health Service, care organised on a geographical basis) and differ in policy regulation and governance. Two elements were associated with higher patient treatment satisfaction: being hospitalised on a mixed-sex ward (p = 0.003) and the availability of rooms to meet family off wards (p = 0.020).

Conclusions

As hospitals are among the most expensive facilities to build, their design should be guided by research evidence. Two design features can potentially improve patient satisfaction: family rooms off wards and mixed-sex wards. This evidence should be considered when designing or renovating psychiatric facilities.
The olfactory deficits of depressed patients are restored after remission with venlafaxine treatment
Authors: Colle Romain , El Asmar Khalil , Verstuyft Céline , Lledo Pierre-Marie , Lazarini Françoise , Chappell Kenneth , Deflesselle Eric , Ait Tayeb Abd El Kader , Falissard Bruno , Duron Emmanuelle , Rotenberg Samuel , Costemale-Lacoste Jean-Francois , David Denis J. , Gressier Florence , Gardier Alain M. , Hummel Thomas , Becquemont Laurent , Corruble Emmanuelle
Published: October 2020

Background

It is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment.

Methods

In the DEP-ARREST-CLIN study, 69 drug-free patients with a current MDE in the context of major depressive disorder (MDD) were assessed for their olfactory performances and depression severity, before and after 1 (M1) and 3 (M3) months of venlafaxine antidepressant treatment. They were compared to 32 age- and sex-matched healthy controls (HCs). Olfaction was assessed with a psychophysical test, the Sniffin’ Sticks test (Threshold: T score; Discrimination: D score; Identification: I score; total score: T + D + I = TDI score) and Pleasantness (pleasantness score: p score; neutral score: N score; unpleasantness score: U score).

Results

As compared to HCs, depressed patients had lower TDI olfactory scores [mean (s.d.) 30.0(4.5) v. 33.3(4.2), p < 0.001], T scores [5.6(2.6) v. 7.4(2.6), p < 0.01], p scores [7.5(3.0) v. 9.8(2.8), p < 0.001)] and higher N scores [3.5(2.6) v. 2.1(1.8), p < 0.01]. T, p and N scores at baseline were independent from depression and anhedonia severity. After venlafaxine treatment, significant increases of T scores [M1: 7.0(2.6) and M3: 6.8(3.1), p < 0.01] and p scores [M1: 8.1(3.0) and M3: 8.4(3.3), p < 0.05] were evidenced, in remitters only (T: p < 0.01; P: p < 0.01). Olfaction improvement was mediated by depression improvement.

Conclusions

The olfactory signature of MDE is restored after venlafaxine treatment. This olfaction improvement is mediated by depression improvement.
Beauty and the Beast: On a Doe, a Devilish Hunter, and Jewish-Christian Polemics
Authors: Offenberg Sara
Published: October 2020

Hunting scenes are common in Jewish illuminated manuscripts and are understood as allegories of the Jew, usually represented as a hare or a deer, being persecuted by the Christian, shown as a hunter and his dogs. This article will discuss a hunt scene from theWorms Maḥzor, an Ashkenazic illuminated prayer book produced in 1272, probably in Würzburg. At the top of folio 130r, an illumination of the piyyut (liturgical poem) “ʾAyelet ʾahavim” (the loving hind, or doe) for Shavuot displays a deer being hunted by a devilish hunter and his dogs. Examining the illustration in the context of contemporary textual evidence, I shall demonstrate that the deer in theWorms Maḥzorportrays the Torah itself being persecuted by the hunter, who can be understood not only as a Christian or Esau, but also as Jesus.
What Is the Subject of Principle 2 in Maimonides'sBook of the Commandments? Towards a New Understanding of Maimonides's Approach to Extrascriptural Law
Authors: Herman Marc
Published: October 2020

Among Maimonides's many statements about extrascriptural laws in rabbinic literature, none has attracted as much attention as principle 2 in hisBook of the Commandments. Modern scholars have largely understood this text to claim that very few of the laws found in rabbinic literature are Sinaitic in origin and of biblical status. Yet, until the twentieth century, principle 2 was primarily read as distinguishing between revealed laws that constitute enumerated commandments and revealed laws that do not. In fact, neither reading is consistent with other Maimonidean statements. By contextualizing principle 2 within theBook of the Commandments, this essay reconsiders Maimonides's enumeration of the commandments and argues that many of the problems that principle 2 was designed to address, and that it also generated, resulted from the incongruity of his project of enumerating precisely 613 commandments alongside his understanding of revelation as a corpus that included not only the Written Torah but innumerable extrascriptural traditions as well. An appendix evaluates pertinent aspects of the most recent monograph dedicated to Maimonides's scriptural hermeneutics.
Reindeer Imagery in the Making at Ust’-Polui in Arctic Siberia
Authors: Nomokonova Tatiana , Losey Robert J. , Fedorova Natalia V. , Gusev Andrei V. , Arzyutov Dmitry V.
Published: October 2020

The history of reindeer domestication is a critical topic in the study of human-animal relationships across Northern Eurasia. The Iamal-Nenets region of Arctic Siberia, now a global centre of reindeer pastoralism, has been the subject of much recent research on reindeer domestication. However, tracking the beginnings of reindeer domestication in this region and elsewhere in Eurasia has proved challenging. Archaeological imagery is an under-utilized source of information for exploring animal domestication. In this paper we explore the abundant reindeer imagery found at the Iron Age site of Ust’-Polui in Iamal, dating from ~260bcetoce140. While reindeer were hunted in Siberia long before the occupation of Ust’-Polui, portable reindeer imagery appears abruptly at this time period, co-occurring at the site with equipment thought to be for training transport reindeer. Training and working with transport reindeer required long-term engagement with specific animals that became well known and precious to their human keepers. Creating, utilizing and depositing the reindeer imagery objects at Ust’-Polui was a way of acknowledging critical new working relationships with specific domestic reindeer.
The idealisation of bottle feeding: content analysis of feeding bottles and teats packages in Uruguay
Authors: Alcaire Florencia , Antúnez Lucía , Vidal Leticia , de León Carolina , Girona Alejandra , Rodríguez Raquel , Giménez Ana , Bove Isabel , Ares Gastón
Published: October 2020

Objective:

The information displayed on the packages of feeding bottles and teats commercialised in Montevideo (Uruguay) was analysed using content analysis with the goal of identifying key marketing practices that may discourage breast-feeding.

Design:

The study was conducted as part of the periodic assessment performed by the Uruguayan government to monitor the marketing of breast milk substitutes. All the feeding bottles and teats sold in forty-four retail outlets selling breast milk substitutes were purchased. The information available on the packages was analysed using content analysis and descriptive statistics.

Setting:

Montevideo, Uruguay.

Results:

A total of 197 feeding bottles and 71 teats were found. The majority of the packages included information to enable caregivers to adequately use the products, including recommended age, instructions on how to use the products and instructions on the use of hygienic practices. However, the packages frequently included information that implied that bottle feeding was equivalent to breast-feeding, particularly from a physiological perspective, or that idealised product use. Idealisations included ability to reduce colic, improvements in the feeding experience and improvements in children’s health, well-being and development. Statements on the superiority of breast-feeding were infrequent.

Conclusions:

The results from the present work showed the high prevalence of marketing practices on the packages of feeding bottles and teats that may discourage breast-feeding. Stricter and more detailed regulations seem necessary to enable caregivers to make informed feeding decisions for infants.
Der Alltag von Jugendlichen mit einer Sichelzellerkrankung – Eine qualitative, explorative und partizipative Photovoice-Studie
Authors: Schönbächler Marcar Claudia , Keller Marianne , Hillewerth Kathrin , van Holten Karin
Published: October 2020

Zusammenfassung. Hintergrund: Die Sichelzellkrankheit (Sickle Cell Disease, SCD) ist eine in der Schweiz seltene, chronische, hämatologische Erbkrankheit. Sie löst unter anderem wiederholt heftige Schmerzkrisen aus, ruft schwere Infektionen hervor und erfordert häufige Hospitalisationen. Gegenwärtig ist wenig bekannt, was aus der Perspektive von Jugendlichen die Alltagserfahrungen mit SCD sind. Ziel: Mit der Studie wurde der Frage nachgegangen was den Alltag von Jugendlichen mit SCD prägt und welche Herausforderungen sich zeigen. Daraus sollten entsprechende Unterstützungsangebote für das Pädiatrische Zentrum für Hämoglobinopathie abgeleitet werden. Methoden: Die qualitative Studie erfolgte mittels der partizipativen Methode Photovoice. Diese umfasst, nebst der Arbeit mit Fotos, eine Gruppendiskussion und eine rekonstruktive Analyse. Ergebnisse: Die Jugendlichen mit SCD beschrieben Alltagsthemen in den Dimensionen Lebenswelt (z. B. Familie), Bewältigungsstrategien (z. B. Peers) und Gesundheitskompetenz (z. B. Krankheitsverständnis), die zugleich Herausforderungen und Ressourcen sind. Daraus konnten die Themen Stärkung des Selbstmanagements und Gestaltung der Leistungserbringung als Grundlage für ein Betreuungs- und Behandlungskonzept identifiziert werden. Schlussfolgerungen: Jugendliche mit SCD zeigen in vielen Bereichen ihres Lebens Anzeichen von Gesundheitskompetenz. Hier kann die Angebotsentwicklung des Pädiatrischen Zentrums ansetzen. Erfolgsversprechende Methoden dafür sind Partizipation und der Einbezug von Peers in Beratung und Forschung.
Exploring the Long‐Term Economic and Social Impact of Green Infrastructure in New York City
Authors: Wong S. M. , Montalto F. A.
Published: October 2020

Across the world, cities are spending billions of dollars to manage urban runoff through decentralized green infrastructure (GI). This research uses an agent‐based model to explore some of the physical, social, and economic consequences of one such urban GI programs. Using the Bronx, NY, as a case study, two alternative approaches to GI application are compared. The first (Model 1) mimics NYC's current GI program by opportunistically selecting sites for GI within the city's priority combined sewer watersheds; the second (Model 2) features a more spatially flexible approach to GI siting, in which the city attempts to maximize opportunities for co‐benefits within the geographic areas considered in Model 1. The effects of both approaches, measured in terms of stormwater captured and co‐benefits (e.g., carbon sequestered) provided, are tracked over 20‐year simulations. While both models suggest it will be difficult to meet the citywide stormwater capture goals (managing the first 2.5 cm of rainfall from 10% of impervious surfaces) in the Bronx solely through public investment in GI, Model 2 shows that by integrating GI with other city initiatives (e.g., sustainability goals and resilience planning), synergistic outcomes are possible. Specifically, Model 2 produces stormwater capture rates comparable to those obtained under Model 1, but these rates are accompanied by elevated co‐benefits for Bronx communities. The results are discussed in the context of future GI policy development in NYC.
Temporal Characteristics of Energetic Magnetospheric Electron Precipitation as Observed During Long‐Term Balloon Observations
Authors: Bazilevskaya G. A. , Kalinin M. S. , Krainev M. B. , Makhmutov V. S. , Stozhkov Y. I. , Svirzhevskaya A. K. , Svirzhevsky N. S. , Gvozdevsky B. B.
Published: October 2020

The paper summarizes the properties of precipitation of magnetospheric electrons with energy above several hundred keV recorded by observing X‐ray bremsstrahlung in the polar stratosphere above the Murmansk region, Russia, in 1961–2019. Precipitation occurrence rate demonstrates a clear dependence on the solar activity with a maximum at the decay phase of the 11‐year solar cycle, similarly to the variability in occurrences of the high‐speed solar wind streams (HSSWS). The energetic electron precipitation (EEP) event series is often initiated by a moderate geomagnetic storm caused by a HSSWS and continues during geomagnetic storm recovery. EEP demonstrates the seasonal rate variation with the maxima in occurrence rate around the spring and the autumn solstices and correlates with fluences of relativistic electrons in the outer radiation belt. For 59 years, 589 events of precipitation were observed. Analysis of the long‐term time series revealed a growing trend in the rate of precipitation occurrence, especially in the 1990s to 2000s that is not properly explained yet.
Physical Controls on Carbonate Intraclasts: Modern Flat Pebbles From Great Salt Lake, Utah
Authors: Smith B. P. , Ingalls M. , Trower E. J. , Lingappa U. F. , Present T. M. , Magyar J. S. , Fischer W. W.
Published: October 2020

In carbonate‐forming environments, authigenic minerals can cement surface sediments into centimeter‐sized intraclasts that are later reworked into “flat‐pebble” or “edgewise” conglomerates. Flat‐pebble conglomerates comprise only a small portion of facies in modern marine environments but are common in ancient strata, implying that seafloor cements were more widespread in the past. Flat‐pebble conglomerates nearly disappeared after the Ordovician radiation, yet it is unclear if this decline was due to changing seawater chemistry or if increased infaunalization and bioturbation simply worked to break down nascent clasts. We discovered a process analog that produces flat‐pebble conglomerates around the Great Salt Lake, Utah, USA, and studied these facies using field observations, wave models, satellite imagery, petrography, and microanalytic chemical data. Clasts were sourced from wave‐rippled grainstone that cemented in situ in offshore environments. Lake floor cements formed under aragonite saturation states that are lower than modern marine settings, suggesting that physical processes are at least as important as chemical ones. Results from our wave models showed that coarse sediments near the field site experience quiescent periods of up to 6 months between suspension events, allowing isopachous cements to form. Using a simple mathematical framework, we show that the main difference between Great Salt Lake and modern, low‐energy marine settings is that the latter has enough bioturbating organisms to break up clasts. Observations from Great Salt Lake demonstrate how geologic trends in flat‐pebble abundance could largely reflect changes in total infaunal biomass and ecology without requiring regional‐to‐global changes in seawater chemistry.
Characterizing Auroral‐Zone Absorption Based on Global Kp and Regional Geomagnetic Hourly Range Indices
Authors: Fiori R. A. D. , Trichtchenko L. , Balch C. , Spanswick E. , Groleau S.
Published: October 2020

Increased ionization in the auroral oval leads to the absorption of high‐frequency radio waves in the auroral zone, or auroral absorption. Auroral absorption is typically characterized by global geomagnetic activity indices, such as the Kp index. In this paper the hourly range of the magnetic field (HR) is examined as an alternative to the 3‐hr Kp index for describing the dynamic and localized features of auroral absorption represented by the hourly range of absorption (HRA). Kp, magnetometer, and riometer data were examined for a 3‐year period for stations spread across typical auroral latitudes. A general linear relationship was shown to exist between Kp and LOG10(HRA) for Kp < 4; for Kp ≥ 4 the correlation was weaker. A stronger linear correlation was demonstrated between LOG10(HRA) and LOG10(HR) for HR > 50 nT, characterized by a correlation coefficient of R = 0.63. Increased variability in the relationship between HRA and Kp was attributed to the following factors: the variability of the magnetic field within the 3‐hr window characterized by the Kp index, which was better represented by a 1‐hr HR; the dependence of the Kp index on subauroral magnetic data, which is not subject to the geomagnetic variations typically experienced within the auroral region; and reduced statistics for Kp > 6.
Coseismic Underground Rupture, Geometry, Historical Surface Deformations, and Seismic Potentials of the 28 March 2019 Mw 5.04 Mangya Earthquake Fault
Authors: Wang Shengli , Wu Wujun , Li Qinghong , Li Chao , Li Yongxiang , Chen Yan , Wang Liangshu , Xu Mingjie , Guo Zhi
Published: October 2020

The 28 March 2019 Mw 5.04 Mangya earthquake damaged eight ongoing drilling boreholes in the oil‐production Yingxiong Ling (YXL) area, southwestern Qaidam of northern Tibet. The borehole damages provide an opportunity to measure directly the coseismic slips, the rupture area, and the seismic moment. The damages reveal the underground rupture area of 45.30 ± 10.24 km2, the maximum slip of 400 ± 13 mm, and the seismogenic fault dip of ~38.6°. These parameters generate a seismic moment of (1.81 ± 0.47) × 1017 Nm and a moment magnitude of 5.47 ± 0.16. Seismic exploration reveals that the geometry of the SZG ramp, the uppermost part of the multibend Yingxiong Ling thrust system, agrees primarily with the rupture plane derived from the borehole damages and one plane of the focal mechanism solution. This suggests that this earthquake resulted from slipping on the ramp. The hanging wall of the YXL thrust system forms the complex fault‐bend fold YXL anticlinorium. Active thrusting and folding along both edges of YXL attest to the southwestern vergence of this thrust system. Growth strata demonstrate average slip rates of the thrust system ranging from ~0.2 to ~0.3 mm/yr. The thrusted and folded recent alluviums along the southwestern edge indicate two thrusting events with coseismic slips of 1.7 ± 0.15 and 3.5 ± 0.15 m at 6.16 ± 0.52 and ~35.91 ka, respectively. The entire rupturing of the thrust system can produce Mw 7.65 ± 0.03 earthquakes.
B-cell clonogenic activity of HIV-1 p17 variants is driven by PAR1-mediated EGF transactivation
Authors: Giagulli Cinzia , Caccuri Francesca , Zorzan Simone , Bugatti Antonella , Zani Alberto , Filippini Federica , Manocha Ekta , D’Ursi Pasqualina , Orro Alessandro , Dolcetti Riccardo , Caruso Arnaldo
Published: October 2020

Combined antiretroviral therapy (cART) for HIV-1 dramatically slows disease progression among HIV+individuals. Currently, lymphoma represents the main cause of death among HIV-1-infected patients. Detection of p17 variants (vp17s) endowed with B-cell clonogenic activity in HIV-1-seropositive patients with lymphoma suggests their possible role in lymphomagenesis. Here, we demonstrate that the clonogenic activity of vp17s is mediated by their binding to PAR1 and to PAR1-mediated EGFR transactivation through Gq protein. The entire vp17s-triggered clonogenic process is MMPs dependent. Moreover, phosphoproteomic and bioinformatic analysis highlighted the crucial role of EGFR/PI3K/Akt pathway in modulating several molecules promoting cancer progression, including RAC1, ABL1, p53, CDK1, NPM, Rb, PTP-1B, and STAT1. Finally, we show that a peptide (F1) corresponding to the vp17s functional epitope is sufficient to trigger the PAR1/EGFR/PI3K/Akt pathway and bind PAR1. Our findings suggest novel potential therapeutic targets to counteract vp17-driven lymphomagenesis in HIV+patients.
Exosomal LGALS9 in the cerebrospinal fluid of glioblastoma patients suppressed dendritic cell antigen presentation and cytotoxic T-cell immunity
Authors: Wang Ming , Cai Yang , Peng Yong , Xu Bo , Hui Wentao , Jiang Yugang
Published: October 2020

Glioblastoma multiforme (GBM) is highly invasive, with a high recurrence rate and limited treatment options, and is the deadliest glioma. Exosomes (Exos) have attracted much attention in the diagnosis and treatment of GBM and are expected to address the severe limitations of biopsy conditions. Exos in the cerebrospinal fluid (CSF) have great potential in GBM dynamic monitoring and intervention strategies. Here, we evaluated the difference in the proteome information of Exos from the CSF (CSF-Exos) between GBM patients and low-grade glioma patients, and the correlations between GBM-CSF-Exos and immunosuppressive properties. Our results indicates that GBM-CSF-Exos contained a unique protein, LGALS9 ligand, which bound to the TIM3 receptor of dendritic cells (DCs) in the CSF to inhibit antigen recognition, processing and presentation by DCs, leading to failure of the cytotoxic T-cell-mediated antitumor immune response. Blocking the secretion of exosomal LGALS9 from GBM tumors could cause mice to exhibit sustained DC tumor antigen-presenting activity and long-lasting antitumor immunity. We concluded that GBM cell-derived exosomal LGALS9 acts as a major regulator of tumor progression by inhibiting DC antigen presentation and cytotoxic T-cell activation in the CSF and that loss of this inhibitory effect can lead to durable systemic antitumor immunity.
Functional validation of a human GLUD2 variant in a murine model of Parkinson’s disease
Authors: Zhang Wenlong , Gong Junwei , Ding Liuyan , Zhang Zhiling , Pan Xiaowen , Chen Xiang , Guo Wenyuan , Zhang Xiaokang , Yang Xinling , Peng Guoyou , Lin Yuwan , Gao Feng , Li Yuanquan , Zhu Xiaoqin , Xuan Aiguo , Wang Shu , Sun Xiangdong , Zhang Yunlong , Xu Pingyi
Published: October 2020

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by Lewy body formation and progressive dopaminergic neuron death in the substantia nigra (SN). Genetic susceptibility is a strong risk factor for PD. Previously, a rare gain-of-function variant of GLUD2 glutamate dehydrogenase (T1492G) was reported to be associated with early onset in male PD patients; however, the function and underlying mechanism of this variant remains elusive. In the present study, we generated adeno-associated virus expressing GLUD2 and its mutant under the control of the glial fibrillary acidic protein promotor and injected the virus into the SN pars compacta of either untreated mice or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Our results demonstrate that GLUD2 mutation in MPTP-induced PD mice exacerbates movement deficits and nigral dopaminergic neuron death and reduces glutamate transporters expression and function. Using GC-Q-TOF/MS-based metabolomics, we determined that GLUD2 mutation damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the tricarboxylic acid cycle in the SN of MPTP-induced PD mice. Accordingly, GLUD2 mutant mice had reduced energy metabolism and increased apoptosis, possibly due to downregulation of brain-derived neurotrophic factor/nuclear factor E2-related factor 2 signaling in in vitro and in vivo PD models. Collectively, our findings verify the function of GLUD2 in PD and unravel a mechanism by which a genetic variant in human GLUD2 may contribute to disease onset.
RPN2 is targeted by miR-181c and mediates glioma progression and temozolomide sensitivity via the wnt/β-catenin signaling pathway
Authors: Sun Jikui , Ma Quanfeng , Li Banban , Wang Chen , Mo Lidong , Zhang Xuebin , Tang Fan , Wang Qiong , Yan Xiaoling , Yao Xiuhua , Wu Qiaoli , Shu Chang , Xiong Jinbiao , Fan Weijia , Wang Jinhuan
Published: October 2020

Accumulating evidence indicates that the dysregulation of the miRNAs/mRNA-mediated carcinogenic signaling pathway network is intimately involved in glioma initiation and progression. In the present study, by performing experiments and bioinformatics analysis, we found that RPN2 was markedly elevated in glioma specimens compared with normal controls, and its upregulation was significantly linked to WHO grade and poor prognosis. Knockdown of RPN2 inhibited tumor proliferation and invasion, promoted apoptosis, and enhanced temozolomide (TMZ) sensitivity in vitro and in vivo. Mechanistic investigation revealed that RPN2 deletion repressed β-catenin/Tcf-4 transcription activity partly through functional activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, we showed that RPN2 is a direct functional target of miR-181c. Ectopic miR-181c expression suppressed β-catenin/Tcf-4 activity, while restoration of RPN2 partly reversed this inhibitory effect mediated by miR-181c, implying a molecular mechanism in which TMZ sensitivity is mediated by miR-181c. Taken together, our data revealed a new miR-181c/RPN2/wnt/β-catenin signaling axis that plays significant roles in glioma tumorigenesis and TMZ resistance, and it represents a potential therapeutic target, especially in GBM.
BET degrader inhibits tumor progression and stem-like cell growth via Wnt/β-catenin signaling repression in glioma cells
Authors: Tian Tao , Guo Tongqi , Zhen Wei , Zou Jianjun , Li Fuyong
Published: October 2020

Based on their histological appearance, gliomas are a very common primary tumor type of the brain and are classified into grades, Grade I to Grade IV, of the World Health Organization. Treatment failure is due to the cancer stem cells (CSC) phenotype maintenance and self-renewal. BET degraders such as ZBC260 represents a novel class of BET inhibitors that act by inducing BET proteins degradation. This study explores the mode of action and effects of ZBC260 in vivo and in vitro against glioma. By inhibiting cell proliferation and inducting cell cycle arrest, the fact that glioma cell lines show sensitivity to ZBC260. Notably, ZBC260 targeted glioma without side effects in vivo. In addition, the stem cell-like properties of glioma cells were inhibited upon ZBC260 treatment. When the mechanism was examined, our findings indicated that Wnt/β-catenin pathway repression is required for ZBC260-induced stem cell-like properties and tumor growth suppression. In conclusion, the growth of tumors and stem cell-like properties were inhibited by ZBC260 via Wnt/β-catenin repression, which suggests ZBC260 as a potential therapeutic agent for glioma.
MSH1-induced heritable enhanced growth vigor through grafting is associated with the RdDM pathway in plants
Authors: Kundariya Hardik , Yang Xiaodong , Morton Kyla , Sanchez Robersy , Axtell Michael J. , Hutton Samuel F. , Fromm Michael , Mackenzie Sally A.
Published: October 2020

Plants transmit signals long distances, as evidenced in grafting experiments that create distinct rootstock-scion junctions. Noncoding small RNA is a signaling molecule that is graft transmissible, participating in RNA-directed DNA methylation; but the meiotic transmissibility of graft-mediated epigenetic changes remains unclear. Here, we exploit the MSH1 system in Arabidopsis and tomato to introduce rootstock epigenetic variation to grafting experiments. Introducing mutations dcl2, dcl3 and dcl4 to the msh1 rootstock disrupts siRNA production and reveals RdDM targets of methylation repatterning. Progeny from grafting experiments show enhanced growth vigor relative to controls. This heritable enhancement-through-grafting phenotype is RdDM-dependent, involving 1380 differentially methylated genes, many within auxin-related gene pathways. Growth vigor is associated with robust root growth of msh1 graft progeny, a phenotype associated with auxin transport based on inhibitor assays. Large-scale field experiments show msh1 grafting effects on tomato plant performance, heritable over five generations, demonstrating the agricultural potential of epigenetic variation.
Reorientation-induced relaxation of free OH at the air/water interface revealed by ultrafast heterodyne-detected nonlinear spectroscopy
Authors: Inoue Ken-ichi , Ahmed Mohammed , Nihonyanagi Satoshi , Tahara Tahei
Published: October 2020

The uniqueness of water originates from its three-dimensional hydrogen-bond network, but this hydrogen-bond network is suddenly truncated at the interface and non-hydrogen-bonded OH (free OH) appears. Although this free OH is the most characteristic feature of interfacial water, the molecular-level understanding of its dynamic property is still limited due to the technical difficulty. We study ultrafast vibrational relaxation dynamics of the free OH at the air/water interface using time-resolved heterodyne-detected vibrational sum frequency generation (TR-HD-VSFG) spectroscopy. With the use of singular value decomposition (SVD) analysis, the vibrational relaxation (T1) times of the free OH at the neat H2O and isotopically-diluted water interfaces are determined to be 0.87 ± 0.06 ps (neat H2O), 0.84 ± 0.09 ps (H2O/HOD/D2O = 1/2/1), and 0.88 ± 0.16 ps (H2O/HOD/D2O = 1/8/16). The absence of the isotope effect on the T1 time indicates that the main mechanism of the vibrational relaxation of the free OH is reorientation of the topmost water molecules. The determined sub-picosecond T1 time also suggests that the free OH reorients diffusively without the switching of the hydrogen-bond partner by the topmost water molecule.
Low cost DNA data storage using photolithographic synthesis and advanced information reconstruction and error correction
Authors: Antkowiak Philipp L. , Lietard Jory , Darestani Mohammad Zalbagi , Somoza Mark M. , Stark Wendelin J. , Heckel Reinhard , Grass Robert N.
Published: October 2020

Due to its longevity and enormous information density, DNA is an attractive medium for archival storage. The current hamstring of DNA data storage systems—both in cost and speed—is synthesis. The key idea for breaking this bottleneck pursued in this work is to move beyond the low-error and expensive synthesis employed almost exclusively in today’s systems, towards cheaper, potentially faster, but high-error synthesis technologies. Here, we demonstrate a DNA storage system that relies on massively parallel light-directed synthesis, which is considerably cheaper than conventional solid-phase synthesis. However, this technology has a high sequence error rate when optimized for speed. We demonstrate that even in this high-error regime, reliable storage of information is possible, by developing a pipeline of algorithms for encoding and reconstruction of the information. In our experiments, we store a file containing sheet music of Mozart, and show perfect data recovery from low synthesis fidelity DNA.
Author Correction: A hypomorphic cystathionine ß-synthase gene contributes to cavefish eye loss by disrupting optic vasculature
Authors: Ma Li , Gore Aniket V. , Castranova Daniel , Shi Janet , Ng Mandy , Tomins Kelly A. , van der Weele Corine M. , Weinstein Brant M. , Jeffery William R.
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Analysis of metabolites and metabolic pathways in three maize (Zea mays L.) varieties from the same origin using GC–MS
Authors: Zhang Liyuan , Yu Yingbo , Yu Runzhong
Published: October 2020

Metabolites of the Jinyu 88, Huanong 18, and Demeiya 9 maize varieties from the same origin were isolated and identified by GC–MS, and the specific metabolites and metabolic mechanisms of these three varieties of maize were preliminarily analysed and discussed. The metabolites were extracted with 80% methanol and derived with N,O-bis(trimethylsilyl)trifluoroacetamide. A total of 59 metabolites were identified. The specific metabolites of these three varieties of maize were identified. Four possible unknown-structure metabolites were hypothesized. The results showed that the specific metabolites of JY88 were only involved in fatty acid metabolism. The specific metabolites of HN18 were determined to be involved in fatty acid metabolism, glucose metabolism, and phytosterol metabolism. The specific metabolites of DM9 were observed to participate in glucose metabolism and fatty acid metabolism. The disease resistance of HN18 was higher than that of DM9, and its grain bulk density was higher than that of DM9. JY88 was determined to be significantly different from the other two varieties, and its appearance and disease resistance were worse than those of the other two varieties. The variety with the highest nutritional value was determined to be HN18, and the variety with the lowest nutritional value was JY88. This finding indicated that different maize varieties from the same origin had different metabolites and different metabolic mechanisms, which caused the three maize varieties to exhibit different characteristics and qualities.
High-throughput continuous-flow microfluidic electroporation of mRNA into primary human T cells for applications in cellular therapy manufacturing
Authors: Lissandrello Charles A. , Santos Jose A. , Hsi Peter , Welch Michaela , Mott Vienna L. , Kim Ernest S. , Chesin Jordan , Haroutunian Nerses J. , Stoddard Aaron G. , Czarnecki Andrew , Coppeta Jonathan R. , Freeman Daniel K. , Flusberg Deborah A. , Balestrini Jenna L. , Tandon Vishal
Published: October 2020

Implementation of gene editing technologies such as CRISPR/Cas9 in the manufacture of novel cell-based therapeutics has the potential to enable highly-targeted, stable, and persistent genome modifications without the use of viral vectors. Electroporation has emerged as a preferred method for delivering gene-editing machinery to target cells, but a major challenge remaining is that most commercial electroporation machines are built for research and process development rather than for large-scale, automated cellular therapy manufacturing. Here we present a microfluidic continuous-flow electrotransfection device designed for precise, consistent, and high-throughput genetic modification of target cells in cellular therapy manufacturing applications. We optimized our device for delivery of mRNA into primary human T cells and demonstrated up to 95% transfection efficiency with minimum impact on cell viability and expansion potential. We additionally demonstrated processing of samples comprising up to 500 million T cells at a rate of 20 million cells/min. We anticipate that our device will help to streamline the production of autologous therapies requiring on the order of 10$$^8$$

8

–10$$^9$$

9

cells, and that it is well-suited to scale for production of trillions of cells to support emerging allogeneic therapies.
Early adolescent adversity alters periaqueductal gray/dorsal raphe threat responding in adult female rats
Authors: Moaddab Mahsa , Wright Kristina M. , McDannald Michael A.
Published: October 2020

Early adolescent adversity increases adult risk for anxiety disorders. The ventrolateral periaqueductal gray (vlPAG) and neighboring dorsal raphe (DR) are integral to threat prediction, and are responsive to acute stressors. Here, we tested the hypothesis that early adolescent adversity reshapes vlPAG/DR threat-related cue activity and threat probability signaling. Female, Long Evans rats experienced a battery of adverse adolescent experiences (n = 12), while controls did not (n = 8). Single-unit activity was recorded 50 + days following the final adverse experience, when the adult rats received fear discrimination consisting of danger, uncertainty and safety cues. Despite achieving fear discrimination that was equivalent to controls, vlPAG/DR threat responding was altered in adverse-experienced rats. Early adolescent adversity resulted in a greater proportion of cue-responsive neurons. Cue-excited neurons showed greater increases in firing and cue-inhibited neurons showed greater decreases. Even more, early adversity reduced flexible, threat probability signaling by cue-excited neurons and promoted more rigid, fear output signaling by cue-inhibited neurons. The results reveal long-lasting changes in vlPAG/DR threat responding resulting from early adolescent adversity.
Impact of hall and ion slip in a thermally stratified nanofluid flow comprising Cu and Al2O3 nanoparticles with nonuniform source/sink
Authors: Gul Nosheen , Ramzan Muhammad , Chung Jae Dong , Kadry Seifedine , Chu Yu-Ming
Published: October 2020

Nanofluids play a pivotal role in the heat transport phenomenon and are essential in the cooling process of small gadgets like computer microchips and other related applications in microfluidics. Having such amazing applications of nanofluids, we intend to present a theoretical analysis of the thermally stratified 3D flow of nanofluid containing nano solid particles (Cu and Al2O3) over a nonlinear stretchable sheet with Ion and Hall slip effects. Moreover, the features of buoyance effect and non-uniform heat source/skin are also analyzed. For the study of numerically better results, Tawari and Das model is adopted here. For the conversion of the system of partial differential equations into ordinary differential equations, apposite transformations are engaged and are tackled by utilizing the bvp4c scheme of MATLAB software. The effects of dimensionless parameters on velocity and temperature profiles are depicted with the help of graphs. Additionally, the Skin friction coefficient and Nusselt number for the practical applications are examined in the tabular form. Verification of the current study by comparing it with an already published work in a special case is also a part of this study. Results show that the thermal performance of copper nanoparticles is more than alumina nanoparticles. An upsurge in the temperature of nanofluid is observed when the strength of the magnetic field is enhanced. However, the temperature of partially ionized nanofluid is significantly lowered because of the collisions of electrons and ions.
Characterizing microfluidic approaches for a fast and efficient reagent exchange in single-molecule studies
Authors: Madariaga-Marcos Julene , Corti Roberta , Hormeño Silvia , Moreno-Herrero Fernando
Published: October 2020

Single-molecule experiments usually take place in flow cells. This experimental approach is essential for experiments requiring a liquid environment, but is also useful to allow the exchange of reagents before or during measurements. This is crucial in experiments that need to be triggered by ligands or require a sequential addition of proteins. Home-fabricated flow cells using two glass coverslips and a gasket made of paraffin wax are a widespread approach. The volume of the flow cell can be controlled by modifying the dimensions of the channel while the reagents are introduced using a syringe pump. In this system, high flow rates disturb the biological system, whereas lower flow rates lead to the generation of a reagent gradient in the flow cell. For very precise measurements it is thus desirable to have a very fast exchange of reagents with minimal diffusion. We propose the implementation of multistream laminar microfluidic cells with two inlets and one outlet, which achieve a minimum fluid switching time of 0.25 s. We additionally define a phenomenological expression to predict the boundary switching time for a particular flow cell cross section. Finally, we study the potential applicability of the platform to study kinetics at the single molecule level.
The fingerprints of climate warming on cereal crops phenology and adaptation options
Authors: Fatima Zartash , Ahmed Mukhtar , Hussain Mubshar , Abbas Ghulam , Ul-Allah Sami , Ahmad Shakeel , Ahmed Niaz , Ali Muhammad Arif , Sarwar Ghulam , Haque Ehsan ul , Iqbal Pakeeza , Hussain Sajjad
Published: October 2020

Growth and development of cereal crops are linked to weather, day length and growing degree-days (GDDs) which make them responsive to the specific environments in specific seasons. Global temperature is rising due to human activities such as burning of fossil fuels and clearance of woodlands for building construction. The rise in temperature disrupts crop growth and development. Disturbance mainly causes a shift in phenological development of crops and affects their economic yield. Scientists and farmers adapt to these phenological shifts, in part, by changing sowing time and cultivar shifts which may increase or decrease crop growth duration. Nonetheless, climate warming is a global phenomenon and cannot be avoided. In this scenario, food security can be ensured by improving cereal production through agronomic management, breeding of climate-adapted genotypes and increasing genetic biodiversity. In this review, climate warming, its impact and consequences are discussed with reference to their influences on phenological shifts. Furthermore, how different cereal crops adapt to climate warming by regulating their phenological development is elaborated. Based on the above mentioned discussion, different management strategies to cope with climate warming are suggested.
Epigenetic alterations in skin homing CD4+CLA+ T cells of atopic dermatitis patients
Authors: Acevedo Nathalie , Benfeitas Rui , Katayama Shintaro , Bruhn Sören , Andersson Anna , Wikberg Gustav , Lundeberg Lena , Lindvall Jessica M. , Greco Dario , Kere Juha , Söderhäll Cilla , Scheynius Annika
Published: October 2020

T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations (CD4+, CD4+CD45RA+naïve, CD4+CLA+, and CD8+) from adult AD patients and healthy controls (HC). Skin homing CD4+CLA+T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in CD4+CLA+T cells from AD patients correlated with increasedIL13mRNA expression in these cells. Sixteen miRNAs showed differential expression in CD4+CLA+T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing CD4+CLA+T cells and uncover putative molecules participating in AD pathways.
Uncovering a superfamily of nickel-dependent hydroxyacid racemases and epimerases
Authors: Desguin Benoît , Urdiain-Arraiza Julian , Da Costa Matthieu , Fellner Matthias , Hu Jian , Hausinger Robert P. , Desmet Tom , Hols Pascal , Soumillion Patrice
Published: October 2020

Isomerization reactions are fundamental in biology. Lactate racemase, which isomerizes L- and D-lactate, is composed of the LarA protein and a nickel-containing cofactor, the nickel-pincer nucleotide (NPN). In this study, we show that LarA is part of a superfamily containing many different enzymes. We overexpressed and purified 13 lactate racemase homologs, incorporated the NPN cofactor, and assayed the isomerization of different substrates guided by gene context analysis. We discovered two malate racemases, one phenyllactate racemase, one α-hydroxyglutarate racemase, two D-gluconate 2-epimerases, and one short-chain aliphatic α-hydroxyacid racemase among the tested enzymes. We solved the structure of a malate racemase apoprotein and used it, along with the previously described structures of lactate racemase holoprotein and D-gluconate epimerase apoprotein, to identify key residues involved in substrate binding. This study demonstrates that the NPN cofactor is used by a diverse superfamily of α-hydroxyacid racemases and epimerases, widely expanding the scope of NPN-dependent enzymes.
Interface-exfoliated graphene-based conductive screen-printing inks: low-loading, low-cost, and additive-free
Authors: Chen Feiyang , Varghese Deepthi , McDermott Sean T. , George Ian , Geng Lijiang , Adamson Douglas H.
Published: October 2020

Paper diagnostics are of growing interest due to their low cost and easy accessibility. Conductive inks, necessary for manufacturing the next generation diagnostic devices, currently face challenges such as high cost, high sintering temperatures, or harsh conditions required to remove stabilizers. Here we report an effective, inexpensive, and environmentally friendly approach to graphene ink that is suitable for screen printing onto paper substrates. The ink formulation contains only pristine graphite, water, and non-toxic alkanes formed by an interfacial trapping method in which graphite spontaneously exfoliates to graphene. The result is a viscous graphene stabilized water-in-oil emulsion-based ink. This ink does not require sintering, but drying at 90 °C or brief microwaving can improve the conductivity. The production requires only 40 s of shaking to form the emulsion. The sheet resistance of the ink is approximately 600 Ω/sq at a thickness of less than 6 µm, and the ink can be stabilized by as little as 1 wt% graphite.
Therapeutic effects of antibiotics loaded cellulose nanofiber and κ-carrageenan oligosaccharide composite hydrogels for periodontitis treatment
Authors: Johnson Athira , Kong Fanbin , Miao Song , Lin Hong-Ting Victor , Thomas Sabu , Huang Yi-Cheng , Kong Zwe-Ling
Published: October 2020

Periodontitis is an inflammatory disease that can lead to the periodontal pocket formation and tooth loss. This study was aimed to develop antimicrobials loaded hydrogels composed of cellulose nanofibers (CNF) and κ-carrageenan oligosaccharides (CO) nanoparticles for the treatment of periodontitis. Two antimicrobial agents such as surfactin and Herbmedotcin were selected as the therapeutic agents and the hydrogels were formulated based on the increasing concentration of surfactin. The proposed material has high thermal stability, controlled release, and water absorption capacity. This study was proceeded by investigating the in vitro antibacterial and anti-inflammatory properties of the hydrogels. This material has strong antibacterial activity against periodontal pathogens such asStreptococcus mutans,Porphyromonas gingivalis,Fusobacterium nucleatum, andPseudomonas aeruginosa. Moreover, a significant increase in malondialdehyde (MDA) production and a decrease in biofilm formation and metabolic activity of the bacteria was observed in the presence of hydrogel. Besides, it reduced the reactive oxygen species (ROS) generation, transcription factor, and cytokines production in human gingival fibroblast cells (HGF) under inflammatory conditions. In conclusion, the hydrogels were successfully developed and proven to have antibacterial and anti-inflammatory properties for the treatment of periodontitis. Thus, it can be used as an excellent candidate for periodontitis treatment.