bluuebunny/crossref_metadata_2025 huggingface dataset:
Information and resources important to the quality of life of people living with multiple sclerosis
Authors: Bishop Malachy , Rumrill Stuart , McDaniels Bradley , Li Jian , Fraser Robert , Rumrill Phillip D. , Bhattarai Muna , Park Mirang
Published: November 2020

Multiple sclerosis (MS) is a chronic, typically progressive immune-mediated disease characterized by inflammation and demyelination in the central nervous system (CNS), and is associated with a wide range of neurological, physical, and psychosocial effects. For people living with MS, access to relevant, timely, and accessible health information and resources may contribute to effective illness management, psychosocial health, and quality of life (QOL). In this study, we sought to increase understanding of the specific types of information most wanted by people with MS, as well as the sources and effects of this information. Specifically, we surveyed 748 adults with MS about (a) the sources from which they obtain information about MS, (b) the type of information that is most important in terms of improving their QOL, and (c) specific topics about which they would like to have more information, services, or resources. Content analysis of the qualitative results demonstrated the diversity of information sources accessed by people with MS and the importance of providing information through different formats and media. The participants prioritized information related to new MS medications and treatments, physical and mental health and wellness, and local opportunities for support. Implications for practicing rehabilitation counselors are discussed.
“Glass half full: cautious optimism and the future of Black women political elites in America”
Authors: Brown Nadia E. , Allen Gershon Sarah
Published: November 2020

In this essay, we place Black women's electoral challenges and opportunities in context. We situate this year of “Black Women Candidates” as an anomaly, but one that has been a long in the making. We also point to the appeal of Black women lawmakers among voters to mirror Alberder Gillespie's claims in this epigraph. We note that Black women have long been the backbone of the Democratic Party and are willing to use their clout for their own political means. Furthermore, given the unique ways that Black women represent their constituents, an influx of Black women into governing bodies may have a substantial, lasting impact on policy-making. We conclude with insights from our own research and that of other scholars on Black women to demonstrate future avenues of scholarly research.
A MULTIPLEX INTERDEPENDENT DURATIONS MODEL
Authors: Lin Zhongjian , Liu Ruixuan
Published: November 2020

We propose a multiplex interdependent durations model and study its empirical content. The model considers an empirical stopping game of multiple agents making optimal timing decisions with incomplete information. We characterize the unique Bayesian Nash equilibrium of the stopping game in a system of simultaneous equations involving the conditional distribution of each duration with a moderate strategic interaction condition. The system of nonlinear simultaneous equations allows us to obtain constructive identification results of the interaction effects and other nonparametric model primitives. We propose two consistent semiparametric estimation methods based on different parameterizations of modeling components with right-censored duration data.
Petri nets based on Lawvere theories
Authors: Master Jade
Published: November 2020

We give a definition of Q-net, a generalization of Petri nets based on a Lawvere theory Q, for which many existing variants of Petri nets are a special case. This definition is functorial with respect to change in Lawvere theory, and we exploit this to explore the relationships between different kinds of Q-nets. To justify our definition of Q-net, we construct a family of adjunctions for each Lawvere theory explicating the way in which Q-nets present free models of Q in Cat. This gives a functorial description of the operational semantics for an arbitrary category of Q-nets. We show how this can be used to construct the semantics for Petri nets, pre-nets, integer nets, and elementary net systems.
Diagnosing functional neurological disorder: seeing the whole picture
Authors: Lidstone Sarah C. , Nassif Walid , Juncos Jorge , Factor Stewart A. , Lang Anthony E.
Published: November 2020

Functional neurological disorder (FND) is a complex neuropsychiatric syndrome with many phenotypes that are commonly encountered in clinical practice. Despite the heterogeneity of FND, the rate of misidentification is consistently low. For the more common motor subtypes, there are clear positive clinical, electrophysiological, and rarely imaging criteria that can establish the diagnosis in the traditional sense. For nonmotor subtypes, the characterization may be less clear. Here, we argue that the current diagnostic criteria are not reflective of the current shared neuropsychiatric understanding of FND, and, as a result, provide an incomplete picture of the diagnosis. We propose a three-step diagnostic triad for FND, in which the traditional neurological diagnosis is only the first element. Other steps include psychiatric/psychological formulation, integration, and follow-up. We advocate that this diagnostic approach should be the shared responsibility of neurology and mental health professionals. Finally, a research agenda is proposed to address the missing factors in the field.
Development of a group-based diabetes education model for migrants with type 2 diabetes, living in Sweden
Authors: Hadziabdic Emina , Pettersson Sara , Marklund Helén , Hjelm Katarina
Published: November 2020

Aim:

To develop a diabetes education model based on individual beliefs, knowledge and risk awareness, aimed at migrants with type 2 diabetes, living in Sweden.

Background:

Type 2 diabetes is rapidly increasing globally, particularly affecting migrants living in developed countries. There is ongoing debate about what kind of teaching method gives the best result, but few studies have evaluated different methods for teaching migrants. Previous studies lack a theoretical base and do not proceed from the individuals’ own beliefs about health and illness, underpinned by their knowledge, guiding their health-related behaviour.

Methods:

A diabetes education model was developed to increase knowledge about diabetes and to influence self-care among migrants with type 2 diabetes. The model was based on literature review, on results from a previous study investigating knowledge about diabetes, on experience from studies of beliefs about health and illness, and on collaboration between researchers in diabetes care and migration and health and staff working in a multi-professional diabetes team.

Findings:

This is a culturally appropriate diabetes education model proceeding from individual beliefs about health and illness and knowledge, conducted in focus-group discussions in five sessions, led by a diabetes specialist nurse in collaboration with a multi-professional team, and completed within three months. The focus groups should include 4–5 persons and last for about 90 min, in the presence of an interpreter. A thematic interview guide should be used, with broad open-ended questions and descriptions of critical situations/health problems. Discussions of individual beliefs based on knowledge are encouraged. When needed, healthcare staff present at the session answer questions, add information and ensure that basic principles for diabetes care are covered. The diabetes education model is tailored to both individual and cultural aspects and can improve knowledge about type 2 diabetes, among migrants and thus increase self-care behaviour and improve health.
Small‐Scale Optical Atmospheric Emissions Discovered Using Citizen Science Photography
Authors: Grandin M.
Published: November 2020

Over the last few years, citizen science has emerged as a powerful tool to investigate natural phenomena, not only alongside measurements taken by calibrated scientific instruments but also through the analysis of data solely provided by citizen scientists. The increasing number of outstanding space physics studies based on citizen science reveals how valuable amateur photographers' data can be for further understanding the complex processes of the upper atmosphere. In some cases, cutting‐edge science is achieved using only citizen scientist photographs, as Semeter et al. (2020, https://doi.org/10.1029/2020AV000183) illustrate in a recent study of small‐scale optical structures associated with Strong Thermal Emission Velocity Enhancement (STEVE), called “streaks.” The altitude, morphology, and motion of the streaks are determined thanks to a clever methodology applied only to night sky photographs taken by citizen scientists. The results suggest that the mechanism responsible for the optical emission might involve a point‐like source of superthermal electrons energized locally, which can excite the atomic oxygen. This study paves the way for future investigations of the complex upper‐atmospheric physics.
Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets
Authors: Adnan-Awad Shady , Kim Daehong , Hohtari Helena , Javarappa Komal Kumar , Brandstoetter Tania , Mayer Isabella , Potdar Swapnil , Heckman Caroline A. , Kytölä Soili , Porkka Kimmo , Doma Eszter , Sexl Veronika , Kankainen Matti , Mustjoki Satu
Published: November 2020

The oncogenic protein Bcr-Abl has two major isoforms, p190Bcr-Abland p210Bcr-Abl. While p210Bcr-Ablis the hallmark of chronic myeloid leukemia (CML), p190Bcr-Abloccurs in the majority of Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients. In CML, p190Bcr-Abloccurs in a minority of patients associating with distinct hematological features and inferior outcomes, yet the pathogenic role of p190Bcr-Abland potential targeting therapies are largely uncharacterized. We employed next generation sequencing, phospho-proteomic profiling, and drug sensitivity testing to characterize p190Bcr-Ablin CML and hematopoietic progenitor cell line models (Ba/f3 and HPC-LSK). p190Bcr-AblCML patients demonstrated poor response to imatinib and frequent mutations in epigenetic modifiers genes. In contrast with p210Bcr-Abl, p190Bcr-Ablexhibited specific transcriptional upregulation of interferon, interleukin-1 receptor, and P53 signaling pathways, associated with hyperphosphorylation of relevant signaling molecules including JAK1/STAT1 and PAK1 in addition to Src hyperphosphorylation. Comparable to p190Bcr-AblCML patients, p190Bcr-Ablcell lines demonstrated similar transcriptional and phospho-signaling signatures. With the drug sensitivity screening we identified targeted drugs with specific activity in p190Bcr-Ablcell lines including IAP-, PAK1-, and Src inhibitors and glucocorticoids. Our results provide novel insights into the mechanisms underlying the distinct features of p190Bcr-AblCML and promising therapeutic targets for this high-risk patient group.
EZH2 facilitates BMI1-dependent hepatocarcinogenesis through epigenetically silencing microRNA-200c
Authors: Xu Leibo , Lin Junlong , Deng Wanyu , Luo Weixin , Huang Yipei , Liu Chao-Qun , Zhang Fa-Peng , Qin Yu-Fei , Wong Ping-Pui , Liu Chao
Published: November 2020

EZH2, a histone methyltransferase, has been shown to involve in cancer development and progression via epigenetic regulation of tumor suppressor microRNAs, whereas BMI1, a driver of hepatocellular carcinoma (HCC), is a downstream target of these microRNAs. However, it remains unclear whether EZH2 can epigenetically regulate microRNA expression to modulate BMI1-dependent hepatocarcinogenesis. Here, we established that high EZH2 expression correlated with enhanced tumor size, elevated metastasis, increased relapse, and poor prognosis in HCC patients. Further clinical studies revealed that EZH2 overexpression was positively correlated to its gene copy number gain/amplification in HCC. Mechanistically, EZH2 epigenetically suppressed miR-200c expression both in vitro and in vivo, and more importantly, miR-200c post-transcriptionally regulated BMI1 expression by binding to the 3′-UTR region of its mRNA. Furthermore, miR-200c overexpression inhibits the growth of HCC cells in vivo. Silencing miR-200c rescued the tumorigenicity of EZH2-depleted HCC cells, whereas knocking down BMI1 reduced the promoting effect of miR-200c depletion on HCC cell migration. Finally, combination treatment of EZH2 and BMI1 inhibitors further inhibited the viability of HCC cells compared with the cells treated with EZH2 or BMI1 inhibitor alone. Our findings demonstrated that alteration of EZH2 gene copy number status induced BMI1-mediated hepatocarcinogenesis via epigenetically silencing miR-200c, providing novel therapeutic targets for HCC treatment.
Triptolide targets super-enhancer networks in pancreatic cancer cells and cancer-associated fibroblasts
Authors: Noel Pawan , Hussein Shaimaa , Ng Serina , Antal Corina E. , Lin Wei , Rodela Emily , Delgado Priscilla , Naveed Sanna , Downes Michael , Lin Yin , Evans Ronald M. , Von Hoff Daniel D. , Han Haiyong
Published: November 2020

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous, fibrotic, and hypovascular, marked by extensive desmoplasia and maintained by the tumor cells, cancer-associated fibroblasts (CAFs) and other stromal cells. There is an urgent need to identify and develop treatment strategies that not only target the tumor cells but can also modulate the stromal cells. A growing number of studies implicate the role of regulatory DNA elements called super-enhancers (SE) in maintaining cell-type-specific gene expression networks in both normal and cancer cells. Using chromatin activation marks, we first mapped SE networks in pancreatic CAFs and epithelial tumor cells and found them to have distinct SE profiles. Next, we explored the role of triptolide (TPL), a natural compound with antitumor activity, in the context of modulating cell-type-specific SE signatures in PDAC. We found that TPL, cytotoxic to both pancreatic tumor cells and CAFs, disrupted SEs in a manner that resulted in the downregulation of SE-associated genes (e.g., BRD4, MYC, RNA Pol II, and Collagen 1) in both cell types at mRNA and protein levels. Our observations suggest that TPL acts as a SE interactive agent and may elicit its antitumor activity through SE disruption to re-program cellular cross talk and signaling in PDAC. Based on our findings, epigenetic reprogramming of transcriptional regulation using SE modulating compounds such as TPL may provide means for effective treatment options for pancreatic cancer patients.
Ag nanoparticles immobilized on new mesoporous triazine-based carbon (MTC) as green and recoverable catalyst for reduction of nitroaromatic in aqueous media
Authors: Vahedi-Notash Narges , Heravi Majid M. , Alhampour Ali , Mohammadi Pourya
Published: November 2020

In this research, we reported an effective method for the synthesis of a new mesoporous triazine-based carbon (MTC) substrate and its application as the green and recoverable catalyst in the synthesis of organic compounds. The porous carbon acted as a substrate for silver active species after its surface modification by chloroacetonitrile (Ag@MTC). The Ag@MTC nanocatalyst was characterized by several techniques namely, Fourier-transform infrared spectroscopy, field emission scanning electron microscopy with energy dispersive spectroscopy, X-ray diffraction, transmission electron microscopy, Brunauer–Emmett–Teller surface area analysis, and inductively coupled plasma. The Ag@MTC catalyst was applied for the reduction of nitroaromatic compounds in aqueous media by using NaBH4 (reducing agent) at room temperature. This nanocatalyst can be readily recovered and recycled for at least nine runs without a notable decrease in its efficiency. Catalytic efficiency studies exhibited that Ag@MTC nanocatalyst had good activity towards reduction reactions.
Targeted sequencing reveals the somatic mutation landscape in a Swedish breast cancer cohort
Authors: Mathioudaki Argyri , Ljungström Viktor , Melin Malin , Arendt Maja Louise , Nordin Jessika , Karlsson Åsa , Murén Eva , Saksena Pushpa , Meadows Jennifer R. S. , Marinescu Voichita D. , Sjöblom Tobias , Lindblad-Toh Kerstin
Published: November 2020

Breast cancer (BC) is a genetically heterogeneous disease with high prevalence in Northern Europe. However, there has been no detailed investigation into the Scandinavian somatic landscape. Here, in a homogeneous Swedish cohort, we describe the somatic events underlying BC, leveraging a targeted next-generation sequencing approach. We designed a 20.5 Mb array targeting coding and regulatory regions of genes with a known role in BC (n = 765). The selected genes were either from human BC studies (n = 294) or from within canine mammary tumor associated regions (n = 471). A set of predominantly estrogen receptor positive tumors (ER +  85%) and their normal tissue counterparts(n=61) were sequenced to ~ 140 × and 85 × mean target coverage, respectively. MuTect2 and VarScan2 were employed to detect single nucleotide variants (SNVs) and copy number aberrations (CNAs), while MutSigCV (SNVs) and GISTIC (CNAs) algorithms estimated the significance of recurrent somatic events. The significantly mutated genes (q ≤ 0.01) werePIK3CA(28% of patients),TP53(21%) andCDH1(11%). However, histone modifying genes contained the largest number of variants(KMT2CandARID1A, together28%). Mutations inKMT2Cwere mutually exclusive withPI3KCAmutations (p ≤ 0. 001) and half of these affect the formation of a functional PHD domain. The tumor suppressorCDK10was deleted in 80% of the cohort while the oncogeneMDM4was amplified. Mutational signature analyses pointed towards APOBEC deaminase activity (COSMIC signature 2) and DNA mismatch repair (COSMIC signature 6). We noticed two significantly distinct patterns related to patient age;TP53being more mutated in the younger group (29% vs 9% of patients) andCDH23mutations were absent from the older group. The increased somatic mutation prevalence in the histone modifying genesKMT2CandARID1Adistinguishes the Swedish cohort from previous studies.KMT2Cregulates enhancer activation and assists tumor proliferation in a hormone-rich environment, possibly pointing to a role in ER + BC, especially in older cases. Finally, age of onset appears to affect the mutational landscape suggesting that a larger age-diverse population incorporating more molecular subtypes should be studied to elucidate the underlying mechanisms.
Comparative analysis of magnetized partially ionized copper, copper oxide–water and kerosene oil nanofluid flow with Cattaneo–Christov heat flux
Authors: Abid Nomana , Ramzan Muhammad , Chung Jae Dong , Kadry Seifedine , Chu Yu-Ming
Published: November 2020

This comparative analysis studies the impact of two different nanoparticles Copper and Copper Oxide in two different partially ionized magnetofluid (water and kerosene oil mixed with Copper/Copper Oxide) flows over a linearly stretching surface. The impacts of electrons and ions collisions in the presence of the Cattaneo-Christov heat transfer model are also investigated. The effects of prominent parameters on velocity and temperature fields are depicted through graphical illustrations. A similarity transformation procedure is applied to transform the nonlinear partial differential equations to the ordinary one. Our numerical methodology is based upon the Finite difference method that is the default method in the bvp4c built-in function of the MATLAB scheme. Nusselt number and Skin drag coefficient are computed numerically and presented in tabular form for both types of nanofluids over a linear stretched surface. Our results demonstrate that the effects of CuO are dominant in comparison to the Cu on fluid velocity. The fluid temperature is more prominent in the case of Cu-water nanofluid when we increase nanoparticles concentration.
Topological transitions in an oscillatory driven liquid crystal cell
Authors: Clerc Marcel G. , Kowalczyk Michał , Zambra Valeska
Published: November 2020

Matter under different equilibrium conditions of pressure and temperature exhibits different states such as solid, liquid, gas, and plasma. Exotic states of matter, such as Bose–Einstein condensates, superfluidity, chiral magnets, superconductivity, and liquid crystalline blue phases are observed in thermodynamic equilibrium. Rather than being a result of an aggregation of matter, their emergence is due to a change of a topological state of the system. These topological states can persist out of thermodynamics equilibrium. Here we investigate topological states of matter in a system with injection and dissipation of energy by means of oscillatory forcing. In an experiment involving a liquid crystal cell under the influence of a low-frequency oscillatory electric field, we observe a transition from a non-vortex state to a state in which vortices persist, topological transition. Depending on the period and the type of the forcing, the vortices self-organise, forming square lattices, glassy states, and disordered vortex structures. The bifurcation diagram is characterised experimentally. A continuous topological transition is observed for the sawtooth and square forcings. The scenario changes dramatically for sinusoidal forcing where the topological transition is discontinuous, which is accompanied by serial transitions between square and glassy vortex lattices. Based on a stochastic amplitude equation, we recognise the origin of the transition as the balance between stochastic creation and deterministic annihilation of vortices. Numerical simulations show topological transitions and the emergence of square vortex lattice. Our results show that the matter maintained out of equilibrium by means of the temporal modulation of parameters can exhibit exotic states.
Momentum dependent $$d_{xz/yz}$$ band splitting in LaFeAsO
Authors: Huh S. S. , Kim Y. S. , Kyung W. S. , Jung J. K. , Kappenberger R. , Aswartham S. , Büchner B. , Ok J. M. , Kim J. S. , Dong C. , Hu J. P. , Cho S. H. , Shen D. W. , Denlinger J. D. , Kim Y. K. , Kim C.
Published: November 2020

The nematic phase in iron based superconductors (IBSs) has attracted attention with a notion that it may provide important clue to the superconductivity. A series of angle-resolved photoemission spectroscopy (ARPES) studies were performed to understand the origin of the nematic phase. However, there is lack of ARPES study on LaFeAsO nematic phase. Here, we report the results of ARPES studies of the nematic phase in LaFeAsO. Degeneracy breaking between the $$d_{xz}$$

d

xz

and $$d_{yz}$$

d

yz

hole bands near the $$\Gamma$$
Γ
and M point is observed in the nematic phase. Different temperature dependent band splitting behaviors are observed at the $$\Gamma$$
Γ
and M points. The energy of the band splitting near the M point decreases as the temperature decreases while it has little temperature dependence near the $$\Gamma$$
Γ
point. The nematic nature of the band shift near the M point is confirmed through a detwin experiment using a piezo device. Since a momentum dependent splitting behavior has been observed in other iron based superconductors, our observation confirms that the behavior is a universal one among iron based superconductors.
Estimation of optimal number of gates in dual gated 18F-FDG cardiac PET
Authors: Klén R. , Teuho J. , Noponen T. , Thielemans K. , Hoppela E. , Lehtonen E. , Sipila H. T. , Teräs M. , Knuuti J.
Published: November 2020

Gating of positron emission tomography images has been shown to reduce the motion effects, especially when imaging small targets, such as coronary plaques. However, the selection of optimal number of gates for gating remains a challenge. Selecting too high number of gates results in a loss of signal-to-noise ratio, while too low number of gates does remove only part of the motion. Here, we introduce a respiratory-cardiac motion model to determine the optimal number of respiratory and cardiac gates. We evaluate the model using a realistic heart phantom and data from 12 cardiac patients (47–77 years, 64.5 on average). To demonstrate the benefits of our model, we compared it with an existing respiratory model. Based on our study, the optimal number of gates was determined to be five respiratory and four cardiac gates in the phantom and patient studies. In the phantom study, the diameter of the most active hot spot was reduced by 24% in the dual gated images compared to non-gated images. In the patient study, the thickness of myocardium wall was reduced on average by 21%. In conclusion, the motion model can be used for estimating the optimal number of respiratory and cardiac gates for dual gating.
Author Correction: Sea ice phenology and primary productivity pulses shape breeding success in Arctic seabirds
Authors: Ramírez Francisco , Tarroux Arnaud , Hovinen Johanna , Navarro Joan , Afán Isabel , Forero Manuela G. , Descamps Sébastien
Published: November 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Characterization of glycosphingolipids from gastrointestinal stromal tumours
Authors: Santos Licínia , Jin Chunsheng , Gazárková Taťána , Thornell Anders , Norlén Olov , Säljö Karin , Teneberg Susann
Published: November 2020

Gastrointestinal stromal tumours (GISTs) are the major nonepithelial neoplasms of the human gastrointestinal tract with a worldwide incidence between 11 and 15 per million cases annually. In this study the acid and non-acid glycosphingolipids of three GISTs were characterized using a combination of thin-layer chromatography, chemical staining, binding of carbohydrate recognizing ligands, and mass spectrometry. In the non-acid glycosphingolipid fractions of the tumors globotetraosylceramide, neolactotetraosylceramide, and glycosphingolipids with terminal blood group A, B, H, Lex, Lea, Ley and Leb determinants were found. The relative amounts of these non-acid compounds were different in the three tumour samples. The acid glycosphingolipid fractions had sulfatide, and the gangliosides GM3, GD3, GM1, Neu5Acα3neolactotetraosylceramide, GD1a, GT1b and GQ1b. In summary, we have characterized the glycosphingolipids of GISTs and found that the pattern differs in tumours from different individuals. This detailed characterization of glycosphingolipid composition of GISTs could contribute to recognition of new molecular targets for GIST treatment and sub-classification.
Modelling of combination therapy using implantable anticancer drug delivery with thermal ablation in solid tumor
Authors: Al-Zu’bi Muneer , Mohan Ananda
Published: November 2020

Local implantable drug delivery system (IDDS) can be used as an effective adjunctive therapy for solid tumor following thermal ablation for destroying the residual cancer cells and preventing the tumor recurrence. In this paper, we develop comprehensive mathematical pharmacokinetic/pharmacodynamic (PK/PD) models for combination therapy using implantable drug delivery system following thermal ablation inside solid tumors with the help of molecular communication paradigm. In this model, doxorubicin (DOX)-loaded implant (act as a transmitter) is assumed to be inserted inside solid tumor (acts as a channel) after thermal ablation. Using this model, we can predict the extracellular and intracellular concentration of both free and bound drugs. Also, Impact of the anticancer drug on both cancer and normal cells is evaluated using a pharmacodynamic (PD) model that depends on both the spatiotemporal intracellular concentration as well as characteristics of anticancer drug and cells. Accuracy and validity of the proposed drug transport model is verified with published experimental data in the literature. The results show that this combination therapy results in high therapeutic efficacy with negligible toxicity effect on the normal tissue. The proposed model can help in optimize development of this combination treatment for solid tumors, particularly, the design parameters of the implant.
The differential effects of isoflurane and sevoflurane on neonatal mice
Authors: Zhao Shuai , Fan Ziqi , Hu Jing , Zhu Yueli , Lin Caixiu , Shen Ting , Li Zheyu , Li Kaicheng , Liu Zhirong , Chen Yanxing , Zhang Baorong
Published: November 2020

Previous research has shown that exposure to volatile anesthetics can induce acute neuroinflammation and neuroapoptopsis in neonatal rodents and that these events can lead to cognitive dysfunction at later stages. Isoflurane and sevoflurane are two of the most popular anesthetics used in the field of pediatrics. However, the relative impact of these two anesthetics on the developing brain at distinct time points after the induction of anesthesia has not been compared. In the present study, we exposed 7-day-old mice to clinically equivalent doses of isoflurane (1.5%) and sevoflurane (2.5%) for 4 h and then investigated consequential changes in the brains of these mice at six different time points. We analyzed the levels of proteins that are directly related to neuroapoptosis, neuroinflammation, synaptic function, and memory, in the brains of neonatal mice. Exposure of neonatal mice to isoflurane and sevoflurane resulted in acute neuronal apoptosis. Our analysis observed significant levels of neuroinflammation and changes in the expression levels of proteins associated with both synaptic transmission and memory in mice from the isoflurane group but not the sevoflurane group. Our results therefore indicate that isoflurane and sevoflurane induce differential effects in the brains of neonatal mice.
Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts
Authors: Jühlen Ramona , Martinelli Valérie , Vinci Chiara , Breckpot Jeroen , Fahrenkrog Birthe
Published: November 2020

Ciliopathies are clinical disorders of the primary cilium with widely recognised phenotypic and genetic heterogeneity. Here, we found impaired ciliogenesis in fibroblasts derived from individuals with fetal akinesia deformation sequence (FADS), a broad spectrum of neuromuscular disorders arising from compromised foetal movement. We show that cells derived from FADS individuals have shorter and less primary cilia (PC), in association with alterations in post-translational modifications in α-tubulin. Similarly, siRNA-mediated depletion of two known FADS proteins, the scaffold protein rapsyn and the nucleoporin NUP88, resulted in defective PC formation. Consistent with a role in ciliogenesis, rapsyn and NUP88 localised to centrosomes and PC. Furthermore, proximity-ligation assays confirm the respective vicinity of rapsyn and NUP88 to γ-tubulin. Proximity-ligation assays moreover show that rapsyn and NUP88 are adjacent to each other and that the rapsyn-NUP88 interface is perturbed in the examined FADS cells. We suggest that the perturbed rapsyn-NUP88 interface leads to defects in PC formation and that defective ciliogenesis contributes to the pleiotropic defects seen in FADS.
Isoprenoid-chained lipid EROCOC17+4: a new matrix for membrane protein crystallization and a crystal delivery medium in serial femtosecond crystallography
Authors: Ihara Kentaro , Hato Masakatsu , Nakane Takanori , Yamashita Keitaro , Kimura-Someya Tomomi , Hosaka Toshiaki , Ishizuka-Katsura Yoshiko , Tanaka Rie , Tanaka Tomoyuki , Sugahara Michihiro , Hirata Kunio , Yamamoto Masaki , Nureki Osamu , Tono Kensuke , Nango Eriko , Iwata So , Shirouzu Mikako
Published: November 2020

In meso crystallization of membrane proteins relies on the use of lipids capable of forming a lipidic cubic phase (LCP). However, almost all previous crystallization trials have used monoacylglycerols, with 1-(cis-9-octadecanoyl)-rac-glycerol (MO) being the most widely used lipid. We now report that EROCOC17+4 mixed with 10% (w/w) cholesterol (Fig. 1) serves as a new matrix for crystallization and a crystal delivery medium in the serial femtosecond crystallography of Adenosine A2A receptor (A2AR). The structures of EROCOC17+4-matrix grown A2AR crystals were determined at 2.0 Å resolution by serial synchrotron rotation crystallography at a cryogenic temperature, and at 1.8 Å by LCP-serial femtosecond crystallography, using an X-ray free-electron laser at 4 and 20 °C sample temperatures, and are comparable to the structure of the MO-matrix grown A2AR crystal (PDB ID: 4EIY). Moreover, X-ray scattering measurements indicated that the EROCOC17+4/water system did not form the crystalline LC phase at least down to − 20 °C, in marked contrast to the equilibrium MO/water system, which transforms into the crystalline LC phase below about 17 °C. As the LC phase formation within the LCP-matrix causes difficulties in protein crystallography experiments in meso, this feature of EROCOC17+4 will expand the utility of the in meso method.
Role of peripheral 5-HT5A receptors in 5-HT-induced cardiac sympatho-inhibition in type 1 diabetic rats
Authors: García-Pedraza José Ángel , Hernández-Abreu Oswaldo , Morán Asunción , Carretero José , García-Domingo Mónica , Villalón Carlos M.
Published: November 2020

5-HT inhibits cardiac sympathetic neurotransmission in normoglycaemic rats, via 5-HT1B, 5-HT1Dand 5-HT5Areceptor activation. Since type 1 diabetes impairs the cardiac sympathetic innervation leading to cardiopathies, this study aimed to investigate whether the serotonergic influence on cardiac noradrenergic control is altered in type 1 diabetic rats. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by electrical preganglionic stimulation (C7-T1) of the cardioaccelerator sympathetic outflow or i.v. noradrenaline bolus injections. Immunohistochemistry was performed to study 5-HT1B, 5-HT1Dand 5-HT5Areceptor expression in the stellate ganglion from normoglycaemic and diabetic rats. In the diabetic group, i) i.v. continuous infusions of 5-HT induced a cardiac sympatho-inhibition that was mimicked by the 5-HT1/5Aagonist 5-carboxamidotryptamine (without modifying noradrenaline-induced tachycardia), but not by the agonists indorenate (5-HT1A), CP 93,129 (5-HT1B), PNU 142633 (5-HT1D), or LY344864 (5-HT1F); ii) SB 699551 (5-HT5Aantagonist; i.v.) completely reversed 5-CT-induced cardiac sympatho-inhibition; and iii) 5-HT5Areceptors were more expressed in the stellate ganglion compared to normoglycaemic rats. These results show the prominent role of the peripheral 5-HT5Areceptors prejunctionally inhibiting the cardiac sympathetic drive in type 1 diabetic rats.
Giant refractometric sensitivity by combining extreme optical Vernier effect and modal interference
Authors: Gomes André D. , Kobelke Jens , Bierlich Jörg , Dellith Jan , Rothhardt Manfred , Bartelt Hartmut , Frazão Orlando
Published: November 2020

The optical Vernier effect consists of overlapping responses of a sensing and a reference interferometer with slightly shifted interferometric frequencies. The beating modulation thus generated presents high magnified sensitivity and resolution compared to the sensing interferometer, if the two interferometers are slightly out of tune with each other. However, the outcome of such a condition is a large beating modulation, immeasurable by conventional detection systems due to practical limitations of the usable spectral range. We propose a method to surpass this limitation by using a few-mode sensing interferometer instead of a single-mode one. The overlap response of the different modes produces a measurable envelope, whilst preserving an extremely high magnification factor, an order of magnification higher than current state-of-the-art performances. Furthermore, we demonstrate the application of that method in the development of a giant sensitivity fibre refractometer with a sensitivity of around 500 µm/RIU (refractive index unit) and with a magnification factor over 850.
Spatial patterns of pathogen prevalence in questing Ixodes ricinus nymphs in southern Scandinavia, 2016
Authors: Kjær Lene Jung , Klitgaard Kirstine , Soleng Arnulf , Edgar Kristin Skarsfjord , Lindstedt Heidi Elisabeth H. , Paulsen Katrine M. , Andreassen Åshild Kristine , Korslund Lars , Kjelland Vivian , Slettan Audun , Stuen Snorre , Kjellander Petter , Christensson Madeleine , Teräväinen Malin , Baum Andreas , Jensen Laura Mark , Bødker René
Published: November 2020

Tick-borne pathogens cause diseases in animals and humans, and tick-borne disease incidence is increasing in many parts of the world. There is a need to assess the distribution of tick-borne pathogens and identify potential risk areas. We collected 29,440 tick nymphs from 50 sites in Scandinavia from August to September, 2016. We tested ticks in a real-time PCR chip, screening for 19 vector-associated pathogens. We analysed spatial patterns, mapped the prevalence of each pathogen and used machine learning algorithms and environmental variables to develop predictive prevalence models. All 50 sites had a pool prevalence of at least 33% for one or more pathogens, the most prevalent being Borrelia afzelii, B. garinii, Rickettsia helvetica, Anaplasma phagocytophilum, and Neoehrlichia mikurensis. There were large differences in pathogen prevalence between sites, but we identified only limited geographical clustering. The prevalence models performed poorly, with only models for R. helvetica and N. mikurensis having moderate predictive power (normalized RMSE from 0.74–0.75, R2 from 0.43–0.48). The poor performance of the majority of our prevalence models suggest that the used environmental and climatic variables alone do not explain pathogen prevalence patterns in Scandinavia, although previously the same variables successfully predicted spatial patterns of ticks in the same area.
Electrically stimulated hind limb muscle contractions increase adult hippocampal astrogliogenesis but not neurogenesis or behavioral performance in male C57BL/6J mice
Authors: Gardner Jennie C. , Dvoretskiy Svyatoslav V. , Yang Yanyu , Venkataraman Sanjana , Lange Dominica A. , Li Shiping , Boppart Alexandria L. , Kim Noah , Rendeiro Catarina , Boppart Marni D. , Rhodes Justin S.
Published: November 2020

Regular exercise is crucial for maintaining cognitive health throughout life. Recent evidence suggests muscle contractions during exercise release factors into the blood which cross into the brain and stimulate adult hippocampal neurogenesis. However, no study has tested whether muscle contractions alone are sufficient to increase adult hippocampal neurogenesis and improve behavioral performance. Adult male, C57BL/6J mice were anesthetized and exposed to bilateral hind limb muscle contractions (both concentric and eccentric) via electrical stimulation (e-stim) of the sciatic nerve twice a week for 8 weeks. Each session lasted approximately 20 min and consisted of a total of 40 muscle contractions. The control group was treated similarly except without e-stim (sham). Acute neuronal activation of the dentate gyrus (DG) using cFos immunohistochemistry was measured as a negative control to confirm that the muscle contractions did not activate the hippocampus, and in agreement, no DG activation was observed. Relative to sham, e-stim training increased DG volume by approximately 10% and astrogliogenesis by 75%, but no difference in neurogenesis was detected and no improvement in behavioral performance was observed. E-stim also increased astrogliogenesis in CA1/CA2 hippocampal subfields but not in the cortex. Results demonstrate that muscle contractions alone, in absence of DG activation, are sufficient to increase adult hippocampal astrogliogenesis, but not neurogenesis or behavioral performance in mice.
Variations in the frequencies of polymorphisms in the CYP2C9 gene in six major ethnicities of Pakistan
Authors: Ahmed Sagheer , Altaf Nadeem , Ejaz Mahnoor , Altaf Aisha , Amin Aneela , Janjua Kholood , Khan Arif Ullah , Imran Imran , Khan Saeed
Published: November 2020

Genetic variation in cytochrome P450 (CYP) 2C9 is known to cause significant inter-individual differences in drug response and adverse effects. The frequencies of CYP2C9*2 and CYP2C9*3, both of which are responsible for the low activity of the enzyme, are not known in the Pakistani population. Therefore, we screened various ethnic groups residing in Pakistan for these polymorphisms. A total of 467 healthy human volunteers were recruited from six major ethnicities of Pakistan after written informed consent. Our results indicate that about 20% of the Pakistani population has a genotype containing at least one low activity allele. Ethnic Punjabi and Pathan populations had the highest frequencies of wild type genotypes while Urdu, Seraiki, and Sindhi populations showed higher rates of both low activity genotypes. The Baloch population showed the highest rates of low activity genotypes with less than 50% of the samples showing wild type genotypes, suggesting that more than half of the Baloch population possesses low activity genotypes. The frequencies found in various ethnic groups in Pakistan were comparable with ethnicities in the South Asian region except for the Baloch population. These results suggest that pharmacogenetics screening for low activity genotypes may be a helpful tool for clinicians while prescribing medications metabolized by CYP2C9.
Cryopreservation of testicular tissue from Murray River Rainbowfish, Melanotaenia fluviatilis
Authors: Rivers Nicola , Daly Jonathan , Jones Robert , Temple-Smith Peter
Published: November 2020

Globally, fish populations are in decline from overfishing, habitat destruction and poor water quality. Recent mass fish deaths in Australia’s Murray–Darling Basin highlight the need for improved conservation methods for endangered fish species. Cryopreservation of testicular tissue allows storage of early sperm precursor cells for use in generating new individuals via surrogacy. We describe successful isolation and cryopreservation of spermatogonia in an Australian rainbowfish. Testis histology showed rainbowfish spermatogonia are large (> 10 μm) and stain positive for Vasa, an early germ line-specific protein. Using size-based flow cytometry, testis cell suspensions were sorted through “A” (> 9 μm) and “B” gates (2–5 μm); the A gate produced significantly more Vasa-positive cells (45.0% ± 15.2%) than the “B” gate (0.0% ± 0.0%) and an unsorted control (22.9% ± 9.5%, p < 0.0001). The most successful cryoprotectant for “large cell” (> 9 μm) viability (72.6% ± 10.5%) comprised 1.3 M DMSO, 0.1 M trehalose and 1.5% BSA; cell viability was similar to fresh controls (78.8% ± 10.5%) and significantly better than other cryoprotectants (p < 0.0006). We have developed a protocol to cryopreserve rainbowfish testicular tissue and recover an enriched population of viable spermatogonia. This is the first step in developing a biobank of reproductive tissues for this family, and other Australian fish species, in the Australian Frozen Zoo.
Gold cauldrons as efficient candidates for plasmonic tweezers
Authors: Khosravi Mohammad Ali , Aqhili Abolfazl , Vasini Shoaib , Khosravi Mohammad Hossein , Darbari Sara , Hajizadeh Faegheh
Published: November 2020

In this report, gold cauldrons are proposed and proved as efficient candidates for plasmonic tweezers. Gold cauldrons benefit from high field localization in the vicinity of their apertures, leading to particle trapping by a reasonably low power source. The plasmonic trapping capability of a single gold cauldron and a cauldrons cluster are studied by investigating the plasmon-induced variations of the optical trap stiffness in a conventional optical tweezers configuration. This study shows that the localized plasmonic fields and the consequent plasmonic forces lead to enhanced trap stiffness in the vicinity of the cauldrons. This observation is pronounced for the cauldrons cluster, due to the additive plasmonic fields of the neighboring cauldrons. Strong direct plasmonic tweezing by the gold cauldrons cluster is also investigated and confirmed by our simulations and experimental results. In addition to the presented plasmonic trapping behavior, gold cauldrons benefit from a low cost and simple fabrication process with acceptable controllability over the structural average dimensions and plasmonic behavior, making them attractive for emerging lab-on-a-chip optophoresis applications.
Environmental dust repelling from hydrophilic/hydrophobic surfaces under sonic excitations
Authors: Abubakar Abba Abdulhamid , Yilbas Bekir Sami , Al-Qahtani Hussain , Alzaydi Ammar
Published: November 2020

Dust repelling from transparent polyvinyl chloride film surface via sonic excitation is examined and dynamics of repelled (inflight) dust particles are analyzed. An experimental rig is designed and built to assess the vibrational characteristics of the polyvinyl chloride film at different frequencies of sonic excitation. A high speed recording system and tracking program are utilized monitoring and evaluating the dynamics of the inflight particles. The dynamics of inflight particles are also simulated numerically and the predictions are compared with those of the experimental data. In order to examine the influence of dust particle adhesion on the dynamics of the inflight particles, the polyvinyl chloride film surface is hydrophobized through dip coating by functionalized nano-silica particles. Improvement of the optical transmittance of the dust mitigated film is determined via outdoor tests. The findings demonstrate that sonic excitation repels the particles from the film surface and it is more pronounced at 64 Hz excitation frequency while demonstrating that sonic excitation can be used for dust removal from transparent surfaces. The mitigation via sonic excitation improves the optical transmittance of the dusty surface by 77%, which becomes more apparent for hydrophobic surfaces.
Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality in Caenorhabditis elegans
Authors: Hammerquist Amy M. , Curran Sean P.
Published: November 2020

The negative regulator of RNA polymerase (pol) III mafr-1 has been shown to affect RNA pol III transcript abundance, lipid biosynthesis and storage, progeny output, and lifespan. We deleted mafr-1 from the Caenorhabditis elegans genome and found that animals lacking mafr-1 replicated many phenotypes from previous RNAi-based studies and discovered a new sperm-specific role. Utilizing a yeast two-hybrid assay, we discovered several novel interactors of MAFR-1 that are expressed in a sperm- and germline-enriched manner. In support of a role for MAFR-1 in the male germline, we found mafr-1 null males have smaller spermatids that are less capable in competition for fertilization; a phenotype that was dependent on RNA pol III activity. Restoration of MAFR-1 expression specifically in the germline rescued the spermatid-related phenotypes, suggesting a cell autonomous role for MAFR-1 in nematode male fertility. Based on the high degree of conservation of Maf1 activity across species, our study may inform similar roles for Maf1 and RNA pol III in mammalian male fertility.