bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergence of collective oscillations in adaptive cells
Authors: Wang Shou-Wen , Tang Lei-Han
Published: December 2019

Collective oscillations of cells in a population appear under diverse biological contexts. Here, we establish a set of common principles by categorising the response of individual cells against a time-varying signal. A positive intracellular signal relay of sufficient gain from participating cells is required to sustain the oscillations, together with phase matching. The two conditions yield quantitative predictions for the onset cell density and frequency in terms of measured single-cell and signal response functions. Through mathematical constructions, we show that cells that adapt to a constant stimulus fulfil the phase requirement by developing a leading phase in an active frequency window that enables cell-to-signal energy flow. Analysis of dynamical quorum sensing in several cellular systems with increasing biological complexity reaffirms the pivotal role of adaptation in powering oscillations in an otherwise dissipative cell-to-cell communication channel. The physical conditions identified also apply to synthetic oscillatory systems.
Solution structure of human myeloid-derived growth factor suggests a conserved function in the endoplasmic reticulum
Authors: Bortnov Valeriu , Tonelli Marco , Lee Woonghee , Lin Ziqing , Annis Douglas S. , Demerdash Omar N. , Bateman Alex , Mitchell Julie C. , Ge Ying , Markley John L. , Mosher Deane F.
Published: December 2019

Human myeloid-derived growth factor (hMYDGF) is a 142-residue protein with a C-terminal endoplasmic reticulum (ER) retention sequence (ERS). Extracellular MYDGF mediates cardiac repair in mice after anoxic injury. Although homologs of hMYDGF are found in eukaryotes as distant as protozoans, its structure and function are unknown. Here we present the NMR solution structure of hMYDGF, which consists of a short α-helix and ten β-strands distributed in three β-sheets. Conserved residues map to the unstructured ERS, loops on the face opposite the ERS, and the surface of a cavity underneath the conserved loops. The only protein or portion of a protein known to have a similar fold is the base domain of VNN1. We suggest, in analogy to the tethering of the VNN1 nitrilase domain to the plasma membrane via its base domain, that MYDGF complexed to the KDEL receptor binds cargo via its conserved residues for transport to the ER.
Facial model collection for medical augmented reality in oncologic cranio-maxillofacial surgery
Authors: Gsaxner Christina , Wallner Jürgen , Chen Xiaojun , Zemann Wolfgang , Egger Jan
Published: December 2019

Medical augmented reality (AR) is an increasingly important topic in many medical fields. AR enables x-ray vision to see through real world objects. In medicine, this offers pre-, intra- or post-interventional visualization of “hidden” structures. In contrast to a classical monitor view, AR applications provide visualization not only on but also in relation to the patient. However, research and development of medical AR applications is challenging, because of unique patient-specific anatomies and pathologies. Working with several patients during the development for weeks or even months is not feasible. One alternative are commercial patient phantoms, which are very expensive. Hence, this data set provides a unique collection of head and neck cancer patient PET-CT scans with corresponding 3D models, provided as stereolitography (STL) files. The 3D models are optimized for effective 3D printing at low cost. This data can be used in the development and evaluation of AR applications for head and neck surgery.
Author Correction: Differentiating between cancer and normal tissue samples using multi-hit combinations of genetic mutations
Authors: Dash Sajal , Kinney Nicholas A. , Varghese Robin T. , Garner Harold R. , Feng Wu-chun , Anandakrishnan Ramu
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mapping the Impact of Non-Tectonic Forcing mechanisms on GNSS measured Coseismic Ionospheric Perturbations
Authors: Bagiya Mala S. , Sunil A. S. , Rolland Lucie , Nayak Srinivas , Ponraj M. , Thomas Dhanya , Ramesh Durbha Sai
Published: December 2019

Global Navigation Satellite System (GNSS) measured Total Electron Content (TEC) is now widely used to study the near and far-field coseismic ionospheric perturbations (CIP). The generation of near field (~500–600 km surrounding an epicenter) CIP is mainly attributed to the coseismic crustal deformation. The azimuthal distribution of near field CIP may contain information on the seismic/tectonic source characteristics of rupture propagation direction and thrust orientations. However, numerous studies cautioned that before deriving the listed source characteristics based on coseismic TEC signatures, the contribution of non-tectonic forcing mechanisms needs to be examined. These mechanisms which are operative at ionospheric altitudes are classified as the i) orientation between the geomagnetic field and tectonically induced atmospheric wave perturbations ii) orientation between the GNSS satellite line of sight (LOS) geometry and coseismic atmospheric wave perturbations and iii) ambient electron density gradients. So far, the combined effects of these mechanisms have not been quantified. We propose a 3D geometrical model, based on acoustic ray tracing in space and time to estimate the combined effects of non-tectonic forcing mechanisms on the manifestations of GNSS measured near field CIP. Further, this model is tested on earthquakes occurring at different latitudes with a view to quickly quantify the collective effects of these mechanisms. We presume that this simple and direct 3D model would induce and enhance a proper perception among the researchers about the tectonic source characteristics derived based on the corresponding ionospheric manifestations.
Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome
Authors: Weinberg Robert P. , Koledova Vera V. , Subramaniam Avinaash , Schneider Kirsten , Artamonova Anastasia , Sambanthamurthi Ravigadevi , Hayes K. C. , Sinskey Anthony J. , Rha ChoKyun
Published: December 2019

Tyrosine hydroxylase (TH) catalyzes the hydroxylation of L-tyrosine to L-DOPA. This is the rate-limiting step in the biosynthesis of the catecholamines – dopamine (DA), norepinephrine (NE), and epinephrine (EP). Catecholamines (CA) play a key role as neurotransmitters and hormones. Aberrant levels of CA are associated with multiple medical conditions, including Parkinson’s disease. Palm Fruit Bioactives (PFB) significantly increased the levels of tyrosine hydroxylase in the brain of the Nile Grass rat (NGR), a novel and potentially significant finding, unique to PFB among known botanical sources. Increases were most pronounced in the basal ganglia, including the caudate-putamen, striatum and substantia nigra. The NGR represents an animal model of diet-induced Type 2 Diabetes Mellitus (T2DM), exhibiting hyperglycemia, hyperinsulinemia, and insulin resistance associated with hyperphagia and accelerated postweaning weight gain induced by a high-carbohydrate diet (hiCHO). The PFB-induced increase of TH in the basal ganglia of the NGR was documented by immuno-histochemical staining (IHC). This increase in TH occurred equally in both diabetes-susceptible and diabetes-resistant NGR fed a hiCHO. PFB also stimulated growth of the colon microbiota evidenced by an increase in cecal weight and altered microbiome.  The metabolites of colon microbiota, e.g. short-chain fatty acids, may influence the brain and behavior significantly.
Clinical relevance of cell-free mitochondrial DNA during the early postoperative period in kidney transplant recipients
Authors: Kim Kipyo , Moon Haena , Lee Yu Ho , Seo Jung-Woo , Kim Yang Gyun , Moon Ju-Young , Kim Jin Sug , Jeong Kyung-Hwan , Lee Tae Won , Ihm Chun-Gyoo , Lee Sang-Ho
Published: December 2019

Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P < 0.001) and cases of deceased donor transplantation (P < 0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P = 0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.
Cdc7 kinase stimulates Aurora B kinase in M-phase
Authors: Ito Sayuri , Goto Hidemasa , Kuniyasu Kinue , Shindo Mayumi , Yamada Masayuki , Tanaka Kozo , Toh Gaik-Theng , Sawa Masaaki , Inagaki Masaki , Bartek Jiri , Masai Hisao
Published: December 2019

The conserved serine-threonine kinase, Cdc7, plays a crucial role in initiation of DNA replication by facilitating the assembly of an initiation complex. Cdc7 is expressed at a high level and exhibits significant kinase activity not only during S-phase but also during G2/M-phases. A conserved mitotic kinase, Aurora B, is activated during M-phase by association with INCENP, forming the chromosome passenger complex with Borealin and Survivin. We show that Cdc7 phosphorylates and stimulates Aurora B kinase activity in vitro. We identified threonine-236 as a critical phosphorylation site on Aurora B that could be a target of Cdc7 or could be an autophosphorylation site stimulated by Cdc7-mediated phosphorylation elsewhere. We found that threonines at both 232 (that has been identified as an autophosphorylation site) and 236 are essential for the kinase activity of Aurora B. Cdc7 down regulation or inhibition reduced Aurora B activity in vivo and led to retarded M-phase progression. SAC imposed by paclitaxel was dramatically reversed by Cdc7 inhibition, similar to the effect of Aurora B inhibition under the similar situation. Our data show that Cdc7 contributes to M-phase progression and to spindle assembly checkpoint most likely through Aurora B activation.
Curie-Weiss behavior of liquid structure and ideal glass state
Authors: Ryu C. W. , Dmowski W. , Kelton K. F. , Lee G. W. , Park E. S. , Morris J. R. , Egami T.
Published: December 2019

We present the results of a structural study of metallic alloy liquids from high temperature through the glass transition. We use high energy X-ray scattering and electro-static levitation in combination with molecular dynamics simulation and show that the height of the first peak of the structure function, S(Q) − 1, follows the Curie-Weiss law. The structural coherence length is proportional to the height of the first peak, and we suggest that its increase with cooling may be related to the rapid increase in viscosity. The Curie temperature is negative, implying an analogy with spin-glass. The Curie-Weiss behavior provides a pathway to an ideal glass state, a state with long-range correlation without lattice periodicity, which is characterized by highly diverse local structures, reminiscent of spin-glass.
Imaging Salt Uptake Dynamics in Plants Using PET
Authors: Ariño-Estrada Gerard , Mitchell Gregory S. , Saha Prasenjit , Arzani Ahmad , Cherry Simon R. , Blumwald Eduardo , Kyme Andre Z.
Published: December 2019

Soil salinity is a global environmental challenge for crop production. Understanding the uptake and transport properties of salt in plants is crucial to evaluate their potential for growth in high salinity soils and as a basis for engineering varieties with increased salt tolerance. Positron emission tomography (PET), traditionally used in medical and animal imaging applications for assessing and quantifying the dynamic bio-distribution of molecular species, has the potential to provide useful measurements of salt transport dynamics in an intact plant. Here we report on the feasibility of studying the dynamic transport of 22Na in millet using PET. Twenty-four green foxtail (Setaria viridis L. Beauv.) plants, 12 of each of two different accessions, were incubated in a growth solution containing 22Na+ ions and imaged at 5 time points over a 2-week period using a high-resolution small animal PET scanner. The reconstructed PET images showed clear evidence of sodium transport throughout the whole plant over time. Quantitative region-of-interest analysis of the PET data confirmed a strong correlation between total 22Na activity in the plants and time. Our results showed consistent salt transport dynamics within plants of the same variety and important differences between the accessions. These differences were corroborated by independent measurement of Na+ content and expression of the NHX transcript, a gene implicated in sodium transport. Our results demonstrate that PET can be used to quantitatively evaluate the transport of sodium in plants over time and, potentially, to discern differing salt-tolerance properties between plant varieties. In this paper, we also address the practical radiation safety aspects of working with 22Na in the context of plant imaging and describe a robust pipeline for handling and incubating plants. We conclude that PET is a promising and practical candidate technology to complement more traditional salt analysis methods and provide insights into systems-level salt transport mechanisms in intact plants.
First detection of white spot syndrome virus (WSSV) in the mud shrimp Austinogebia edulis in Taiwan
Authors: Zhu Fei , Twan Wen-Hung , Tseng Li-Chun , Peng Shao-Hung , Hwang Jiang-Shiou
Published: December 2019

The white spot syndrome virus (WSSV) causes mass mortalities in the aquaculture of shrimps worldwide. The mud shrimp Austinogebia edulis (Ngoc-Ho & Chan, 1992) is an economically important sea food item occurring along the west coast of Taiwan. While the population of A. edulis began to decrease with some fluctuations in the last decade, the current study aims to discover the causes for such sporadic population decline. This study explores the effects of microbial pathogens and innate immunity on the populations of A. edulis. Here, we report firstly about WSSV infection of A. edulis from the coastal zone of western Taiwan which is one of the possible causes of population decrease of A. edulis in Shengang. However, WSSV infection is not the only reason for its population decrease because a similar infection rate of WSSV was found in Wangong. Population changes may be related to both environmental pollution stress and WSSV. Both factors likely caused a massive reduction of hemocytes and an abnormal increase of phenoloxidase and superoxide dismutase activity, which were spectrophotometrically measured. Since there is no effective way to treat WSSV infection, improving the coastal environment appears the most effective way to increase the population size of feral shrimps.
Oceanographic Variability induced by Tides, the Intraseasonal Cycle and Warm Subsurface Water intrusions in Maxwell Bay, King George Island (West-Antarctica)
Authors: Llanillo P. J. , Aiken C. M. , Cordero R. R. , Damiani A. , Sepúlveda E. , Fernández-Gómez B.
Published: December 2019

We examine the hydrographic variability induced by tides, winds, and the advance of the austral summer, in Maxwell Bay and tributary fjords, based on two recent oceanographic campaigns. We provide the first description in this area of the intrusion of relatively warm subsurface waters, which have led elsewhere in Antarctica to ice-shelf disintegration and tidewater glacier retreat. During flood tide, meltwater was found to accumulate toward the head of Maxwell Bay, freshening and warming the upper 70 m. Below 70 m, the flood tide enhances the intrusion and mixing of relatively warm modified Upper Circumpolar Deep Water (m-UCDW). Tidal stirring progressively erodes the remnants of Winter Waters found at the bottom of Marian Cove. There is a buoyancy gain through warming and freshening as the summer advances. In Maxwell Bay, the upper 105 m were 0.79 °C warmer and 0.039 PSU fresher in February than in December, changes that cannot be explained by tidal or wind-driven processes. The episodic intrusion of m-UCDW into Maxwell Bay leads to interleaving and eventually to warming, salinification and deoxygenation between 80 and 200 m, with important implications for biological productivity and for the mass balance of tidewater glaciers in the area.
MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia
Authors: Morales María Luz , Arenas Alicia , Ortiz-Ruiz Alejandra , Leivas Alejandra , Rapado Inmaculada , Rodríguez-García Alba , Castro Nerea , Zagorac Ivana , Quintela-Fandino Miguel , Gómez-López Gonzalo , Gallardo Miguel , Ayala Rosa , Linares María , Martínez-López Joaquín
Published: December 2019

FMS-like tyrosine kinase 3 (FLT3) is a key driver of acute myeloid leukemia (AML). Several tyrosine kinase inhibitors (TKIs) targeting FLT3 have been evaluated clinically, but their effects are limited when used in monotherapy due to the emergence of drug-resistance. Thus, a better understanding of drug-resistance pathways could be a good strategy to explore and evaluate new combinational therapies for AML. Here, we used phosphoproteomics to identify differentially-phosphorylated proteins in patients with AML and TKI resistance. We then studied resistance mechanisms in vitro and evaluated the efficacy and safety of rational combinational therapy in vitro, ex vivo and in vivo in mice. Proteomic and immunohistochemical studies showed the sustained activation of ERK1/2 in bone marrow samples of patients with AML after developing resistance to FLT3 inhibitors, which was identified as a common resistance pathway. We examined the concomitant inhibition of MEK-ERK1/2 and FLT3 as a strategy to overcome drug-resistance, finding that the MEK inhibitor trametinib remained potent in TKI-resistant cells and exerted strong synergy when combined with the TKI midostaurin in cells with mutated and wild-type FLT3. Importantly, this combination was not toxic to CD34+ cells from healthy donors, but produced survival improvements in vivo when compared with single therapy groups. Thus, our data point to trametinib plus midostaurin as a potentially beneficial therapy in patients with AML.
Peripheral blood neuroendocrine hormones are associated with clinical indices of sport-related concussion
Authors: Di Battista Alex P. , Rhind Shawn G. , Churchill Nathan , Richards Doug , Lawrence David W. , Hutchison Michael G.
Published: December 2019

The purpose of this study was to evaluate the relationship between neuroendocrine hormones and clinical recovery following sport-related concussion (SRC). Ninety-five athletes (n = 56 male, n = 39 female) from a cohort of 11 interuniversity sport teams at a single institution provided blood samples; twenty six athletes with SRC were recruited 2–7 days post-injury, and 69 uninjured athletes recruited prior to the start of their competitive season. Concentrations of seven neuroendocrine hormones were quantitated in either plasma or serum by solid-phase chemiluminescent immunoassay. The Sport Concussion Assessment Tool version 5 (SCAT-5) was used to evaluate symptoms at the time of blood sampling in all athletes. Multivariate partial least squares (PLS) analyses were used to evaluate the relationship between blood hormone concentrations and both (1) time to physician medical clearance and (2) initial symptom burden. A negative relationship was observed between time to medical clearance and both dehydroepiandrosterone sulfate (DHEA-S) and progesterone; a positive relationship was found between time to medical clearance and prolactin. Cognitive, somatic, fatigue and emotion symptom clusters were associated with distinct neuroendocrine signatures. Perturbations to the neuroendocrine system in athletes following SRC may contribute to initial symptom burden and longer recovery times.
New Labyrinth Microfluidic Device Detects Circulating Tumor Cells Expressing Cancer Stem Cell Marker and Circulating Tumor Microemboli in Hepatocellular Carcinoma
Authors: Wan Shanshan , Kim Tae Hyun , Smith Kaylee J. , Delaney Ryan , Park G-Su , Guo Hui , Lin Eric , Plegue Thomas , Kuo Ning , Steffes John , Leu Christopher , Simeone Diane M. , Razimulava Nataliya , Parikh Neehar D. , Nagrath Sunitha , Welling Theodore H.
Published: December 2019

Hepatocellular Carcinoma (HCC) is one of the most lethal cancers with a high mortality and recurrence rate. Circulating tumor cell (CTC) detection offers various opportunities to advance early detection and monitoring of HCC tumors which is crucial for improving patient outcome. We developed and optimized a novel Labyrinth microfluidic device to efficiently isolate CTCs from peripheral blood of HCC patients. CTCs were identified in 88.1% of the HCC patients over different tumor stages. The CTC positivity rate was significantly higher in patients with more advanced HCC stages. In addition, 71.4% of the HCC patients demonstrated CTCs positive for cancer stem cell marker, CD44, suggesting that the major population of CTCs could possess stemness properties to facilitate tumor cell survival and dissemination. Furthermore, 55% of the patients had the presence of circulating tumor microemboli (CTM) which also correlated with advanced HCC stage, indicating the association of CTM with tumor progression. Our results show effective CTC capture from HCC patients, presenting a new method for future noninvasive screening and surveillance strategies. Importantly, the detection of CTCs with stemness markers and CTM provides unique insights into the biology of CTCs and their mechanisms influencing metastasis, recurrence and therapeutic resistance.
Interaction of human hemoglobin and semi-hemoglobins with the Staphylococcus aureus hemophore IsdB: a kinetic and mechanistic insight
Authors: Gianquinto Eleonora , Moscetti Ilaria , De Bei Omar , Campanini Barbara , Marchetti Marialaura , Luque F. Javier , Cannistraro Salvatore , Ronda Luca , Bizzarri Anna Rita , Spyrakis Francesca , Bettati Stefano
Published: December 2019

Among multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus is emerging as one of the most threatening pathogens. S. aureus exploits different mechanisms for its iron supply, but the preferred one is acquisition of organic iron through the expression of hemoglobin (Hb) receptors. One of these, IsdB, belonging to the Isd (Iron-Regulated Surface Determinant) system, was shown to be essential for bacterial growth and virulence. Therefore, interaction of IsdB with Hb represents a promising target for the rational design of a new class of antibacterial molecules. However, despite recent investigations, many structural and mechanistic details of complex formation and heme extraction process are still elusive. By combining site-directed mutagenesis, absorption spectroscopy, surface plasmon resonance and molecular dynamics simulations, we tackled most of the so far unanswered questions: (i) the exact complex stoichiometry, (ii) the microscopic kinetic rates of complex formation, (iii) the IsdB selectivity for binding to, and extracting heme from, α and β subunits of Hb, iv) the role of specific amino acid residues and structural regions in driving complex formation and heme transfer, and (v) the structural/dynamic effect played by the hemophore on Hb.
Developing a preoperative serum metabolome-based recurrence-predicting nomogram for patients with resected pancreatic ductal adenocarcinoma
Authors: Rho Seoung Yoon , Lee Sang-Guk , Park Minsu , Lee Jinae , Lee Sung Hwan , Hwang Ho Kyoung , Lee Min Jung , Paik Young-Ki , Lee Woo Jung , Kang Chang Moo
Published: December 2019

We investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.
Applied Veterinary Informatics: Development of a Semantic and Domain-Specific Method to Construct a Canine Data Repository
Authors: Boland Mary Regina , Casal Margret L. , Kraus Marc S. , Gelzer Anna R.
Published: December 2019

Animals are used to study the pathogenesis of various human diseases, but typically as animal models with induced disease. However, companion animals develop disease spontaneously in a way that mirrors disease development in humans. The purpose of this study is to develop a semantic and domain-specific method to enable construction of a data repository from a veterinary hospital that would be useful for future studies. We developed a two-phase method that combines semantic and domain-specific approaches to construct a canine data repository of clinical data collected during routine care at the Matthew J Ryan Veterinary Hospital of the University of Pennsylvania (PennVet). Our framework consists of two phases: (1) a semantic data-cleaning phase and (2) a domain-specific data-cleaning phase. We validated our data repository using a gold standard of known breed predispositions for certain diseases (i.e., mitral valve disease, atrial fibrillation and osteosarcoma). Our two-phase method allowed us to maximize data retention (99.8% of data retained), while ensuring the quality of our result. Our final population contained 84,405 dogs treated between 2000 and 2017 from 194 distinct dog breeds. We observed the expected breed associations with mitral valve disease, atrial fibrillation, and osteosarcoma (P < 0.05) after adjusting for multiple comparisons. Precision ranged from 60.0 to 83.3 for the three diseases (avg. 74.2) and recall ranged from 31.6 to 83.3 (avg. 53.3). Our study describes a two-phase method to construct a clinical data repository using canine data obtained during routine clinical care at a veterinary hospital.
Interaction between androgen receptor and coregulator SLIRP is regulated by Ack1 tyrosine kinase and androgen
Authors: De Silva Dinuka , Zhang Zhentao , Liu Yuanbo , Parker Joel S. , Xu Chenxi , Cai Ling , Wang Gang Greg , Earp H. Shelton , Whang Young E.
Published: December 2019

Aberrant activation of the androgen receptor (AR) may play a critical role in castration resistant prostate cancer. After ligand binding, AR is recruited to the androgen responsive element (ARE) sequences on the DNA where AR interaction with coactivators and corepressors modulates transcription. We demonstrated that phosphorylation of AR at Tyr-267 by Ack1/TNK2 tyrosine kinase results in nuclear translocation, DNA binding, and androgen-dependent gene transcription in a low androgen environment. In order to dissect downstream mechanisms, we searched for proteins whose interaction with AR was regulated by Ack1. SLIRP (SRA stem-loop interacting RNA binding protein) was identified as a candidate protein. Interaction between AR and SLIRP was disrupted by Ack1 kinase activity as well as androgen or heregulin treatment. The noncoding RNA, SRA, was required for AR-SLIRP interaction. SLIRP was bound to ARE’s of AR target genes in the absence of androgen. Treatment with androgen or heregulin led to dissociation of SLIRP from the ARE. Whole transcriptome analysis of SLIRP knockdown in androgen responsive LNCaP cells showed that SLIRP affects a significant subset of androgen-regulated genes. Our data suggest that Ack1 kinase and androgen regulate interaction between AR and SLIRP and that SLIRP functions as a coregulator of AR with properties of a corepressor in a context-dependent manner.
Use of different RT-QuIC substrates for detecting CWD prions in the brain of Norwegian cervids
Authors: Bistaffa Edoardo , Vuong Tram Thu , Cazzaniga Federico Angelo , Tran Linh , Salzano Giulia , Legname Giuseppe , Giaccone Giorgio , Benestad Sylvie L. , Moda Fabio
Published: December 2019

Chronic wasting disease (CWD) is a highly contagious prion disease affecting captive and free-ranging cervid populations. CWD has been detected in United States, Canada, South Korea and, most recently, in Europe (Norway, Finland and Sweden). Animals with CWD release infectious prions in the environment through saliva, urine and feces sustaining disease spreading between cervids but also potentially to other non-cervids ruminants (e.g. sheep, goats and cattle). In the light of these considerations and due to CWD unknown zoonotic potential, it is of utmost importance to follow specific surveillance programs useful to minimize disease spreading and transmission. The European community has already in place specific surveillance measures, but the traditional diagnostic tests performed on nervous or lymphoid tissues lack sensitivity. We have optimized a Real-Time Quaking-Induced Conversion (RT-QuIC) assay for detecting CWD prions with high sensitivity and specificity to try to overcome this problem. In this work, we show that bank vole prion protein (PrP) is an excellent substrate for RT-QuIC reactions, enabling the detection of trace-amounts of CWD prions, regardless of prion strain and cervid species. Beside supporting the traditional diagnostic tests, this technology could be exploited for detecting prions in peripheral tissues from live animals, possibly even at preclinical stages of the disease.
Cinnamaldehyde and Phenyl Ethyl Alcohol promote the entrapment of intermediate species of HEWL, as revealed by structural, kinetics and thermal stability studies
Authors: Seraj Zahra , Groves Matthew R. , Seyedarabi Arefeh
Published: December 2019

Numerous efforts have been directed towards investigating the different stages leading to the fibrillation process in neurodegenerative diseases and finding the factors modulating it. In this study, using a wide range of molecular techniques as well as fibrillation kinetics coupled with differential scanning fluorimetry (DSF) and crystal structure determination of HEWL treated with cinnamaldehyde (Cin) and Phenyl ethyl alcohol (PEA) in their aroma form during fibrillation, we were able to identify the binding positions of Cin and PEA in HEWL. Additionally, crystal structures were used to suggest residues Thr43, Asn44, Arg45 and Arg68 as a plausible ‘hotspot’ promoting entrapment of intermediate species in the process of fibril formation in HEWL. We were also able to use DSF to show that Cin can significantly decrease the thermal stability of HEWL, promoting the formation of partially unfolded intermediate species. In conclusion, our data led us to emphasize that compounds in their ‘aroma form’ can influence the structure and stability of protein molecules and suggest reconsideration of HEWL as a model protein for fibrillation studies related to neurodegenerative diseases based on the initial structure of the proteins, whether globular (HEWL) or intrinsically disordered.
Genome investigations show host adaptation and transmission of LA-MRSA CC398 from pigs into Danish healthcare institutions
Authors: Sieber Raphael Niklaus , Larsen Anders Rhod , Urth Tinna Ravnholt , Iversen Søren , Møller Camilla Holten , Skov Robert Leo , Larsen Jesper , Stegger Marc
Published: December 2019

Over the last decade, an increasing number of infections with livestock-associated methicillin-resistant Staphylococcus aureus of clonal complex 398 (LA-MRSA CC398) in persons without contact to livestock has been registered in Denmark. These infections have been suggested to be the result of repeated spillover of random isolates from livestock into the community. However, other studies also found emerging sub-lineages spreading among humans. Based on genome-wide SNPs and genome-wide association studies (GWAS), we assessed the population structure and genomic content of Danish LA-MRSA CC398 isolates from healthcare-associated infections from 2014 to 2016 (n = 73) and compared these to isolates from pigs in Denmark from 2014 (n = 183). Phylogenetic analyses showed that most human isolates were closely related to and scattered among pig isolates showing that the majority of healthcare-associated infections are the result of repeated spillover from pig farms, even though cases of human-to-human transmission also were identified. GWAS revealed frequent loss of antimicrobial resistance genes and acquisition of human-specific virulence genes in the human isolates showing adaptation in response to changes in selective pressures in different host environments, which over time could lead to the emergence of LA-MRSA CC398 lineages more adapted to human colonization and transmission.
Chronic voluntary alcohol consumption causes persistent cognitive deficits and cortical cell loss in a rodent model
Authors: Charlton Annai J. , May Carlos , Luikinga Sophia J. , Burrows Emma L. , Hyun Kim Jee , Lawrence Andrew J. , Perry Christina J.
Published: December 2019

Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies.
A Biogeographic Barrier Test Reveals a Strong Genetic Structure for a Canopy-Emergent Amazon Tree Species
Authors: Nazareno Alison G. , Dick Christopher W. , Lohmann Lúcia G.
Published: December 2019

Wallace’s (1854) Riverine Barrier hypothesis is one of the earliest explanations for Amazon biotic diversification. Despite the importance of this hypothesis for explaining speciation in some animal groups, it has not been studied extensively for plant species. In this study we use a prominent Amazon tree, Buchenavia oxycarpa (Mart.) Eichler (Combretaceae), to evaluate Wallace’s hypothesis along the Rio Negro, a major Amazon tributary that has driven allopatric speciation for several animal taxa. We sampled six individuals from sixteen localities along both river banks, and used a modified ddRADseq protocol to identify SNP markers. Our population genomic data revealed strong genetic structure for B. oxycarpa sampled across banks of the Rio Negro (ϕCT = 0.576, P < 0.001), supporting the hypothesis that the Rio Negro acted as a significant genetic barrier for B. oxycarpa. Our study shows that gene flow for this large and well-dispersed Amazon tree is impeded by riverine barriers, though this has not yet resulted in speciation. Future studies focused on species with different life histories, including species restricted to non-flooded forests, are needed to further advance our understanding of Amazon rivers as drivers of biotic diversification.
Expression of Metazoan Annexins in Yeast Provides Protection Against Deleterious Effects of the Biofuel Isobutanol
Authors: Creutz Carl E.
Published: December 2019

The ability of microorganisms to produce biofuels by fermentation is adversely affected by the perturbing effects of the hydrophobic biofuel on plasma membrane structure. It is demonstrated here that heterologous expression of metazoan, calcium-dependent, membrane-binding proteins of the annexin class can reduce deleterious effects of isobutanol on Saccharomyces cerevisiae viability and complex membrane functions. Therefore, expression of annexins in industrial strains of yeast or bacteria may prove beneficial in biofuel production.
Antifungal potential of secondary metabolites involved in the interaction between citrus pathogens
Authors: Costa Jonas Henrique , Wassano Cristiane Izumi , Angolini Célio Fernando Figueiredo , Scherlach Kirstin , Hertweck Christian , Pacheco Fill Taícia
Published: December 2019

Numerous postharvest diseases have been reported that cause substantial losses of citrus fruits worldwide. Penicillium digitatum is responsible for up to 90% of production losses, and represent a problem for worldwide economy. In order to control phytopathogens, chemical fungicides have been extensively used. Yet, the use of some artificial fungicides cause concerns about environmental risks and fungal resistance. Therefore, studies focusing on new approaches, such as the use of natural products, are getting attention. Co-culture strategy can be applied to discover new bioactive compounds and to understand microbial ecology. Mass Spectrometry Imaging (MSI) was used to screen for potential antifungal metabolites involved in the interaction between Penicillium digitatum and Penicillium citrinum. MSI revealed a chemical warfare between the fungi: two tetrapeptides, deoxycitrinadin A, citrinadin A, chrysogenamide A and tryptoquialanines are produced in the fungi confrontation zone. Antimicrobial assays confirmed the antifungal activity of the investigated metabolites. Also, tryptoquialanines inhibited sporulation of P. citrinum. The fungal metabolites reported here were never described as antimicrobials until this date, demonstrating that co-cultures involving phytopathogens that compete for the same host is a positive strategy to discover new antifungal agents. However, the use of these natural products on the environment, as a safer strategy, needs further investigation. This paper aimed to contribute to the protection of agriculture, considering health and ecological risks.
First identification of mammalian orthoreovirus type 3 by gut virome analysis in diarrheic child in Brazil
Authors: Rosa Ulisses Alves , Ribeiro Geovani de Oliveira , Villanova Fabiola , Luchs Adriana , Milagres Flávio Augusto de Pádua , Komninakis Shirley Vasconcelos , Tahmasebi Roozbeh , Lobato Márcia Cristina Alves Brito Sayão , Brustulin Rafael , Chagas Rogério Togisaki das , Abrão Maria de Fátima Neves dos Santos , Soares Cassia Vitória de Deus Alves , Tinker Rory J , Pandey Ramendra Pati , Raj V. Samuel , Sabino Ester Cerdeira , Deng Xutao , Delwart Eric , Costa Antonio Charlys da , Leal Élcio
Published: December 2019

Diarrhea remains one of the most common causes of deaths in children. Although many studies have investigated the prevalence of enteric pathogens around the globe some diarrheal episodes remain unexplained. It is possible that some yet-unidentified viral agents could be related to these cases of gastroenteritis. By using viral metagenomics techniques, we screened 251 fecal samples of children between 0.5 to 2.5-year-old with acute diarrhea not associated with common pathogens. These children live in rural areas and have different levels of contact with animals such as pigs, cows and bats. Here we report a complete genome of one mammalian orthoreovirus (MRV) type 3, denoted TO-151/BR, detected in a female child in the state of Tocantins (north of Brazil). Brazilian TO-151/BR strain was classified as MRV-3 based on S1 phylogeny and was closely related to porcine Asian strains. Phylogenetic analyses showed that other segments were more similar to MRV-3s of different geographic locations and hosts, including human and bats, highlighting genome reassortment and lack of host-specific barriers. This is the first report of MRV-3 in South America and a hypothesis of a silent long-term circulation of this virus in Brazil has been raised.
Electrospray patterning of yeast cells for applications in alcoholic fermentation
Authors: Jeong Sang Bin , Chong Eui-seok , Heo Ki Joon , Lee Gun Woong , Kim Hyung Joo , Lee Byung Uk
Published: December 2019

Yeast cells patterned by pulsed jet electrospray showed a high alcoholic fermentation rate. Multi-dimensional patterns of individual yeast cells were produced by varying the experimental parameters of the electrospray system. The electrospray process, which employed a vibrational electric field, could control patterns of viable yeast cells at a cellular resolution. This novel system for electrospraying viable cells can be applied to biological process engineering including whole cell biochip techniques and micro fermentation processes for biochemical studies.
Bottom Sediments Reveal Inter-Annual Variability of Interaction between the Ob and Yenisei Plumes in the Kara Sea
Authors: Osadchiev A. A. , Asadulin En. E. , Miroshnikov A. Yu. , Zavialov I. B. , Dubinina E. O. , Belyakova P. A.
Published: December 2019

River discharge is the main source of terrigenous sediments in many coastal areas adjacent to estuaries and deltas of large rivers. Spreading and mixing dynamics of river plumes governs transport of suspended sediments and their deposition at sea bottom at these areas. Generally river plumes have very large synoptic and seasonal variability, which cannot be reconstructed from structure of bottom sediments due to their small accumulation velocity. However, bottom sediments can be indicative of variability of river plumes on inter-annual and decadal time scales. In this study we focus on the large Ob and Yenisei buoyant plumes formed in the central part of the Kara Sea. These plumes interact and mix in the area adjacent to the closely located Ob and Yenisei gulfs. Suspended sediments carried by these river plumes have significantly different geochemical characteristics that can be used to detect Ob or Yenisei origin of bottom sediments. Using new geochemical methods we revealed dependence between spreading patterns of these plumes and spatial distribution and vertical structure of bottom sediments in the study area. This relation is confirmed by a good agreement between local wind and discharge conditions reconstructed for 1948–2001 and vertical structure of bottom sediments.
Author Correction: Bases of Bacterial Sodium Channel Selectivity Among Organic Cations
Authors: Wang Yibo , Finol-Urdaneta Rocio K. , Ngo Van Anh , French Robert J. , Noskov Sergei Yu.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Cretaceous amber fossils highlight the evolutionary history and morphological conservatism of land snails
Authors: Hirano Takahiro , Asato Kaito , Yamamoto Shûhei , Takahashi Yui , Chiba Satoshi
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Flow chemistry controls self-assembly and cargo in Belousov-Zhabotinsky driven polymerization-induced self-assembly
Authors: Hou Liman , Dueñas-Díez Marta , Srivastava Rohit , Pérez-Mercader Juan
Published: December 2019

Amphiphilic block-copolymer vesicles are increasingly used for medical and chemical applications, and a novel method for their transient self-assembly orchestrated by periodically generated radicals during the oscillatory Belousov-Zhabotinsky (BZ) reaction was recently developed. Here we report how combining this one pot polymerization-induced self-assembly (PISA) method with a continuously stirred tank reactor (CSTR) strategy allows for continuous and reproducible control of both the PISA process and the chemical features (e.g. the radical generation and oscillation) of the entrapped cargo. By appropriately tuning the residence time (τ), target degree of polymerization (DP) and the BZ reactants, intermediate self-assembly structures are also obtained (micelles, worms and nano-sized vesicles). Simultaneously, the chemical properties of the cargo at encapsulation are known and tunable, a key advantage over batch operation. Finally, we also show that BZ-driven polymerization in CSTR additionally supports more non-periodic dynamics such as bursting.
Direct bioelectrocatalysis by redox enzymes immobilized in electrostatically condensed oppositely charged polyelectrolyte electrode coatings
Authors: Lim Koun , Sima Monika , Stewart Russell J. , Minteer Shelley D.
Published: December 2019

The ionic induced phase inversion of two oppositely charged electrolytes for enzyme immobilization and its application in bioelectrocatalysis.
Advanced space- and time-resolved techniques for photocatalyst studies
Authors: Gao Yuying , Nie Wei , Wang Xiuli , Fan Fengtao , Li Can
Published: December 2019

Nanoparticle photocatalysts present the obvious characteristic of heterogeneity in structure, energy, and function at spatial and temporal scales.
Hermetically encapsulating sulfur by FePS3 flakes for high-performance lithium sulfur batteries
Authors: Zhang Shuai , Xu Danyun , Su Chenliang , Tang Wei , Ju Huanxin , Zhang Jinyong , Tian Bingbing
Published: December 2019

FePS3 flakes could encapsulate hollow sulfur spheres and trap lithium polysulfides, which will be beneficial to high-performance lithium sulfur batteries.
Electrospun Ru–RuO2/MoO3carbon nanorods with multi-active components: a Pt-like catalyst for the hydrogen evolution reaction
Authors: Fan Libing , Li Qun , Wang Dewen , Meng Tian , Yan Mengxia , Xing Zhicai , Wang Erkang , Yang Xiurong
Published: December 2019

Ru, RuO2, and MoO3embedded carbon nanorods with superior HER performance were synthesized through electrospinning and subsequent calcination.
Optical performance and growth mechanism of a 2D WS2–MoWS2 hybrid heterostructure fabricated by a one-step CVD strategy
Authors: Chen Fei , Yao Yi , Su Weitao , Ding Su , Fu Li
Published: December 2019

A large-scale 2D WS2-Mo1−xWxS2 hybrid heterostructure can be realized by the reaction of S powder and sputtered Mo/W films through the chemical vapor deposition method.