bluuebunny/crossref_metadata_2025 huggingface dataset:
RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas
Authors: Garcia-Rendueles Angela R. , Chenlo Miguel , Oroz-Gonjar Fernando , Solomou Antonia , Mistry Anisha , Barry Sayka , Gaston-Massuet Carles , Garcia-Lavandeira Montserrat , Perez-Romero Sihara , Suarez-Fariña Maria , Pradilla-Dieste Alberto , Dieguez Carlos , Mehlen Patrick , Korbonits Márta , Alvarez Clara V.
Published: September 2021

It is unclear how loss-of-function germline mutations in the widely-expressed co-chaperone AIP, result in young-onset growth hormone secreting pituitary tumours. The RET receptor, uniquely co-expressed in somatotrophs with PIT1, induces apoptosis when unliganded, while RET supports cell survival when it is bound to its ligand. We demonstrate that at the plasma membrane, AIP is required to form a complex with monomeric-intracellular-RET, caspase-3 and PKCδ resulting in PIT1/CDKN2A-ARF/p53-apoptosis pathway activation. AIP-deficiency blocks RET/caspase-3/PKCδ activation preventing PIT1 accumulation and apoptosis. The presence or lack of the inhibitory effect on RET-induced apoptosis separated pathogenic AIP variants from non-pathogenic ones. We used virogenomics in neonatal rats to demonstrate the effect of mutant AIP protein on the RET apoptotic pathway in vivo. In adult male rats altered AIP induces elevated IGF-1 and gigantism, with pituitary hyperplasia through blocking the RET-apoptotic pathway. In females, pituitary hyperplasia is induced but IGF-1 rise and gigantism are blunted by puberty. Somatotroph adenomas from pituitary-specific Aip-knockout mice overexpress the RET-ligand GDNF, therefore, upregulating the survival pathway. Somatotroph adenomas from patients with or without AIP mutation abundantly express GDNF, but AIP-mutated tissues have less CDKN2A-ARF expression. Our findings explain the tissue-specific mechanism of AIP-induced somatotrophinomas and provide a previously unknown tumorigenic mechanism, opening treatment avenues for AIP-related tumours.
Visions for a JACIE Quality Management System 4.0
Authors: Snowden John A. , McGrath Eoin , Orchard Kim , Kröger Nicolaus , Sureda Anna , Gratwohl Alois
Published: September 2021

Quality management has been part of hematopoietic stem cell transplantation (HSCT) from the very beginning. It evolved step-wise from open data exchange up to the introduction of the FACT/JACIE-based quality management system (QMS) 2 decades ago. This formal step has eased cooperation, and improved outcome for patients. Today’s expansion of cellular and targeted therapies and new drugs, and the regulatory requirements for advanced therapeutic medicinal products have touched the limits of the current system. Based on the Medicine 4.0 concept, the next step should integrate novel views of QMS. The old definition “Best Quality Transplant” will be replaced by “Optimal Treatment,” and encompass the entire health care journey. “Best outcome” will refer to overall survival, quality of life and costs, with or without HSCT, and will be compatible with all requirements by competent authorities. Decisions will be based on high-level evidence, supported by real-time digitized data collection, data analysis, incorporated into artificial-intelligence systems. To reach this goal, EBMT/JACIE will be challenged to start the process by further fostering harmonization within and between organizations at institutional, national, and European levels. Acceleration in information technology and modifications to working practices during the pandemic should facilitate this development to the next stage.
Bayesian inference with incomplete knowledge explains perceptual confidence and its deviations from accuracy
Authors: Khalvati Koosha , Kiani Roozbeh , Rao Rajesh P. N.
Published: September 2021

In perceptual decisions, subjects infer hidden states of the environment based on noisy sensory information. Here we show that both choice and its associated confidence are explained by a Bayesian framework based on partially observable Markov decision processes (POMDPs). We test our model on monkeys performing a direction-discrimination task with post-decision wagering, demonstrating that the model explains objective accuracy and predicts subjective confidence. Further, we show that the model replicates well-known discrepancies of confidence and accuracy, including the hard-easy effect, opposing effects of stimulus variability on confidence and accuracy, dependence of confidence ratings on simultaneous or sequential reports of choice and confidence, apparent difference between choice and confidence sensitivity, and seemingly disproportionate influence of choice-congruent evidence on confidence. These effects may not be signatures of sub-optimal inference or discrepant computational processes for choice and confidence. Rather, they arise in Bayesian inference with incomplete knowledge of the environment.
CHARGE syndrome protein CHD7 regulates epigenomic activation of enhancers in granule cell precursors and gyrification of the cerebellum
Authors: Reddy Naveen C. , Majidi Shahriyar P. , Kong Lingchun , Nemera Mati , Ferguson Cole J. , Moore Michael , Goncalves Tassia M. , Liu Hai-Kun , Fitzpatrick James A. J. , Zhao Guoyan , Yamada Tomoko , Bonni Azad , Gabel Harrison W.
Published: September 2021

Regulation of chromatin plays fundamental roles in the development of the brain. Haploinsufficiency of the chromatin remodeling enzyme CHD7 causes CHARGE syndrome, a genetic disorder that affects the development of the cerebellum. However, how CHD7 controls chromatin states in the cerebellum remains incompletely understood. Using conditional knockout of CHD7 in granule cell precursors in the mouse cerebellum, we find that CHD7 robustly promotes chromatin accessibility, active histone modifications, and RNA polymerase recruitment at enhancers. In vivo profiling of genome architecture reveals that CHD7 concordantly regulates epigenomic modifications associated with enhancer activation and gene expression of topologically-interacting genes. Genome and gene ontology studies show that CHD7-regulated enhancers are associated with genes that control brain tissue morphogenesis. Accordingly, conditional knockout of CHD7 triggers a striking phenotype of cerebellar polymicrogyria, which we have also found in a case of CHARGE syndrome. Finally, we uncover a CHD7-dependent switch in the preferred orientation of granule cell precursor division in the developing cerebellum, providing a potential cellular basis for the cerebellar polymicrogyria phenotype upon loss of CHD7. Collectively, our findings define epigenomic regulation by CHD7 in granule cell precursors and identify abnormal cerebellar patterning upon CHD7 depletion, with potential implications for our understanding of CHARGE syndrome.
Multiplex suppression of four quadruplet codons via tRNA directed evolution
Authors: DeBenedictis Erika A. , Carver Gavriela D. , Chung Christina Z. , Söll Dieter , Badran Ahmed H.
Published: September 2021

Genetic code expansion technologies supplement the natural codon repertoire with assignable variants in vivo, but are often limited by heterologous translational components and low suppression efficiencies. Here, we explore engineered Escherichia coli tRNAs supporting quadruplet codon translation by first developing a library-cross-library selection to nominate quadruplet codon–anticodon pairs. We extend our findings using a phage-assisted continuous evolution strategy for quadruplet-decoding tRNA evolution (qtRNA-PACE) that improved quadruplet codon translation efficiencies up to 80-fold. Evolved qtRNAs appear to maintain codon-anticodon base pairing, are typically aminoacylated by their cognate tRNA synthetases, and enable processive translation of adjacent quadruplet codons. Using these components, we showcase the multiplexed decoding of up to four unique quadruplet codons by their corresponding qtRNAs in a single reporter. Cumulatively, our findings highlight how E. coli tRNAs can be engineered, evolved, and combined to decode quadruplet codons, portending future developments towards an exclusively quadruplet codon translation system.
Collective patterns of social diffusion are shaped by individual inertia and trend-seeking
Authors: Ye Mengbin , Zino Lorenzo , Mlakar Žan , Bolderdijk Jan Willem , Risselada Hans , Fennis Bob M. , Cao Ming
Published: September 2021

Social conventions change when individuals collectively adopt an alternative over the status quo, in a process known as social diffusion. Our repeated trials of a multi-round experiment provided data that helped motivate the proposal of an agent-based model of social diffusion that incorporates inertia and trend-seeking, two behavioural mechanisms that are well documented in the social psychology literature. The former causes people to stick with their current decision, the latter creates sensitivity to population-level changes. We show that such inclusion resolves the contradictions of existing models, allowing to reproduce patterns of social diffusion which are consistent with our data and existing empirical observations at both the individual and population level. The model reveals how the emergent population-level diffusion pattern is critically shaped by the two individual-level mechanisms; trend-seeking guarantees the diffusion is explosive after the diffusion process takes off, but inertia can greatly delay the time to take-off.
Chemically driven energetic molecular ferroelectrics
Authors: Hu Yong , Liu Zhiyu , Wu Chi-Chin , Gottfried Jennifer L. , Pesce-Rodriguez Rose , Walck Scott D. , Chung Peter W. , Ren Shenqiang
Published: September 2021

Chemically driven thermal wave triggers high energy release rate in covalently-bonded molecular energetic materials. Molecular ferroelectrics bridge thermal wave and electrical energy by pyroelectric associated with heating frequency, thermal mass and heat transfer. Herein we design energetic molecular ferroelectrics consisting of imidazolium cations (energetic ion) and perchlorate anions (oxidizer), and describe its thermal wave energy conversion with a specific power of 1.8 kW kg−1. Such a molecular ferroelectric crystal shows an estimated detonation velocity of 7.20 ± 0.27 km s−1 comparable to trinitrotoluene and hexanitrostilbene. A polarization-dependent heat transfer and specific power suggests the role of electron-phonon interaction in tuning energy density of energetic molecular ferroelectrics. These findings represent a class of molecular ferroelectric energetic compounds for emerging energy applications demanding high power density.
Low-field onset of Wannier-Stark localization in a polycrystalline hybrid organic inorganic perovskite
Authors: Berghoff Daniel , Bühler Johannes , Bonn Mischa , Leitenstorfer Alfred , Meier Torsten , Kim Heejae
Published: September 2021

Methylammonium lead iodide perovskite (MAPbI3) is renowned for an impressive power conversion efficiency rise and cost-effective fabrication for photovoltaics. In this work, we demonstrate that polycrystalline MAPbI3s undergo drastic changes in optical properties at moderate field strengths with an ultrafast response time, via transient Wannier Stark localization. The distinct band structure of this material - the large lattice periodicity, the narrow electronic energy bandwidths, and the coincidence of these two along the same high-symmetry direction – enables relatively weak fields to bring this material into the Wannier Stark regime. Its polycrystalline nature is not detrimental to the optical switching performance of the material, since the least dispersive direction of the band structure dominates the contribution to the optical response, which favors low-cost fabrication. Together with the outstanding photophysical properties of MAPbI3, this finding highlights the great potential of this material in ultrafast light modulation and novel photonic applications.
Extremely anisotropic van der Waals thermal conductors
Authors: Kim Shi En , Mujid Fauzia , Rai Akash , Eriksson Fredrik , Suh Joonki , Poddar Preeti , Ray Ariana , Park Chibeom , Fransson Erik , Zhong Yu , Muller David A. , Erhart Paul , Cahill David G. , Park Jiwoong
Published: September 2021

The densification of integrated circuits requires thermal management strategies and high thermal conductivity materials1–3. Recent innovations include the development of materials with thermal conduction anisotropy, which can remove hotspots along the fast-axis direction and provide thermal insulation along the slow axis4,5. However, most artificially engineered thermal conductors have anisotropy ratios much smaller than those seen in naturally anisotropic materials. Here we report extremely anisotropic thermal conductors based on large-area van der Waals thin films with random interlayer rotations, which produce a room-temperature thermal anisotropy ratio close to 900 in MoS2, one of the highest ever reported. This is enabled by the interlayer rotations that impede the through-plane thermal transport, while the long-range intralayer crystallinity maintains high in-plane thermal conductivity. We measure ultralow thermal conductivities in the through-plane direction for MoS2(57 ± 3 mW m−1 K−1) and WS2(41 ± 3 mW m−1 K−1) films, and we quantitatively explain these values using molecular dynamics simulations that reveal one-dimensional glass-like thermal transport. Conversely, the in-plane thermal conductivity in these MoS2films is close to the single-crystal value. Covering nanofabricated gold electrodes with our anisotropic films prevents overheating of the electrodes and blocks heat from reaching the device surface. Our work establishes interlayer rotation in crystalline layered materials as a new degree of freedom for engineering-directed heat transport in solid-state systems.
Diagnostic performance of the Abbott RealTime MTB assay for tuberculosis diagnosis in people living with HIV
Authors: Saavedra Belén , Mambuque Edson , Gomes Neide , Nguenha Dinis , Mabunda Rita , Faife Luis , Langa Ruben , Munguambe Shilzia , Manjate Filomena , Cossa Anelsio , Scott Lesley , García-Basteiro Alberto L.
Published: September 2021

Strengthening tuberculosis diagnosis is an international priority and the advocacy for multi-disease testing devices raises the possibility of improving laboratory efficiency. However, the advantages of centralized platforms might not translate into real improvements under operational conditions. This study aimed to evaluate the field use of the Abbott RealTime MTB (RT-MTB) and Xpert MTB/RIF assays, in a large cohort of HIV-positive and TB presumptive cases in Southern Mozambique. Over a 6-month period, 255 HIV-positive TB presumptive cases were consecutively recruited in the high TB/HIV burden district of Manhiça. The diagnostic performance of both assays was evaluated against two different reference standards: a microbiological gold standard (MGS) and a composite reference standard (CRS). Results from the primary analysis (MGS) showed improved sensitivity (Se) and reduced specificity (Sp) for the Abbott RT-MTB assay compared to the Xpert MTB/RIF (RT-MTB Se: 0.92 (95% CI: 0.75;0.99) vs Xpert Se: 0.73 (95% CI: 0.52;0.88) p value = 0.06; RT-MTB Sp: 0.80 (0.72;0.86) vs Xpert Sp: 0.96 (0.92;0.99) p value < 0.001). The lower specificity may be due to cross-reactivity with non-tuberculous mycobacteria (NTMs), the detection of non-viable MTBC, or the identification of true TB cases missed by the gold standard.
Experience of symptom control, anxiety and associating factors in a palliative care unit evaluated with Support Team Assessment Schedule Japanese version
Authors: Ito Tetsuya , Tomizawa Emi , Yano Yuki , Takei Kiyozumi , Takahashi Naoko , Shaku Fumio
Published: September 2021

Various physical and psychosocial difficulties including anxiety affect cancer patients. Patient surroundings also have psychological effects on caregiving. Assessing the current status of palliative care intervention, specifically examining anxiety and its associated factors, is important to improve palliative care unit (PCU) patient quality of life (QOL). This study retrospectively assessed 199 patients admitted to a PCU during August 2018–June 2019. Data for symptom control, anxiety level, disease insight, and communication level obtained using Support Team Assessment Schedule Japanese version (STAS-J) were evaluated on admission and after 2 weeks. Palliative Prognostic Index (PPI) and laboratory data were collected at admission. Patient anxiety was significantly severer and more frequent in groups with severer functional impairment (p = 0.003) and those requiring symptom control (p = 0.006). Nevertheless, no relation was found between dyspnea and anxiety (p = 0.135). Patients with edema more frequently experienced anxiety (p = 0.068). Patient survival was significantly shorter when family anxiety was higher after 2 weeks (p = 0.021). Symptoms, edema, and disabilities in daily living correlate with patient anxiety. Dyspnea is associated with anxiety, but its emergence might be attributable mainly to physical factors in this population. Family members might sensitize changes reflecting worsened general conditions earlier than the patients.
Asymmetric Little–Parks oscillations in full shell double nanowires
Authors: Vekris Alexandros , Estrada Saldaña Juan Carlos , de Bruijckere Joeri , Lorić Sara , Kanne Thomas , Marnauza Mikelis , Olsteins Dags , Nygård Jesper , Grove-Rasmussen Kasper
Published: September 2021

Little–Parks oscillations of a hollow superconducting cylinder are of interest for flux-driven topological superconductivity in single Rashba nanowires. The oscillations are typically symmetric in the orientation of the applied magnetic flux. Using double InAs nanowires coated by an epitaxial superconducting Al shell which, despite the non-centro-symmetric geometry, behaves effectively as one hollow cylinder, we demonstrate that a small misalignment of the applied parallel field with respect to the axis of the nanowires can produce field-asymmetric Little–Parks oscillations. These are revealed by the simultaneous application of a magnetic field perpendicular to the misaligned parallel field direction. The asymmetry occurs in both the destructive regime, in which superconductivity is destroyed for half-integer quanta of flux through the shell, and in the non-destructive regime, where superconductivity is depressed but not fully destroyed at these flux values.
Fluorescence quenching based detection of nitroaromatics using luminescent triphenylamine carboxylic acids
Authors: Mishra Aamnayee , Dheepika R. , Parvathy P. A. , Imran P. M. , Bhuvanesh N. S. P. , Nagarajan S.
Published: September 2021

Detection of nitroaromatics employing greener techniques has been one of the most active research fields in chemistry. A series of triphenylamine (TPA) functionalized carboxylic acids were synthesized and characterized using various spectroscopic techniques including single-crystal X-ray diffraction analysis. The interaction of carboxylic acid-decorated TPAs with nitroaromatic compounds was photophysically explored using absorption and emission spectroscopy. Stern–Volmer plot accounts for the appreciable quenching constant of the TPA-acids. Density functional theory calculations were carried out to study the new compounds' frontier molecular orbital energy levels and the possible interactions with picrate anion and revealed an unusual charge transfer interaction between acids and picrate anion. The contact mode detection shows the TPA-acids can be used as dip-strip sensors for picric acid detection.
Early type 1 diabetes aggravates renal ischemia/reperfusion-induced acute kidney injury
Authors: de Ponte Mariana Charleaux , Cardoso Vanessa Gerolde , Gonçalves Guilherme Lopes , Costa-Pessoa Juliana Martins , Oliveira-Souza Maria
Published: September 2021

The present study aimed to investigate the interaction between early diabetes and renal IR-induced AKI and to clarify the mechanisms involved. C57BL/6J mice were assigned to the following groups: (1) sham-operated; (2) renal IR; (3) streptozotocin (STZ—55 mg/kg/day) and sham operation; and (4) STZ and renal IR. On the 12th day after treatments, the animals were subjected to bilateral IR for 30 min followed by reperfusion for 48 h, at which time the animals were euthanized. Renal function was assessed by plasma creatinine and urea levels, as well urinary protein contents. Kidney morphology and gene and protein expression were also evaluated. Compared to the sham group, renal IR increased plasma creatinine, urea and albuminuria levels and decreased Nphs1 mRNA expression and nephrin and WT1 protein staining. Tubular injury was observed with increased Havcr1 and Mki67 mRNA expression accompanied by reduced megalin staining. Renal IR also resulted in increased SQSTM1 protein expression and increased proinflammatory and profibrotic factors mRNA expression. Although STZ treatment resulted in hyperglycemia, it did not induce significant changes in renal function. On the other hand, STZ treatment aggravated renal IR-induced AKI by exacerbating renal dysfunction, glomerular and tubular injury, inflammation, and profibrotic responses. Thus, early diabetes constitutes a relevant risk factor for renal IR-induced AKI.
Inferring entire spiking activity from local field potentials
Authors: Ahmadi Nur , Constandinou Timothy G. , Bouganis Christos-Savvas
Published: September 2021

Extracellular recordings are typically analysed by separating them into two distinct signals: local field potentials (LFPs) and spikes. Previous studies have shown that spikes, in the form of single-unit activity (SUA) or multiunit activity (MUA), can be inferred solely from LFPs with moderately good accuracy. SUA and MUA are typically extracted via threshold-based technique which may not be reliable when the recordings exhibit a low signal-to-noise ratio (SNR). Another type of spiking activity, referred to as entire spiking activity (ESA), can be extracted by a threshold-less, fast, and automated technique and has led to better performance in several tasks. However, its relationship with the LFPs has not been investigated. In this study, we aim to address this issue by inferring ESA from LFPs intracortically recorded from the motor cortex area of three monkeys performing different tasks. Results from long-term recording sessions and across subjects revealed that ESA can be inferred from LFPs with good accuracy. On average, the inference performance of ESA was consistently and significantly higher than those of SUA and MUA. In addition, local motor potential (LMP) was found to be the most predictive feature. The overall results indicate that LFPs contain substantial information about spiking activity, particularly ESA. This could be useful for understanding LFP-spike relationship and for the development of LFP-based BMIs.
Optimization of epilepsy surgery through virtual resections on individual structural brain networks
Authors: Nissen Ida A. , Millán Ana P. , Stam Cornelis J. , van Straaten Elisabeth C. W. , Douw Linda , Pouwels Petra J. W. , Idema Sander , Baayen Johannes C. , Velis Demetrios , Van Mieghem Piet , Hillebrand Arjan
Published: September 2021

The success of epilepsy surgery in patients with refractory epilepsy depends upon correct identification of the epileptogenic zone (EZ) and an optimal choice of the resection area. In this study we developed individualized computational models based upon structural brain networks to explore the impact of different virtual resections on the propagation of seizures. The propagation of seizures was modelled as an epidemic process [susceptible-infected-recovered (SIR) model] on individual structural networks derived from presurgical diffusion tensor imaging in 19 patients. The candidate connections for the virtual resection were all connections from the clinically hypothesized EZ, from which the seizures were modelled to start, to other brain areas. As a computationally feasible surrogate for the SIR model, we also removed the connections that maximally reduced the eigenvector centrality (EC) (large values indicate network hubs) of the hypothesized EZ, with a large reduction meaning a large effect. The optimal combination of connections to be removed for a maximal effect were found using simulated annealing. For comparison, the same number of connections were removed randomly, or based on measures that quantify the importance of a node or connection within the network. We found that 90% of the effect (defined as reduction of EC of the hypothesized EZ) could already be obtained by removing substantially less than 90% of the connections. Thus, a smaller, optimized, virtual resection achieved almost the same effect as the actual surgery yet at a considerably smaller cost, sparing on average 27.49% (standard deviation: 4.65%) of the connections. Furthermore, the maximally effective connections linked the hypothesized EZ to hubs. Finally, the optimized resection was equally or more effective than removal based on structural network characteristics both regarding reducing the EC of the hypothesized EZ and seizure spreading. The approach of using reduced EC as a surrogate for simulating seizure propagation can suggest more restrictive resection strategies, whilst obtaining an almost optimal effect on reducing seizure propagation, by taking into account the unique topology of individual structural brain networks of patients.
Mapping of static magnetic fields near the surface of mobile phones
Authors: Zastko L. , Makinistian L. , Tvarožná A. , Ferreyra F. L. , Belyaev I.
Published: September 2021

Whether the use of mobile phones (MP) represents a health hazard is still under debate. As part of the attempts to resolve this uncertainty, there has been an extensive characterization of the electromagnetic fields MP emit and receive. While the radiofrequencies (RF) have been studied exhaustively, the static magnetic fields (SMF) have received much less attention, regardless of the fact there is a wealth of evidence demonstrating their biological effects. We performed 2D maps of the SMF at several distances from the screen of 5 MP (models between 2013 and 2018) using a tri-axis magnetometer. We built a mathematical model to fit our measurements, extrapolated them down to the phones’ screen, and calculated the SMF on the skin of a 3D head model, showing that exposure is in the µT to mT range. Our literature survey prompts the need of further research not only on the biological effects of SMF and their gradients, but also on their combination with extremely low frequency (ELF) and RF fields. The study of combined fields (SMF, ELF, and RF) as similar as possible to the ones that occur in reality should provide a more sensible assessment of potential risks.
Temporal trends in tolvaptan use after revision of national heart failure guidelines in Japan
Authors: Yamazaki Yusuke , Shiraishi Yasuyuki , Kohsaka Shun , Nagatomo Yuji , Fukuda Keiichi , Kohno Takashi , Yoshikawa Tsutomu
Published: September 2021

Within no definite diuretic protocol for acute heart failure (AHF) patients and its variation in regional clinical guidelines, the latest national guidelines in Japan commends use of tolvaptan in diuretic-resistant patients. This study aimed to examine trends in tolvaptan usage and associated outcomes of AHF patients requiring hospitalization. Between April, 2018 and October, 2019, 1343 consecutive AHF patients (median 78 [69–85] year-old) were enrolled in a prospective, multicenter registry in Japan. Trends over time in tolvaptan usage, along with the severity of heart failure status based on the Get With The Guideline-Heart Failure [GWTG-HF] risk score, and in-hospital outcomes were investigated. During the study period, tolvaptan usage has increased from 13.0 to 28.7% over time (p for trend = 0.07), and 49.4% started tolvaptan within 3 days after admission. The GWTG-HF risk score in the tolvaptan group has significantly decreased over time, while that in the non-tolvaptan group has unchanged. There were no differences in the in-hospital mortality rate between the patients with and without tolvaptan (6.7% vs. 5.8%). After revision of the Japanese clinical practice guidelines for AHF in March 2018, tolvaptan usage for AHF patients has steadily increased. However, in-hospital outcomes including mortality do not seem to be affected.
Galectin-3 for prediction of cardiac function compared to NT-proBNP in individuals with prediabetes and type 2 diabetes mellitus
Authors: Schmitt Volker H. , Prochaska Jürgen H. , Föll Annegret S. , Schulz Andreas , Keller Karsten , Hahad Omar , Koeck Thomas , Tröbs Sven-Oliver , Rapp Steffen , Beutel Manfred , Pfeiffer Norbert , Strauch Konstantin , Lackner Karl J. , Münzel Thomas , Wild Philipp S.
Published: September 2021

Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35–74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β − 0.36, 95% CI − 0.63/− 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β − 0.34, 95% CI − 0.53/− 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β − 0.656, 95% CI − 1.07/− 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HRperSD) 1.60, 95% CI 1.39–1.85; P < 0.0001) and all-cause mortality (HRperSD 1.36, 95% CI 1.25–1.47; P < 0.0001) in T2DM. No relationship between galectin-3 and cardiac function was found in euglycaemia, whereas NT-proBNP consistently related to reduced cardiac function. Prospective value of NT-proBNP on cardiovascular and all-cause mortality was higher. NT-proBNP was superior to galectin-3 to assess reduced systolic and diastolic function.
Analysis of the optical properties of the silvery spots on the wings of the Gulf Fritillary, Dione vanillae
Authors: Dolinko Andrés , Borgmann Luisa , Lutz Christian , Curticean Ernest Ronald , Wacker Irene , Vidal María Sol , Szischik Candela , Donie Yidenekachew , Inchaussandague Marina , Skigin Diana , Hölscher Hendrik , Tubaro Pablo , Barreira Ana
Published: September 2021

The ventral face of the wings of the butterfly Dione vanillae is covered with bright and shiny silvery spots. These areas contain densely packed ground- and coverscales with a bright metallic appearance reflecting more than 50% of light uniformly over the visible range. Our analysis shows that this optically attractive feature is caused by the inner microstructure of the scales located in these areas. Electron microscopy of cross sections through the scales shows that upper and lower lamina, supporting trabeculae, and topping ridges can be approximated by a ‘circus tent’-like geometry. By simulating its optical properties, we show that a moderate disorder of this geometry is important for the uniform reflection of light resulting in the silvery appearance.
CuATSM improves motor function and extends survival but is not tolerated at a high dose in SOD1G93A mice with a C57BL/6 background
Authors: Lum Jeremy S. , Brown Mikayla L. , Farrawell Natalie E. , McAlary Luke , Ly Diane , Chisholm Christen G. , Snow Josh , Vine Kara L. , Karl Tim , Kreilaus Fabian , McInnes Lachlan E. , Nikseresht Sara , Donnelly Paul S. , Crouch Peter J. , Yerbury Justin J.
Published: September 2021

The synthetic copper-containing compound, CuATSM, has emerged as one of the most promising drug candidates developed for the treatment of amyotrophic lateral sclerosis (ALS). Multiple studies have reported CuATSM treatment provides therapeutic efficacy in various mouse models of ALS without any observable adverse effects. Moreover, recent results from an open label clinical study suggested that daily oral dosing with CuATSM slows disease progression in patients with both sporadic and familial ALS, providing encouraging support for CuATSM in the treatment of ALS. Here, we assessed CuATSM in high copy SOD1G93A mice on the congenic C57BL/6 background, treating at 100 mg/kg/day by gavage, starting at 70 days of age. This dose in this specific model has not been assessed previously. Unexpectedly, we report a subset of mice initially administered CuATSM exhibited signs of clinical toxicity, that necessitated euthanasia in extremis after 3–51 days of treatment. Following a 1-week washout period, the remaining mice resumed treatment at the reduced dose of 60 mg/kg/day. At this revised dose, treatment with CuATSM slowed disease progression and increased survival relative to vehicle-treated littermates. This work provides the first evidence that CuATSM produces positive disease-modifying outcomes in high copy SOD1G93A mice on a congenic C57BL/6 background. Furthermore, results from the 100 mg/kg/day phase of the study support dose escalation determination of tolerability as a prudent step when assessing treatments in previously unassessed models or genetic backgrounds.
A late-surviving stem-ctenophore from the Late Devonian of Miguasha (Canada)
Authors: Klug Christian , Kerr Johanne , Lee Michael S. Y. , Cloutier Richard
Published: September 2021

Like other soft-bodied organisms, ctenophores (comb jellies) produce fossils only under exceptional taphonomic conditions. Here, we present the first record of a Late Devonian ctenophore from the Escuminac Formation from Miguasha in eastern Canada. Based on the 18-fold symmetry of this disc-shaped fossil, we assign it to the total-group Ctenophora. Our phylogenetic analyses suggest that the new taxon Daihuoides jakobvintheri gen. et sp. nov. falls near Cambrian stem ctenophores such as ‘dinomischids’ and 'scleroctenophorans'. Accordingly, Daihuoides is a Lazarus-taxon, which post-dates its older relatives by over 140 million years, and overlaps temporally with modern ctenophores, whose oldest representatives are known from the Early Devonian. Our analyses also indicate that the fossil record of ctenophores does not provide strong evidence for or against the phylogenomic hypothesis that ctenophores are sister to all other metazoans.
Prediction﻿ research on sedimentation balance of Three Gorges Reservoir under new conditions of water and sediment
Authors: Chen Peng , Deng Jinyun , Tan Guangming , Lu Jinyou , Jin Zhongwu , Zhou Yinjun , Shu Caiwen , Feng Zhiyong , Tang Rouxin , Lve Yiwei , Wang Yuxuan
Published: September 2021

Influenced by climate change and human activities, especially the completion and operation of cascade reservoirs in the middle and lower reaches of Jinsha River since 2012, new changes have taken place in the water and sediment characteristics of the Three Gorges Reservoir (TGR) in recent years. In this paper, a one-dimensional unsteady water and sediment mathematical model of the main and tributary rivers of the TGR is established, and the main calculation parameters of the model are calibrated with the measured water and sediment data from January 1, 2008 to December 31, 2017. In view of the different combinations of inflow water and sediment that may occur in the TGR under the condition of new water and sediment, the long-term changes of sediment erosion and deposition and the balance of reservoir deposition in the TGR are studied using the model. The results show that: (1) Under the new conditions of water and sediment, the amount of sediment in the TGR accounts for only 14.8% and 35.8% of that in 1956–1990 and 2003–2012, respectively; (2) The variation process of water level, discharge and sediment concentration of each station along the route calculated by the model is basically consistent with the measured results, and the calculated values of total deposition amount and deposition distribution are also basically consistent with the measured results. The verification results of the model are in accordance with the measured values; (3) Under the water-sediment conditions during 1961–1970 and 1991–2000, the model predicted the estimates of 320 and 430 years for the TGR to reach a sedimentation balance, respectively. Under the new water-sediment conditions, it takes 560 years at most and 450 years at least to reach the sedimentation balance for the TGR, and the corresponding condition is the typical year with less water-less sediment and more water-more sediment, respectively. The research results of this paper can provide a new reference for the long-term safe operation and operation optimization of the TGR.
Influence of air supply on coal spontaneous combustion during support withdrawal in fully mechanized coal mining and its prevention
Authors: Zhang Xiaowen , Zhou Xihua , Bai Gang , Wang Cheng
Published: September 2021

It is necessary to change the air supply rate of the working face during the withdrawal of fully mechanized mining, making it important to study the oxidation characteristics of coal samples under different air supply rates. Through a self-made temperature-programmed experimental device, our focus was on studying the change laws of indicator gases released during the low-temperature (303.15–473.15 K) oxidation stage when the air supply rates of the coal samples were 0.67, 1.33, 2, 2.67, and 3.33 mL/s. The experimental results showed that the air supply increased, the concentrations of CO, C2H6, C3H8, C2H4, and C2H2 generated by the coal sample at the same temperature decreased, and the oxidation process decelerated. The initial temperatures of the four hydrocarbon gases were delayed to varying degrees with the increase in the air volume, and C2H4 was found to be more suitable as a hydrocarbon gas for the early warning of coal spontaneous combustion. Surface fitting was applied to analyze the change law of the CO generation rate under the combined effect of temperature and air supply; the change was divided into three stages. The CO concentration model at the upper corner of the working face during the withdrawal period was deduced, and comprehensive safety measures were put forward to prevent coal spontaneous combustion during the withdrawal period.
Dicer-mediated miRNA processing is not involved in controlling muscle mass during muscle atrophy
Authors: Oikawa Satoshi , Shin Jaehoon , Akama Takao , Akimoto Takayuki
Published: September 2021

Muscle atrophy occurs in a variety of physiological and pathological conditions. Specific molecular networks that govern protein synthesis and degradation play important roles in controlling muscle mass under diverse catabolic states. MicroRNAs (miRNAs) were previously found to be regulators of protein synthesis and degradation, and their expressions in skeletal muscle were altered in muscle wasting conditions. However, functional roles of miRNAs in muscle atrophy are poorly understood. In this study, we generated tamoxifen-inducible Dicer knockout (iDicer KO) mice and subjected them to 2 weeks of single hindlimb denervation. The expression of Dicer mRNA was significantly reduced in muscle of the iDicer KO mice compared to that of WT mice. The loss of Dicer moderately reduced levels of muscle-enriched miRNAs, miR-1, miR-133a and miR-206 in both innervated and denervated muscles of the iDicer KO mice. We also found that the extent of denervation-induced muscle atrophy as well as changes of signaling molecules related to protein synthesis/degradation pathways in the iDicer KO mice were comparable to these in WT mice. Taken together, Dicer knockout in adult skeletal muscle did not affect denervation-induced muscle atrophy.
Glucose inhibits haemostasis and accelerates diet-induced hyperlipidaemia in zebrafish larvae
Authors: Morris Simone , Cholan Pradeep Manuneedhi , Britton Warwick J. , Oehlers Stefan H.
Published: September 2021

Hyperglycaemia damages the microvasculature in part through the reduced recruitment of immune cells and interference with platelet signalling, leading to poor wound healing and accelerated lipid deposition in mammals. We investigated the utility of zebrafish larvae to model the effect of exogenous glucose on neutrophil and macrophage recruitment to a tail wound, wound-induced haemostasis, and chicken egg yolk feed challenge-induced hyperlipidaemia by supplementing larvae with exogenous glucose by immersion or injection. Neither method of glucose supplementation affected the recruitment of neutrophils and macrophages following tail transection. Glucose injection reduced thrombocyte retention and fibrin plug formation while only thrombocyte retention was reduced by glucose immersion following tail transection. We observed accelerated lipid accumulation in glucose-injected larvae challenged with high fat chicken egg yolk feeding. Our study identifies conserved and divergent effects of high glucose on inflammation, haemostasis, and hyperlipidaemia in zebrafish larvae compared to mammals.
Establishment of a striped catfish skin explant model for studying the skin response in Aeromonas hydrophila infections
Authors: Siao Ru-Fang , Lin Chia-Hsuan , Chen Li-Hsuan , Wang Liang-Chun
Published: September 2021

Teleost fish skin serves as the first line of defense against pathogens. The interaction between pathogen and host skin determines the infection outcome. However, the mechanism(s) that modulate infection remain largely unknown. A proper tissue culture model that is easier to handle but can quantitatively and qualitatively monitor infection progress may shed some lights. Here, we use striped catfish (Pangasius hypophthalmus) to establish an ex vivo skin explant tissue culture model to explore host pathogen interactions. The skin explant model resembles in vivo skin in tissue morphology, integrity, and immune functionality. Inoculation of aquatic pathogen Aeromonas hydrophila in this model induces epidermal exfoliation along with epithelial cell dissociation and inflammation. We conclude that this ex vivo skin explant model could serve as a teleost skin infection model for monitoring pathogenesis under various infection conditions. The model can also potentially be translated into a platform to study prevention and treatment of aquatic infection on the skin in aquaculture applications.
The effect of estuarine system on the meiofauna and nematodes in the East Siberian Sea
Authors: Portnova Daria A. , Garlitska Lesya A. , Polukhin Alexander A.
Published: September 2021

Arctic meiofauna and nematodes were examined at 12 stations in the East Siberian Sea, covering a depth range of 13–59 m and an estuarine-shelf system from the Indigirka and Kolyma rivers to the adjacent shelf. Our data reveal the low diversity of the meiofauna at the East Siberian Sea shelf. The meiobenthos abundance was influenced by river run-off and the sea bottom landscape. The samples comprised a total of 28 families and 72 genera, and the number of genera per station ranged from 15 to 32. The Comesomatidae was the dominant family with genus Sabatieria. Among all factors, depth, water temperature and the total organic carbon appeared to be important variables explaining spatial variations in meiofauna and nematodes abundance. Depth and river run-off were defining in controlling the density of nematodes in the study area.
Analysis on the healing of gastrointestinal ulceration by using Hemospray
Authors: Werner Christoph R. , Brücklmeier Lena , Kratt Thomas , Malek Nisar P. , Sipos Bence , Wichmann Dörte , Götz Martin
Published: September 2021

Healing of gastrointestinal ulcers after Hemospray application was reported in literature. The pathophysiological mechanism of action of hemostatic powders is not elucidated so far. A prospective animal model was performed to evaluate the effect of Hemospray application on the healing process of artificially induced ulcers of the upper and lower gastrointestinal tract. In 10 pigs, 20 ulcers were created in each the upper and the lower gastrointestinal tract by endoscopic mucosal resection. 50% of the pigs were immediately treated with Hemospray application, the others were not treated. Ulcer size was measured endoscopically on day 0, 2, and 7. On day 7 the ulcers were histopathological evaluated for capillary ingrowth and the thickness of the collagen layer. After 7 days the sizes of the ulcers decreased significantly (stomach: − 22.8% with Hemospray application, − 19% without Hemospray application; rectum: − 50.8% with Hemospray application, − 49.5% without Hemospray application; p = 0.005–0.037), but without significant difference between both groups. This study shows no significant effect of the hemostatic powder Hemospray on ulcer healing in the upper and lower gastrointestinal tract compared with untreated controls, neither harmful nor beneficial. However, some trends merit further trials in patients and may indicate a possible mechanism of accelerated mucosal healing.
Behavioral gain following isolation of attention
Authors: Edwards Grace , Berestova Anna , Battelli Lorella
Published: September 2021

Stable sensory perception is achieved through balanced excitatory-inhibitory interactions of lateralized sensory processing. In real world experience, sensory processing is rarely equal across lateralized processing regions, resulting in continuous rebalancing. Using lateralized attention as a case study, we predicted rebalancing lateralized processing following prolonged spatial attention imbalance could cause a gain in attention in the opposite direction. In neurotypical human adults, we isolated covert attention to one visual field with a 30-min attention-demanding task and found an increase in attention in the opposite visual field after manipulation. We suggest a gain in lateralized attention in the previously unattended visual field is due to an overshoot through attention rebalancing. The offline post-manipulation effect is suggestive of long-term potentiation affecting behavior. Our finding of visual field specific attention increase could be critical for the development of clinical rehabilitation for patients with a unilateral lesion and lateralized attention deficits. This proof-of-concept study initiates the examination of overshoot following the release of imbalance in other lateralized control and sensory domains, important in our basic understanding of lateralized processing.
Comparing texture and digestion properties between white and brown rice of indica cultivars preferred by Chinese consumers
Authors: Huang Min , Li Xing , Hu Liqin , Xiao Zhengwu , Chen Jiana , Cao Fangbo
Published: September 2021

The consumption of good tasting rice, mainly soft-textured white rice with low amylose content, has substantially increased in China as living standards improve. However, this diet change may increase the risk of developing type II diabetes because the soft-textured white rice is generally less resistant to digestion and has a higher glycemic index. In contrast, intake of brown rice is inversely associated with type II diabetes risk. This study was conducted to test the possibility that brown rice processed from soft-textured cultivars has both acceptable texture and improved health benefits. Texture and digestion properties were compared between white and brown rice of five indica cultivars preferred by Chinese consumers. Mean hardness was 33% higher while mean springiness was 5% lower for cooked brown rice than for cooked white rice. As compared to cooked white rice, cooked brown rice had a 41% longer mean active digestion duration but 31% lower mean glucose production rate and 11% lower mean total glucose production from starch digestion. However, the differences in texture and starch digestion properties between cooked brown and white rice were affected by cultivar identity. Brown rice processed from suitable cultivars with both a relatively thinner bran layer and relatively higher grain amylose content met consumer requirements in terms of acceptable texture and improved health benefits.