bluuebunny/crossref_metadata_2025 huggingface dataset:
CME/Antworten: Kranke und ihre Berufe in der Allgemeinarztpraxis
Authors: Stadtmüller Klaus Ernst
Published: April 2021

Zusammenfassung. Mehr Gesundheitsstörungen als erwartet, die zu einem Arztbesuch führen, haben ursächlich mit Belastungen am Arbeitsplatz zu tun. Auch wenn die meisten dieser arbeitsbedingten Erkrankungen nicht zur Anerkennung als Berufskrankheit qualifizieren, kann die Hausärztin/der Hausarzt wichtige Weichen für Heilbehandlung und Prävention stellen. Für eine effiziente Beratung seiner Patientinnen und Patienten muss sie/er jedoch ein Konzept der Regulation von Arbeitssicherheit und Gesundheitsschutz haben und wissen, welche Sozialversicherung welche Rolle bei der Prävention spielt.
Empirical Loss Timescales of Slot Region Electrons due to Plasmaspheric Hiss Based on Van Allen Probes Observations
Authors: Zhu Qi , Cao Xing , Gu Xudong , Ni Binbin , Xiang Zheng , Fu Song , Summers Danny , Hua Man , Lou Yuequn , Ma Xin , Guo Yingjie , Guo Deyu , Zhang Wenxun
Published: April 2021

Based on Van Allen Probes observations, in this study we perform a statistical analysis of the spectral intensities of plasmaspheric hiss at L‐shells of 1.8–3.0 in the slot region. Our results show that slot region hiss power intensifies with a strong day‐night asymmetry as the level of substorm activity or L‐shell increases. Using the statistical spectral profiles of plasmaspheric hiss, we calculate the drift‐ and bounce‐averaged electron pitch angle diffusion coefficients and subsequently obtain the resultant electron loss timescales through 1‐D Fokker‐Planck simulations. We find that slot region electron loss timescales vary significantly from <1 day to several years, showing a strong dependence on electron energy, L‐shell and substorm activity. We also construct an empirical model of slot region electron loss timescales due to scattering by plasmaspheric hiss, which agrees well with the 1‐D simulation results and can be readily used in modeling the dynamics of slot region electrons.
Making the Universe Blurrier
Authors: Benningfield Damond
Published: April 2021

Climate change appears to be directly and indirectly affecting the view from at least one observatory while threatening the existence of others.
Silica optical fiber integrated with two-dimensional materials: towards opto-electro-mechanical technology
Authors: Chen Jin-hui , Xiong Yi-feng , Xu Fei , Lu Yan-qing
Published: April 2021

In recent years, the integration of graphene and related two-dimensional (2D) materials in optical fibers have stimulated significant advances in all-fiber photonics and optoelectronics. The conventional passive silica fiber devices with 2D materials are empowered for enhancing light-matter interactions and are applied for manipulating light beams in respect of their polarization, phase, intensity and frequency, and even realizing the active photo-electric conversion and electro-optic modulation, which paves a new route to the integrated multifunctional all-fiber optoelectronic system. This article reviews the fast-progress field of hybrid 2D-materials-optical-fiber for the opto-electro-mechanical devices. The challenges and opportunities in this field for future development are discussed.
Integrated impedance sensing of liquid sample plug flow enables automated high throughput NMR spectroscopy
Authors: Nassar Omar , Jouda Mazin , Rapp Michael , Mager Dario , Korvink Jan G. , MacKinnon Neil
Published: April 2021

A novel approach for automated high throughput NMR spectroscopy with improved mass-sensitivity is accomplished by integrating microfluidic technologies and micro-NMR resonators. A flow system is utilized to transport a sample of interest from outside the NMR magnet through the NMR detector, circumventing the relatively vast dead volume in the supplying tube by loading a series of individual sample plugs separated by an immiscible fluid. This dual-phase flow demands a real-time robust sensing system to track the sample position and velocities and synchronize the NMR acquisition. In this contribution, we describe an NMR probe head that possesses a microfluidic system featuring: (i) a micro saddle coil for NMR spectroscopy and (ii) a pair of interdigitated capacitive sensors flanking the NMR detector for continuous position and velocity monitoring of the plugs with respect to the NMR detector. The system was successfully tested for automating flow-based measurement in a 500 MHz NMR system, enabling high resolution spectroscopy and NMR sensitivity of 2.18 nmol s1/2with the flow sensors in operation. The flow sensors featured sensitivity to an absolute difference of 0.2 in relative permittivity, enabling distinction between most common solvents. It was demonstrated that a fully automated NMR measurement of nine individual 120 μL samples could be done within 3.6 min or effectively 15.3 s per sample.
Metformin for early comorbid glucose dysregulation and schizophrenia spectrum disorders: a pilot double-blind randomized clinical trial
Authors: Agarwal Sri Mahavir , Panda Roshni , Costa-Dookhan Kenya A. , MacKenzie Nicole E. , Treen Quinn Casuccio , Caravaggio Fernando , Hashim Eyesha , Leung General , Kirpalani Anish , Matheson Kelly , Chintoh Araba F. , Kramer Caroline K. , Voineskos Aristotle N. , Graff-Guerrero Ariel , Remington Gary J. , Hahn Margaret K.
Published: April 2021

Patients with schizophrenia have exceedingly high rates of metabolic comorbidity including type 2 diabetes and lose 15–20 years of life due to cardiovascular diseases, with early accrual of cardiometabolic disease. In this study, thirty overweight or obese (Body Mass Index (BMI) > 25) participants under 40 years old with schizophrenia spectrum disorders and early comorbid prediabetes or type 2 diabetes receiving antipsychotic medications were randomized, in a double-blind fashion, to metformin 1500 mg/day or placebo (2:1 ratio; n = 21 metformin and n = 9 placebo) for 4 months. The primary outcome measures were improvements in glucose homeostasis (HbA1c, fasting glucose) and insulin resistance (Matsuda index—derived from oral glucose tolerance tests and homeostatic model of insulin resistance (HOMA-IR)). Secondary outcome measures included changes in weight, MRI measures of fat mass and distribution, symptom severity, cognition, and hippocampal volume. Twenty-two patients (n = 14 metformin; n = 8 placebo) completed the trial. The metformin group had a significant decrease over time in the HOMA-IR (p = 0.043) and fasting blood glucose (p = 0.007) vs. placebo. There were no differences between treatment groups in the Matsuda index, HbA1c, which could suggest liver-specific effects of metformin. There were no between group differences in other secondary outcome measures, while weight loss in the metformin arm correlated significantly with decreases in subcutaneous, but not visceral or hepatic adipose tissue. Our results show that metformin improved dysglycemia and insulin sensitivity, independent of weight loss, in a young population with prediabetes/diabetes and psychosis spectrum illness, that is at extremely high risk of early cardiovascular mortality. Trial Registration: This protocol was registered with clinicaltrials.gov (NCT02167620).
Radiation enhances the delivery of antisense oligonucleotides and improves chemo-radiation efficacy in brain tumor xenografts
Authors: Ambady Prakash , Wu Yingjen Jeffrey , Kersch Cymon N. , Walker Joshua M. , Holland Samantha , Muldoon Leslie L. , Neuwelt Edward A.
Published: April 2021

Overexpression of O6-methylguanine DNA methyltransferase (MGMT) contributes to resistance to chemo-radiation therapy (CRT) in brain tumors. We previously demonstrated that non-ablative radiation improved delivery of anti-MGMT morpholino oligonucleotides (AMONs) to reduce MGMT levels in subcutaneous tumor xenografts. We evaluate this approach to enhance CRT efficacy in rat brain tumor xenograft models. The impact of radiation on targeted delivery was evaluated using fluorescent oligonucleotides (f-ON). In vitro, f-ON was localized to clathrin-coated vesicles, endosomes, and lysosomes using confocal microscopy in T98G glioma cells. In vivo, fluorescence was detected in pre-radiated, but not non-radiated Long Evans (non-tumor bearing) rat brains. Cranial radiation (2 Gy) followed by AMONs (intravenous, 10.5 mg/kg) reduced MGMT expression by 50% in both orthotopic cerebellar D283 medulloblastoma and intracerebral H460 non-small cell lung carcinoma (NSCLC) xenograft models. To evaluate the efficacy, AMONs concurrent with CRT (2 Gy radiation plus oral 20 mg/kg temozolomide ×4 days) reduced tumor volumes in the medulloblastoma model (p = 0.012), and a similar trend was found in the NSCLC brain metastasis model. We provide proof of concept for the use of non-ablative radiation to guide and enhance the delivery of morpholino oligonucleotides into brain tumor xenograft models to reduce MGMT levels and improve CRT efficacy.
Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells
Authors: Bi Yanli , Gong Longyuan , Liu Pengyuan , Xiong Xiufang , Zhao Yongchao
Published: April 2021

ErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.
TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8+ T cells in conjunction with CEACAM1
Authors: Lake Camille M. , Voss Kelsey , Bauman Bradly M. , Pohida Katherine , Jiang Timothy , Dveksler Gabriela , Snow Andrew L.
Published: April 2021

Immune homeostasis depends upon effective clearance of pathogens while simultaneously preventing autoimmunity and immunopathology in the host. Restimulation-induced cell death (RICD) is one such mechanism where by activated T cells receive subsequent antigenic stimulation, reach a critical signal threshold through the T cell receptor (TCR), and commit to apoptosis. Many details of this process remain unclear, including the role of co-stimulatory and co-inhibitory proteins that influence the TCR signaling cascade. Here we characterize the role of T cell immunoglobulin and mucin domain containing 3 (TIM-3) in RICD regulation. TIM-3 protected newly activated CD8+ effector T cells from premature RICD during clonal expansion. Surprisingly, however, we found that TIM-3 potentiated RICD in late-stage effector T cells. The presence of TIM-3 increased proximal TCR signaling and proapoptotic protein expression in late-stage effector T cells, with no consistent signaling effects noted in newly activated cells with or without TIM-3. To better explain these differences in TIM-3 function as T cells aged, we characterized the temporal pattern of TIM-3 expression in effector T cells. We found that TIM-3 was expressed on the surface of newly activated effector T cells, but remained largely intracellular in late-stage effector cells. Consistent with this, TIM-3 required a ligand to prevent early RICD, whereas ligand manipulation had no effects at later stages. Of the known TIM-3 ligands, carcinoembryonic antigen‐related cell adhesion molecule (CEACAM1) showed the greatest difference in surface expression over time and also protected newly activated cells from premature RICD, with no measurable effects in late-stage effectors. Indeed, CEACAM1 enabled TIM-3 surface expression on T cells, implying a co-dependency for these proteins in protecting expanding T cells from premature RICD. Our findings suggest that co-signaling proteins like TIM-3 and CEACAM1 can alter RICD sensitivity at different stages of the effector T cell response, with important implications for checkpoint blockade therapy.
In situ architecture of neuronal α-Synuclein inclusions
Authors: Trinkaus Victoria A. , Riera-Tur Irene , Martínez-Sánchez Antonio , Bäuerlein Felix J. B. , Guo Qiang , Arzberger Thomas , Baumeister Wolfgang , Dudanova Irina , Hipp Mark S. , Hartl F. Ulrich , Fernández-Busnadiego Rubén
Published: April 2021

The molecular architecture of α-Synuclein (α-Syn) inclusions, pathognomonic of various neurodegenerative disorders, remains unclear. α-Syn inclusions were long thought to consist mainly of α-Syn fibrils, but recent reports pointed to intracellular membranes as the major inclusion component. Here, we use cryo-electron tomography (cryo-ET) to image neuronal α-Syn inclusions in situ at molecular resolution. We show that inclusions seeded by α-Syn aggregates produced recombinantly or purified from patient brain consist of α-Syn fibrils crisscrossing a variety of cellular organelles. Using gold-labeled seeds, we find that aggregate seeding is predominantly mediated by small α-Syn fibrils, from which cytoplasmic fibrils grow unidirectionally. Detailed analysis of membrane interactions revealed that α-Syn fibrils do not contact membranes directly, and that α-Syn does not drive membrane clustering. Altogether, we conclusively demonstrate that neuronal α-Syn inclusions consist of α-Syn fibrils intermixed with membranous organelles, and illuminate the mechanism of aggregate seeding and cellular interaction.
Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland
Authors: Lee Hye Kyung , Willi Michaela , Kuhns Tyler , Liu Chengyu , Hennighausen Lothar
Published: April 2021

Enhancers are transcription factor platforms that synergize with promoters to control gene expression. Here, we investigate enhancers that activate gene expression several hundred-fold exclusively in the lactating mouse mammary gland. Using ChIP-seq for activating histone marks and transcription factors, we identify two candidate enhancers and one super-enhancer in the Csn1s2b locus. Through experimental mouse genetics, we dissect the lactation-specific distal enhancer bound by the mammary-enriched transcription factors STAT5 and NFIB and the glucocorticoid receptor. While deletions of canonical binding motifs for NFIB and STAT5, individually or combined, have a limited biological impact, a non-canonical STAT5 site is essential for enhancer activity during lactation. In contrast, the intronic enhancer contributes to gene expression only in late pregnancy and early lactation, possibly by interacting with the distal enhancer. A downstream super-enhancer, which physically interacts with the distal enhancer, is required for the functional establishment of the Csn1s2b promoter and gene activation. Lastly, NFIB binding in the promoter region fine-tunes Csn1s2b expression. Our study provides comprehensive insight into the anatomy and biology of regulatory elements that employ the JAK/STAT signaling pathway and preferentially activate gene expression during lactation.
Cell barrier function of resident peritoneal macrophages in post-operative adhesions
Authors: Ito Tomoya , Shintani Yusuke , Fields Laura , Shiraishi Manabu , Podaru Mihai‑Nicolae , Kainuma Satoshi , Yamashita Kizuku , Kobayashi Kazuya , Perretti Mauro , Lewis-McDougall Fiona , Suzuki Ken
Published: April 2021

Post-operative adhesions are a leading cause of abdominal surgery-associated morbidity. Exposed fibrin clots on the damaged peritoneum, in which the mesothelial barrier is disrupted, readily adhere to surrounding tissues, resulting in adhesion formation. Here we show that resident F4/80HighCD206−peritoneal macrophages promptly accumulate on the lesion and form a ‘macrophage barrier’ to shield fibrin clots in place of the lost mesothelium in mice. Depletion of this macrophage subset or blockage of CD11b impairs the macrophage barrier and exacerbates adhesions. The macrophage barrier is usually insufficient to fully preclude the adhesion formation; however, it could be augmented by IL-4-based treatment or adoptive transfer of this macrophage subset, resulting in robust prevention of adhesions. By contrast, monocyte-derived recruited peritoneal macrophages are not involved in the macrophage barrier. These results highlight a previously unidentified cell barrier function of a specific macrophage subset, also proposing an innovative approach to prevent post-operative adhesions.
Self-powered ultraflexible photonic skin for continuous bio-signal detection via air-operation-stable polymer light-emitting diodes
Authors: Jinno Hiroaki , Yokota Tomoyuki , Koizumi Mari , Yukita Wakako , Saito Masahiko , Osaka Itaru , Fukuda Kenjiro , Someya Takao
Published: April 2021

Ultraflexible optical devices have been used extensively in next-generation wearable electronics owing to their excellent conformability to human skins. Long-term health monitoring also requires the integration of ultraflexible optical devices with an energy-harvesting power source; to make devices self-powered. However, system-level integration of ultraflexible optical sensors with power sources is challenging because of insufficient air operational stability of ultraflexible polymer light-emitting diodes. Here we develop an ultraflexible self-powered organic optical system for photoplethysmogram monitoring by combining air-operation-stable polymer light-emitting diodes, organic solar cells, and organic photodetectors. Adopting an inverted structure and a doped polyethylenimine ethoxylated layer, ultraflexible polymer light-emitting diodes retain 70% of the initial luminance even after 11.3 h of operation under air. Also, integrated optical sensors exhibit a high linearity with the light intensity exponent of 0.98 by polymer light-emitting diode. Such self-powered, ultraflexible photoplethysmogram sensors perform monitoring of blood pulse signals as 77 beats per minute.
A compartmental model that predicts the effect of social distancing and vaccination on controlling COVID-19
Authors: Dashtbali Mohammadali , Mirzaie Mehdi
Published: April 2021

The understanding of the interaction between disease dynamics and human behavior is an important and essential point to control infectious. Disease outbreak can be influenced by social distancing and vaccination. In this study, we introduce two compartmental models to derive the epidemic curve and analyze the individual’s behavior in spreading and controlling the COVID-19 epidemic. The first model includes Susceptible, Exposed, Infectious, Hospitalized, Recovered and Death compartments and in the second model, we added a new compartment namely, semi-susceptible individuals that are assumed to be more immune than the susceptible. A comparison of the two models shows that the second model provides a better fit to the daily infected cases from Egypt, Belgium, Japan, Nigeria, Italy, and Germany released by WHO. Finally, we added a vaccinated term to the model to predict how vaccination could control the epidemic. The model was applied on the record data from WHO.
Stock delineation of striped snakehead, Channa striata using multivariate generalised linear models with otolith shape and chemistry data
Authors: Khan Salman , Schilling Hayden T. , Khan Mohammad Afzal , Patel Devendra Kumar , Maslen Ben , Miyan Kaish
Published: April 2021

Otoliths are commonly used to discriminate between fish stocks, through both elemental composition and otolith shape. Typical studies also have a large number of elemental compositions and shape measures relative to the number of otolith samples, with these measures exhibiting strong mean–variance relationships. These properties make otolith composition and shape data highly suitable for use within a multivariate generalised linear model (MGLM) framework, yet MGLMs have never been applied to otolith data. Here we apply both a traditional distance based permutational multivariate analysis of variance (PERMANOVA) and MGLMs to a case study of striped snakehead (Channa striata) in India. We also introduce the Tweedie and gamma distributions as suitable error structures for the MGLMs, drawing similarities to the properties of Biomass data. We demonstrate that otolith elemental data and combined otolith elemental and shape data violate the assumption of homogeneity of variance of PERMANOVA and may give misleading results, while the assumptions of the MGLM with Tweedie and gamma distributions are shown to be satisfied and are appropriate for both otolith shape and elemental composition data. Consistent differences between three groups ofC. striatawere identified using otolith shape, otolith chemistry and a combined otolith shape and chemistry dataset. This suggests that future research should be conducted into whether there are demographic differences between these groups which may influence management considerations. The MGLM method is widely applicable and could be applied to any multivariate otolith shape or elemental composition dataset.
A Raman probe of phonons and electron–phonon interactions in the Weyl semimetal NbIrTe4
Authors: Shojaei Iraj Abbasian , Pournia Seyyedesadaf , Le Congcong , Ortiz Brenden R. , Jnawali Giriraj , Zhang Fu-Chun , Wilson Stephen D. , Jackson Howard E. , Smith Leigh M.
Published: April 2021

There is tremendous interest in measuring the strong electron–phonon interactions seen in topological Weyl semimetals. The semimetal NbIrTe4 has been proposed to be a Type-II Weyl semimetal with 8 pairs of opposite Chirality Weyl nodes which are very close to the Fermi energy. We show using polarized angular-resolved micro-Raman scattering at two excitation energies that we can extract the phonon mode dependence of the Raman tensor elements from the shape of the scattering efficiency versus angle. This van der Waals semimetal with broken inversion symmetry and 24 atoms per unit cell has 69 possible phonon modes of which we measure 19 modes with frequencies and symmetries consistent with Density Functional Theory calculations. We show that these tensor elements vary substantially in a small energy range which reflects a strong variation of the electron–phonon coupling for these modes.
Optimisation of a PC12 cell-based in vitro stroke model for screening neuroprotective agents
Authors: Chua PinFen , Lim William K.
Published: April 2021

Stroke causes death and disability globally but no neuroprotectant is approved for post-stroke neuronal injury. Neuroprotective compounds can be identified using oxygen glucose deprivation (OGD) of neuronal cells as an in vitro stroke model. Nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells are frequently used. However, investigators often find their clonal variant undifferentiable and are uncertain of optimal culture conditions. Hence we studied 3 commonly used PC12 variants: PC12 Adh, PC12 from Riken Cell Bank (PC12 Riken) and Neuroscreen-1 (NS-1) cells. We found DMEM the optimal media for PC12 Riken and NS-1 cells. Using a novel serum-free media approach, we identified collagen IV as the preferred adhesive substrate for both cell lines. We found PC12 Adh cells cannot attach without serum and is unable to differentiate using NGF. NS-1 cells differentiated to a maximal 72.7 ± 5.2% %, with substantial basal differentiation. We optimised differentiated NS-1 cells for an in vitro stroke model using 3 h of OGD resulting in ~ 70% viable cells. We screened 5 reported neuroprotectants and provide the first report that serotonin is antiapoptotic in a stroke model and the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) is neuroprotective in PC12 cells. Thus we demonstrate the optimisation and validation for a PC12 cell-based in vitro stroke model.
Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors
Authors: Koc Michal , Wald Martin , Varaliová Zuzana , Ondrůjová Barbora , Čížková Terezie , Brychta Milan , Kračmerová Jana , Beranová Lenka , Pala Jan , Šrámková Veronika , Šiklová Michaela , Gojda Jan , Rossmeislová Lenka
Published: April 2021

Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT. AT samples were acquired from upper limbs of 11 women with unilateral breast cancer-related lymphedema and 11 healthy women without lymphedema. Additional control group of 11 female breast cancer survivors without lymphedema was used to assess systemic effects of lymphedema. AT was analysed for adipocyte size, lipolysis, angiogenesis, secretion of cytokines, immune and stem cell content and mRNA gene expression. Further, adipose precursors were isolated and tested for their proliferative and adipogenic capacity. The effect of undrained LAT- derived fluid on adipogenesis was also examined. Lymphedema did not have apparent systemic effect on metabolism and cytokine levels, but it was linked with higher lymphocyte numbers and altered levels of several miRNAs in blood. LAT showed higher basal lipolysis, (lymph)angiogenic capacity and secretion of inflammatory cytokines when compared to healthy AT. LAT contained more activated CD4+ T lymphocytes than healthy AT. mRNA levels of (lymph)angiogenic markers were deregulated in LAT and correlated with markers of lipolysis. In vitro, adipose cells derived from LAT did not differ in their proliferative, adipogenic, lipogenic and lipolytic potential from cells derived from healthy AT. Nevertheless, exposition of preadipocytes to LAT-derived fluid improved their adipogenic conversion when compared with the effect of serum. This study presents results of first complex analysis of LAT from upper limb of breast cancer survivors. Identified LAT alterations indicate a possible link between (lymph)angiogenesis and lipolysis. In addition, our in vitro results imply that AT expansion in lymphedema could be driven partially by exposition of adipose precursors to undrained LAT-derived fluid.
In situ novel environment assay reveals acoustic exploration as a repeatable behavioral response in migratory bats
Authors: Schabacker Theresa , Lindecke Oliver , Rizzi Sofia , Marggraf Lara , Pētersons Gunārs , Voigt Christian C. , Snijders Lysanne
Published: April 2021

Integrating information on species-specific sensory perception with spatial activity provides a high-resolution understanding of how animals explore environments, yet frequently used exploration assays commonly ignore sensory acquisition as a measure for exploration. Echolocation is an active sensing system used by hundreds of mammal species, primarily bats. As echolocation call activity can be reliably quantified, bats present an excellent model system to investigate intraspecific variation in environmental cue sampling. Here, we developed an in situ roost-like novel environment assay for tree-roosting bats. We repeatedly tested 52 individuals of the migratory bat species,Pipistrellus nathusii, across 24 h, to examine the role of echolocation when crawling through a maze-type arena and test for consistent intraspecific variation in sensory-based exploration. We reveal a strong correlation between echolocation call activity and spatial activity. Moreover, we show that during the exploration of the maze, individuals consistently differed in spatial activity as well as echolocation call activity, given their spatial activity, a behavioral response we term ’acoustic exploration’. Acoustic exploration was correlated with other exploratory behaviors, but not with emergence latency. We here present a relevant new measure for exploration behavior and provide evidence for consistent (short-term) intra-specific variation in the level at which wild bats collect information from a novel environment.
Land use in urban areas impacts the composition of soil bacterial communities involved in nitrogen cycling. A case study from Lefkosia (Nicosia) Cyprus
Authors: Stephanou Coralea , Omirou Michalis , Philippot Laurent , Zissimos Andreas M. , Christoforou Irene C. , Trajanoski Slave , Oulas Anastasis , Ioannides Ioannis M.
Published: April 2021

The different types of land-use and soil lithology in urban and peri-urban areas of modern cities compose a complex mosaic of soil ecosystems. It is largely unknown how these differences result in changes in bacterial community composition and structure as well as in functional guilds involved in N cycling. To investigate the bacterial composition and the proportion of denitrifiers in agricultural, forested, schoolyard and industrial areas, 24 samples were collected from urban and peri-urban sites of Lefkosia. Bacterial diversity and the proportion of denitrifiers were assessed by NGS and qPCR, respectively. Proteobacteria, Actinobacteria, Bacteriodetes, Chloroflexi, Acidobacteria and Planctomycetes were identified as the most dominant phyla across all sites, while agricultural sites exhibited the highest bacterial diversity. Heavy metals such as Co, Pb, V and Al were identified as key factors shaping bacterial composition in industrial and schoolyard sites, while the bacterial assemblages in agricultural and forested sites were associated with Ca. Variance partitioning analysis showed that 10.2% of the bacterial community variation was explained by land use management, 5.1% by chemical elements due to soil lithology, and 1.4% by sampling location. The proportion of denitrifiers varied with land use management. In industrial and schoolyard sites, the abundance of thenosZII bacterial community increased whilenirK abundance declined. Our data showed that land use and lithology have a moderate impact on the bacterial assemblages in urban and peri-urban areas of Lefkosia. As thenosZII bacterial community is important to the N2O sink capacity of soils, it would be interesting to elucidate the factors contributing to the proliferation of thenosZII clade in these soils.
Impact of clinical targeted sequencing on endocrine responsiveness in estrogen receptor-positive, HER2-negative metastatic breast cancer
Authors: Hagio Kanako , Amano Toraji , Hayashi Hideyuki , Takeshita Takashi , Oshino Tomohiro , Kikuchi Junko , Ohhara Yoshihito , Yabe Ichiro , Kinoshita Ichiro , Nishihara Hiroshi , Yamashita Hiroko
Published: April 2021

Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients’ prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice.
Identification and functional analysis of a biflavone as a novel inhibitor of transient receptor potential vanilloid 4-dependent atherogenic processes
Authors: Alharbi Mazen O. , Dutta Bidisha , Goswami Rishov , Sharma Shweta , Lei Kai Y. , Rahaman Shaik O.
Published: April 2021

Atherosclerosis, a chronic inflammatory disease of large arteries, is the major contributor to the growing burden of cardiovascular disease-related mortality and morbidity. During early atherogenesis, as a result of inflammation and endothelial dysfunction, monocytes transmigrate into the aortic intimal areas, and differentiate into lipid-laden foam cells, a critical process in atherosclerosis. Numerous natural compounds such as flavonoids and polyphenols are known to have anti-inflammatory and anti-atherogenic properties. Herein, using a fluorometric imaging plate reader-supported Ca2+ influx assay, we report semi high-throughput screening-based identification of ginkgetin, a biflavone, as a novel inhibitor of transient receptor potential vanilloid 4 (TRPV4)-dependent proatherogenic and inflammatory processes in macrophages. We found that ginkgetin (1) blocks TRPV4-elicited Ca2+ influx into macrophages, (2) inhibits oxidized low-density lipoprotein (oxLDL)-induced foam cell formation by suppressing the uptake but not the binding of oxLDL in macrophages, and (3) attenuates oxLDL-induced phosphorylation of JNK2, expression of TRPV4 proteins, and induction of inflammatory mRNAs. Considered all together, the results of this study show that ginkgetin inhibits proatherogenic/inflammatory macrophage function in a TRPV4-dependent manner, thus strengthening the rationale for the use of natural compounds for developing therapeutic and/or chemopreventive molecules.
Managed honeybees and South American bumblebees exhibit complementary foraging patterns in highbush blueberry
Authors: Estravis-Barcala M. Cecilia , Palottini Florencia , Macri Ivana , Nery Denise , Farina Walter M.
Published: April 2021

DespiteApis melliferabeing the most widely managed pollinator to enhance crop production, they are not the most suitable species for highbush blueberries, which possess restrictive floral morphology and require buzz-pollination. Thus, the South American bumblebeeBombus pauloensisis increasingly managed as an alternative species in this crop alongside honeybees. Herein, we evaluated the foraging patterns of the two species, concerning the potential pollen transfer between two blueberry co-blooming cultivars grown under open high tunnels during two seasons considering different colony densities. Both managed pollinators showed different foraging patterns, influenced by the cultivar identity which varied in their floral morphology and nectar production. Our results demonstrate that both species are efficient foragers on highbush blueberry and further suggest that they contribute positively to its pollination in complementary ways: while bumblebees were more effective at the individual level (visited more flowers and carried more pollen), the greater densities of honeybee foragers overcame the difficulties imposed by the flower morphology, irrespective of the stocking rate. This study supports the addition of managed native bumblebees alongside honeybees to enhance pollination services and emphasizes the importance of examining behavioural aspects to optimize management practices in pollinator-dependent crops.
Nitric oxide attenuated transforming growth factor-β induced myofibroblast differentiation of human keratocytes
Authors: Park Joo-Hee , Kim Martha , Yim Bora , Park Choul Yong
Published: April 2021

Nitric oxide (NO) has the potential to modulate myofibroblast differentiation. In this study, we investigated the effect of exogenous NO on the myofibroblast differentiation of human keratocytes using sodium nitrite as a NO donor. Myofibroblasts were induced by exposing resting keratocytes to transforming growth factor (TGF)-β1. N-cadherin and α-smooth muscle actin (αSMA) were used as myofibroblast markers. Both resting keratocytes and -stimulated keratocytes were exposed to various concentrations of sodium nitrite (1 μM to 1000 mM) for 24 to 72 h. Exposure to sodium nitrite did not alter keratocytes’ viability up to a 10 mM concentration for 72 h. However, significant cytotoxicity was observed in higher concentrations of sodium nitrite (over 100 mM). The expression of αSMA and N-cadherin was significantly increased in keratocytes by TGF-β1 stimulation after 72 h incubation. The addition of sodium nitrite (1 mM) to TGF-β1-stimulated keratocytes significantly decreased αSMA and N cadherin expression. Smad3 phosphorylation decreased after sodium nitrite (1 mM) exposure in TGF-β1-stimulated keratocytes. The effect of NO was reversed when NO scavenger, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) was added in the culture medium. Application of sodium nitrite resulted in significant decrease of corneal opacity when measured at 2 weeks after the chemical burn in the mouse. These results verified the potential therapeutic effect of NO to decrease myofibroblast differentiation of human keratocytes and corneal opacity after injury.
The fragility of opinion formation in a complex world
Authors: Medo Matúš , Mariani Manuel S. , Lü Linyuan
Published: April 2021

How does the complexity of the world around us affect the reliability of our opinions? Motivated by this question, we quantitatively study an opinion formation mechanism whereby an uninformed observer gradually forms opinions about a world composed of subjects interrelated by a signed network of mutual trust and distrust. We show numerically and analytically that the observer’s resulting opinions are highly inconsistent (they tend to be independent of the observer’s initial opinions) and unstable (they exhibit wide stochastic variations). Opinion inconsistency and instability increase with the world’s complexity, intended as the number of subjects and their interactions. This increase can be prevented by suitably expanding the observer’s initial amount of information. Our findings imply that an individual who initially trusts a few credible information sources may end up trusting the deceptive ones even if only a small number of trust relations exist between the credible and deceptive sources.
Legacies of Indigenous land use shaped past wildfire regimes in the Basin-Plateau Region, USA
Authors: Carter Vachel A. , Brunelle Andrea , Power Mitchell J. , DeRose R. Justin , Bekker Matthew F. , Hart Isaac , Brewer Simon , Spangler Jerry , Robinson Erick , Abbott Mark , Maezumi S. Yoshi , Codding Brian F.
Published: April 2021

Climatic conditions exert an important influence on wildfire activity in the western United States; however, Indigenous farming activity may have also shaped the local fire regimes for millennia. The Fish Lake Plateau is located on the Great Basin–Colorado Plateau boundary, the only region in western North America where maize farming was adopted then suddenly abandoned. Here we integrate sedimentary archives, tree rings, and archeological data to reconstruct the past 1200 years of fire, climate, and human activity. We identify a period of high fire activity during the apex of prehistoric farming between 900 and 1400 CE, and suggest that farming likely obscured the role of climate on the fire regime through the use of frequent low-severity burning. Climatic conditions again became the dominant driver of wildfire when prehistoric populations abandoned farming around 1400 CE. We conclude that Indigenous populations shaped high-elevation mixed-conifer fire regimes on the Fish Lake Plateau through land-use practices.
Phytoplankton community structuring and succession in a competition-neutral resource landscape
Authors: Behrenfeld Michael J , Boss Emmanuel S , Halsey Kimberly H
Published: April 2021

Phytoplankton community composition and succession affect aquatic food webs and biogeochemistry. Resource competition is commonly viewed as an important governing factor for community structuring and this perception is imbedded in modern ecosystem models. Quantitative consideration of the physical spacing between phytoplankton cells, however, suggests that direct competition for growth-limiting resources is uncommon. Here we describe how phytoplankton size distributions and temporal successions are compatible with a competition-neutral resource landscape. Consideration of phytoplankton-herbivore interactions with proportional feeding size ranges yields small-cell dominated size distributions consistent with observations for stable aquatic environments, whereas predator–prey temporal lags and blooming physiologies shift this distribution to larger mean cell sizes in temporally dynamic environments. We propose a conceptual mandala for understanding phytoplankton community composition where species successional series are initiated by environmental disturbance, guided by the magnitude of these disturbances and nutrient stoichiometry, and terminated with the return toward a ‘stable solution’. Our conceptual mandala provides a framework for interpreting and modeling the environmental structuring of natural phytoplankton populations.
The detrimental invasiveness of glioma cells controlled by gadolinium chelate-coated gold nanoparticles
Authors: Durand Maxime , Lelievre Elodie , Chateau Alicia , Berquand Alexandre , Laurent Gautier , Carl Philippe , Roux Stéphane , Chazee Lise , Bazzi Rana , Eghiaian Frederic , Jubreaux Justine , Ronde Philippe , Barberi-Heyob Muriel , Chastagner Pascal , Devy Jérôme , Pinel Sophie
Published: April 2021

The invasive phenotype of glioma cells is thought to be responsible for recurrences. Ultrasmall Gd3+ chelate-coated gold nanoparticles interfere with cells capacities to migrate and invade due to induced changes in intrinsic biomechanical properties.
Alginate gels crosslinked with chitosan oligomers – a systematic investigation into alginate block structure and chitosan oligomer interaction
Authors: Kopplin Georg , Lervik Anders , Draget Kurt I. , Aachmann Finn L.
Published: April 2021

Three alginates with different block structures, poly-M, poly-G, and poly-MG, were investigated upon ionic crosslinking with chitosan oligomers, using circular dichroism, rheology, and simulations, revealing a unique high gel strength poly-MG chitosan gelling system.
Flame retardancy effects between expandable graphite and halloysite nanotubes in silicone rubber foam
Authors: Pang Qingtao , Kang Furu , Deng Jun , Lei Lei , Lu Jie , Shao Shuiyuan
Published: April 2021

The effect of expandable graphite (EG) and modified halloysite nanotubes (HNTs) on the flame retardant properties of silicone rubber foam (SiF) was studied in this paper.
Direct use of the solid waste from oxytetracycline fermentation broth to construct Hf-containing catalysts for Meerwein–Ponndorf–Verley reactions
Authors: Chen Yuxin , Yao Xuefeng , Wang Xiaolu , Zhang Xuefeng , Zhou Huacong , He Runxia , Liu Quansheng
Published: April 2021

An efficient Hf-OFR catalyst was designed in which Hf4+ interacts with oxygen-containing acidic groups in oxytetracycline fermentation broth residues for MPV reactions.
Evaluation von Sekundäreingriffen nach mikrochirurgischer Lappentransplantation zur Rekonstruktion der oberen Extremität
Authors: Kotsougiani-Fischer Dimitra , Fischer Sebastian , Platte Juliana , Nagel Sarah Sophie , Kneser Ulrich , Harhaus Leila
Published: April 2021

Hintergrund Das primäre ästhetische und funktionelle Ergebnis nach freiem Gewebetransfer zur oberen Extremität kann suboptimal ausfallen und Folgeoperationen notwendig machen. Diese Studie soll erstmalig Art und Anzahl von Sekundäreingriffen evaluieren und prädiktive Faktoren hierfür identifizieren.

Patienten und Methoden Patienten, die im Zeitraum 2010–2017 eine freie Lappenplastik zur oberen Extremität erhielten, wurden in eine retrospektive Kohortenstudie eingeschlossen: Patienten mit einem oder mehreren Sekundäreingriffen zur Optimierung des funktionellen oder ästhetischen Lappendesigns (S-Kohorte) und Patienten ohne Sekundäreingriff, welche als Kontrolle (K-Kohorte) dienten. Prädiktoren für Sekundäreingriffe wurden mittels multivariater logistischer Regressionsanalyse identifiziert.

Ergebnisse Es konnten 128 Patienten eingeschlossen werden (S-Kohorte 36, K-Kohorte 92). Insgesamt erfolgten 56 Sekundäroperationen nach durchschnittlich 8 Monaten. Die S-Kohorte wies vermehrt Defekte an der Hand (53 %) auf und es erfolgte mehrheitlich eine Rekonstruktion mittels Faszio- bzw. Adipokutanlappen (89 %). Die häufigsten Sekundäreingriffe stellten die chirurgische Dermolipektomie/Teilexzision (61 %), gefolgt von der Liposuktion (16 %) und einer Kombination beider Eingriffe (17 %) dar. Zusätzlich erfolgten bei 64 % der Patienten aus der S-Kohorte im Rahmen der formverändernden Sekundäreingriffe weitere operative Interventionen zur Funktionsoptimierung. Patienten mit einer Defektlokalisation an der Hand erhielten 2,4-fach häufiger Sekundäroperationen (p = 0,05). Darüber hinaus war die Wahrscheinlichkeit für eine Korrekturoperation bei gutem Allgemeinzustand (ASA1/2) um das 6-Fache erhöht (p = 0,03).

Schlussfolgerung Sekundäreingriffe stellen häufige und sichere Verfahren dar, die häufig von Patienten in gutem Allgemeinzustand mit einer Defektrekonstruktion mittels freier Lappenplastik an der Hand gewünscht werden. Wir empfehlen daher die Implementierung von Sekundäreingriffen in den rekonstruktiven Plan, um die Patienten-Compliance und Zufriedenheit zu steigern.
Handekzem – Gleiche Therapie für alle Formen?
Authors: Bayerl C.
Published: April 2021

Es gibt nicht einen einzigen Typ des chronischen Handekzems (CHE) – weder morphologisch noch immunologisch. Schutz und Präventionsmaßnahmen können für alle Typen des CHE definiert werden. Die Therapie muss passen und zielgerichtet sein. Einige Therapien können jedoch für alle Typen des Handekzems angeboten werden wie topische Kortikosteroide, Calcineurinantagonisten, UV-Therapie und Alitretinoin, ggf. auch Dupilumab, was in größeren Studien untersucht werden sollte. Die Wahrnehmung des Handekzems sollte gerade in Zeiten der Irritation durch Desinfektion der Hände erhöht werden, damit Prävention und frühzeitige Therapie erfolgen können.
Novel artificial intelligence-driven software significantly shortens the time required for annotation in computer vision projects
Authors: Hansen Ulrik Stig , Landau Eric , Patel Mehul , Hayee BuʼHussain
Published: April 2021

Background and study aims The contribution of artificial intelligence (AI) to endoscopy is rapidly expanding. Accurate labelling of source data (video frames) remains the rate-limiting step for such projects and is a painstaking, cost-inefficient, time-consuming process. A novel software platform, Cord Vision (CdV) allows automated annotation based on “embedded intelligence.” The user manually labels a representative proportion of frames in a section of video (typically 5 %), to create ‘micro-modelsʼ which allow accurate propagation of the label throughout the remaining video frames. This could drastically reduce the time required for annotation.

Methods We conducted a comparative study with an open-source labelling platform (CVAT) to determine speed and accuracy of labelling.

Results Across 5 users, CdV resulted in a significant increase in labelling performance (P < 0.001) compared to CVAT for bounding box placement.

Conclusions This advance represents a valuable first step in AI-image analysis projects.