bluuebunny/crossref_metadata_2025 huggingface dataset:
Melittin, a honeybee venom derived peptide for the treatment of chemotherapy-induced peripheral neuropathy
Authors: Tender Tenzin , Rahangdale Rakesh Ravishankar , Balireddy Sridevi , Nampoothiri Madhavan , Sharma K. Krishna , Raghu Chandrashekar Hariharapura
Published: April 2021

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction. Severe CIPN has been reported in around 5% of patients treated with single and up to 38% of patients treated with multiple chemotherapeutic agents. Present medications available for CIPN are the use of opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants, which are only marginally effective in treating neuropathic symptoms. In reality, symptom reappears after these drugs are discontinued. The pathogenesis of CIPN has not been sufficiently recognized and methods for the prevention and treatment of CIPN remain vulnerable to therapeutic problems. It has witnessed that the present medicines available for the disease offer only symptomatic relief for the short term and have severe adverse side effects. There is no standard treatment protocol for preventing, reducing, and treating CIPN. Therefore, there is a need to develop curative therapy that can be used to treat this complication. Melittin is the main pharmacological active constituent of honeybee venom and has therapeutic values including in chemotherapeutic-induced peripheral neuropathy. It has been shown that melittin and whole honey bee venom are effective in treating paclitaxel and oxaliplatin-induced peripheral neuropathy. The use of melittin against peripheral neuropathy caused by chemotherapy has been limited despite having strong therapeutic efficacy against the disease. Melittin mediated haemolysis is the key reason to restrict its use. In our study, it is found that α-Crystallin (an eye lens protein) is capable of inhibiting melittin-induced haemolysis which gives hope of using an appropriate combination of melittin and α-Crystallin in the treatment of CIPN. The review summarizes the efforts made by different research groups to address the concern with melittin in the treatment of chemotherapeutic-induced neuropathy. It also focuses on the possible approaches to overcome melittin-induced haemolysis.

Graphic Abstract
A new antisarcoma strategy: multisubtype heat shock protein/peptide immunotherapy combined with PD-L1 immunological checkpoint inhibitors
Authors: Li H. , Sui X. , Wang Z. , Fu H. , Wang Z. , Yuan M. , Liu S. , Wang G. , Guo Q.
Published: April 2021

Osteosarcoma, a common malignant tumor in orthopedics, often has a very poor prognosis after lung metastasis. Immunotherapy has not achieved much progress in the treatment because of the characteristics of solid tumors and immune environment of osteosarcoma. The tumor environment is rather essential for sarcoma treatment. Our previous study demonstrated that heat shock proteins could be used as antitumor vaccines by carrying tumor antigen peptides, and we hypothesize that an anti-osteosarcoma effect may be increased with an immune check point inhibitor (PD-L1 inhibitor) as a combination treatment strategy. The present study prepared a multisubtype mixed heat shock protein osteosarcoma vaccine (mHSP/peptide vaccine) and concluded that the mHSP/peptide vaccine was more effective than a single subtype heat shock protein, like Grp94. Therefore, we used the mHSP/peptide vaccine in combination with a PD-L1 inhibitor to treat osteosarcoma, and the deterioration of osteosarcoma was effectively hampered. The mechanism of combined therapy was investigated, and AKT expression participates with sarcoma lung metastasis. This study proposed an antisarcoma strategy via stimulation of the immune system as a further alternative approach for sarcoma treatment and elucidated the mechanism of combined therapy.
Navigating Trust and Distrust in the Refugee Community of Malta
Authors: Gandolfo Luisa
Published: April 2021

This article considers how trust is constructed in the refugee community of Malta, against the backdrop of ongoing and recurrent unrest in Libya. As social trust is re-evaluated, social spaces have become sites of tension where divisions re-emerge along political, ideological, and economic lines. By focusing on the Libyan diaspora, the article presents an insight into the ways that conflict trauma shapes trust-building, and considers the challenges faced by civil society organisations and government bodies in their efforts to facilitate support and community-building on the island. The article is based on 14 interviews conducted in 2015 with members of the Libyan diaspora, and Maltese civil society organisations and government bodies. The interviewees discussed the multifaceted aspects of trust-building, including the legacy of 42 years of political distrust during the regime of the former Libyan leader, Muammar Gaddafi, regional affiliations and divisions, and the continuum of trauma that unfolds in the Maltese Open Centres and in the host community. The findings of the study indicate that there are additional structural impediments that extend beyond the ongoing conflict, including the Maltese detention process, the redrawing of political boundaries around social spaces in the towns, and the role of identity, which present determining factors in the building of social trust. Collectively, these aspects hold implications for integration into the diaspora community on the island, while in the long term, individual recovery from conflict trauma is dependent on the trust-networks that are constructed, or joined, by the refugees.
Optimizing contrast-enhanced echocardiography by employing a sonographer driven protocol
Authors: Usry Courtney R. , Shin Satoshi R. , Aden James K. , Gore Rosco
Published: April 2021

Background

The use of enhancing agents in echocardiography has been shown to facilitate improved study quality. Despite the known benefits, its use remains limited by institutional policies.

Methods

We aimed to retrospectively evaluate if allowing sonographers to place a peripheral intravenous catheter and administer enhancing agent led to a decrease in time to complete outpatient transthoracic echocardiograms in comparison to using nursing personnel. Three separate protocols were employed. The ‘nurse driven protocol’ utilized nurses to place a peripheral intravenous catheter and inject enhancing agent. In a ‘mixed protocol,’ a nurse placed a peripheral intravenous catheter and the sonographer gave the enhancing agent. The ‘sonographer driven protocol’ involved the sonographer placing the peripheral intravenous catheter and delivering enhancing agent.

Results

A total of 232 echocardiograms were included for analysis. Patient characteristics across the three protocols were not statistically significant. The ‘mixed protocol’ had an average study time that was significantly less than the ‘nurse driven protocol’ (49.4 min ± 11.4 vs 54.6 min ± 12.9; p = 0.024). The ‘sonographer driven protocol’ also showed a significant reduction in study time (50.3 min ± 12.6) when compared to the ‘nurse driven protocol’ (p = 0.017). The additional task for the sonographer to place the peripheral intravenous catheter did not significantly increase the time to complete the study.

Conclusion

Allowing sonographers to administer enhancing agent reduced individual echocardiogram study times by approximately 5 min, supporting that a ‘sonographer driven protocol’ is more efficient with potential downstream economic benefits.
Effect of galena contained in dust from Zn–Pb metallurgical processes on environment
Authors: Nowińska Katarzyna , Adamczyk Zdzisław
Published: April 2021

This paper assesses the effect of galena emitted with dust from an electrostatic precipitator at Miasteczko Śląskie Zinc Smelting Plant (Poland) onto a soil and water environment. The Eh–pH diagrams plotted in the temperature range of − 3 to 25 °C serve to determine the conditions of PbS stability and conditions under which its decomposition may occur, resulting in the release of ionic forms of lead into the soil and water environment. Determination of the mobility of galena emitted with metallurgical dust is a current and important issue in view of the geochemistry of mineral components in the environment.
High-order compact LOD methods for solving high-dimensional advection equations
Authors: Hou Bo , Ge Yongbin
Published: April 2021

In this paper, by using the local one-dimensional (LOD) method, Taylor series expansion and correction for the third derivatives in the truncation error remainder, two high-order compact LOD schemes are established for solving the two- and three- dimensional advection equations, respectively. They have the fourth-order accuracy in both time and space. By the von Neumann analysis method, it shows that the two schemes are unconditionally stable. Besides, the consistency and convergence of them are also proved. Finally, numerical experiments are given to confirm the accuracy and efficiency of the present schemes.
Support of Dynamic Measurements Through Similitude Formulations
Authors: Casaburo A. , Petrone G. , Meruane V. , Franco F. , De Rosa S.
Published: April 2021

Up to now, similitude methods have been used in order to overcome the typical drawbacks of experimental testing and numerical simulations by reconstructing the full-scale model behavior from that of the scaled model. The novelty of this work is the application of similitude theory not as a tool for predicting the prototype dynamic response, but for supporting, and eventually validating, experimental measurements polluted by noise. Two Aluminium Foam Sandwich (AFS) plates are analyzed with Digital Image Correlation (DIC) cameras. First, an algorithm for blind source separation problems is used to extract information about the excitation; then, SAMSARA (Similitude and Asymptotic Models for Structural-Acoustic Research Applications) similitude method is applied to both the force spectra and velocity responses of prototype and model. The reconstruction of force and velocity curves demonstrates that the similitude results are coherent with the quality of the experimental measurements: when the spatial pattern in resonance is recognizable, then the curves overlap. Instead, when the displacement field of just one model is not well identified, the reconstruction exhibits discrepancies. Therefore, similitude methods reveal to be an interesting tool for understanding if a set of measurements is reliable or not and their application should not be underestimated, especially in the light of the expanding range of approaches which can extract important information from noisy observations.
Tax evasion and government size: evidence from Italian provinces
Authors: D’Agostino Elena , De Benedetto Marco Alberto , Sobbrio Giuseppe
Published: April 2021

We analyze the impact of government size, measured by total spending per capita, on tax evasion at the provincial level in Italy over the period 2001–2015. In order to solve endogeneity issues we rely on a system GMM and find that public expenditure negatively affects tax evasion, as taxpayers perceive the government is efficiently spending resources coming from the tax levy. Results are confirmed when we (1) consider expenditures related to long-term investments, namely capital spending per capita, and (2) directly test the impact of government efficiency on tax evasion. In addition, we show that the impact of public spending is heterogeneous across geographical areas: an increase in public expenditure leads to a downward shift in tax evasion only in the northern part of Italy, characterized by a relatively larger initial level of public goods provision.
Correction to: Understanding the characteristics of rapid intensity changes of Tropical Cyclones over North Indian Ocean
Authors: Nadimpalli Raghu , Mohanty Shyama , Pathak Nishant , Osuri Krishna K. , Mohanty U. C. , Chatterjee Somoshree
Published: April 2021

There was an error in footnote no. 1 in the initial online publication. The original article has been corrected.
Seismic rocking effects on a mine tower under induced and natural earthquakes
Authors: Bońkowski Piotr Adam , Kuś Juliusz , Zembaty Zbigniew
Published: April 2021

Recent research in engineering seismology demonstrated that in addition to three translational seismic excitations along x, y and z axes, one should also consider rotational components about these axes when calculating design seismic loads for structures. The objective of this paper is to present the results of a seismic response numerical analysis of a mine tower (also called in the literature a headframe or a pit frame). These structures are used in deep mining on the ground surface to hoist output (e.g. copper ore or coal). The mine towers belong to the tall, slender structures, for which rocking excitations may be important. In the numerical example, a typical steel headframe 64 m high is analysed under two records of simultaneous rocking and horizontal seismic action of an induced mine shock and a natural earthquake. As a result, a complicated interaction of rocking seismic effects with horizontal excitations is observed. The contribution of the rocking component may sometimes reduce the overall seismic response, but in most cases, it substantially increases the seismic response of the analysed headframe. It is concluded that in the analysed case of the 64 m mining tower, the seismic response, including the rocking ground motion effects, may increase up to 31% (for natural earthquake ground motion) or even up to 135% (for mining-induced, rockburst seismic effects). This means that not only in the case of the design of very tall buildings or industrial chimneys but also for specific yet very common structures like mine towers, including the rotational seismic effects may play an important role.
My Group or Myself? How Black, Latino, and White Americans Choose a Neighborhood, Job, and Candidate when Personal and Group Interest Diverge
Authors: Hochschild Jennifer , Piston Spencer , Weaver Vesla Mae
Published: April 2021

Amid growing inequality within racial and ethnic groups, how do Americans decide where to live, where to work, and for whom to vote? While previous research has examined racial patterns in voting decisions, it provides less insight into individual-level decisions about neighborhoods, candidates, and employment—even while these decisions also organize the political world. We theorize about the role of a key variable stratifying these individual-level decisions: education. To test our argument, we analyze nationally representative survey data and a new survey experiment that varies incentives to leave one’s racial group environment. We find that among Blacks and Latinos, but not whites, those with higher levels of formal education are disproportionately likely to respond to incentives to leave their own group. We conclude with reflections on the implications of this educational divide for intra-racial inequality.
Evolution of the Oceanic 13C Suess Effect in the Southeastern Indian Ocean Between 1994 and 2018
Authors: Williams Thomas J. , Wagner Amy J. , Sikes Elisabeth L. , Martin Ellen E.
Published: April 2021

The decrease in δ13C of dissolved inorganic carbon (δ13CDIC) owing to uptake of anthropogenic CO2 (the oceanic 13C Suess effect) in the Southeastern Indian Ocean over the last decade was calculated using an extended multiparameter linear regression technique. Samples collected on the CROCCA‐2S (Coring to Reconstruct Ocean Circulation and Carbon Dioxide Across 2 Seas) cruise in November–December 2018 were compared to samples from the CLIVAR (Climate and Ocean: Variability, Predictability, and Change) and OISO (Océan Indien Service d'Observation) programs from 2007 to 2009. Surface ocean δ13CDIC decreased by an average of −0.53 ± 0.04‰ across this period, at an average rate of −0.053 ± 0.004‰ per year. This rate of δ13CDIC change is an increase from −0.021 ± 0.024‰ per year between 1994 and 2008. We find that the interior water mass most impacted by the oceanic 13C Suess effect between 2008 and 2018 was Subantarctic Mode Water (SAMW), within which δ13CDIC decreased by −0.044 ± 0.002‰ per year. Using previously published relationships between the oceanic 13C Suess effect and anthropogenic carbon, we estimate the annual storage of anthropogenic carbon within SAMW in the southeastern Indian Ocean has increased from ∼2.0 ± 0.2 μmol/kg per year between 1994 and 2008 to 5.5 ± 0.6 μmol/kg per year between 2008 and 2018.
Refining Higher Modes of Rayleigh Waves Using Seismoelectric Signals Excited by a Weight‐Drop Source: Study From Numerical Simulation Aspect
Authors: Yuan Shichuan , Ren Hengxin , Huang Qinghua , Zheng Xu‐Zhen , Yang Zhentao , He Zhanxiang , Zhang Wei , Chen Xiaofei
Published: April 2021

Effective extraction of higher mode dispersion information has been a research hotspot in the study of surface waves. In this study, we introduce a novel approach of refining Rayleigh wave higher modes by using seismoelectric signals, namely, electromagnetic (EM) signals originating from seismoelectric conversion. Adopting a weight‐drop source, we simulate seismic and EM signals for several porous models. An extended version of the frequency‐Bessel transform method is introduced to extract dispersion information from seismic and EM signals. Results suggest that the evanescent seismoelectric waves, which are induced at subsurface interfaces penetrated by Rayleigh waves and finally are recorded nearby the ground surface after undergoing amplitude decay, can reflect dispersion characteristics of Rayleigh waves and can provide extra higher‐mode dispersion information that seismic waves cannot. We find the vadose zone with higher water saturation will cause the seismoelectric signals to have stronger strengths and change their frequency coverage of dispersion information. Electric fields obtained from potential differences between longer dipole electrodes suffer more severe distortion. In an electrically resistive environment, predicted seismoelectric signal amplitudes in the frequency band with dominant energy are well above expected background noise levels. We also find seismoelectric signals have a stronger antialiasing ability than seismic waves and their dispersion energy values are sensitive to salinity and fluid viscosity. Generally speaking, our study suggests Rayleigh wave dispersion information with abundant higher modes and good frequency‐range coverage can be obtained by using seismic and seismoelectric signals together due to their complementarity.
Study on the 1906 Colombia‐Ecuador Megathrust Earthquake Based on Tsunami Waveforms Observed at Tide Gauges: Release Variation of Accumulated Slip Deficits in the Source Area
Authors: Yamanaka Yusuke , Tanioka Yuichiro
Published: April 2021

A tsunami that followed the 1906 Colombia‐Ecuador megathrust earthquake was observed and recorded by several tide gauges. In this study, tide gauge records were first digitized from documents comparing the estimated astronomical tide level changes, and the observed tsunami waveforms were extracted. An inverse analysis was conducted using the observed tsunami waveforms, and we successfully developed a slip distribution model that produced improved tsunami waveforms for tide gauge stations compared with previous studies. Based on a comparison of the developed source model and ruptured areas of other significant earthquakes around Colombia and Ecuador, the 1906 earthquake already ruptured an area affected by the 1979 earthquake, resulting in a substantial release of accumulated slip deficits. In contrast, although the ruptured area of the 1906 earthquake likely covered the source areas of the 1958 and 1942 earthquakes, the release in these areas during the earthquake was moderate and insignificant, and large slip deficits remained after the 1906 earthquake. These results demonstrate that the extent of the release of accumulated slip deficits varied greatly in the source area of the 1906 earthquake.
Multi‐Year Estimates of Daily Heat Transport by the Atlantic Meridional Overturning Circulation at 34.5°S
Authors: Kersalé M. , Meinen C. S. , Perez R. C. , Piola A. R. , Speich S. , Campos E. J. D. , Garzoli S. L. , Ansorge I. , Volkov D. L. , Le Hénaff M. , Dong S. , Lamont T. , Sato O. T. , van den Berg M.
Published: April 2021

Variations in the mass and heat transported by the meridional overturning circulation (MOC) have important, well‐documented, influences on global and regional climate, weather, ecosystems, and coastal sea levels. However, continuous, high‐frequency, observations of these quantities have been limited to date. Multiple years of full‐depth daily observations from moored instruments in the South Atlantic at 34.5°S are combined with satellite observations to resolve the volume transports in both the upper and abyssal MOC cells, and the associated full‐depth meridional heat transport (MHT), on daily to interannual timescales. A newly developed method for combining satellite sea level observations with historical hydrographic measurements was used to estimate daily full‐depth ocean profiles of temperature in the ocean interior where mooring coverage is sparse. The average MHT during 2013–2017 is 0.5 PW, with a daily standard deviation of 0.8 PW. The MHT variability is most strongly driven by the geostrophic relative velocity contributions (horizontal density‐gradient changes). This variability is highly correlated with the volume transport variability of the MOC upper cell (r = 0.96) and modestly anti‐correlated (r = −0.52) with the abyssal cell variations. An empirical relationship between the MHT and MOC values was developed allowing the reconstruction of a longer MHT time series including the pilot array period (2009–2010). Seasonal variation of the MHT is significant, and results from strong variations of all terms (Ekman, barotropic, and baroclinic). Although the 2013–2017 shows an increasing MHT trend (0.14 PW/year), the longer time period record suggests that the apparent trend may simply be interannual modulation of MHT at 34.5°S.
Simulating Miocene Warmth: Insights From an Opportunistic Multi‐Model Ensemble (MioMIP1)
Authors: Burls N. J. , Bradshaw C. D. , De Boer A. M. , Herold N. , Huber M. , Pound M. , Donnadieu Y. , Farnsworth A. , Frigola A. , Gasson E. , von der Heydt A. S. , Hutchinson D. K. , Knorr G. , Lawrence K. T. , Lear C. H. , Li X. , Lohmann G. , Lunt D. J. , Marzocchi A. , Prange M. , Riihimaki C. A. , Sarr A.‐C. , Siler N. , Zhang Z.
Published: April 2021

The Miocene epoch, spanning 23.03–5.33 Ma, was a dynamic climate of sustained, polar amplified warmth. Miocene atmospheric CO2 concentrations are typically reconstructed between 300 and 600 ppm and were potentially higher during the Miocene Climatic Optimum (16.75–14.5 Ma). With surface temperature reconstructions pointing to substantial midlatitude and polar warmth, it is unclear what processes maintained the much weaker‐than‐modern equator‐to‐pole temperature difference. Here, we synthesize several Miocene climate modeling efforts together with available terrestrial and ocean surface temperature reconstructions. We evaluate the range of model‐data agreement, highlight robust mechanisms operating across Miocene modeling efforts and regions where differences across experiments result in a large spread in warming responses. Prescribed CO2 is the primary factor controlling global warming across the ensemble. On average, elements other than CO2, such as Miocene paleogeography and ice sheets, raise global mean temperature by ∼2°C, with the spread in warming under a given CO2 concentration (due to a combination of the spread in imposed boundary conditions and climate feedback strengths) equivalent to ∼1.2 times a CO2 doubling. This study uses an ensemble of opportunity: models, boundary conditions, and reference data sets represent the state‐of‐art for the Miocene, but are inhomogeneous and not ideal for a formal intermodel comparison effort. Acknowledging this caveat, this study is nevertheless the first Miocene multi‐model, multi‐proxy comparison attempted so far. This study serves to take stock of the current progress toward simulating Miocene warmth while isolating remaining challenges that may be well served by community‐led efforts to coordinate modeling and data activities within a common analytical framework.
Normal Fault Kinematics and the Role of Lateral Tip Retreat: An Example From Offshore NW Australia
Authors: Lathrop Bailey A. , Jackson Christopher A.‐L. , Bell Rebecca E. , Rotevatn Atle
Published: April 2021

Understanding how normal faults grow is key to determining the tectono‐stratigraphic evolution of rifts. According to recent studies, normal faults tend to grow in two temporally distinct stages: a lengthening stage, followed by a throw/displacement accumulation stage. However, this model is still debated and not widely supported by many additional studies. Relatively few studies have investigated what happens to a fault as it becomes inactive, that is, does it abruptly die, or does the at‐surface trace‐length progressively shorten by so‐called tip retreat? We, here, use a 3D seismic reflection data set from the Exmouth Plateau, offshore Australia, to develop a three‐stage fault growth model for seven normal faults of various sizes and to show how the throw‐length scaling relationship changes as a fault dies. We show that during the lengthening stage, which lasted <30% of the faults’ lives, faults reached their near‐maximum lengths, yet accumulated only 10%–20% of their total throw. During the throw/displacement accumulation stage, which accounts for c. 30%–75% of the faults’ lives, throw continued to accumulate along the entire length of the faults. All of the studied faults also underwent a stage of lateral tip‐retreat (last c. 25% of the faults’ lives), where the active at‐surface trace‐length decreased by up to 25%. The results of our study may have broader implications for fault growth models, slip rate variability during fault growth, and the way in which faults die, in particular the role of lateral tip‐retreat.
Scientists Map Africa’s Groundwater Recharge for the First Time
Authors: Makoni Munyaradzi
Published: April 2021

The continent-wide survey provides an assessment of the resilience of groundwater resources.
Sublytic C5b-9 induces glomerular mesangial cell proliferation via ERK1/2-dependent SOX9 phosphorylation and acetylation by enhancing Cyclin D1 in rat Thy-1 nephritis
Authors: Xie Mengxiao , Wu Zhijiao , Ying Shuai , Liu Longfei , Zhao Chenhui , Yao Chunlei , Zhang Zhiwei , Luo Can , Wang Wenbo , Zhao Dan , Zhang Jing , Qiu Wen , Wang Yingwei
Published: April 2021

Glomerular mesangial cell (GMC) proliferation is a histopathological alteration in human mesangioproliferative glomerulonephritis (MsPGN) or in animal models of MsPGN, e.g., the rat Thy‐1 nephritis (Thy-1N) model. Although sublytic C5b-9 assembly on the GMC membrane can trigger cell proliferation, the mechanisms are still undefined. We found that sublytic C5b-9-induced rat GMC proliferation was driven by extracellular signal‐regulated kinase 1/2 (ERK1/2), sry-related HMG-box 9 (SOX9), and Cyclin D1. Here, ERK1/2 phosphorylation was a result of the calcium influx-PKC-α-Raf-MEK1/2 axis activated by sublytic C5b-9, and Cyclin D1 gene transcription was enhanced by ERK1/2-dependent SOX9 binding to the Cyclin D1 promoter (−582 to −238 nt). In addition, ERK1/2 not only interacted with SOX9 in the cell nucleus to mediate its phosphorylation at serine residues 64 (a new site identified by mass spectrometry) and 181 (a known site), but also indirectly induced SOX9 acetylation by elevating the expression of general control non-repressed protein 5 (GCN5), which together resulted in Cyclin D1 synthesis and GMC proliferation. Moreover, our in vivo experiments confirmed that silencing these genes ameliorated the lesions of Thy‐1N rats and reduced SOX9 phosphorylation, acetylation and Cyclin D1 expression. Furthermore, the renal tissue sections of MsPGN patients also showed higher phosphorylation or expression of ERK1/2, SOX9, and Cyclin D1. In summary, these findings suggest that sublytic C5b-9-induced GMC proliferation in rat Thy-1N requires SOX9 phosphorylation and acetylation via enhanced Cyclin D1 gene transcription, which may provide a new insight into human MsPGN pathogenesis.
Fabrication of freestanding Pt nanowires for use as thermal anemometry probes in turbulence measurements
Authors: Le-The Hai , Küchler Christian , van den Berg Albert , Bodenschatz Eberhard , Lohse Detlef , Krug Dominik
Published: April 2021

We report a robust fabrication method for patterning freestanding Pt nanowires for use as thermal anemometry probes for small-scale turbulence measurements. Using e-beam lithography, high aspect ratio Pt nanowires (~300 nm width, ~70 µm length, ~100 nm thickness) were patterned on the surface of oxidized silicon (Si) wafers. Combining wet etching processes with dry etching processes, these Pt nanowires were successfully released, rendering them freestanding between two silicon dioxide (SiO2) beams supported on Si cantilevers. Moreover, the unique design of the bridge holding the device allowed gentle release of the device without damaging the Pt nanowires. The total fabrication time was minimized by restricting the use of e-beam lithography to the patterning of the Pt nanowires, while standard photolithography was employed for other parts of the devices. We demonstrate that the fabricated sensors are suitable for turbulence measurements when operated in constant-current mode. A robust calibration between the output voltage and the fluid velocity was established over the velocity range from 0.5 to 5 m s−1in a SF6atmosphere at a pressure of 2 bar and a temperature of 21 °C. The sensing signal from the nanowires showed negligible drift over a period of several hours. Moreover, we confirmed that the nanowires can withstand high dynamic pressures by testing them in air at room temperature for velocities up to 55 m s−1.
Identification of sex differentiation-related microRNA and long non-coding RNA in Takifugu rubripes gonads
Authors: Yan Hongwei , Liu Qi , Jiang Jieming , Shen Xufang , Zhang Lei , Yuan Zhen , Wu Yumeng , Liu Ying
Published: April 2021

Although sex determination and differentiation are key developmental processes in animals, the involvement of non-coding RNA in the regulation of this process is still not clarified. The tiger pufferfish (Takifugu rubripes) is one of the most economically important marine cultured species in Asia, but analyses of miRNA and long non-coding RNA (lncRNA) at early sex differentiation stages have not been conducted yet. In our study, high-throughput sequencing technology was used to sequence transcriptome libraries from undifferentiated gonads of T. rubripes. In total, 231 (107 conserved, and 124 novel) miRNAs were obtained, while 2774 (523 conserved, and 2251 novel) lncRNAs were identified. Of these, several miRNAs and lncRNAs were predicted to be the regulators of the expression of sex-related genes (including fru-miR-15b/foxl2, novel-167, novel-318, and novel-538/dmrt1, novel-548/amh, lnc_000338, lnc_000690, lnc_000370, XLOC_021951, and XR_965485.1/gsdf). Analysis of differentially expressed miRNAs and lncRNAs showed that three mature miRNAs up-regulated and five mature miRNAs were down-regulated in male gonads compared to female gonads, while 79 lncRNAs were up-regulated and 51 were down-regulated. These findings could highlight a group of interesting miRNAs and lncRNAs for future studies and may reveal new insights into the function of miRNAs and lncRNAs in sex determination and differentiation.
Effectiveness of decontamination protocols when analyzing ancient DNA preserved in dental calculus
Authors: Farrer Andrew G. , Wright Sterling L. , Skelly Emily , Eisenhofer Raphael , Dobney Keith , Weyrich Laura S.
Published: April 2021

Ancient DNA analysis of human oral microbial communities within calcified dental plaque (calculus) has revealed key insights into human health, paleodemography, and cultural behaviors. However, contamination imposes a major concern for paleomicrobiological samples due to their low endogenous DNA content and exposure to environmental sources, calling into question some published results. Decontamination protocols (e.g.an ethylenediaminetetraacetic acid (EDTA) pre-digestion or ultraviolet radiation (UV) and 5% sodium hypochlorite immersion treatments) aim to minimize the exogenous content of the outer surface of ancient calculus samples prior to DNA extraction. While these protocols are widely used, no one has systematically compared them in ancient dental calculus. Here, we compare untreated dental calculus samples to samples from the same site treated with four previously published decontamination protocols: a UV only treatment; a 5% sodium hypochlorite immersion treatment; a pre-digestion in EDTA treatment; and a combined UV irradiation and 5% sodium hypochlorite immersion treatment. We examine their efficacy in ancient oral microbiota recovery by applying 16S rRNA gene amplicon and shotgun sequencing, identifying ancient oral microbiota, as well as soil and skin contaminant species. Overall, the EDTA pre-digestion and a combined UV irradiation and 5% sodium hypochlorite immersion treatment were both effective at reducing the proportion of environmental taxa and increasing oral taxa in comparison to untreated samples. This research highlights the importance of using decontamination procedures during ancient DNA analysis of dental calculus to reduce contaminant DNA.
An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina
Authors: Patnaik Satish , Rai Meenakshi , Jalali Subhadra , Agarwal Komal , Badakere Akshay , Puppala Lavanya , Vishwakarma Sushma , Balakrishnan Divya , Rani Padmaja K. , Kekunnaya Ramesh , Chhablani Preeti Patil , Chakrabarti Subhabrata , Kaur Inderjeet
Published: April 2021

Inflammation plays a key role in the pathogenesis of retinal vascular diseases. We have shown earlier an increase in the activity of matrix metalloproteinases in the vitreous and tears of preterm born babies with retinopathy of prematurity (ROP) compared to those with no-ROP leading to a shift in the balance of angiogenic (vascular endothelial growth factor [VEGF], matrix metalloproteinase [MMPs], complement component [C3]) and anti-angiogenic (opticin, thrombospondin) in ROP eyes. We now confirmed that tear MMP levels in premature infants perfectly correlates with disease severity. Next, we demonstrated that a reduced opticin levels in ROP vitreous are regulated by MMPs secreted by activated microglia. Upon exposing the human microglia cell line (CHME3) to hypoxia, an increased expression of inflammatory proteins (MMP9, VEGF) was noticed while opticin reduced significantly (p = 0.005). Further, the reduced opticin’s expression by microglial cells under hypoxia could be rescued by inhibiting the MMP activity using doxycycline and EDTA. The inhibition of MMP activity altered the expression of other key signaling molecules under hypoxia. Our study clearly explains that increased activity of MMPs under hypoxia regulates the expression of opticin as seen in the vitreous humor of ROP and could serve as a potential target for ROP management.
Innovative motor and cognitive dual-task approaches combining upper and lower limbs may improve dementia early detection
Authors: Mancioppi Gianmaria , Fiorini Laura , Rovini Erika , Zeghari Radia , Gros Auriane , Manera Valeria , Robert Philippe , Cavallo Filippo
Published: April 2021

Motor and Cognitive Dual-Task (MCDT) represents an innovative chance to assess Mild Cognitive Impairment (MCI). We compare two novel MCDTs, fore-finger tapping (FTAP), toe-tapping (TTHP), to gold standards for cognitive screening (Mini-Mental State Examination—MMSE), and to a well-established MCDT (GAIT). We administered the aforementioned MCDTs to 44 subjects (MCIs and controls). Motor parameters were extracted, and correlations with MMSE investigated. Logistic regression models were built, and AUC areas computed. Spearman’s correlation demonstrated that FTAP and TTHP significantly correlate with MMSE, at each cognitive load. AUC areas computed report similar (FTAP, 0.87), and even higher (TTHP, 0.97) capability to identify MCIs, if compared to GAIT (0.92). We investigated the use of novel MCDT approaches to assess MCI, aiming to enrich the clinical repertoire with objective and non-invasive tools. Our protocol shows good correlations with MMSE, and reaches high performances in identifying MCI, adopting simpler exercises.
Shocked quartz in distal ejecta from the Ries impact event (Germany) found at ~ 180 km distance, near Bernhardzell, eastern Switzerland
Authors: Holm-Alwmark Sanna , Alwmark Carl , Ferrière Ludovic , Meier Matthias M. M. , Lindström Sofie , Kenny Gavin G. , Sheldon Emma , Schweigert Günter , Spötl Christoph , Whitehouse Martin J. , Hofmann Beda A.
Published: April 2021

Impact ejecta formation and emplacement is of great importance when it comes to understanding the process of impact cratering and consequences of impact events in general. Here we present a multidisciplinary investigation of a distal impact ejecta layer, the Blockhorizont, that occurs near Bernhardzell in eastern Switzerland. We provide unambiguous evidence that this layer is impact-related by confirming the presence of shocked quartz grains exhibiting multiple sets of planar deformation features. Average shock pressures recorded by the quartz grains are ~ 19 GPa for the investigated sample. U–Pb dating of zircon grains from bentonites in close stratigraphic context allows us to constrain the depositional age of the Blockhorizont to ~ 14.8 Ma. This age, in combination with geochemical and paleontological analysis of ejecta particles, is consistent with deposition of this material as distal impact ejecta from the Ries impact structure, located ~ 180 km away, in Germany. Our observations are important for constraining models of impact ejecta emplacement as ballistically and non-ballistically transported fragments, derived from vastly different depths in the pre-impact target, occur together within the ejecta layer. These observations make the Ries ejecta one of the most completely preserved ejecta deposit on Earth for an impact structure of that size.
Role of the fronto-parietal cortex in prospective action judgments
Authors: Geers Laurie , Pesenti Mauro , Derosiere Gerard , Duque Julie , Dricot Laurence , Andres Michael
Published: April 2021

Prospective judgments about one’s capability to perform an action are assumed to involve mental simulation of the action. Previous studies of motor imagery suggest this simulation is supported by a large fronto-parietal network including the motor system. Experiment 1 used fMRI to assess the contribution of this fronto-parietal network to judgments about one’s capacity to grasp objects of different sizes between index and thumb. The neural network underlying prospective graspability judgments overlapped the fronto-parietal network involved in explicit motor imagery of grasping. However, shared areas were located in the right hemisphere, outside the motor cortex, and were also activated during perceptual length judgments, suggesting a contribution to object size estimate rather than motor simulation. Experiment 2 used TMS over the motor cortex to probe transient excitability changes undetected with fMRI. Results show that graspability judgments elicited a selective increase of excitability in the thumb and index muscles, which was maximal before the object display and intermediate during the judgment. Together, these findings suggest that prospective action judgments do not rely on the motor system to simulate the action per se but to refresh the memory of one’s maximal grip aperture and facilitate its comparison with object size in right fronto-parietal areas.
Inactivation of genes in oxidative respiration and iron acquisition pathways in pediatric clinical isolates of Small colony variant Enterobacteriaceae
Authors: Greninger Alexander L. , Addetia Amin , Tao Yue , Adler Amanda , Qin Xuan
Published: April 2021

Isolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the same sample. The basis of SCV emergence in vivo is not well understood in Gram-negative bacteria. In this study, we interrogated the causal genetic lesions of SCV growth in three pairs of NCV and SCV co-isolates of Escherichia coli, Citrobacter freundii, and Enterobacter hormaechei. We confirmed SCV emergence was attributed to limited genomic mutations: 4 single nucleotide variants in the E. coli SCV, 5 in C. freundii, and 8 in E. hormaechei. In addition, a 10.2 kb chromosomal segment containing 11 genes was deleted in the E. hormaechei SCV isolate. Each SCV had at least one coding change in a gene associated with bacterial oxidative respiration and another involved in iron capture. Chemical and genetic rescue confirmed defects in heme biosynthesis for E. coli and C. freundii and lipoic acid biosynthesis in E. hormaachei were responsible for the SCV phenotype. Prototrophic growth in all 3 SCV Enterobacteriaceae species was unaffected under anaerobic culture conditions in vitro, illustrating how SCVs may persist in vivo.
Preseismic atmospheric radon anomaly associated with 2018 Northern Osaka earthquake
Authors: Muto Jun , Yasuoka Yumi , Miura Nao , Iwata Daichi , Nagahama Hiroyuki , Hirano Mitsuhiro , Ohmomo Yoshiro , Mukai Takahiro
Published: April 2021

Despite the challenges in identifying earthquake precursors in intraplate (inland) earthquakes, various hydrological and geochemical measurements have been conducted to establish a possible link to seismic activities. Anomalous increases in radon (222Rn) concentration in soil, groundwater, and atmosphere have been reported prior to large earthquakes. Although the radon concentration in the atmosphere is lower than that in groundwater and soils, a recent statistical analysis has suggested that the average atmospheric concentration over a relatively wide area reflects crustal deformation. However, no study has sought to determine the underlying physico-chemical relationships between crustal deformation and anomalous atmospheric radon concentrations. Here, we show a significant decrease in the atmospheric radon concentration temporally linked to the seismic quiescence before the 2018 Northern Osaka earthquake occurring at a hidden fault with complex rupture dynamics. During seismic quiescence, deep-seated sedimentary layers in Osaka Basin, which might be the main sources of radon, become less damaged and fractured. The reduction in damage leads to a decrease in radon exhalation to the atmosphere near the fault, causing the preseismic radon decrease in the atmosphere. Herein, we highlight the necessity of continuous monitoring of the atmospheric radon concentration, combined with statistical anomaly detection method, to evaluate future seismic risks.
Hierarchical carrier transport simulator for defected nanoparticle solids
Authors: Hansen Chase , Unruh Davis , Alba Miguel , Qian Caroline , Abelson Alex , Law Matt , Zimanyi Gergely T.
Published: April 2021

The efficiency of nanoparticle (NP) solar cells has grown impressively in recent years, exceeding 16%. However, the carrier mobility in NP solar cells, and in other optoelectronic applications remains low, thus critically limiting their performance. Therefore, carrier transport in NP solids needs to be better understood to further improve the overall efficiency of NP solar cell technology. However, it is technically challenging to simulate experimental scale samples, as physical processes from atomic to mesoscopic scales all crucially impact transport. To rise to this challenge, here we report the development of TRIDENS: the Transport in Defected Nanoparticle Solids Simulator, that adds three more hierarchical layers to our previously developed HINTS code for nanoparticle solar cells. In TRIDENS, we first introduced planar defects, such as twin planes and grain boundaries into individual NP SLs superlattices (SLs) that comprised the order of 103 NPs. Then we used HINTS to simulate the transport across tens of thousands of defected NP SLs, and constructed the distribution of the NP SL mobilities with planar defects. Second, the defected NP SLs were assembled into a resistor network with more than 104 NP SLs, thus representing about 107 individual NPs. Finally, the TRIDENS results were analyzed by finite size scaling to explore whether the percolation transition, separating the phase where the low mobility defected NP SLs percolate, from the phase where the high mobility undefected NP SLs percolate drives a low-mobility-to-highmobility transport crossover that can be extrapolated to genuinely macroscopic length scales. For the theoretical description, we adapted the Efros-Shklovskii bimodal mobility distribution percolation model. We demonstrated that the ES bimodal theory’s two-variable scaling function is an effective tool to quantitatively characterize this low-mobility-to-high-mobility transport crossover.
The evolutionary fate of rpl32 and rps16 losses in the Euphorbia schimperi (Euphorbiaceae) plastome
Authors: Alqahtani Aldanah A. , Jansen Robert K.
Published: April 2021

Gene transfers from mitochondria and plastids to the nucleus are an important process in the evolution of the eukaryotic cell. Plastid (pt) gene losses have been documented in multiple angiosperm lineages and are often associated with functional transfers to the nucleus or substitutions by duplicated nuclear genes targeted to both the plastid and mitochondrion. The plastid genome sequence of Euphorbia schimperi was assembled and three major genomic changes were detected, the complete loss of rpl32 and pseudogenization of rps16 and infA. The nuclear transcriptome of E. schimperi was sequenced to investigate the transfer/substitution of the rpl32 and rps16 genes to the nucleus. Transfer of plastid-encoded rpl32 to the nucleus was identified previously in three families of Malpighiales, Rhizophoraceae, Salicaceae and Passifloraceae. An E. schimperi transcript of pt SOD-1-RPL32 confirmed that the transfer in Euphorbiaceae is similar to other Malpighiales indicating that it occurred early in the divergence of the order. Ribosomal protein S16 (rps16) is encoded in the plastome in most angiosperms but not in Salicaceae and Passifloraceae. Substitution of the E. schimperi pt rps16 was likely due to a duplication of nuclear-encoded mitochondrial-targeted rps16 resulting in copies dually targeted to the mitochondrion and plastid. Sequences of RPS16-1 and RPS16-2 in the three families of Malpighiales (Salicaceae, Passifloraceae and Euphorbiaceae) have high sequence identity suggesting that the substitution event dates to the early divergence within Malpighiales.