bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurring exposure to low humidity induces transcriptional and protein level changes in the vocal folds of rabbits
Authors: Bailey Taylor W. , dos Santos Andrea Pires , do Nascimento Naila Cannes , Xie Jun , Sivasankar M. Preeti , Cox Abigail
Published: December 2021

Voice disorders are an important human health condition. Hydration is a commonly recommended preventive measure for voice disorders though it is unclear how vocal fold dehydration is harmful at the cellular level. Airway surface dehydration can result from exposure to low humidity air. Here we have induced airway surface dehydration in New Zealand White rabbits exposed to a recurring 8-h low humidity environment over 15 days. This model mimics an occupational exposure to a low humidity environment. Exposure to moderate humidity was the control condition. Full thickness soft-tissue samples, including the vocal folds and surrounding laryngeal tissue, were collected for molecular analysis. RT-qPCR demonstrated a significant upregulation of MUC4 (mucin 4) and SCL26A9 (chloride channel) and a large fold-change though statistically non-significant upregulation of SCNNA1 (epithelial sodium channel). Proteomic analysis demonstrated differential regulation of proteins clustering into prospective functional groups of muscle structure and function, oxidative stress response, and protein chaperonin stress response. Together, the data demonstrate that recurring exposure to low humidity is sufficient to induce both transcriptional and translational level changes in laryngeal tissue and suggest that low humidity exposure induces cellular stress at the level of the vocal folds.
Screening of selected ageing-related proteins that extend chronological life span in yeast Saccharomyces cerevisiae
Authors: Lee Jee Whu , Ong Tee Gee , Samian Mohammed Razip , Teh Aik-Hong , Watanabe Nobumoto , Osada Hiroyuki , Ong Eugene Boon Beng
Published: December 2021

Ageing-related proteins play various roles such as regulating cellular ageing, countering oxidative stress, and modulating signal transduction pathways amongst many others. Hundreds of ageing-related proteins have been identified, however the functions of most of these ageing-related proteins are not known. Here, we report the identification of proteins that extended yeast chronological life span (CLS) from a screen of ageing-related proteins. Three of the CLS-extending proteins, Ptc4, Zwf1, and Sme1, contributed to an overall higher survival percentage and shorter doubling time of yeast growth compared to the control. The CLS-extending proteins contributed to thermal and oxidative stress responses differently, suggesting different mechanisms of actions. The overexpression of Ptc4 or Zwf1 also promoted rapid cell proliferation during yeast growth, suggesting their involvement in cell division or growth pathways.
Synthesis and characterization of ternary chitosan–TiO2–ZnO over graphene for photocatalytic degradation of tetracycline from pharmaceutical wastewater
Authors: Asadzadeh Patehkhor Hossein , Fattahi Moslem , Khosravi-Nikou Mohammadreza
Published: December 2021

Various nanocomposites of TiO2–ZnO, TiO2–ZnO/CS, and TiO2–ZnO/CS–Gr with different molar ratios were synthesized by sol–gel and ultrasound-assisted methods and utilized under UV irradiation to enhance the photocatalytic degradation of tetracycline. Characterization of prepared materials were carried out by XRD, FT-IR, FE-SEM, EDX and BET techniques. The TiO2–ZnO with the 1:1 molar ratio supported with 1:2 weight ratio CS–Gr (T1‒Z1/CS1‒Gr2 sample) appeared as the most effective material at the optimized operational conditions including the tetracycline concentration of 20 mg/L, pH = 4, catalyst dosage of 0.5 g/L, and 3 h of irradiation time. As expected, the graphene had a significant effect in improving degradation results. The detailed performances of the T1‒Z1/CS1‒Gr2 were compared with ternary nanocomposites from EDX and BET results as well as from the degradation viewpoint. This novel photocatalyst can be effective in actual pharmaceutical wastewater treatment considering the applied operational parameters.
Predicting regional COVID-19 hospital admissions in Sweden using mobility data
Authors: Gerlee Philip , Karlsson Julia , Fritzell Ingrid , Brezicka Thomas , Spreco Armin , Timpka Toomas , Jöud Anna , Lundh Torbjörn
Published: December 2021

The transmission of COVID-19 is dependent on social mixing, the basic rate of which varies with sociodemographic, cultural, and geographic factors. Alterations in social mixing and subsequent changes in transmission dynamics eventually affect hospital admissions. We employ these observations to model and predict regional hospital admissions in Sweden during the COVID-19 pandemic. We use an SEIR-model for each region in Sweden in which the social mixing is assumed to depend on mobility data from public transport utilisation and locations for mobile phone usage. The results show that the model could capture the timing of the first and beginning of the second wave of the pandemic 3 weeks in advance without any additional assumptions about seasonality. Further, we show that for two major regions of Sweden, models with public transport data outperform models using mobile phone usage. We conclude that a model based on routinely collected mobility data makes it possible to predict future hospital admissions for COVID-19 3 weeks in advance.
Rapid and concise quantification of mycelial growth by microscopic image intensity model and application to mass cultivation of fungi
Authors: Lee Soo Kweon , Lee Ju Hun , Kim Hyeong Ryeol , Chun Youngsang , Lee Ja Hyun , Park Chulhwan , Yoo Hah Young , Kim Seung Wook
Published: December 2021

The microbial food fermentation industry requires real-time monitoring and accurate quantification of cells. However, filamentous fungi are difficult to quantify as they have complex cell types such as pellet, spores, and dispersed hyphae. In this study, numerous data of microscopic image intensity (MII) were used to develop a simple and accurate quantification method of Cordyceps mycelium. The dry cell weight (DCW) of the sample collected during the fermentation was measured. In addition, the intensity values were obtained through the ImageJ program after converting the microscopic images. The prediction model obtained by analyzing the correlation between MII and DCW was evaluated through a simple linear regression method and found to be statistically significant (R2 = 0.941, p < 0.001). In addition, validation with randomly selected samples showed significant accuracy, thus, this model is expected to be used as a valuable tool for predicting and quantifying fungal growth in various industries.
Archaeometric evidence for the earliest exploitation of lignite from the bronze age Eastern Mediterranean
Authors: Buckley Stephen , Power Robert C. , Andreadaki-Vlazaki Maria , Akar Murat , Becher Julia , Belser Matthias , Cafisso Sara , Eisenmann Stefanie , Fletcher Joann , Francken Michael , Hallager Birgitta , Harvati Katerina , Ingman Tara , Kataki Efthymia , Maran Joseph , Martin Mario A. S. , McGeorge Photini J. P. , Milevski Ianir , Papadimitriou Alkestis , Protopapadaki Eftychia , Salazar-García Domingo C. , Schmidt-Schultz Tyede , Schuenemann Verena J. , Shafiq Rula , Stuijts Ingelise , Yegorov Dmitry , Yener K. Aslιhan , Schultz Michael , Spiteri Cynthianne , Stockhammer Philipp W.
Published: December 2021

This paper presents the earliest evidence for the exploitation of lignite (brown coal) in Europe and sheds new light on the use of combustion fuel sources in the 2nd millennium BCE Eastern Mediterranean. We applied Thermal Desorption/Pyrolysis–Gas Chromatography-Mass Spectrometry and Polarizing Microscopy to the dental calculus of 67 individuals and we identified clear evidence for combustion markers embedded within this calculus. In contrast to the scant evidence for combustion markers within the calculus samples from Egypt, all other individuals show the inhalation of smoke from fires burning wood identified as Pinaceae, in addition to hardwood, such as oak and olive, and/or dung. Importantly, individuals from the Palatial Period at the Mycenaean citadel of Tiryns and the Cretan harbour site of Chania also show the inhalation of fire-smoke from lignite, consistent with the chemical signature of sources in the northwestern Peloponnese and Western Crete respectively. This first evidence for lignite exploitation was likely connected to and at the same time enabled Late Bronze Age Aegean metal and pottery production, significantly by both male and female individuals.
Spatial attention in encoding letter combinations
Authors: Ramamurthy Mahalakshmi , White Alex L. , Chou Clementine , Yeatman Jason D.
Published: December 2021

Reading requires the correct identification of letters and letter positions within words. Selective attention is, therefore, required to select chunks of the text for sequential processing. Despite the extensive literature on visual attention, the well-known effects of spatial cues in simple perceptual tasks cannot inform us about the role of attention in a task as complex as reading. Here, we systematically manipulate spatial attention in a multi-letter processing task to understand the effects of spatial cues on letter encoding in typical adults. Overall, endogenous (voluntary) cue benefits were larger than exogenous (reflexive). We show that cue benefits are greater in the left than in the right visual field and larger for the most crowded letter positions. Endogenous valid cues reduced errors due to confusing letter positions more than misidentifications, specifically for the most crowded letter positions. Therefore, shifting endogenous attention along a line of text is likely an important mechanism to alleviate the effects of crowding on encoding letters within words. Our results help set the premise for constructing theories about how specific mechanisms of attention support reading development in children. Understanding the link between reading development and attention mechanisms has far-reaching implications for effectively addressing the needs of children with reading disabilities.
Association analysis for resistance to Striga hermonthica in diverse tropical maize inbred lines
Authors: Stanley A. E. , Menkir A. , Ifie B. , Paterne A. A. , Unachukwu N. N. , Meseka S. , Mengesha W. A. , Bossey B. , Kwadwo O. , Tongoona P. B. , Oladejo O. , Sneller C. , Gedil M.
Published: December 2021

Striga hermonthica is a widespread, destructive parasitic plant that causes substantial yield loss to maize productivity in sub-Saharan Africa. Under severe Striga infestation, yield losses can range from 60 to 100% resulting in abandonment of farmers’ lands. Diverse methods have been proposed for Striga management; however, host plant resistance is considered the most effective and affordable to small-scale famers. Thus, conducting a genome-wide association study to identify quantitative trait nucleotides controlling S. hermonthica resistance and mining of relevant candidate genes will expedite the improvement of Striga resistance breeding through marker-assisted breeding. For this study, 150 diverse maize inbred lines were evaluated under Striga infested and non-infested conditions for two years and genotyped using the genotyping-by-sequencing platform. Heritability estimates of Striga damage ratings, emerged Striga plants and grain yield, hereafter referred to as Striga resistance-related traits, were high under Striga infested condition. The mixed linear model (MLM) identified thirty SNPs associated with the three Striga resistance-related traits based on the multi-locus approaches (mrMLM, FASTmrMLM, FASTmrEMMA and pLARmEB). These SNPs explained up to 14% of the total phenotypic variation. Under non-infested condition, four SNPs were associated with grain yield, and these SNPs explained up to 17% of the total phenotypic variation. Gene annotation of significant SNPs identified candidate genes (Leucine-rich repeats, putative disease resistance protein and VQ proteins) with functions related to plant growth, development, and defense mechanisms. The marker-effect prediction was able to identify alleles responsible for predicting high yield and low Striga damage rating in the breeding panel. This study provides valuable insight for marker validation and deployment for Striga resistance breeding in maize.
Human Achilles tendon mechanical behavior is more strongly related to collagen disorganization than advanced glycation end-products content
Authors: Zellers Jennifer A. , Eekhoff Jeremy D. , Walk Remy E. , Hastings Mary K. , Tang Simon Y. , Lake Spencer P.
Published: December 2021

Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear. Advanced glycation end-products (AGEs) accumulate with diabetes and have been suggested to alter tendon function. In vivo imaging in humans has suggested collagen disorganization is more frequent in individuals with diabetes, which could also impair tendon mechanical function. The purpose of this study was to examine relationships between tendon tensile mechanics in human Achilles tendon with accumulation of advanced glycation end-products and collagen disorganization. Achilles tendon specimens (n = 16) were collected from individuals undergoing lower extremity amputation or from autopsy. Tendons were tensile tested with simultaneous quantitative polarized light imaging to assess collagen organization, after which AGEs content was assessed using a fluorescence assay. Moderate to strong relationships were observed between measures of collagen organization and tendon tensile mechanics (range of correlation coefficients: 0.570–0.727), whereas no statistically significant relationships were observed between AGEs content and mechanical parameters (range of correlation coefficients: 0.020–0.210). Results suggest that the relationship between AGEs content and tendon tensile mechanics may be masked by multifactorial collagen disorganization at larger length scales (i.e., the fascicle level).
Excessive energy expenditure due to acute physical restraint disrupts Drosophila motivational feeding response
Authors: Gordon Jacob , Masek Pavel
Published: December 2021

To study the behavior of Drosophila, it is often necessary to restrain and mount individual flies. This requires removal from food, additional handling, anesthesia, and physical restraint. We find a strong positive correlation between the length of time flies are mounted and their subsequent reflexive feeding response, where one hour of mounting is the approximate motivational equivalent to ten hours of fasting. In an attempt to explain this correlation, we rule out anesthesia side-effects, handling, additional fasting, and desiccation. We use respirometric and metabolic techniques coupled with behavioral video scoring to assess energy expenditure in mounted and free flies. We isolate a specific behavior capable of exerting large amounts of energy in mounted flies and identify it as an attempt to escape from restraint. We present a model where physical restraint leads to elevated activity and subsequent faster nutrient storage depletion among mounted flies. This ultimately further accelerates starvation and thus increases reflexive feeding response. In addition, we show that the consequences of the physical restraint profoundly alter aerobic activity, energy depletion, taste, and feeding behavior, and suggest that careful consideration is given to the time-sensitive nature of these highly significant effects when conducting behavioral, physiological or imaging experiments that require immobilization.
Comparing different nonlinearities in readout systems for optical neuromorphic computing networks
Authors: Ma Chonghuai , Lambrecht Joris , Laporte Floris , Yin Xin , Dambre Joni , Bienstman Peter
Published: December 2021

Nonlinear activation is a crucial building block of most machine-learning systems. However, unlike in the digital electrical domain, applying a saturating nonlinear function in a neural network in the analog optical domain is not as easy, especially in integrated systems. In this paper, we first investigate in detail the photodetector nonlinearity in two main readout schemes: electrical readout and optical readout. On a 3-bit-delayed XOR task, we show that optical readout trained with backpropagation gives the best performance. Furthermore, we propose an additional saturating nonlinearity coming from a deliberately non-ideal voltage amplifier after the detector. Compared to an all-optical nonlinearity, these two kinds of nonlinearities are extremely easy to obtain at no additional cost, since photodiodes and voltage amplifiers are present in any system. Moreover, not having to design ideal linear amplifiers could relax their design requirements. We show through simulation that for long-distance nonlinear fiber distortion compensation, using only the photodiode nonlinearity in an optical readout delivers BER improvements over three orders of magnitude. Combined with the amplifier saturation nonlinearity, we obtain another three orders of magnitude improvement of the BER.
Analysis of avian Usutu virus infections in Germany from 2011 to 2018 with focus on dsRNA detection to demonstrate viral infections
Authors: Störk Theresa , de le Roi Madeleine , Haverkamp Ann-Kathrin , Jesse Sonja T. , Peters Martin , Fast Christine , Gregor Katharina M. , Könenkamp Laura , Steffen Imke , Ludlow Martin , Beineke Andreas , Hansmann Florian , Wohlsein Peter , Osterhaus Albert D. M. E. , Baumgärtner Wolfgang
Published: December 2021

Usutu virus (USUV) is a zoonotic arbovirus causing avian mass mortalities. The first outbreak in North-Western Germany occurred in 2018. This retrospective analysis focused on combining virological and pathological findings in birds and immunohistochemistry. 25 common blackbirds, one great grey owl, and one kingfisher collected from 2011 to 2018 and positive for USUV by qRT-PCR were investigated. Macroscopically, most USUV infected birds showed splenomegaly and hepatomegaly. Histopathological lesions included necrosis and lymphohistiocytic inflammation within spleen, Bursa fabricii, liver, heart, brain, lung and intestine. Immunohistochemistry revealed USUV antigen positive cells in heart, spleen, pancreas, lung, brain, proventriculus/gizzard, Bursa fabricii, kidney, intestine, skeletal muscle, and liver. Analysis of viral genome allocated the virus to Europe 3 or Africa 2 lineage. This study investigated whether immunohistochemical detection of double-stranded ribonucleic acid (dsRNA) serves as an alternative tool to detect viral intermediates. Tissue samples of six animals with confirmed USUV infection by qRT-PCR but lacking viral antigen in liver and spleen, were further examined immunohistochemically. Two animals exhibited a positive signal for dsRNA. This could indicate either an early state of infection without sufficient formation of virus translation products, occurrence of another concurrent virus infection or endogenous dsRNA not related to infectious pathogens and should be investigated in more detail in future studies.
Removal of Ag remanence and improvement in structural attributes of silicon nanowires array via sintering
Authors: Kale Paresh , Sahoo Mihir Kumar
Published: December 2021

Metal-assisted chemical etching (MACE) is popular due to the large-area fabrication of silicon nanowires (SiNWs) exhibiting a high aspect ratio at a low cost. The remanence of metal, i.e., silver nanoparticles (AgNPs) used in the MACE, deteriorates the device (especially solar cell) performance by acting as a defect center. The superhydrophobic behavior of nanowires (NWs) array prohibits any liquid-based solution (i.e., thorough cleaning with HNO3 solution) from removing the AgNPs. Thermal treatment of NWs is an alternative approach to reduce the Ag remanence. Sintering temperature variation is chosen between the melting temperature of bulk-Ag (962 °C) and bulk-Si (1412 °C) to reduce the Ag particles and improve the crystallinity of the NWs. The melting point of NWs decreases due to surface melting that restricts the sintering temperature to 1200 °C. The minimum sintering temperature is set to 1000 °C to eradicate the Ag remanence. The SEM–EDS analysis is carried out to quantify the reduction in Ag remanence in the sintered NWs array. The XRD analysis is performed to study the oxides (SiO and Ag2O) formed in the NWs array due to the trace oxygen level in the furnace. The TG-DSC characterization is carried out to know the critical sintering temperature at which remanence of AgNPs removes without forming any oxides. The Raman analysis is studied to determine the crystallinity, strain, and size of Si nanocrystals (SiNCs) formed on the NWs surface due to sidewalls etching. An optimized polynomial equation is derived to find the SiNCs size for various sintering temperatures.
Placental acute inflammation infiltrates and pregnancy outcomes: a retrospective cohort study
Authors: Orsaria Maria , Liviero Stefania , Rossetti Emma , Pittini Carla , Driul Lorenza , Londero Ambrogio P. , Mariuzzi Laura
Published: December 2021

Chorioamnionitis can be either an infection or a sterile inflammation. This study aims to analyze the prevalence of acute inflammatory lesions of the placenta, the association with a positive result of the microbiological examination, and the fetal-maternal outcomes. This retrospective study considered all single, consecutive pregnancies and their placental pathological examination during 2014–2017. The evidence of funisitis, chorionic vasculitis, and chorioamnionitis was assessed by a pathologist, including stage and grade. Moreover, maternal fever, placental microbiological examination, and neonatal outcomes were also recorded. Among the 5910 pregnancies in the considered period, 1770 had a placental pathological examination, and 358 (6.06%) had acute placental inflammation. Microbiological examination was performed in 125 cases, revealing 64 cases with a positive microbiological outcome. In the presence of acute placental inflammation, there was a higher rate of neonatal cardiopulmonary resuscitation, admission to neonatal intensive care unit, and postnatal death of the newborn. Multivariate analysis inferred that acute inflammation of membranes was a risk factor for neonatal cardiopulmonary resuscitation (OR 2.12; CI.95 1.36–3.31; p < 0.05), acute funisitis was a risk factor for admission to intensive neonatal care unit (OR 3.2; CI.95 1.67–6.12; p < 0.05), and chorionic vasculitis was a risk factor for postnatal death of the newborn (OR 5.38; CI.95 1.37–21.06; p < 0.05). The prevalence of chorioamnionitis was 6.06%, and about half of the cases were sterile inflammation. Chorioamnionitis was associated with higher rates of adverse fetal and neonatal outcomes; in particular, chorionic vasculitis was a risk factor for postnatal death.
Optimization of use-wear detection and characterization on stone tool surfaces
Authors: Borel Antony , Deltombe Raphaël , Moreau Philippe , Ingicco Thomas , Bigerelle Maxence , Marteau Julie
Published: December 2021

Debates and doubt around the interpretation of use-wear on stone tools called for the development of quantitative analysis of surfaces to complement the qualitative description of traces. Recently, a growing number of studies showed that prehistoric activities can be discriminated thanks to quantitative characterization of stone tools surface alteration due to use. However, stone tool surfaces are microscopically very heterogeneous and the calculated parameters may highly vary depending on the areas selected for measurement. Indeed, it may be impacted by the effects from the raw material topography and not from the altered zones only, if non-altered part of the surface is included in the measurement. We propose here to discuss this issue and present a workflow involving the use of masks to separate worn and unworn parts of the surface. Our results show that this step of extraction, together with suitable filtering, could have a high impact on the optimization of the detection and thus characterization of use traces. This represents the basis for future automatic routines allowing the detection, extraction and characterization of wear on stone tools.
Comparative genome characterization of Echinicola marina sp. nov., isolated from deep-sea sediment provide insight into carotenoid biosynthetic gene cluster evolution
Authors: Pang Yu , Chen Mengru , Lu Wei , Chen Ming , Yan Yongliang , Lin Min , Zhang Wei , Zhou Zhengfu
Published: December 2021

Echinicola, carotenoid-pigmented bacteria, are isolated from various hypersaline environments. Carotenoid accumulation in response to salt stress can stabilize the cell membrane in order to survive. A pink-colored strain SCS 3–6 was isolated from the deep-sea sediment of the South China Sea. Growth was found to occur at 10–45 °C. The strain could tolerate 10% (w/v) NaCl concentration and grow at pH 5–9. The complete genome of SCS 3–6 comprises 5053 putative genes with a total 5,693,670 bp and an average G + C content of 40.11 mol%. The 16S rRNA gene sequence analysis indicated that strain SCS 3–6 was affiliated with the genus Echinicola, with the closely strains were Echinicola arenosa CAU 1574T (98.29%)and Echinicola shivajiensis AK12T (97.98%). For Echinicola species with available genome sequences, pairwise comparisons for average nucleotide identity (ANI) and in silico DNA-DNA hybridization (DDH) revealed ANIb values from 70.77 to 74.71%, ANIm values from 82.72 to 88.88%, and DDH values from 18.00 to 23.40%. To identify their genomic features, we compared their genomes with those of other Echinicola species. Phylogenetic analysis showed that strain SCS 3–6 formed a monophyletic clade. Genomic analysis revealed that strain SCS 3–6 possessed a complete synthetic pathway of carotenoid and speculated that the production was astaxanthin. Based on phenotypic and genotypic analyses in this study, strain SCS 3–6 is considered to represent a novel species of the genus Echinicola for which the name Echinicola marina sp. nov. is proposed. The type strain is SCS 3-6T (= GDMCC 1.2220T = JCM 34403T).
No neutralizing effect of pre-existing tick-borne encephalitis virus antibodies against severe acute respiratory syndrome coronavirus-2: a prospective healthcare worker study
Authors: Kohler Philipp , Jonsdottir Hulda R. , Risch Lorenz , Vernazza Pietro , Ackermann-Gäumann Rahel , Kahlert Christian R.
Published: December 2021

Certain immunizations including vaccination against tick-borne encephalitis virus (TBEV) have been suggested to confer cross-protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Within a prospective healthcare worker (HCW) cohort, we assessed the potentially protective role of anti-TBEV antibodies against SARS-CoV-2 infection. Among 3352 HCW, those with ≥ 1 previous TBEV vaccination (n = 2018, 60%) showed a reduced risk of SARS-CoV-2 seroconversion (adjusted odds ratio: 0.8, 95% CI: 0.7–1.0, P = 0.02). However, laboratory testing of a subgroup of 26 baseline and follow-up samples did not demonstrate any neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 in live-virus neutralization assay. However, we observed significantly higher anti-TBEV antibody titers in follow-up samples of participants with previous TBEV vaccination compared to baseline, both TBEV neutralizing (p = 0.001) and total IgG (P < 0.0001), irrespective of SARS-CoV-2 serostatus. Based on these data, we conclude that the observed association of previous TBEV vaccination and reduced risk of SARS-CoV-2 infection is likely due to residual confounding factors. The increase in TBEV follow-up antibody titers can be explained by natural TBEV exposure or potential non-specific immune activation upon exposure to various pathogens, including SARS-CoV-2. We believe that these findings, although negative, contribute to the current knowledge on potential cross-immunity against SARS-CoV-2 from previous immunizations.
Exquisite air sac histological traces in a hyperpneumatized nanoid sauropod dinosaur from South America
Authors: Aureliano Tito , Ghilardi Aline M. , Navarro Bruno A. , Fernandes Marcelo A. , Ricardi-Branco Fresia , Wedel Mathew J.
Published: December 2021

This study reports the occurrence of pneumosteum (osteohistological structure related to an avian-like air sac system) in a nanoid (5.7-m-long) saltasaurid titanosaur from Upper Cretaceous Brazil. We corroborate the hypothesis of the presence of an air sac system in titanosaurians based upon vertebral features identified through external observation and computed tomography. This is the fifth non-avian dinosaur taxon in which histological traces of air sacs have been found. We provided a detailed description of pneumatic structures from external osteology and CT scan data as a parameter for comparison with other taxa. The camellate pattern found in the vertebral centrum (ce) of this taxon and other titanosaurs shows distinct architectures. This might indicate whether cervical or lung diverticula pneumatized different elements. A cotylar internal plate of bone tissue sustains radial camellae (rad) in a condition similar to Alamosaurus and Saltasaurus. Moreover, circumferential chambers (cc) near the cotyle might be an example of convergence between diplodocoids and titanosaurs. Finally, we also register for the first time pneumatic foramina (fo) and fossae connecting camellate structures inside the neural canal in Titanosauria and the second published case in non-avian dinosaurs. The extreme pneumaticity observed in this nanoid titanosaur contrasts with previous assumptions that this feature correlates with the evolution of gigantic sizes in sauropodomorphs. This study reinforces that even small-bodied sauropod clades could present a hyperpneumatized postcranial skeleton, a character inherited from their large-bodied ancestors.
Clonal dynamics of BRAF-driven drug resistance in EGFR-mutant lung cancer
Authors: Schaufler Diana , Ast David F. , Tumbrink Hannah L. , Abedpour Nima , Maas Lukas , Schwäbe Ayla E. , Spille Inga , Lennartz Stefanie , Fassunke Jana , Aldea Mihaela , Besse Benjamin , Planchard David , Nogova Lucia , Michels Sebastian , Kobe Carsten , Persigehl Thorsten , Westphal Theresa , Koleczko Sophia , Fischer Rieke , Weber Jan-Phillip , Altmüller Janine , Thomas Roman K. , Merkelbach-Bruse Sabine , Gautschi Oliver , Mezquita Laura , Büttner Reinhard , Wolf Jürgen , Peifer Martin , Brägelmann Johannes , Scheffler Matthias , Sos Martin L.
Published: December 2021

Activation of MAPK signaling viaBRAFmutations may limit the activity of EGFR inhibitors inEGFR-mutant lung cancer patients. However, the impact ofBRAFmutations on the selection and fitness of emerging resistant clones during anti-EGFR therapy remains elusive. We tracked the evolution of subclonal mutations by whole-exome sequencing and performed clonal analyses of individual metastases during therapy. Complementary functional analyses of polyclonalEGFR-mutant cell pools showed a dose-dependent enrichment ofBRAFV600Eand a loss of EGFR inhibitor susceptibility. The clones remain stable and become vulnerable to combined EGFR, RAF, and MEK inhibition. Moreover, only osimertinib/trametinib combination treatment, but not monotherapy with either of these drugs, leads to robust tumor shrinkage inEGFR-driven xenograft models harboringBRAFV600Emutations. These data provide insights into the dynamics of clonal evolution ofEGFR-mutant tumors and the therapeutic implications ofBRAFco-mutations that may facilitate the development of treatment strategies to improve the prognosis of these patients.
High TGF-β signature predicts immunotherapy resistance in gynecologic cancer patients treated with immune checkpoint inhibition
Authors: Ni Ying , Soliman Ahmed , Joehlin-Price Amy , Rose Peter G. , Vlad Anda , Edwards Robert P. , Mahdi Haider
Published: December 2021

Various immune signatures predictive of resistance to immune checkpoint inhibitors (ICI) have been described in multiple solid cancers, but still under-investigated in gynecological (GYN) cancer. For 49 GYN cancer patients included in our study, without transcriptome signature, immune-related toxicity was the only clinical predictor of ICI treatment response (p = 0.008). The objective clinical response was the only predictor of progression-free survival (ICI-PFS, p = 0.0008) and overall survival (ICI-OS, p = 0.01). Commonly used ICI marker PD-L1 expression negatively correlated with progression-free survival (ICI-PFS) (p = 0.0019). We performed transcriptome and signaling pathway enrichment analyses based on ICI treatment responses and the survival outcome, and further estimated immune cell abundance using 547 gene markers. Our data revealed that TGF-β regulated signaling pathway was noted to play an important role in immunotherapy failure. Using our 6-genes TGF-β score, we observed longer ICI-PFS associated with lower TGF-β score (8.1 vs. 2.8 months, p = 0.046), which was especially more prominent in ovarian cancer (ICI-PFS 16.6 vs. 2.65 months, p = 0.0012). Further, abundant immunosuppressive cells like T-regulatory cells, eosinophils, and M2 macrophages were associated with shorter ICI-OS and correlated positively with CD274 and CTLA4 expressions. This study provides insight on the potential role of TGF-β in mediating immunotherapy resistance and cross-talking to immunosuppressive environment in GYN cancer. The TGF-β score, if validated in a larger cohort, can identify patients who likely to fail ICI and benefit from targeting this pathway to enhance the response to ICI.
Lewis acid-mediated Suzuki–Miyaura cross-coupling reaction
Authors: Niwa Takashi , Uetake Yuta , Isoda Motoyuki , Takimoto Tadashi , Nakaoka Miki , Hashizume Daisuke , Sakurai Hidehiro , Hosoya Takamitsu
Published: December 2021

The palladium-catalysed Suzuki–Miyaura cross-coupling reaction of organohalides and organoborons is a reliable method for carbon–carbon bond formation. This reaction involves a base-mediated transmetalation process, but the presence of a base also promotes competitive protodeborylation. Herein, we established a Suzuki–Miyaura cross-coupling reaction via Lewis acid-mediated transmetalation of an organopalladium(II) intermediate with organoborons. Experimental and theoretical investigations indicate that the controlled release of the transmetalation-active intermediate enables base-independent transmetalation under heating conditions and enhances the applicable scope of this process. This system enables us to avoid the addition of a traditional base and, thus, renders substrates with base-sensitive moieties available. Results from this research further expand the overall utility of cross-coupling chemistry.
Co-option of an extracellular protease for transcriptional control of nutrient degradation in the fungus Aspergillus nidulans
Authors: Li Ang , Parsania Chirag , Tan Kaeling , Todd Richard B. , Wong Koon Ho
Published: December 2021

Nutrient acquisition is essential for all organisms. Fungi regulate their metabolism according to environmental nutrient availability through elaborate transcription regulatory programs. In filamentous fungi, a highly conserved GATA transcription factor AreA and its co-repressor NmrA govern expression of genes involved in extracellular breakdown, uptake, and metabolism of nitrogen nutrients. Here, we show that the Aspergillus nidulans PnmB protease is a moonlighting protein with extracellular and intracellular functions for nitrogen acquisition and metabolism. PnmB serves not only as a secreted protease to degrade extracellular nutrients, but also as an intracellular protease to control the turnover of the co-repressor NmrA, accelerating AreA transcriptional activation upon nitrogen starvation. PnmB expression is controlled by AreA, which activates a positive feedback regulatory loop. Hence, we uncover a regulatory mechanism in the well-established controls determining the response to nitrogen starvation, revealing functional evolution of a protease gene for transcriptional regulation and extracellular nutrient breakdown.
Epigenetic models developed for plains zebras predict age in domestic horses and endangered equids
Authors: Larison Brenda , Pinho Gabriela M. , Haghani Amin , Zoller Joseph A. , Li Caesar Z. , Finno Carrie J. , Farrell Colin , Kaelin Christopher B. , Barsh Gregory S. , Wooding Bernard , Robeck Todd R. , Maddox Dewey , Pellegrini Matteo , Horvath Steve
Published: December 2021

Effective conservation and management of threatened wildlife populations require an accurate assessment of age structure to estimate demographic trends and population viability. Epigenetic aging models are promising developments because they estimate individual age with high accuracy, accurately predict age in related species, and do not require invasive sampling or intensive long-term studies. Using blood and biopsy samples from known age plains zebras (Equus quagga), we model epigenetic aging using two approaches: the epigenetic clock (EC) and the epigenetic pacemaker (EPM). The plains zebra EC has the potential for broad application within the genus Equus given that five of the seven extant wild species of the genus are threatened. We test the EC’s ability to predict age in sister taxa, including two endangered species and the more distantly related domestic horse, demonstrating high accuracy in all cases. By comparing chronological and estimated age in plains zebras, we investigate age acceleration as a proxy of health status. An interaction between chronological age and inbreeding is associated with age acceleration estimated by the EPM, suggesting a cumulative effect of inbreeding on biological aging throughout life.
Orientation of mouse H19 ICR affects imprinted H19 gene expression through promoter methylation-dependent and -independent mechanisms
Authors: Matsuzaki Hitomi , Miyajima Yu , Fukamizu Akiyoshi , Tanimoto Keiji
Published: December 2021

The mouse Igf2/H19 locus is regulated by genomic imprinting, in which the paternally methylated H19 imprinting control region (ICR) plays a critical role in mono-allelic expression of the genes in the locus. Although the maternal allele-specific insulator activity of the H19 ICR in regulating imprinted Igf2 expression has been well established, the detailed mechanism by which the H19 ICR controls mono-allelic H19 gene expression has not been fully elucidated. In this study, we evaluated the effect of H19 ICR orientation on imprinting regulation in mutant mice in which the H19 ICR sequence was inverted at the endogenous locus. When the inverted-ICR allele was paternally inherited, the methylation level of the H19 promoter was decreased and the H19 gene was derepressed, suggesting that methylation of the H19 promoter is essential for complete repression of H19 gene expression. Unexpectedly, when the inverted allele was maternally inherited, the expression level of the H19 gene was lower than that of the WT allele, even though the H19 promoter remained fully hypomethylated. These observations suggested that the polarity of the H19 ICR is involved in controlling imprinted H19 gene expression on each parental allele, dependent or independent on DNA methylation of the H19 promoter.
A solution to the complement of the generalized Luneburg lens problem
Authors: Fonseca Nelson J. G. , Tyc Tomáš , Quevedo–Teruel Oscar
Published: December 2021

Lenses are of interest for the design of directive antennas and multi-optics instruments in the microwave, terahertz and optical domains. Here, we introduce an optical problem defined as the complement of the well-known generalized Luneburg lens problem. The spherically symmetric inhomogeneous lenses obtained as solutions of this problem transform a given sphere in the homogeneous region outside of the lens into a virtual conjugate sphere, forming a virtual image from a real source. An analytical solution is proposed for the equivalent geodesic lens using the analogy between classical mechanics and geometrical optics. The refractive index profile of the corresponding inhomogeneous lens is then obtained using transformation optics. The focusing properties of this family of lenses are validated using ray-tracing models, further corroborated with full-wave simulations. The numerical results agree well with the predictions over the analyzed frequency bandwidth (10–30 GHz). This virtual focusing property may further benefit from recent developments in the fields of metamaterials and transformation optics.
Electron localization induced by intrinsic anion disorder in a transition metal oxynitride
Authors: Oka Daichi , Hirose Yasushi , Nakao Shoichiro , Fukumura Tomoteru , Hasegawa Tetsuya
Published: December 2021

Anderson localization derived from randomness plays a crucial role in various kinds of phase transitions. Although treated as a free variable parameter in theory, randomness in electronic materials is hard to control experimentally owing to the coexisting Coulomb interaction. Here we demonstrate that the intrinsic anion disorder in a mixed-anion system of SrNbO2N induces a significant random potential that overwhelms the Coulomb potential while maintaining the lattice structure. A metal-to-insulator transition is triggered by a chemical modulation of the electron density where the critical electron density is more than three orders of magnitude greater than that predicted by the well-known Mott criterion. The localized electrons show characteristic electrical properties such as temperature-dependent multiple crossovers of conduction mechanisms and a positive magnetoresistance above 50% at low temperature. The large magnetoresistance is attributed to wave-function shrinkage of the localized states and clearly visualizes the anisotropy in the band structure, which indicates a compatibility of the periodicity and randomness.
Microvolume DNA extraction methods for microscale amplicon and metagenomic studies
Authors: Bramucci Anna R , Focardi Amaranta , Rinke Christian , Hugenholtz Philip , Tyson Gene W , Seymour Justin R , Raina Jean-Baptiste
Published: December 2021

Investigating the composition and metabolic capacity of aquatic microbial assemblages usually requires the filtration of multi-litre samples, which are up to 1 million-fold larger than the microenvironments within which microbes are predicted to be spatially organised. To determine if community profiles can be reliably generated from microlitre volumes, we sampled seawater at a coastal and an oceanic site, filtered and homogenised them, and extracted DNA from bulk samples (2 L) and microvolumes (100, 10 and 1 μL) using two new approaches. These microvolume DNA extraction methods involve either physical or chemical lysis (through pH/thermal shock and lytic enzymes/surfactants, respectively), directly followed by the capture of DNA on magnetic beads. Downstream analysis of extracted DNA using both amplicon sequencing and metagenomics, revealed strong correlation with standard large volume approaches, demonstrating the fidelity of taxonomic and functional profiles of microbial communities in as little as 1 μL of seawater. This volume is six orders of magnitude smaller than most standard operating procedures for marine metagenomics, which will allow precise sampling of the heterogenous landscape that microbes inhabit.
Development and comparison of various rod-shaped mini-reference electrode compositions based on Ag/AgCl for potentiometric applications
Authors: Nigde Mustafa , Agir Ismail , Yıldırım Rıdvan , Isildak Ibrahim
Published: December 2021

Herein, various reference electrode compositions were assembled, their performances were determined, and some simulated real-world tests were conducted with the best electrode.
An improved capillary isoelectric focusing-mass spectrometry method for high-resolution characterization of monoclonal antibody charge variants
Authors: Xu Tian , Han Linjie , George Thompson Alayna M. , Sun Liangliang
Published: December 2021

We developed an automated cIEF-MS method with good stability and high resolution for characterizing charge variants of mAbs by bettering capillary neutral coating, reducing catholyte pH to 10, and optimizing the cIEF separation conditions.
A highly selective and sensitive electrochemical sensor for dopamine based on a functionalized multi-walled carbon nanotube and poly(N-methylaniline) composite
Authors: Direksilp Chatrawee , Scheiger Johannes M. , Ariyasajjamongkol Nuttha , Sirivat Anuvat
Published: December 2021

A poly(N-methylaniline) composite, shown for the first time, is well-suited to sense dopamine due to a low LOD (2.23 μmol L−1).
Blatter-type radicals as polarizing agents for electrochemical overhauser dynamic nuclear polarization
Authors: Saenz Felipe , Tamski Mika , Milani Jonas , Roussel Christophe , Frauenrath Holger , Ansermet Jean-Philippe
Published: December 2021

Overhauser dynamic nuclear polarization (O-DNP) allows a significant increase of the NMR signal intensity of a target substance. We report herein the use of Blatter-type radicals as air-stable, chemically tunable polarizing agents for O-DNP.
Ethyl-, vinyl- and ethynylcyanoborates: room temperature borate ionic liquids with saturated and unsaturated hydrocarbon chains
Authors: Schopper Nils , Zapf Ludwig , Sprenger Jan A. P. , Ignat’ev Nikolai V. , Finze Maik
Published: December 2021

Salts of the anions [RB(CN)3]− and [RBF(CN)2]− (R = ethyl, vinyl, ethynyl) provide high thermal and electrochemical stabilities. The EMIm-salts are low viscosity room temperature ionic liquids with a wide liquid range.
Templated synthesis of zirconium(iv)-based metal–organic layers (MOLs) with accessible chelating sites
Authors: Gimeno-Fonquernie Pol , Liang Weibin , Albalad Jorge , Kuznicki Andrew , Price Jason R. , Bloch Eric D. , Doonan Christian J. , Sumby Christopher J.
Published: December 2021

A two-step templating/delamination strategy can provide access to metal–organic layers with accessible chelating sites poised for quantitative post-synthetic metalation.
Are luminescent Ru2+ chelated complexes selective coordinative sensors for the detection of heavy cations?
Authors: Gourlaouen Christophe , Schweitzer Benjamin , Daniel Chantal
Published: December 2021

The question of the selectivity of [Ru(bpy)2(bpym)]2+ (bpy = 2,2′-bipyridine; bpym = 2,2′-bipyrimidine), a potential luminescent coordinative sensor for the detection of metal cations, is raised and discussed in detail.
Pressure-stabilized hexafluorides of first-row transition metals
Authors: Lin Jianyan , Yang Qiuping , Li Xing , Zhang Xiaohua , Li Fei , Yang Guochun
Published: December 2021

Fluorine chemistry was demonstrated to show the importance of stretching the limits of chemical synthesis, oxidation state, and chemical bonding at ambient conditions.
Nitrogen reduction reaction on single cluster catalysts of defective PC6-trimeric or tetrameric transition metal
Authors: Du Peiyuan , Huang Yuhong , Zhu Gangqiang , Ma Fei , Zhang Jianmin , Wei Xiumei , Hou Pengfei , Wang Min , Liu Jing
Published: December 2021

The traditional Haber–Bosch method of ammonia (NH3) synthesis has low production efficiency and can lead to greenhouse gas emission due to high temperature and pressure dependent reactions.
Two-dimensional ferroelasticity and negative Poisson's ratios in monolayer YbX (X = S, Se, Te)
Authors: Lan Qingwen , Chen Changpeng
Published: December 2021

Two-dimensional ferroelastic materials and two-dimensional materials with negative Poisson's ratios have attracted great interest.
A two-photon tandem black phosphorus quantum dot-sensitized BiVO4 photoanode for solar water splitting
Authors: Jin Bingjun , Cho Yoonjun , Park Cheolwoo , Jeong Jeehun , Kim Sungsoon , Jin Jie , Kim Wooyul , Wang Luyang , Lu Siyu , Zhang Shengli , Oh Sang Ho , Zhang Kan , Park Jong Hyeok
Published: December 2021

A two-photon tandem absorption E-BiVO4/BPQDs/OL-OEC photoanode with superior light absorbability and photocurrent density.
Selenium nanoparticles: a review on synthesis and biomedical applications
Authors: Bisht Neha , Phalswal Priyanka , Khanna Pawan K.
Published: December 2021

Selenium is a trace and essential micronutrient for the health of humans, animals, and microorganisms.