bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing
Authors: Atcha Hamza , Jairaman Amit , Holt Jesse R. , Meli Vijaykumar S. , Nagalla Raji R. , Veerasubramanian Praveen Krishna , Brumm Kyle T. , Lim Huy E. , Othy Shivashankar , Cahalan Michael D. , Pathak Medha M. , Liu Wendy F.
Published: May 2021

Macrophages perform diverse functions within tissues during immune responses to pathogens and injury, but molecular mechanisms by which physical properties of the tissue regulate macrophage behavior are less well understood. Here, we examine the role of the mechanically activated cation channel Piezo1 in macrophage polarization and sensing of microenvironmental stiffness. We show that macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Additionally, macrophages expressing the transgenic Ca2+ reporter, Salsa6f, reveal that Ca2+ influx is dependent on Piezo1, modulated by soluble signals, and enhanced on stiff substrates. Furthermore, stiffness-dependent changes in macrophage function, both in vitro and in response to subcutaneous implantation of biomaterials in vivo, require Piezo1. Finally, we show that positive feedback between Piezo1 and actin drives macrophage activation. Together, our studies reveal that Piezo1 is a mechanosensor of stiffness in macrophages, and that its activity modulates polarization responses.
3,3-Difluoroallyl ammonium salts: highly versatile, stable and selective gem-difluoroallylation reagents
Authors: Ye Fei , Ge Yao , Spannenberg Anke , Neumann Helfried , Xu Li-Wen , Beller Matthias
Published: May 2021

The selective synthesis of fluorinated organic molecules continues to be of major importance for the development of bioactive compounds (agrochemicals and pharmaceuticals) as well as unique materials. Among the established synthetic toolbox for incorporation of fluorine-containing units, efficient and general reagents for introducing -CF2- groups have been largely neglected. Here, we present the synthesis of 3,3-difluoropropen-1-yl ammonium salts (DFPAs) as stable, and scalablegem-difluoromethylation reagents, which allow for the direct reaction with a wide range of fascinating nucleophiles. DFPAs smoothly react withN-,O-,S-,Se-, andC-nucleophiles under mild conditions without necessity of metal catalysts with exclusive regioselectivity. In this way, the presented reagents also permit the straightforward preparation of many analogues of existing pharmaceuticals.
Model-based analysis uncovers mutations altering autophagy selectivity in human cancer
Authors: Han Zhu , Zhang Weizhi , Ning Wanshan , Wang Chenwei , Deng Wankun , Li Zhidan , Shang Zehua , Shen Xiaofei , Liu Xiaohui , Baba Otto , Morita Tsuyoshi , Chen Lu , Xue Yu , Jia Da
Published: May 2021

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.
Revealing composition and structure dependent deep-level defect in antimony trisulfide photovoltaics
Authors: Lian Weitao , Jiang Chenhui , Yin Yiwei , Tang Rongfeng , Li Gang , Zhang Lijian , Che Bo , Chen Tao
Published: May 2021

Antimony trisulfide (Sb2S3) is a kind of emerging light-harvesting material with excellent stability and abundant elemental storage. Due to the quasi-one-dimensional symmetry, theoretical investigations have pointed out that there exist complicated defect properties. However, there is no experimental verification on the defect property. Here, we conduct optical deep-level transient spectroscopy to investigate defect properties in Sb2S3 and show that there are maximum three kinds of deep-level defects observed, depending on the composition of Sb2S3. We also find that the Sb-interstitial (Sbi) defect does not show critical influence on the carrier lifetime, indicating the high tolerance of the one-dimensional crystal structure where the space of (Sb4S6)n ribbons is able to accommodate impurities to certain extent. This study provides basic understanding on the defect properties of quasi-one-dimensional materials and a guidance for the efficiency improvement of Sb2S3 solar cells.
The LINC01119-SOCS5 axis as a critical theranostic in triple-negative breast cancer
Authors: Tu Zhenbo , Schmoellerl Johannes , Mariani Odette , Zheng Yurong , Hu Yi , Vincent-Salomon Anne , Karnoub Antoine E.
Published: May 2021

The development of triple-negative breast cancer (TNBC) is critically regulated by certain tumor-microenvironment-associated cells called mesenchymal stem/stromal cells (MSCs), which we and others have shown promote TNBC progression by activating pro-malignant signaling in neighboring cancer cells. Characterization of these cascades would better our understanding of TNBC biology and bring about therapeutics that eliminate the morbidity and mortality associated with advanced disease. Here, we focused on the emerging class of RNAs called long non-coding RNAs or lncRNAs and utilized a MSC-supported TNBC progression model to identify specific family members of functional relevance to TNBC pathogenesis. Indeed, although some have been described to play functional roles in TNBC, activities of lncRNAs as mediators of tumor-microenvironment-driven TNBC development remain to be fully explored. We report that MSCs stimulate robust expression of LINC01119 in TNBC cells, which in turn induces suppressor of cytokine signaling 5 (SOCS5), leading to accelerated cancer cell growth and tumorigenesis. We show that LINC01119 and SOCS5 exhibit tight correlation across multiple breast cancer gene sets and that they are highly enriched in TNBC patient cohorts. Importantly, we present evidence that the LINC01119-SOCS5 axis represents a powerful prognostic indicator of adverse outcomes in TNBC patients, and demonstrate that its repression severely impairs cancer cell growth. Altogether, our findings identify LINC01119 as a major driver of TNBC development and delineate critical non-coding RNA theranostics of potential translational utility in the management of advanced TNBC, a class of tumors in most need of effective and targeted therapy.
Incorporation of expanded organic cations in dysprosium(III) borohydrides for achieving luminescent molecular nanomagnets
Authors: Wegner Wojciech , Zakrzewski Jakub J. , Zychowicz Mikolaj , Chorazy Szymon
Published: May 2021

Luminescent single-molecule magnets (SMMs) constitute a class of molecular materials offering optical insight into magnetic anisotropy, magnetic switching of emission, and magnetic luminescent thermometry. They are accessible using lanthanide(III) complexes with advanced organic ligands or metalloligands. We present a simple route to luminescent SMMs realized by the insertion of well-known organic cations, tetrabutylammonium and tetraphenylphosphonium, into dysprosium(III) borohydrides, the representatives of metal borohydrides investigated due to their hydrogen storage properties. We report two novel compounds, [n-Bu4N][DyIII(BH4)4] (1) and [Ph4P][DyIII(BH4)4] (2), involving DyIII centers surrounded by four pseudo-tetrahedrally arranged BH4– ions. While 2 has higher symmetry and adopts a tetragonal unit cell (I41/a), 1 crystallizes in a less symmetric monoclinic unit cell (P21/c). They exhibit yellow room-temperature photoluminescence related to the f–f electronic transitions. Moreover, they reveal DyIII-centered magnetic anisotropy generated by the distorted arrangement of four borohydride anions. It leads to field-induced slow magnetic relaxation, well-observed for the magnetically diluted samples, [n-Bu4N][YIII0.9DyIII0.1(BH4)4] (1@Y) and [Ph4P][YIII0.9DyIII0.1(BH4)4] (2@Y). 1@Y exhibits an Orbach-type relaxation with an energy barrier of 26.4(5) K while only the onset of SMM features was found in 2@Y. The more pronounced single-ion anisotropy of DyIII complexes of 1 was confirmed by the results of the ab initio calculations performed for both 1–2 and the highly symmetrical inorganic DyIII borohydrides, α/β-Dy(BH4)3, 3 and 4. The magneto-luminescent character was achieved by the implementation of large organic cations that lower the symmetry of DyIII centers inducing single-ion anisotropy and separate them in the crystal lattice enabling the emission property. These findings are supported by the comparison with 3 and 4, crystalizing in cubic unit cells, which are not emissive and do not exhibit SMM behavior.
Environmental influences on sinking rates and distributions of transparent exopolymer particles after a typhoon surge at the Western Pacific
Authors: Islam M. Shahanul , Sun Jun , Zhang Guicheng , Chen Zhuo , Zhou Hui
Published: May 2021

A multidisciplinary approach was used to investigate the causes of the distributions and sinking rates of transparent exopolymer particles (TEPs) during the period of September–October (2017) in the Western Pacific Ocean (WPO); the study period was closely dated to a northwest typhoon surge. The present study discussed the impact of biogeophysical features on TEPs and their sinking rates (sTEP) at depths of 0–150 m. During the study, the concentration of TEPs was found to be higher in areas adjacent to the Kuroshio current and in the bottom water layer of the Mindanao upwelling zone due to the widespread distribution of cyanobacteria, i.e., Trichodesmium hildebrandti and T. theibauti. The positive significant regressions of TEP concentrations with Chl-a contents in eddy-driven areas (R2 = 0.73, especially at 100 m (R2 = 0.75)) support this hypothesis. However, low TEP concentrations and TEPs were observed at mixed layer depths (MLDs) in the upwelling zone (Mindanao). Conversely, high TEP concentrations and high sTEP were found at the bottom of the downwelling zone (Halmahera). The geophysical directions of eddies may have caused these conditions. In demonstrating these relations, the average interpretation showed the negative linearity of TEP concentrations with TEPs (R2 = 0.41 ~ 0.65) at such eddies. Additionally, regression curves (R2 = 0.78) indicated that atmospheric pressure played a key role in the changes in TEPs throughout the study area. Diatoms and cyanobacteria also curved the TEPs significantly (R2 = 0.5, P < 0.05) at the surface of the WPO. This study also revealed that TEP concentration contributes less to the average particulate organic carbon in this oligotrophic WPO.
Magnetic and structural properties of the solid solution CuAl2(1−x)Ga2xO4
Authors: Bullard T. J. , Susner M. A. , Taddei K. M. , Brant J. A. , Haugan T. J.
Published: May 2021

CuAl2O4 is a ternary oxide spinel with Cu2+ ions ($$s=1/2$$

s
=
1
/
2

) primarily populating the A-site diamond sublattice. The compound is reported to display evidence of spin glass behavior but possess a non-frozen magnetic ground state below the transition temperature. On the other hand, the spinel CuGa2O4 displays spin glass behavior at ~ 2.5 K with Cu2+ ions more readily tending to the B-site pyrochlore sublattice. Therefore, we investigate the magnetic and structural properties of the solid solution CuAl2(1-x)Ga2xO4 examining the evolution of the magnetic behavior as Al3+ is replaced with a much larger Ga3+ ion. Our results show that the Cu2+ ions tend to migrate from tetrahedral to octahedral sites as the Ga3+ ion concentration increases, resulting in a concomitant change in the glassy magnetic properties of the solution. Results indicate glassy behavior for much of the solution with a general trend towards decreasing magnetic frustration as the Cu2+ ion shifts to the B-site. However, the $$x=0.1$$

x
=
0.1

and 0.2 members of the system do not show glassy behavior down to our measurement limit (1.9 K) suggesting a delayed spin glass transition. We suggest that these two members are additional candidates for investigation to access highly frustrated exotic quantum states.
Publisher Correction: Fish telocytes and their relation to rodlet cells in ruby-red-fin shark (rainbow shark) Epalzeorhynchos frenatum (Teleostei: Cyprinidae)
Authors: Abd-Elhafeez Hanan H. , Abdo Walied , Kamal Basma Mohamed , Soliman Soha A.
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Heat stress and immune response phenotype affect DNA methylation in blood mononuclear cells from Holstein dairy cows
Authors: Livernois A. M. , Mallard B. A. , Cartwright S. L. , Cánovas A.
Published: May 2021

Heat stress negatively affects health and production in cows. Examining the cellular response to heat stress could reveal underlying protective molecular mechanisms associated with superior resilience and ultimately enable selection for more resilient cattle. This type of investigation is increasingly important as future predictions for the patterns of heat waves point to increases in frequency, severity, and duration. Cows identified as high immune responders based on High Immune Response technology (HIR) have lower disease occurrence compared to their average and low immune responder herd-mates. In this study, our goal was to identify epigenetic differences between high and low immune responder cows in response to heat stress. We examined genome-wide DNA methylation of blood mononuclear cells (BMCs) isolated from high and low cows, before and after in vitro heat stress. We identified differential methylation of promoter regions associated with a variety of biological processes including immune function, stress response, apoptosis, and cell signalling. The specific differentially methylated promoter regions differed between samples from high and low cows, and results revealed pathways associated with cellular protection during heat stress.
Response to perturbation during quiet standing resembles delayed state feedback optimized for performance and robustness
Authors: Zelei Ambrus , Milton John , Stepan Gabor , Insperger Tamas
Published: May 2021

Postural sway is a result of a complex action–reaction feedback mechanism generated by the interplay between the environment, the sensory perception, the neural system and the musculation. Postural oscillations are complex, possibly even chaotic. Therefore fitting deterministic models on measured time signals is ambiguous. Here we analyse the response to large enough perturbations during quiet standing such that the resulting responses can clearly be distinguished from the local postural sway. Measurements show that typical responses very closely resemble those of a critically damped oscillator. The recovery dynamics are modelled by an inverted pendulum subject to delayed state feedback and is described in the space of the control parameters. We hypothesize that the control gains are tuned such that (H1) the response is at the border of oscillatory and nonoscillatory motion similarly to the critically damped oscillator; (H2) the response is the fastest possible; (H3) the response is a result of a combined optimization of fast response and robustness to sensory perturbations. Parameter fitting shows that H1 and H3 are accepted while H2 is rejected. Thus, the responses of human postural balance to “large” perturbations matches a delayed feedback mechanism that is optimized for a combination of performance and robustness.
Author Correction: Morphological and immunohistochemical phenotype of TCs in the intestinal bulb of Grass carp and their potential role in intestinal immunity
Authors: Abd-Elhafeez Hanan H. , Abou-Elhamd Alaa S. , Soliman Soha A.
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Transient incubation of cultured hippocampal neurons in the absence of magnesium induces rhythmic and synchronized epileptiform-like activity
Authors: Mele Miranda , Vieira Ricardo , Correia Bárbara , De Luca Pasqualino , Duarte Filipe V. , Pinheiro Paulo S. , Duarte Carlos B.
Published: May 2021

Cell culture models are important tools to study epileptogenesis mechanisms. The aim of this work was to characterize the spontaneous and synchronized rhythmic activity developed by cultured hippocampal neurons after transient incubation in zero Mg2+ to model Status Epilepticus. Cultured hippocampal neurons were transiently incubated with a Mg2+-free solution and the activity of neuronal networks was evaluated using single cell calcium imaging and whole-cell current clamp recordings. Here we report the development of synchronized and spontaneous [Ca2+]i transients in cultured hippocampal neurons immediately after transient incubation in a Mg2+-free solution. Spontaneous and synchronous [Ca2+]i oscillations were observed when the cells were then incubated in the presence of Mg2+. Functional studies also showed that transient incubation in Mg2+-free medium induces neuronal rhythmic burst activity that was prevented by antagonists of glutamate receptors. In conclusion, we report the development of epileptiform-like activity, characterized by spontaneous and synchronized discharges, in cultured hippocampal neurons transiently incubated in the absence of Mg2+. This model will allow studying synaptic alterations contributing to the hyperexcitability that underlies the development of seizures and will be useful in pharmacological studies for testing new drugs for the treatment of epilepsy.
Electromechanical impedance based self-diagnosis of piezoelectric smart structure using principal component analysis and LibSVM
Authors: Jiang Xie , Zhang Xin , Tang Tao , Zhang Yuxiang
Published: May 2021

The long-term use of a piezoelectric smart structure make it difficult to judge whether the structure or piezoelectric lead zirconate titanate (PZT) is damaged when the signal changes. If the sensor fault occurs, the cases and degrees of the fault are unknown based on the electromechanical impedance method. Therefore, after the principal component analysis (PCA) of six characteristic indexes, a two-component solution that could explain 99.2% of the variance in the original indexes was obtained to judge whether the damage comes from the PZT. Then LibSVM was used to make an effective identification of four sensor faults (pseudo soldering, debonding, wear, and breakage) and their three damage degrees. The result shows that the identification accuracy of damaged PZT reached 97.5%. The absolute scores of PCA comprehensive evaluation for structural damages are less than 0.5 while for sensor faults are greater than 0.6. By comparing the scores of the samples under unknown conditions with the set threshold, whether the sensor faults occur is effectively judged; the intact and 12 possible damage states of PZT can be all classified correctly with the model trained by LibSVM. It is feasible to use LibSVM to classify the cases and degrees of sensor faults.
Cytogenetic markers using single-sequence probes reveal chromosomal locations of tandemly repetitive genes in scleractinian coral Acropora pruinosa
Authors: Vacarizas Joshua , Taguchi Takahiro , Mezaki Takuma , Okumura Masatoshi , Kawakami Rei , Ito Masumi , Kubota Satoshi
Published: May 2021

The short and similar sized chromosomes ofAcroporapose a challenge for karyotyping. Conventional methods, such as staining of heterochromatic regions, provide unclear banding patterns that hamper identification of such chromosomes. In this study, we used short single-sequence probes from tandemly repetitive 5S ribosomal RNA (rRNA) and core histone coding sequences to identify specific chromosomes ofAcropora pruinosa. Both the probes produced intense signals in fluorescence in situ hybridization, which distinguished chromosome pairs. The locus of the 5S rDNA probe was on chromosome 5, whereas that of core histone probe was on chromosome 8. The sequence of the 5S rDNA probe was composed largely of U1 and U2 spliceosomal small nuclear RNA (snRNA) genes and their interspacers, flanked by short sequences of the 5S rDNA. This is the first report of a tandemly repetitive linkage of snRNA and 5S rDNA sequences in Cnidaria. Based on the constructed tentative karyogram and whole genome hybridization, the longest chromosome pair (chromosome 1) was heteromorphic. The probes also hybridized effectively with chromosomes of otherAcroporaspecies and population, revealing an additional core histone gene locus.We demonstrated the applicability of short-sequence probes as chromosomal markers with potential for use across populations and species ofAcropora.
Energetic context determines the effects of multiple upwelling-associated stressors on sea urchin performance
Authors: Murie Kindall A. , Bourdeau Paul E.
Published: May 2021

Globally, kelp forests are threatened by multiple stressors, including increasing grazing by sea urchins. With coastal upwelling predicted to increase in intensity and duration in the future, understanding whether kelp forest and urchin barren urchins are differentially affected by upwelling-related stressors will give insight into how future conditions may affect the transition between kelp forests and barrens. We assessed how current and future-predicted changes in the duration and magnitude of upwelling-associated stressors (low pH, dissolved oxygen, and temperature) affected the performance of purple sea urchins (Strongylocentrotus purpuratus) sourced from rapidly-declining bull kelp (Nereocystis leutkeana) forests and nearby barrens and maintained on habitat-specific diets. Kelp forest urchins were of superior condition to barrens urchins, with ~ 6–9 times more gonad per body mass. Grazing and condition in kelp forest urchins were more negatively affected by distant-future and extreme upwelling conditions, whereas grazing and survival in urchins from barrens were sensitive to both current-day and all future-predicted upwelling, and to increases in acidity, hypoxia, and temperature regardless of upwelling. We conclude that urchin barren urchins are more susceptible to increases in the magnitude and duration of upwelling-related stressors than kelp forest urchins. These findings have important implications for urchin population dynamics and their interaction with kelp.
Disruption of the odorant coreceptor Orco impairs foraging and host finding behaviors in the New World screwworm fly
Authors: Paulo Daniel F. , Junqueira Ana C. M. , Arp Alex P. , Vieira André S. , Ceballos Jorge , Skoda Steven R. , Pérez-de-León Adalberto A. , Sagel Agustin , McMillan William O. , Scott Maxwell J. , Concha Carolina , Azeredo-Espin Ana M. L.
Published: May 2021

The evolution of obligate ectoparasitism in blowflies (Diptera: Calliphoridae) has intrigued scientists for over a century, and surprisingly, the genetics underlying this lifestyle remain largely unknown. Blowflies use odors to locate food and oviposition sites; therefore, olfaction might have played a central role in niche specialization within the group. In insects, the coreceptor Orco is a required partner for all odorant receptors (ORs), a major gene family involved in olfactory-evoked behaviors. Hence, we characterized the Orco gene in the New World screwworm, Cochliomyia hominivorax, a blowfly that is an obligate ectoparasite of warm-blooded animals. In contrast, most of the closely related blowflies are scavengers that lay their eggs on dead animals. We show that the screwworm Orco orthologue (ChomOrco) is highly conserved within Diptera, showing signals of strong purifying selection. Expression of ChomOrco is broadly detectable in chemosensory appendages, and is related to morphological, developmental, and behavioral aspects of the screwworm biology. We used CRISPR/Cas9 to disrupt ChomOrco and evaluate the consequences of losing the OR function on screwworm behavior. In two-choice assays, Orco mutants displayed an impaired response to floral-like and animal host-associated odors, suggesting that OR-mediated olfaction is involved in foraging and host-seeking behaviors in C. hominivorax. These results broaden our understanding of the chemoreception basis of niche occupancy by blowflies.
Degradation of soil quality by the waste leachate in a Mediterranean semi-arid ecosystem
Authors: Yeilagi Sh. , Rezapour Salar , Asadzadeh F.
Published: May 2021

The assessment of soil quality indices in waste leachate-affected soils is vital to understand the threats of land quality degradation and how to control it. In this respect, a study was conducted on the effects of uncontrolled landfill leachate on soil quality index (SQI) in calcareous agricultural lands using 28 soil variables. Using the total data set (TDS) and minimum data set (MDS) approaches, the SQI was compared between leachate-affected soils (LAS) and control soils by the integrated quality index (IQI) and nemoro quality index (NQI) methods. The results revealed that LAS were significantly enriched by soil salinity-sodicity indices including electrical conductivity (EC), sodium adsorption ratio (SAR), and exchangeable sodium percentage (ESP), fertility indices including total N, available P and K, organic carbon, and cation exchange capacity (CEC), exchangeable cations (Ca, Mg, K, and Na), the available and total fractions of heavy metals (Zn, Cu, Cd, Pb, Ni). After the leachate got its way into the soil, the values of IQI and NQI were dropped ranging 5–16% and 6.5–13% for the TDS approach and 5–15.2% and 7.5–12.2 for the MDS approach, respectively. Clearly, the data showed that soil quality degradation was encouraged and stimulated by the leachate. Among the different models of SQI applied in the present study, IQI determined by MDS was the optimal model to estimate soil quality and predict crop yields given the analysis of the correlations among the SQI models, the correlations between the SQI models and wheat yield, and sensitivity index values.
Ammonia-based enrichment and long-term propagation of zone I hepatocyte-like cells
Authors: Tsuneishi Ruri , Saku Noriaki , Miyata Shoko , Akiyama Saeko , Javaregowda Palaksha Kanive , Ite Kenta , Takashima Nagisa , Toyoda Masashi , Kimura Tohru , Kuroda Masahiko , Nakazawa Atsuko , Kasahara Mureo , Nonaka Hidenori , Kamiya Akihide , Kiyono Tohru , Yamauchi Junji , Umezawa Akihiro
Published: May 2021

Ammonia has a cytotoxic effect and can therefore be used as a selection agent for enrichment of zone I hepatocytes. However, it has not yet been determined whether ammonia-treated hepatocyte-like cells are able to proliferate in vitro. In this study, we employed an ammonia selection strategy to purify hepatocyte-like cells that were differentiated from human embryonic stem cells (ESCs) and from induced pluripotent stem cells (iPSCs). The resistance to cytotoxicity or cell death by ammonia is likely attributable to the metabolism of ammonia in the cells. In addition to ammonia metabolism-related genes, ammonia-selected hepatocytes showed increased expression of the cytochrome P450 genes. Additionally, the ammonia-selected cells achieved immortality or at least an equivalent life span to human pluripotent stem cells without affecting expression of the liver-associated genes. Ammonia treatment in combination with in vitro propagation is useful for obtaining large quantities of hepatocytes.
Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy
Authors: Fedrigo Nayara Helisandra , Shinohara Danielle Rosani , Mazucheli Josmar , Nishiyama Sheila Alexandra Belini , Carrara-Marroni Floristher Elaine , Martins Frederico Severino , Zhu Peijuan , Yu Mingming , Sy Sherwin Kenneth B. , Tognim Maria Cristina Bronharo
Published: May 2021

The emergence of polymyxin resistance in Gram-negative bacteria infections has motivated the use of combination therapy. This study determined the mutant selection window (MSW) of polymyxin B alone and in combination with meropenem and fosfomycin against A. baumannii strains belonging to clonal lineages I and III. To evaluate the inhibition of in vitro drug resistance, we investigate the MSW-derived pharmacodynamic indices associated with resistance to polymyxin B administrated regimens as monotherapy and combination therapy, such as the percentage of each dosage interval that free plasma concentration was within the MSW (%TMSW) and the percentage of each dosage interval that free plasma concentration exceeded the mutant prevention concentration (%T>MPC). The MSW of polymyxin B varied between 1 and 16 µg/mL for polymyxin B-susceptible strains. The triple combination of polymyxin B with meropenem and fosfomycin inhibited the polymyxin B-resistant subpopulation in meropenem-resistant isolates and polymyxin B plus meropenem as a double combination sufficiently inhibited meropenem-intermediate, and susceptible strains. T>MPC 90% was reached for polymyxin B in these combinations, while %TMSW was 0 against all strains. TMSW for meropenem and fosfomycin were also reduced. Effective antimicrobial combinations significantly reduced MSW. The MSW-derived pharmacodynamic indices can be used for the selection of effective combination regimen to combat the polymyxin B-resistant strain.
Barriers and potential solutions for improved surgical care for children with hernia in Eastern Uganda
Authors: Ajiko Mary Margaret , Löfgren Jenny , Ekblad Solvig
Published: May 2021

Five billion people lack timely, affordable access to surgery. A large proportion of these are children. Qualitative research investigating the barriers to surgical care for children and ways of overcoming them is lacking. This study focused on children with hernia, a very common paediatric surgical condition for which surgery is the only effective treatment. The main aim of this qualitative study was to explore barriers to surgical care for children and identify potential solutions. Data were collected from parents of children with hernia and from health care providers at Soroti Regional Referral Hospital in eastern Uganda. Parents’ experiences, motives and barriers when accessing care were explored. The health care providers’ knowledge, perceptions and practices relating to children with hernia were investigated. The data were analysed using thematic content analysis. Traditional beliefs and gender inequality were considered major issues. Possible solutions included partnering with the local community in efforts to increase knowledge and acceptability in the community in general and by parents in particular. A formation of a surgical team dedicated to the management of children with surgical conditions was suggested as way to improve quality and increase volume of surgery for children.
Effective phase noise considerations in magnon based parametric excitations
Authors: Venugopal Aneesh , Victora R. H.
Published: May 2021

Magnon-phase is an important entity in the parametric processes involving magnons, yet the general qualitative and quantitative consequences of the phase-noise on nonlinear properties remain far from understood. In the current simulation-based theoretical study, we explore the direct impact the phase-noise has on non-linearity. We use analytical techniques usually employed in the study of hydrodynamics to explain the magnon-based nonlinear phenomena. The behavior of the threshold-field and growth rate of the magnons in the presence of Gaussian phase-noise is analytically predicted. These predictions are verified by micromagnetic simulations. Such results are of crucial importance in the design and engineering of both traditional and futuristic devices.
Distinct microbial community along the chronic oil pollution continuum of the Persian Gulf converge with oil spill accidents
Authors: Rezaei Somee Maryam , Dastgheib Seyed Mohammad Mehdi , Shavandi Mahmoud , Ghanbari Maman Leila , Kavousi Kaveh , Amoozegar Mohammad Ali , Mehrshad Maliheh
Published: May 2021

The Persian Gulf, hosting ca. 48% of the world’s oil reserves, has been chronically exposed to natural oil seepage. Oil spill studies show a shift in microbial community composition in response to oil pollution; however, the influence of chronic oil exposure on the microbial community remains unknown. We performed genome-resolved comparative analyses of the water and sediment samples along Persian Gulf’s pollution continuum (Strait of Hormuz, Asalouyeh, and Khark Island). Continuous exposure to trace amounts of pollution primed the intrinsic and rare marine oil-degrading microbes such as Oceanospirillales, Flavobacteriales, Alteromonadales, and Rhodobacterales to bloom in response to oil pollution in Asalouyeh and Khark samples. Comparative analysis of the Persian Gulf samples with 106 oil-polluted marine samples reveals that the hydrocarbon type, exposure time, and sediment depth are the main determinants of microbial response to pollution. High aliphatic content of the pollution enriched for Oceanospirillales, Alteromonadales, and Pseudomonadales whereas, Alteromonadales, Cellvibrionales, Flavobacteriales, and Rhodobacterales dominate polyaromatic polluted samples. In chronic exposure and oil spill events, the community composition converges towards higher dominance of oil-degrading constituents while promoting the division of labor for successful bioremediation.
Genome-wide identification of the BASS gene family in four Gossypium species and functional characterization of GhBASSs against salt stress
Authors: Myo Thwin , Wei Fang , Zhang Honghao , Hao Jianfeng , Zhang Bin , Liu Zhixian , Cao Gangqiang , Tian Baoming , Shi Gongyao
Published: May 2021

Bile acid sodium symporter (BASS) family proteins encode a class of sodium/solute symporters. Even though the sodium transporting property of BASSs in mammals was well studied, their sodium transportability and functional roles in plant salt tolerance remained largely unknown. Here, BASS family members from 4 cotton species, as well as 30 other species were identified. Then, they were designated as members of BASS1 to BASS5 subfamilies according to their sequence similarity and phylogenetic relationships. There were 8, 11, 16 and 18 putative BASS genes in four cotton species. While whole-genome duplications (WGD) and segmental duplications rendered the expansion of the BASS gene family in cotton, BASS gene losses occurred in the tetraploid cotton during the evolution from diploids to allotetraploids. Concerning functional characterizations, the transcript profiling of GhBASSs revealed that they not only preferred tissue-specific expression but also were differently induced by various stressors and phytohormones. Gene silencing and overexpression experiments showed that GhBASS1 and GhBASS3 positively regulated, whereas GhBASS2, GhBASS4 and GhBASS5 negatively regulated plant salt tolerance. Taken together, BASS family genes have evolved before the divergence from the common ancestor of prokaryotes and eukaryotes, and GhBASSs are plastidial sodium-dependent metabolite co-transporters that can influence plant salt tolerance.
Freeze–thaw characterization process to minimize aggregation and enable drug product manufacturing of protein based therapeutics
Authors: Jain Keethkumar , Salamat-Miller Nazila , Taylor Katherine
Published: May 2021

Physical instabilities of proteins in the form of protein aggregation continue to be a major challenge in the development of protein drug candidates. Aggregation can occur during different stages of product lifecycle such as freeze–thaw, manufacturing, shipping, and storage, and can potentially delay commercialization of candidates. A lack of clear understanding of the underlying mechanism(s) behind protein aggregation and the potential immunogenic reactions renders the presence of aggregates in biotherapeutic products undesirable. Understanding and minimizing aggregation can potentially reduce immunogenic responses and make protein therapeutics safer. Therefore, it is imperative to identify, understand, and control aggregation during early formulation development and develop reliable and orthogonal analytical methodologies to detect and monitor levels of aggregation. Freezing and thawing are typical steps involved in the manufacturing of drug product and could result in complex physical and chemical changes, which in turn could potentially cause protein aggregation. This study provides a systematic approach in understanding and selecting the ideal freeze–thaw conditions for manufacturing of protein-based therapeutics. It identifies the importance of balancing different excipients with an overall goal of sufficiently reducing or eliminating aggregation and developing a stable and scalable formulation. The results demonstrated that the freeze–thaw damage of mAb-1 in aqueous solutions was significantly reduced by identification of optimal freeze–thaw conditions using first a small-scale model with subsequent at-scale verifications. The work provides a framework for successful transfer of drug product manufacturing process from small-scale to the manufacturing scale production environment especially for molecules that are susceptible to freeze–thaw induced degradations.
Characterization and description of Faecalibacterium butyricigenerans sp. nov. and F. longum sp. nov., isolated from human faeces
Authors: Zou Yuanqiang , Lin Xiaoqian , Xue Wenbin , Tuo Li , Chen Ming-Sheng , Chen Xiao-Hui , Sun Cheng-hang , Li Feina , Liu Shao-wei , Dai Ying , Kristiansen Karsten , Xiao Liang
Published: May 2021

Exploiting a pure culture strategy to investigate the composition of the human gut microbiota, two novel anaerobes, designated strains AF52-21T and CM04-06T, were isolated from faeces of two healthy Chinese donors and characterized using a polyphasic approach. The two strains were observed to be gram-negative, non-motile, and rod-shaped. Both strains grew optimally at 37 °C and pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the two strains clustered with species of the genus Faecalibacterium and were most closely related to Faecalibacterium prausnitzii ATCC 27768T with sequence similarity of 97.18% and 96.87%, respectively. The two isolates shared a 16S rRNA gene sequence identity of 98.69%. Draft genome sequencing was performed for strains AF52-21T and CM04-06T, generating genome sizes of 2.85 Mbp and 3.01 Mbp. The calculated average nucleotide identity values between the genomes of the strains AF52-21T and CM04-06T compared to Faecalibacterium prausnitzii ATCC 27768T were 83.20% and 82.54%, respectively, and 90.09% when comparing AF52-21T and CM04-06T. Both values were below the previously proposed species threshold (95–96%), supporting their recognition as novel species in the genus Faecalibacterium. The genomic DNA G + C contents of strains AF52-21T and CM04-06T calculated from genome sequences were 57.77 mol% and 57.51 mol%, respectively. Based on the phenotypic, chemotaxonomic and phylogenetic characteristics, we conclude that both strains represent two new Faecalibacterium species, for which the names Faecalibacterium butyricigenerans sp. nov. (type strain AF52-21T = CGMCC 1.5206T = DSM 103434T) and Faecalibacterium longum sp. nov. (type strain CM04-06T = CGMCC 1.5208T = DSM 103432T) are proposed.
Author Correction: Highly dampened blood transcriptome response in HIV patients after respiratory infection
Authors: Sellers Subhashini A. , Fischer William A. , Heise Mark T. , Schughart Klaus
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Comparative and evolutionary analyses reveal conservation and divergence of the notch pathway in lophotrochozoa
Authors: He Xin , Wu Fucun , Zhang Linlin , Li Li , Zhang Guofan
Published: May 2021

Lophotrochozoan species exhibit wide morphological diversity; however, the molecular basis underlying this diversity remains unclear. Here, we explored the evolution of Notch pathway genes across 37 metazoan species via phylogenetic and molecular evolutionary studies with emphasis on the lophotrochozoans. We displayed the components of Notch pathway in metazoans and found that Delta and Hes/Hey-related genes, as well as their functional domains, are duplicated in lophotrochozoans. Comparative transcriptomics analyses allow us to pinpoint sequence divergence of multigene families in the Notch signalling pathway. We identified the duplication mechanism of a mollusc-specific gene, Delta2, and found it displayed complementary expression throughout development. Furthermore, we found the functional diversification not only in expanded genes in the Notch pathway (Delta and Hes/Hey-related genes), but also in evolutionary conservative genes (Notch, Presenilin, and Su(H)). Together, this comprehensive study demonstrates conservation and divergence within the Notch pathway, reveals evolutionary relationships among metazoans, and provides evidence for the occurrence of developmental diversity in lophotrochozoans, as well as a basis for future gene function studies.
Crystal growth of clathrate hydrate formed with H2 + CO2 mixed gas and tetrahydropyran
Authors: Maruyama Meku , Matsuura Riku , Ohmura Ryo
Published: May 2021

Hydrate-based gas separation technology is applicable to the CO2 capture and storage from synthesis gas mixture generated through gasification of fuel sources including biomass. This paper reports visual observations of crystal growth dynamics and crystal morphology of hydrate formed in the H2 + CO2 + tetrahydropyran (THP) + water system with a target for developing the hydrate-based CO2 separation process design. Experiments were conducted at a temperature range of 279.5–284.9 K under the pressure of 4.9–5.3 MPa. To simulate the synthesis gas, gas composition in the gas phase was maintained around H2:CO2 = 0.6:0.4 in mole fraction. Hydrate crystals were formed and extended along the THP/water interface. After the complete coverage of the interface to shape a polycrystalline shell, hydrate crystals continued to grow further into the bulk of liquid water. The individual crystals were identified as hexagonal, tetragonal and other polygonal-shaped formations. The crystal growth rate and the crystal size varied depending on thermodynamic conditions. Implications from the obtained results for the arrangement of operating conditions at the hydrate formation-, transportation-, and dissociation processes are discussed.
A practice of using five-colour chart to guide the control of COVID-19 and resumption of work in Zhejiang Province, China
Authors: He Fan , Shang Xiaopeng , Ling Feng , Chen Zhiping , Fu Tiehong , Lin Junfen , Wang Zhen
Published: May 2021

Since the outbreak of COVID-19 in December 2019 in Wuhan, Zhejiang has become the province with the largest number of cases. The aim of this article is to present Zhejiang province’s experience of establishing an accurate and smart control mechanism for epidemic prevention and control and resumption of work and production using a ‘five-colour epidemic chart’. The number of confirmed cases, proportion of local cases, and occurrence of clustered outbreaks were used as evaluation indicators to calculate the county-level epidemic risk and were assigned different weight coefficients; the absence of cases for 3 and 7 consecutive days was used as the adjustment index. When the first chart was published on February 9, there were 1 very-high-risk, 12 high-risk, and 12 low-risk counties. Under the five-colour chart, Zhejiang began to adopt precise measures to prevent and control the epidemic and resume work and production. By February 24, the low-risk counties had expanded to 82, with no high-risk and very-high-risk counties. The epidemic situation in Zhejiang province has been effectively controlled. The experience of epidemic prevention and control in Zhejiang is worthy to be emulated and learned by other countries and regions.
Intensity correlation OCT is a classical mimic of quantum OCT providing up to twofold resolution improvement
Authors: Kolenderska Sylwia M. , Kolenderski Piotr
Published: May 2021

Quantum Optical Coherence Tomography (Q-OCT) uses quantum properties of light to provide several advantages over its classical counterpart, OCT: it achieves a twice better axial resolution with the same spectral bandwidth and it is immune to even orders of dispersion. Since these features are very sought-after in OCT imaging, many hardware and software techniques have been created to mimic the quantum behaviour of light and achieve these features using traditional OCT systems. The most recent, purely algorithmic scheme—an improved version of Intensity Correlation Spectral Domain OCT named ICA-SD-OCT—showed even-order dispersion cancellation and reduction of artefacts. The true capabilities of this method were unfortunately severely undermined, both in terms of its relation to Q-OCT and its main performance parameters. In this work, we provide experimental demonstrations as well as numerical and analytical arguments to show that ICA-SD-OCT is a true classical equivalent of Q-OCT, more specifically its Fourier domain version, and therefore it enables a true two-fold axial resolution improvement. We believe that clarification of all the misconceptions about this very promising algorithm will highlight the great value of this method for OCT and consequently lead to its practical applications for resolution- and quality-enhanced OCT imaging.
Differential gene expression in Drosophila melanogaster and D. nigrosparsa infected with the same Wolbachia strain
Authors: Detcharoen Matsapume , Schilling Martin P. , Arthofer Wolfgang , Schlick-Steiner Birgit C. , Steiner Florian M.
Published: May 2021

Wolbachiaare maternally inherited endosymbionts that infect nearly half of all arthropod species.Wolbachiamanipulate their hosts to maximize their transmission, but they can also provide benefits such as nutrients and resistance against viruses to their hosts. TheWolbachiastrainwMel was recently found to increase locomotor activities and possibly trigger cytoplasmic incompatibility in the transinfected flyDrosophilanigrosparsa. Here, we investigated, in females of bothD.melanogasterandD.nigrosparsa, the gene expression between animals uninfected and infected withwMel, using RNA sequencing to see if the twoDrosophilaspecies respond to the infection in the same or different ways. A total of 2164 orthologous genes were used. The two fly species responded to the infection in different ways. Significant changes shared by the fly species belong to the expression of genes involved in processes such as oxidation–reduction process, iron-ion binding, and voltage-gated potassium-channel activity. We discuss our findings also in the light of howWolbachiasurvive within both the native and the novel host.