bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary results of a vaginal constraint for reducing G2 late vaginal complications after postoperative brachytherapy in endometrial cancer: a prospective analysis
Authors: Zhang Y. , Gomez G. , Ascaso C. , Herreros A. , Fornes B. , Mases J. , Rochera J. , Tagliaferri L. , Sabater S. , Torne A. , Biete A. , Rovirosa Á.
Published: December 2021

Purpose

To evaluate the preliminary results of the use of 68 Gy EQD2(α/β=3 Gy) as a dose limit to the lowest dose in the most exposed 2 cm3 of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC).

Methods

From November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44–50.4 Gy), 1.8−2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49–3.5 cm, 6–3 cm, and 1–2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of < 68 Gy EQD2(α/β=3 Gy) at 2 cm3. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina.

Results

With a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening.

Conclusions

In postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2(α/β=3 Gy) as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up.
Silicon Seed Priming Combined with Foliar Spray of Sulfur Regulates Photosynthetic and Antioxidant Systems to Confer Drought Tolerance in Maize (Zea mays L.)
Authors: Farman Muhammad , Nawaz Fahim , Majeed Sadia , Javeed Hafiz Muhammad Rashad , Ahsan Muhammad , Ahmad Khawaja Shafique , Aurangzaib Muhammad , Bukhari Muhammad Adnan , Shehzad Muhammad Asif , Hussain Muhammad Baqir
Published: December 2021

The present study evaluated the effect of silicon (Si) seed priming and sulfur (S) foliar spray on drought tolerance of two contrasting maize hybrids viz. drought tolerant Hi-Corn 11 and susceptible P-1574. The maize seeds were primed with (3 mM Na2SiO3) or without Si (hydropriming) and later sown in pots filled with sandy loam soil. Drought stress (25–30% water holding capacity or WHC) was initiated at cob development stage (V5) for two weeks, whereas the well-watered plants were grown at 65–70% WHC. On appearance of drought symptoms, foliar spray of S was done using 0.5% and 1.0% (NH4)2SO4, whereas water spray was used as a control. The drought-stressed plants were grown for further two weeks at 25–30% WHC before the final harvest. The results showed a marked effect of Si seed priming and foliar S spray on biomass, physiological and enzymatic processes as well as macronutrient concentrations of maize. In comparison to control, the highest increase in leaf relative water content (25%), chlorophyll a content (56%), carotenoids (26%), photosynthetic rate (64%), stomatal conductance (56%) and intercellular CO2 concentration (48%) was observed by Si seed priming + S foliar spray (Si + S) under water deficit conditions. Also, Si + S application stimulated the activity of catalase (45%), guaiacol peroxidase (38%) and superoxide dismutase (55%), and improved NPK concentrations (40–63%) under water limitations. Our results suggest that Si seed priming + foliar spray of S is more effective than the individual application of these nutrients to enhance drought tolerance in maize.
Mitophagy in carcinogenesis and cancer treatment
Authors: Denisenko Tatiana V. , Gogvadze Vladimir , Zhivotovsky Boris
Published: December 2021

In order to maintain a functional mitochondrial network, cells have developed a quality control mechanism, namely mitophagy. This process can be induced through different pathways. The most studied is the so-called PINK1/Parkin pathway, which is associated with ubiquitylation of several mitochondrial proteins that were initially found to be related to Parkinson’s disease. Another type of mitophagy is known as receptor-mediated mitophagy, which includes proteins, such as BNIP3 and BNIP3L, also known as Nix. Through these two mechanisms, mitophagy fulfills its functions and maintains cellular homeostasis. Here, we summarize the current knowledge about the mechanisms of mitophagy regulation and their interplay with cancer progression as well as anticancer treatment.
Student and faculty perceptions of, and experiences with, academic dishonesty at a medium-sized Canadian university
Authors: Awosoga Oluwagbohunmi , Nord Christina M. , Varsanyi Stephanie , Barley Randall , Meadows Jeff
Published: December 2021

There is a paucity of research into the prevalence of academic dishonesty within Canada compared to other countries. Recently, there has been a call for a better understanding of the particular characteristics of educational integrity in Canada so that Canada can more meaningfully contribute to current discussions surrounding academic integrity. Here, we present findings from student (N = 1142) and faculty (N = 130) surveys conducted within a medium-sized (~ 8700 students) Canadian university. These surveys probed perceptions towards, and experiences with, academic dishonesty, in which we aimed to understand how students and faculty regarded academically dishonest practices during their postsecondary careers. We also aimed to understand how often students engaged in, and faculty had witnessed, academic dishonesty, whether or not witnessing incidents of academic dishonesty corresponded with gender, year of experience, highest level of educational attainment, discipline, or their personal perceptions towards the importance of academic honesty, and whether students had been adequately taught what constitutes academic dishonesty. We found that an overwhelming majority of students viewed academic honesty as important, and that most students reported not engaging in academic dishonesty themselves despite 45.8% reporting that they had witnessed others engage in academic dishonesty. We also found that students were more likely to witness cheating as their postsecondary experience increased, that witnessing varied across disciplines and educational attainment, and that witnessing varied with student perceptions. However, we found no such patterns in faculty responses, but found that faculty are split on whether or not they believe incidents of academic honesty are increasing.
Lektüren des Ästhetischen – Ästhetische Lektüren. Alte und neue Hermeneutik
Authors: Gerok-Reiter Annette
Published: December 2021

Lektüren des Ästhetischen bilden einen ›Paradefall‹ hermeneutischen Verstehens. Zugleich jedoch kommt der hermeneutische Zugriff gerade hier an seine Grenze, werden Lektüren des Ästhetischen zu dessen ›Härtefall‹. Die grundsätzliche Skepsis gegenüber einem hermeneutischen Zugriff ebenso wie gegenüber Interpretationen, die vorrangig ästhetische Aspekte fokussieren, ist daher in den letzten Jahrzehnten durchaus in Relation zu sehen. Vor diesem Hintergrund möchte die Skizze pointieren, inwiefern die derzeitige ›Rückkehr der Ästhetik‹ mit einem Perspektivwechsel korreliert ist, der auch eine Neujustierung hermeneutischen Verstehens einfordert.
Verstandenhaben
Authors: Baßler Moritz
Published: December 2021

Das ›Verstandenhaben‹, das, mit Gadamer gesprochen, zu den Grundeigenschaften des hermeneutischen Zirkels gehört, charakterisiert prominente gegenwärtige Tendenzen auch akademischer Literaturrezeption, denen eine wissenschaftliche Ausrichtung des Faches, so wird hier argumentiert, eher entgegenzuwirken hätte. Gerade das theoretisch-methodische Angebot der Hermeneutik bietet in dieser Auseinandersetzung keine zukunftsweisenden Perspektiven.
Proletarische Allegorese
Authors: Pornschlegel Clemens
Published: December 2021

Ausgehend von zwei Texten Simone Weils und Charles Baudelaires untersucht der Beitrag die religiöse Signatur der literarischen und politischen Moderne des 19. und 20. Jahrhunderts. Manifest wird sie in einem genuin allegorischen Sprach- und Weltverständnis, das sich gegen die schlechte Unendlichkeit einer techno-wissenschaftlich verdinglichten Welt richtet, die sich jeder Alteritätserfahrung verschließt. Religiöse Begriffe und Figuren sind in der literarischen Moderne nicht je schon uneigentliche Rede, sondern verlangen nach einer vorurteilsfreien Lektüre, die theologische Fragen nicht aus-, sondern miteinschließt. Dafür steht nicht zuletzt auch Walter Benjamins Lektüre Baudelaires ein.
Weathering events recorded in uppermost Hauterivian–lower Barremian clay-dominated continental successions from the NW Iberian Range: climatic vs. tectonic controls
Authors: Laita Elisa , Bauluz Blanca , Aurell Marcos , Bádenas Beatriz , Yuste Alfonso
Published: December 2021

The facies and clay mineral study of clay/marl-rich levels from the Torrelapaja Formation (latest Hauterivian–early Barremian, NW Iberian Range, NE Spain) allowed to establish the palaeoclimatic and palaeoenvironmental conditions under they were generated. The muddy levels and pisoids contained therein of two logs were sampled and studied by X-ray diffraction and optical and electron microscopy. A similar mineralogical upwards trend is recorded in both logs, with a decrease in calcite coupled with an increase in quartz and orthoclase content and constant proportions in goethite, hematite, diaspore, anatase, rutile, ilmenite, and clay mineral content. The lower muddy levels have higher kaolinite content than the upper levels, where illitic phases are the dominant clay minerals. Smectite and intergrowths of illitic phases and kaolinite are also detected upwards. The kaolinite and smectite textures indicate an authigenic origin, whereas the illitic phases are former phases acting as a substrate for kaolinite crystallization. Pisoids mineralogy and texture show an in-situ origin, but some are fractured, indicating reworking processes. The mineral association found in the muddy levels is characteristic of oxisols formed under warm and humid conditions. The upward decrease in kaolinite content is coeval with an increase in the illitic phases and quartz content, related to siliciclastic input, but is also coeval with the presence of authigenic smectite. This indicates a decrease in chemical weathering, not fully registered due to the siliciclastic contribution, which was possibly associated with a change to colder, drier conditions during the latest Hauterivian–early Barremian in the studied area.
Trends in the molecular epidemiology and population genetics of emergingSporothrixspecies
Authors: Roberto T.N. , de Carvalho J.A. , Beale M.A. , Hagen F. , Fisher M.C. , Hahn R.C. , de Camargo Z.P. , Rodrigues A.M.
Published: December 2021

Paracoccidioidomycosis (PCM) is a life-threatening systemic fungal infection acquired after inhalation ofParacoccidioidespropagules from the environment. The main agents include members of theP. brasiliensiscomplex (phylogenetically-defined species S1, PS2, PS3, and PS4) andP. lutzii. DNA-sequencing of protein-coding loci (e.g.,GP43,ARF, andTUB1) is the reference method for recognizingParacoccidioidesspecies due to a lack of robust phenotypic markers. Thus, developing new molecular markers that are informative and cost-effective is key to providing quality information to explore genetic diversity withinParacoccidioides. We report using new amplified fragment length polymorphism (AFLP) markers and mating-type analysis for genotypingParacoccidioidesspecies. The bioinformatic analysis generated 144in silicoAFLP profiles, highlighting two discriminatory primer pairs combinations (#1 EcoRI-AC/MseI-CT and #2 EcoRI-AT/MseI-CT). The combinations #1 and #2 were usedin vitroto genotype 165Paracoccidioidesisolates recovered from across a vast area of South America. Considering the overall scored AFLP markersin vitro(67-87 fragments), the values of polymorphism information content (PIC= 0.3345-0.3456), marker index (MI= 0.0018), effective multiplex ratio (E= 44.6788-60.3818), resolving power (Rp= 22.3152-34.3152), discriminating power (D= 0.5183-0.5553), expected heterozygosity (H= 0.4247-0.4443), and mean heterozygosity (Havp = 0.00002-0.00004), demonstrated the utility of AFLP markers to speciateParacoccidioidesand to dissect both deep and fine-scale genetic structures. Analysis of molecular variance (AMOVA) revealed that the total genetic variance (65-66 %) was due to variability amongP. brasiliensiscomplex andP. lutzii(PhiPT = 0.651-0.658,P < 0.0001), supporting a highly structured population. Heterothallism was the exclusive mating strategy, and the distributions ofMAT1-1orMAT1-2idiomorphs were not significantly skewed (1:1 ratio) forP. brasiliensis s. str.(χ2= 1.025;P= 0.3113),P. venezuelensis(χ2= 0.692;P= 0.4054), andP. lutzii(χ2= 0.027;P= 0.8694), supporting random mating within each species. In contrast, skewed distributions were found forP. americana(χ2= 8.909;P= 0.0028) andP. restrepiensis(χ2= 4.571;P= 0.0325) with a preponderance ofMAT1-1. Geographical distributions confirmed thatP. americana,P. restrepiensis, andP. lutziiare more widespread than previously thought.P. brasiliensis s. str.is by far the most widely occurring lineage in Latin America countries, occurring in all regions of Brazil. Our new DNA fingerprint assay proved to be rapid, reproducible, and highly discriminatory, to give insights into the taxonomy, ecology, and epidemiology ofParacoccidioidesspecies, guiding disease-control strategies to mitigate PCM.
Scale-space energy density for inhomogeneous turbulence based on filtered velocities
Authors: Hamba Fujihiro
Published: December 2021

The energy spectrum is commonly used to describe the scale dependence of turbulent fluctuations in homogeneous isotropic turbulence. In contrast, one-point statistical quantities, such as the turbulent kinetic energy, are mainly employed for inhomogeneous turbulence models. Attempts have been made to describe the scale dependence of inhomogeneous turbulence using the second-order structure function and two-point velocity correlation. However, unlike the energy spectrum, expressions for the energy density in the scale space fail to satisfy the requirement of being non-negative. In this study, a new expression for the scale-space energy density based on filtered velocities is proposed to clarify the reasons behind the negative values of the energy density and to obtain a better understanding of inhomogeneous turbulence. The new expression consists of homogeneous and inhomogeneous parts; the former is always non-negative, while the latter can be negative because of the turbulence inhomogeneity. Direct numerical simulation data of homogeneous isotropic turbulence and a turbulent channel flow are used to evaluate the two parts of the energy density and turbulent energy. It was found that the inhomogeneous part of the turbulent energy shows non-zero values near the wall and at the centre of a channel flow. In particular, the inhomogeneous part of the energy density changes its sign depending on the scale. A concave profile of the filtered-velocity variance at the wall accounts for the negative value of the energy density in the region very close to the wall.
Non-bifurcation of critical periods from semi-hyperbolic polycycles of quadratic centres
Authors: Marín D. , Saavedra M. , Villadelprat J.
Published: December 2021

In this paper we consider the unfolding of saddle-node
\[ X= \frac{1}{xU_a(x,y)}\Big(x(x^{\mu}-\varepsilon)\partial_x-V_a(x)y\partial_y\Big), \]parametrized by $(\varepsilon,\,a)$ with $\varepsilon \approx 0$ and $a$ in an open subset $A$ of $ {\mathbb {R}}^{\alpha },$ and we study the Dulac time $\mathcal {T}(s;\varepsilon,\,a)$ of one of its hyperbolic sectors. We prove (theorem 1.1) that the derivative $\partial _s\mathcal {T}(s;\varepsilon,\,a)$ tends to $-\infty$ as $(s,\,\varepsilon )\to (0^{+},\,0)$ uniformly on compact subsets of $A.$ This result is addressed to study the bifurcation of critical periods in the Loud's family of quadratic centres. In this regard we show (theorem 1.2) that no bifurcation occurs from certain semi-hyperbolic polycycles.
COMPARING ANALYSIS OF PRETREATMENT METHODS OF WOOD AND BONE MATERIALS FOR THE CHRONOLOGY OF PERIPHERAL BURIALS AT TUNNUG 1, TUVA REPUBLIC, RUSSIA
Authors: Pawełczyk Fatima , Hajdas Irka , Sadykov Timur , Blochin Jegor , Caspari Gino
Published: December 2021

Nine burials from Tunnug 1 site in Tuva Republic, which contained human and animal bones as well as remains of wood, were chosen for intercomparison study of preparation methods. Nine human bones, nine animal bones and 11 pieces of wood were prepared. Gelatin extracted from bones was purified using the UF method but the extraction from bones was modified with respect to acid and base treatment. Wood samples were treated as whole using acid-base-acid and cellulose was extracted for comparison. The results confirmed a highly consistent chronology of the sites centered at 200–400 CE, however, a few bones resulted in an offset between ages obtained by different methods. The extraction of cellulose was limited due to the poor preservation of wood. Our results highlight problems of dating poorly preserved bones and wood.
Probing Ferroelectric Behavior in Sub-10 nm Bismuth-Rich Aurivillius Films by Piezoresponse Force Microscopy
Authors: Keeney Lynette , Colfer Louise , Schmidt Michael
Published: December 2021

Sub-10 nm ferroelectric and multiferroic materials are attracting increased scientific and technological interest, owing to their exciting physical phenomena and prospects in miniaturized electronic devices, neuromorphic computing, and ultra-compact data storage. The Bi6Ti2.9Fe1.5Mn0.6O18 (B6TFMO) Aurivillius system is a rare example of a multiferroic that operates at room temperature. Since the formation of magnetic impurity phases can complicate attempts to measure ferromagnetic signal intrinsic to the B6TFMO multiferroic phase and thus limits its use, herein we minimize this by utilizing relatively large (49%) bismuth excess to counteract its volatility during sub-10 nm growth. X-ray diffraction, electron microscopy, and atomic force microscopy show sample crystallinity and purity are substantially improved on increasing bismuth excess from 5 to 49%, with the volume fraction of surface impurities decreasing from 2.95–3.97 vol% down to 0.02–0.31 vol%. Piezoresponse force microscopy reveals 8 nm B6TFMO films are ferroelectric, with an isotropic random distribution of stable in-plane domains and weaker out-of-plane piezoresponse. By reducing the volume fraction of magnetic impurities, this work demonstrates the recent progress in the optimization of ultra-thin B6TFMO for future multiferroic technologies. We show how the orientation of the ferroelectric polarization can be switched in 8 nm B6TFMO and arrays can be “written” and “read” to express states permitting anti-parallel information storage.
Moisture Fluctuations Modulate Abiotic and Biotic Limitations of H2 Soil Uptake
Authors: Bertagni Matteo B. , Paulot Fabien , Porporato Amilcare
Published: December 2021

Soil uptake by H2‐oxidizing bacteria is the main sink of the global hydrogen cycle, accounting for nearly 80% of the atmospheric H2 consumption. Although the H2 uptake is strongly influenced by soil moisture, little attention has been paid to coherently couple the water and hydrogen dynamics in soils. Toward this goal, we improve the mechanistic representation of the H2 uptake as a function of soil moisture and highlight the role of the moisture temporal fluctuations on the biotic consumption of H2. The results show that, due to the strongly nonlinear relationship between soil moisture and H2 uptake, addressing the dry‐wet sequences is necessary to characterize the H2 uptake in semi‐arid regions correctly. From novel analytical relationships validated with field data, we also infer the biotic and abiotic limitations in the global soil H2 uptake. It is shown that, diffusion generally limits the uptake in humid temperate and tropical regions, while biotic limitations tend to occur in very arid or cold soils. Finally, we discuss the implications that climate change may have on the H2 soil sink.
SETD5 modulates homeostasis of hematopoietic stem cells by mediating RNA Polymerase II pausing in cooperation with HCF-1
Authors: Li Mengke , Qiu Chen , Bian Yujie , Shi Deyang , Wang Bichen , Ma Qiuyi , Wang Xiaomin , Shi Jun , Zhang Lianfeng , Ma Yuanwu , Zhu Ping , Cheng Tao , Chu Yajing , Yuan Weiping
Published: December 2021

SETD5mutations were identified as the genetic causes of neurodevelopmental disorders. While the whole-body knockout ofSetd5in mice leads to embryonic lethality, the role of SETD5 in adult stem cell remains unexplored. Here, a critical role ofSetd5in hematopoietic stem cells (HSCs) is identified. Specific deletion ofSetd5in hematopoietic system significantly increased the number of immunophenotypic HSCs by promoting HSC proliferation.Setd5-deficient HSCs exhibited impaired long-term self-renewal capacity and multiple-lineage differentiation potentials under transplantation pressure. Transcriptome analysis ofSetd5-deficient HSCs revealed a disruption of quiescence state of long-term HSCs, a cause of the exhaustion of functional HSCs. Mechanistically, SETD5 was shown to regulate HSC quiescence by mediating the release of promoter-proximal paused RNA polymerase II (Pol II) on E2F targets in cooperation with HCF-1 and PAF1 complex. Taken together, these findings reveal an essential role of SETD5 in regulating Pol II pausing-mediated maintenance of adult stem cells.
Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship
Authors: Ratajczak Mariusz Z. , Kucia Magdalena
Published: December 2021

Hematopoietic and immune cells originate from a common hematopoietic/lymphopoietic stem cell what explains that these different cell types often share the same receptors and respond to similar factors. Moreover, the common goal of both lineages is to ensure tissue homeostasis under steady-state conditions, fight invading pathogens, and promote tissue repair. We will highlight accumulating evidence that innate and adaptive immunity modulate several aspects of hematopoiesis within the hormetic zone in which the biological response to low exposure to potential stressors generally is favorable and benefits hematopoietic stem/progenitor cells (HSPCs). Innate immunity impact on hematopoiesis is pleiotropic and involves both the cellular arm, comprised of innate immunity cells, and the soluble arm, whose major component is the complement cascade (ComC). In addition, several mediators released by innate immunity cells, including inflammatory cytokines and small antimicrobial cationic peptides, affect hematopoiesis. There are intriguing observations that HSPCs and immune cells share several cell-surface pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and cytosol-expressed NOD, NOD-like, and RIG-I-like receptors and thus can be considered “pathogen sensors”. In addition, not only lymphocytes but also HSPCs express functional intracellular complement proteins, defined as complosome which poses challenging questions for further investigation of the intracellular ComC-mediated intracrine regulation of hematopoiesis.
Predation increases multiple components of microbial diversity in activated sludge communities
Authors: Burian Alfred , Pinn Daisy , Peralta-Maraver Ignacio , Sweet Michael , Mauvisseau Quentin , Eyice Ozge , Bulling Mark , Röthig Till , Kratina Pavel
Published: December 2021

Protozoan predators form an essential component of activated sludge communities that is tightly linked to wastewater treatment efficiency. Nonetheless, very little is known how protozoan predation is channelled via bacterial communities to affect ecosystem functioning. Therefore, we experimentally manipulated protozoan predation pressure in activated-sludge communities to determine its impacts on microbial diversity, composition and putative functionality. Different components of bacterial diversity such as taxa richness, evenness, genetic diversity and beta diversity all responded strongly and positively to high protozoan predation pressure. These responses were non-linear and levelled off at higher levels of predation pressure, supporting predictions of hump-shaped relationships between predation pressure and prey diversity. In contrast to predation intensity, the impact of predator diversity had both positive (taxa richness) and negative (evenness and phylogenetic distinctiveness) effects on bacterial diversity. Furthermore, predation shaped the structure of bacterial communities. Reduction in top-down control negatively affected the majority of taxa that are generally associated with increased treatment efficiency, compromising particularly the potential for nitrogen removal. Consequently, our findings highlight responses of bacterial diversity and community composition as two distinct mechanisms linking protozoan predation with ecosystem functioning in activated sludge communities.
Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma
Authors: Zhong Chenxi , Chen Ming , Chen Yu , Yao Feng , Fang Wentao
Published: December 2021

Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.
Defense responses of arbuscular mycorrhizal fungus-colonized poplar seedlings against gypsy moth larvae: a multiomics study
Authors: Jiang Dun , Tan Mingtao , Wu Shuai , Zheng Lin , Wang Qing , Wang Guirong , Yan Shanchun
Published: December 2021

Arbuscular mycorrhizal (AM) fungi may help protect plants against herbivores; however, their use for the pest control of woody plants requires further study. Here, we investigated the effect of Glomus mosseae colonization on the interactions between gypsy moth larvae and Populus alba × P. berolinensis seedlings and deciphered the regulatory mechanisms underlying the mycorrhizal-induced resistance in the leaves of mycorrhizal poplar using RNA-seq and nontargeted metabolomics. The resistance assay showed that AM fungus inoculation protected poplar seedlings against gypsy moth larvae, as evidenced by the decreased larval growth and reduced larval survival. A transcriptome analysis revealed that differentially expressed genes (DEGs) were involved in jasmonic acid biosynthesis (lipoxygenase, hydroperoxide dehydratase, and allene oxide cyclase) and signal transduction (jasmonate-ZIM domain and transcription factor MYC2) and identified the genes that were upregulated in mycorrhizal seedlings. Except for chalcone synthase and anthocyanidin synthase, which were downregulated in mycorrhizal seedlings, all DEGs related to flavonoid biosynthesis were upregulated, including 4-coumarate-CoA ligase, chalcone isomerase, flavanone 3-hydroxylase, flavonol synthase, and leucoanthocyanidin reductase. The metabolome analysis showed that several metabolites with insecticidal properties, including coumarin, stachydrine, artocarpin, norizalpinin, abietic acid, 6-formylumbelliferone, and vanillic acid, were significantly accumulated in the mycorrhizal seedlings. These findings suggest the potential of mycorrhiza-induced resistance for use in pest management of woody plants and demonstrate that the priming of JA-dependent responses in poplar seedlings contributes to mycorrhiza-induced resistance to insect pests.
A novel transcription factor CmMYB012 inhibits flavone and anthocyanin biosynthesis in response to high temperatures in chrysanthemum
Authors: Zhou Li-Jie , Geng Zhiqiang , Wang Yuxi , Wang Yiguang , Liu Shenhui , Chen Chuwen , Song Aiping , Jiang Jiafu , Chen Sumei , Chen Fadi
Published: December 2021

Flavones are among the major colorless pigments synthesized through branches of the flavonoid pathway in plants. However, due to the absence of a gene encoding flavone synthase (FNS) in the model plant Arabidopsis thaliana species, the regulatory mechanism of FNS-catalyzed flavone biosynthesis has rarely been studied in plants. Here, it was found that flavones play a predominant role in the elimination of excess reactive oxygen species (ROS) at high temperatures in colorless plant organs. A novel atypical subgroup 7 (SG7) R2R3-MYB transcription factor, CmMYB012, was found to be induced in response to prolonged high temperatures and to inhibit flavone biosynthesis by directly regulating CmFNS. Moreover, CmMYB012 was also found to inhibit anthocyanin biosynthesis by suppressing the expression of CmCHS, CmDFR, CmANS, and CmUFGT. CmMYB012 overexpression exerted a negative influence on plant fitness and pink flower color formation, while CmMYB012 suppression had the opposite effect in response to high temperatures. Our findings provide new insights into the mechanisms by which high temperatures regulate the metabolism of flavones and anthocyanins to affect plant fitness and flower color formation.
Functions of silicon in plant drought stress responses
Authors: Wang Min , Wang Ruirui , Mur Luis Alejandro Jose , Ruan Jianyun , Shen Qirong , Guo Shiwei
Published: December 2021

Silicon (Si), the second most abundant element in Earth’s crust, exerts beneficial effects on the growth and productivity of a variety of plant species under various environmental conditions. However, the benefits of Si and its importance to plants are controversial due to differences among the species, genotypes, and the environmental conditions. Although Si has been widely reported to alleviate plant drought stress in both the Si-accumulating and nonaccumulating plants, the underlying mechanisms through which Si improves plant water status and maintains water balance remain unclear. The aim of this review is to summarize the morphoanatomical, physiological, biochemical, and molecular processes that are involved in plant water status that are regulated by Si in response to drought stress, especially the integrated modulation of Si-triggered drought stress responses in Si accumulators and intermediate- and excluder-type plants. The key mechanisms influencing the ability of Si to mitigate the effects of drought stress include enhancing water uptake and transport, regulating stomatal behavior and transpirational water loss, accumulating solutes and osmoregulatory substances, and inducing plant defense- associated with signaling events, consequently maintaining whole-plant water balance. This study evaluates the ability of Si to maintain water balance under drought stress conditions and suggests future research that is needed to implement the use of Si in agriculture. Considering the complex relationships between Si and different plant species, genotypes, and the environment, detailed studies are needed to understand the interactions between Si and plant responses under stress conditions.
Disruption of the bHLH transcription factor Abnormal Tapetum 1 causes male sterility in watermelon
Authors: Zhang Ruimin , Chang Jingjing , Li Jiayue , Lan Guangpu , Xuan Changqing , Li Hao , Ma Jianxiang , Zhang Yong , Yang Jianqiang , Tian Shujuan , Yuan Li , Zhang Xian , Wei Chunhua
Published: December 2021

Although male sterility has been identified as a useful trait for hybrid vigor utilization and hybrid seed production, its underlying molecular mechanisms in Cucurbitaceae species are still largely unclear. Here, a spontaneous male-sterile watermelon mutant, Se18, was reported to have abnormal tapetum development, which resulted in completely aborted pollen grains. Map-based cloning demonstrated that the causal gene Citrullus lanatus Abnormal Tapetum 1 (ClATM1) encodes a basic helix-loop-helix (bHLH) transcription factor with a 10-bp deletion and produces a truncated protein without the bHLH interaction and functional (BIF) domain in Se18 plants. qRT–PCR and RNA in situ hybridization showed that ClATM1 is specifically expressed in the tapetum layer and in microsporocytes during stages 6–8a of anther development. The genetic function of ClATM1 in regulating anther development was verified by CRISPR/Cas9-mediated mutagenesis. Moreover, ClATM1 was significantly downregulated in the Se18 mutant, displaying a clear dose effect at the transcriptional level. Subsequent dual-luciferase reporter, β-glucuronidase (GUS) activity, and yeast one-hybrid assays indicated that ClATM1 could activate its own transcriptional expression through promoter binding. Collectively, ClATM1 is the first male sterility gene cloned from watermelon, and its self-regulatory activity provides new insights into the molecular mechanism underlying anther development in plants.
Transcriptome analysis in LRRK2 and idiopathic Parkinson’s disease at different glucose levels
Authors: Fernández-Santiago Rubén , Esteve-Codina Anna , Fernández Manel , Valldeoriola Francesc , Sanchez-Gómez Almudena , Muñoz Esteban , Compta Yaroslau , Tolosa Eduardo , Ezquerra Mario , Martí María J.
Published: December 2021

Type-2 diabetes (T2D) and glucose metabolic imbalances have been linked to neurodegenerative diseases, including Parkinson’s disease (PD). To detect potential effects of different glucose levels on gene expression, by RNA-seq we analyzed the transcriptome of dermal fibroblasts from idiopathic PD (iPD) patients, LRRK2-associated PD (L2PD) patients, and healthy controls (total n = 21 cell lines), which were cultured at two different glucose concentrations (25 and 5 mM glucose). In PD patients we identified differentially expressed genes (DEGs) that were related to biological processes mainly involving the plasmatic cell membrane, the extracellular matrix, and also neuronal functions. Such pathway deregulation was largely similar in iPD or L2PD fibroblasts. Overall, the gene expression changes detected in this study were associated with PD independently of glucose concentration.
Quantum generative adversarial networks with multiple superconducting qubits
Authors: Huang Kaixuan , Wang Zheng-An , Song Chao , Xu Kai , Li Hekang , Wang Zhen , Guo Qiujiang , Song Zixuan , Liu Zhi-Bo , Zheng Dongning , Deng Dong-Ling , Wang H. , Tian Jian-Guo , Fan Heng
Published: December 2021

Generative adversarial networks are an emerging technique with wide applications in machine learning, which have achieved dramatic success in a number of challenging tasks including image and video generation. When equipped with quantum processors, their quantum counterparts—called quantum generative adversarial networks (QGANs)—may even exhibit exponential advantages in certain machine learning applications. Here, we report an experimental implementation of a QGAN using a programmable superconducting processor, in which both the generator and the discriminator are parameterized via layers of single- and two-qubit quantum gates. The programmed QGAN runs automatically several rounds of adversarial learning with quantum gradients to achieve a Nash equilibrium point, where the generator can replicate data samples that mimic the ones from the training set. Our implementation is promising to scale up to noisy intermediate-scale quantum devices, thus paving the way for experimental explorations of quantum advantages in practical applications with near-term quantum technologies.
The effect of sex on social cognition and functioning in schizophrenia
Authors: Ferrer-Quintero Marta , Green Michael F. , Horan William P. , Penn David L. , Kern Robert S. , Lee Junghee
Published: December 2021

Social cognitive impairment is a core feature of schizophrenia and plays a critical role in poor community functioning in the disorder. However, our understanding of the relationship between key biological variables and social cognitive impairment in schizophrenia is limited. This study examined the effect of sex on the levels of social cognitive impairment and the relationship between social cognitive impairment and social functioning in schizophrenia. Two hundred forty-eight patients with schizophrenia (61 female) and 87 healthy controls (31 female) completed five objective measures and one subjective measure of social cognition. The objective measures included the Facial Affect Identification, Emotion in Biological Motion, Self-Referential Memory, MSCEIT Branch 4, and Empathic Accuracy tasks. The subjective measure was the Interpersonal Reactivity Index (IRI), which includes four subscales. Patients completed measures of social and non-social functional capacity and community functioning. For objective social cognitive tasks, we found a significant sex difference only on one measure, the MSCEIT Branch 4, which in both patient and control groups, females performed better than males. Regarding the IRI, females endorsed higher empathy-related items on one subscale. The moderating role of sex was found only for the association between objective social cognition and non-social functional capacity. The relationship was stronger in male patients than female patients. In this study, we found minimal evidence of a sex effect on social cognition in schizophrenia across subjective and objective measures. Sex does not appear to moderate the association between social cognition and functioning in schizophrenia.
Linking migratory performance to breeding phenology and productivity in an Afro-Palearctic long-distance migrant
Authors: Costa Joana S. , Hahn Steffen , Araújo Pedro M. , Dhanjal-Adams Kiran L. , Rocha Afonso D. , Alves José A.
Published: December 2021

Understanding the relationship between migratory performance and fitness is crucial for predicting population dynamics of migratory species. In this study, we used geolocators to explore migration performance (speed and duration of migratory movements, migratory timings) and its association with breeding phenology and productivity in an Afro-Palearctic insectivore, the European bee-eater (Merops apiaster), breeding in Iberian Peninsula. Bee-eaters migrated at higher travel speeds and had shorter travel duration in spring compared to autumn. Individuals that departed earlier or spent fewer days in-flight arrived earlier to the breeding areas. Our results show overall positive, but year-specific, linkages between arrival and laying dates. In one year, laying was earlier and productivity was higher, remaining constant throughout the season, while in the subsequent year productivity was lower and, importantly, declined with laying date. These results suggest that arriving earlier can be advantageous for bee-eaters, as in years when breeding conditions are favourable, early and late breeders produce high and similar number of fledglings, but when conditions are unfavourable only early breeders experience high productivity levels.
Losartan improves intestinal mucositis induced by 5-fluorouracil in mice
Authors: Oliveira Maisie Mitchele Barbosa , de Araújo Aurigena Antunes , Ribeiro Susana Barbosa , de Sales Mota Polyana Crislayne Moreira , Marques Vitória Barros , da Silva Martins Rebouças Conceição , Figueiredo Jozi Godoy , Barra Patrícia Batista , de Castro Brito Gerly Anne , de Carvalho Leitão Renata Ferreira , Guerra Gerlane Coelho Bernardo , de Medeiros Caroline Addison Carvalho Xavier
Published: December 2021

Intestinal mucositis (IM) is a common side effect of 5-fluorouracil (5-FU)-based chemotherapy, which negatively impacts therapeutic outcomes and delays subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. In search of new pharmacological alternatives that minimize your symptoms, this work set out to study the effect of losartan (LOS), a receptor type I (AT1) angiotensin II antagonist, on intestinal mucositis induced by 5-FU. Intestinal mucositis was induced by a single intraperitoneal administration of 5-FU (450 mg/kg) in Swiss mice. Losartan (5, 25 or 50 mg/kg) or saline was orally administered 30 min before 5-FU and daily for 4 days. On 4th day, the animals were euthanized and segments of small intestine were collected to evaluate histopathological alterations (morphometric analysis), concentration of inflammatory cytokines, oxidative stress markers and genic expression of NF-κB p65, Fn-14 and TWEAK. Weight evaluation and changes in leukogram were also analyzed. 5-FU induced intense weight loss, leukopenia and reduction in villus height compared to saline group. Losartan (50 mg/kg) prevented 5-FU-induced inflammation by decreasing in the analyzed parameters compared to the 5-FU group. Our findings suggest that 50 mg/kg of losartan prevents the effects of 5-FU on intestinal mucosa in mice.
The effects of molecular crowding and CpG hypermethylation on DNA G-quadruplexes formed by the C9orf72 nucleotide repeat expansion
Authors: Ozcan Kadir. A. , Ghaffari Layla T. , Haeusler Aaron R.
Published: December 2021

A nucleotide repeat expansion (NRE), (G4C2)n, located in a classically noncoding region of C9orf72 (C9), is the most common genetic mutation associated with ALS/FTD. There is increasing evidence that nucleic acid structures formed by the C9-NRE may both contribute to ALS/FTD, and serve as therapeutic targets, but there is limited characterization of these nucleic acid structures under physiologically and disease relevant conditions. Here we show in vitro that the C9-NRE DNA can form both parallel and antiparallel DNA G-quadruplex (GQ) topological structures and that the structural preference of these DNA GQs can be dependent on the molecular crowding conditions. Additionally, 5-methylcytosine DNA hypermethylation, which is observed in the C9-NRE locus in some patients, has minimal effects on GQ topological preferences. Finally, molecular dynamic simulations of methylated and nonmethylated GQ structures support in vitro data showing that DNA GQ structures formed by the C9-NRE DNA are stable, with structural fluctuations limited to the cytosine-containing loop regions. These findings provide new insight into the structural polymorphic preferences and stability of DNA GQs formed by the C9-NRE in both the methylated and nonmethylated states, as well as reveal important features to guide the development of upstream therapeutic approaches to potentially attenuate C9-NRE-linked diseases.
Communication pathways bridge local and global conformations in an IgG4 antibody
Authors: Tarenzi Thomas , Rigoli Marta , Potestio Raffaello
Published: December 2021

The affinity of an antibody for its antigen is primarily determined by the specific sequence and structural arrangement of the complementarity-determining regions (CDRs). Recent evidence, however, points toward a nontrivial relation between the CDR and distal sites: variations in the binding strengths have been observed upon mutating residues separated from the paratope by several nanometers, thus suggesting the existence of a communication network within antibodies, whose extension and relevance might be deeper than insofar expected. In this work, we test this hypothesis by means of molecular dynamics (MD) simulations of the IgG4 monoclonal antibody pembrolizumab, an approved drug that targets the programmed cell death protein 1 (PD-1). The molecule is simulated in both the apo and holo states, totalling 4 μs of MD trajectory. The analysis of these simulations shows that the bound antibody explores a restricted range of conformations with respect to the apo one, and that the global conformation of the molecule correlates with that of the CDR. These results support the hypothesis that pembrolizumab featues a multi-scale hierarchy of intertwined global and local conformational changes. The analysis pipeline developed in this work is general, and it can help shed further light on the mechanistic aspects of antibody function.
Nonspecific binding of common anti-CFTR antibodies in ciliated cells of human airway epithelium
Authors: Sato Yukiko , Mustafina Kamila R. , Luo Yishan , Martini Carolina , Thomas David Y. , Wiseman Paul W. , Hanrahan John W.
Published: December 2021

There is evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is highly expressed at the apical pole of ciliated cells in human bronchial epithelium (HBE), however recent studies have detected little CFTR mRNA in those cells. To understand this discrepancy we immunostained well differentiated primary HBE cells using CFTR antibodies. We confirmed apical immunofluorescence in ciliated cells and quantified the covariance of the fluorescence signals and that of an antibody against the ciliary marker centrin-2 using image cross-correlation spectroscopy (ICCS). Super-resolution stimulated emission depletion (STED) imaging localized the immunofluorescence in distinct clusters at the bases of the cilia. However, similar apical fluorescence was observed when the monoclonal CFTR antibodies 596, 528 and 769 were used to immunostain ciliated cells expressing F508del-CFTR, or cells lacking CFTR due to a Class I mutation. A BLAST search using the CFTR epitope identified a similar amino acid sequence in the ciliary protein rootletin X1. Its expression level correlated with the intensity of immunostaining by CFTR antibodies and it was detected by 596 antibody after transfection into CFBE cells. These results may explain the high apparent expression of CFTR in ciliated cells and reports of anomalous apical immunofluorescence in well differentiated cells that express F508del-CFTR.
E. coli Nissle 1917 modulates host glucose metabolism without directly acting on glucose
Authors: Chavkin Theodore A. , Pham Loc-Duyen , Kostic Aleksandar
Published: December 2021

Managing postprandial glycemic response, or the increase in blood sugar following a meal, is a crucial component to maintaining healthy blood sugar in patients with diabetes. To test whether oral probiotics can impact postprandial glycemic response, E. coli Nissle 1917 (EcN) was evaluated in an oral glucose tolerance test. Oral gavage of EcN concurrent with a glucose bolus reduced the post-gavage glycemic response in mice. However, there was no difference in glycemic response when comparing EcN to a mutant deficient in glucose metabolism. This suggests that while EcN can alter glycemic response to a glucose bolus, this effect is not mediated by direct uptake of glucose. Of the possible indirect effects EcN could have, gastric emptying rate was highlighted as a likely cause, but EcN had no effect on gastric emptying rate in mice. This leaves many more possible indirect explanations for the interaction between EcN and host glucose metabolism to be explored in future work.