bluuebunny/crossref_metadata_2025 huggingface dataset:
OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression
Authors: Masi Mirco , Garattini Enrico , Bolis Marco , Di Marino Daniele , Maraccani Luisa , Morelli Elena , Grolla Ambra A. , Fagiani Francesca , Corsini Emanuela , Travelli Cristina , Govoni Stefano , Racchi Marco , Buoso Erica
Published: December 2020

Recent data indicate that receptor for activated C kinase 1 (RACK1) is a putative prognostic marker and drug target in breast cancer (BC). High RACK1 expression is negatively associated with overall survival, as it seems to promote BC progression. In tumors, RACK1 expression is controlled by a complex balance between glucocorticoids and androgens. Given the fact that androgens and androgenic derivatives can inhibit BC cell proliferation and migration, the role of androgen signaling in regulating RACK1 transcription in mammary tumors is of pivotal interest. Here, we provide evidence that nandrolone (19-nortosterone) inhibits BC cell proliferation and migration by antagonizing the PI3K/Akt/NF-κB signaling pathway, which eventually results in RACK1 downregulation. We also show that nandrolone impairs the PI3K/Akt/NF-κB signaling pathway and decreases RACK1 expression via binding to the membrane-bound receptor, oxoeicosanoid receptor 1 (OXER1). High levels of OXER1 are observed in several BC cell lines and correlate with RACK1 expression and poor prognosis. Our data provide evidence on the role played by the OXER1-dependent intracellular pathway in BC progression and shed light on the mechanisms underlying membrane-dependent androgen effects on RACK1 regulation. Besides the mechanistic relevance, the results of the study are of interest from a translational prospective. In fact, they identify a new and actionable pathway to be used for the design of innovative and rational therapeutic strategies in the context of the personalized treatment of BC. In addition, they draw attention on nandrolone-based compounds that lack hormonal activity as potential anti-tumor agents.
Anti-PD1 therapy induces lymphocyte-derived exosomal miRNA-4315 release inhibiting Bim-mediated apoptosis of tumor cells
Authors: Guyon Nina , Garnier Delphine , Briand Joséphine , Nadaradjane Arulraj , Bougras-Cartron Gwenola , Raimbourg Judith , Campone Mario , Heymann Dominique , Vallette François M. , Frenel Jean-Sébastien , Cartron Pierre-François
Published: December 2020

Anti-PD1 immunotherapy, as a single agent or in combination with standard chemotherapies, has significantly improved the outcome of many patients with cancers. However, resistance to anti-PD1 antibodies often decreases the long-term therapeutic benefits. Despite this observation in clinical practice, the molecular mechanisms associated with resistance to anti-PD1 antibody therapy have not yet been elucidated. To identify the mechanisms of resistance associated with anti-PD1 antibody therapy, we developed cellular models including purified T cells and different cancer cell lines from glioblastoma, lung adenocarcinoma, breast cancer and ovarian carcinoma. A murine model of lung cancer was also used. Longitudinal blood samples of patients treated with anti-PD1 therapy were also used to perform a proof-of-concept study of our findings. We found that anti-PD1 exposure of T-cell promotes an enrichment of exosomal miRNA-4315. We also noted that exosomal miRNA-4315 induced a phenomenon of apopto-resistance to conventional chemotherapies in cancer cells receiving exosomal miRNA-4315. At molecular level, we discern that the apopto-resistance phenomenon was associated with the miRNA-4315-mediated downregulation of Bim, a proapoptotic protein. In cellular and mice models, we observed that the BH3 mimetic agent ABT263 circumvented this resistance. A longitudinal study using patient blood showed that miRNA-4315 and cytochrome c can be used to define the time period during which the addition of ABT263 therapy may effectively increase cancer cell death and bypass anti-PD1 resistance.This work provides a blood biomarker (exosomal miRNA-4315) for patient stratification developing a phenomenon of resistance to anti-PD1 antibody therapy and also identifies a therapeutic alternative (the use of a BH3 mimetic drug) to limit this resistance phenomenon.
Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA
Authors: Hao Qiongyu , Wang Piwen , Dutta Pranabananda , Chung Seyung , Li Qun , Wang Kun , Li Jieqing , Cao Wei , Deng Wenhong , Geng Qing , Schrode Katrina , Shaheen Magda , Wu Ke , Zhu Donghui , Chen Qiao-Hong , Chen Guanglin , Elshimali Yahya , Vadgama Jay , Wu Yong
Published: December 2020

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.
mtDNA-STING pathway promotes necroptosis-dependent enterocyte injury in intestinal ischemia reperfusion
Authors: Zhang Xufei , Wu Jie , Liu Qinjie , Li Xuanheng , Li Sicheng , Chen Jun , Hong Zhiwu , Wu Xiuwen , Zhao Yun , Ren Jianan
Published: December 2020

Intestinal ischemia reperfusion (I/R) injury is the important pathogenesis for acute intestinal barrier disruption. The STING signaling is associated with gut homeostasis and barrier integrity. However, the biological function and regulation of STING signaling in intestinal I/R injury are not yet fully understood. As the ligand of STING signaling, the mitochondrial DNA (mtDNA) has been found to be associated with necroptosis. It still remains unknown whether mtDNA-STING signaling triggers intestinal necroptosis in intestinal I/R injury. We found that circulating RIPK3 was significantly increased and had a positive correlation with markers of enterocyte injury in critically ill patients with intestinal injury. Moreover, the levels of circulating mtDNA were also associated with the levels of circulating RIPK3. To explore the relationship between mtDNA and intestinal necroptosis, mice were treated with the intraperitoneal injection of mtDNA, and necroptosis signaling was remarkably activated and the inhibition of necroptosis alleviated mtDNA-induced intestinal injury. Furthermore, STING knockout mice showed an alleviated intestinal necroptosis. In intestinal I/R injury, mtDNA was released from IECs and necroptosis was also triggered, companied with a significant decrease of RIPK3 in the intestine. STING knockout mice markedly attenuated intestinal necroptosis and intestinal I/R injury. Finally, we found that mtDNA-mediated STING signaling triggered necroptosis through synergistic IFN and TNF-α signaling in primary IECs. Our results indicated that mtDNA-STING signaling can contribute to intestinal I/R injury by promoting IEC necroptosis. STING-mediated both IFN and TNF-α signaling can trigger intestinal nercroptosis.
Loss of the tumor suppressor BTG3 drives a pro-angiogenic tumor microenvironment through HIF-1 activation
Authors: Cheng Yu-Che , Chiang Hsin-Yi , Cheng Shang-Jung , Chang Hung-Wei , Li Yi-Ju , Shieh Sheau-Yann
Published: December 2020

B-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG gene family and is a downstream target of p53. Here, we show that senescence triggered by BTG3 depletion was accompanied by a secretome enriched with cytokines, growth factors, and matrix-remodeling enzymes, which could promote angiogenesis and cell scattering in vitro. We present evidence that at least part of these activities can be explained by elevated HIF-1α activity. Mechanistically, the BTG3 C-terminal domain competes with the coactivator p300 for binding the HIF-1α transactivation domain. The angiogenic promoting effect of BTG3 knockdown was largely diminished upon co-depletion of HIF-1α, indicating that HIF-1α is a major downstream target of BTG3 in the control of angiogenesis. In vivo, ectopic expression of BTG3 suppresses angiogenesis in xenograft tumors; and syngenic tumor growth and metastasis were enhanced in Btg3-null mice. Moreover, analysis of clinical datasets revealed that a higher BTG3/VEGFA expression ratio correlates with improved patient survival in a number of cancer types. Taken together, our findings highlight the non-autonomous regulation of tumor microenvironment by BTG3 while suppressing tumor progression.
SEMG1/2 augment energy metabolism of tumor cells
Authors: Shuvalov Oleg , Kizenko Alyona , Petukhov Alexey , Fedorova Olga , Daks Alexandra , Bottrill Andrew , Snezhkina Anastasiya V. , Kudryavtseva Anna V. , Barlev Nikolai
Published: December 2020

SEMG1 and SEMG2 genes belong to the family of cancer-testis antigens (CTAs), whose expression normally is restricted to male germ cells but is often restored in various malignancies. High levels of SEMG1 and SEMG2 expression are detected in prostate, renal, and lung cancer as well as hemoblastosis. However, the functional importance of both SEMGs proteins in human neoplasms is still largely unknown. In this study, by using a combination of the bioinformatics and various cellular and molecular assays, we have demonstrated that SEMG1 and SEMG2 are frequently expressed in lung cancer clinical samples and cancer cell lines of different origins and are negatively associated with the survival rate of cancer patients. Using the pull-down assay followed by LC-MS/MS mass-spectrometry, we have identified 119 proteins associated with SEMG1 and SEMG2. Among the SEMGs interacting proteins we noticed two critical glycolytic enzymes-pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Importantly, we showed that SEMGs increased the protein level and activity of both PKM2 and LDHA. Further, both SEMGs increased the membrane mitochondrial potential (MMP), glycolysis, respiration, and ROS production in several cancer cell lines. Taken together, these data provide first evidence that SEMGs can up-regulate the energy metabolism of cancer cells, exemplifying their oncogenic features.
Importance of tailoring lattice strain in halide perovskite crystals
Authors: Kim Hui-Seon , Park Nam-Gyu
Published: December 2020

In this review paper, the residual strain of a polycrystalline halide perovskite film is systematically studied based on its structural inhomogeneity, which is closely correlated to the local carrier dynamics caused by a modulated electronic band structure. Long-range collective strain ordering is responsible for the overall structural properties, consequently determining the optoelectronic properties of the perovskite film. Notably, the perovskite phase stability is strongly affected by the internal strain, favoring a lower energy state. The important parameters affecting the residual strain in a real perovskite film, ranging from thermal stress to lattice mismatch and compositional inhomogeneity, are subsequently introduced along with their impacts on the optoelectronic properties and/or the stability of the crystals.
SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8+ T cells
Authors: Loyal Lucie , Warth Sarah , Jürchott Karsten , Mölder Felix , Nikolaou Christos , Babel Nina , Nienen Mikalai , Durlanik Sibel , Stark Regina , Kruse Beate , Frentsch Marco , Sabat Robert , Wolk Kerstin , Thiel Andreas
Published: December 2020

The prevailing ‘division of labor’ concept in cellular immunity is that CD8+ T cells primarily utilize cytotoxic functions to kill target cells, while CD4+ T cells exert helper/inducer functions. Multiple subsets of CD4+ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8+ memory T-cell subsets exist, characterized by identical chemokine receptor expression signatures and controlled by similar generic programs. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17 + 1 cells, express IL-6R but not SLAMF7, completely lack cytotoxicity and instead display helper functions including CD40L expression. CD8+ helper T cells exhibit a unique TCR repertoire, express genes related to skin resident memory T cells (TRM) and are altered in the inflammatory skin disease psoriasis. Our findings reveal that the conventional view of CD4+ and CD8+ T cell capabilities and functions in human health and disease needs to be revised.
One-dimensional confinement and width-dependent bandgap formation in epitaxial graphene nanoribbons
Authors: Karakachian Hrag , Nguyen T. T. Nhung , Aprojanz Johannes , Zakharov Alexei A. , Yakimova Rositsa , Rosenzweig Philipp , Polley Craig M. , Balasubramanian Thiagarajan , Tegenkamp Christoph , Power Stephen R. , Starke Ulrich
Published: December 2020

The ability to define an off state in logic electronics is the key ingredient that is impossible to fulfill using a conventional pristine graphene layer, due to the absence of an electronic bandgap. For years, this property has been the missing element for incorporating graphene into next-generation field effect transistors. In this work, we grow high-quality armchair graphene nanoribbons on the sidewalls of 6H-SiC mesa structures. Angle-resolved photoelectron spectroscopy (ARPES) and scanning tunneling spectroscopy measurements reveal the development of a width-dependent semiconducting gap driven by quantum confinement effects. Furthermore, ARPES demonstrates an ideal one-dimensional electronic behavior that is realized in a graphene-based environment, consisting of well-resolved subbands, dispersing and non-dispersing along and across the ribbons respectively. Our experimental findings, coupled with theoretical tight-binding calculations, set the grounds for a deeper exploration of quantum confinement phenomena and may open intriguing avenues for new low-power electronics.
Direct observation of the formation and stabilization of metallic nanoparticles on carbon supports
Authors: Huang Zhennan , Yao Yonggang , Pang Zhenqian , Yuan Yifei , Li Tangyuan , He Kun , Hu Xiaobing , Cheng Jian , Yao Wentao , Liu Yuzi , Nie Anmin , Sharifi-Asl Soroosh , Cheng Meng , Song Boao , Amine Khalil , Lu Jun , Li Teng , Hu Liangbing , Shahbazian-Yassar Reza
Published: December 2020

Direct formation of ultra-small nanoparticles on carbon supports by rapid high temperature synthesis method offers new opportunities for scalable nanomanufacturing and the synthesis of stable multi-elemental nanoparticles. However, the underlying mechanisms affecting the dispersion and stability of nanoparticles on the supports during high temperature processing remain enigmatic. In this work, we report the observation of metallic nanoparticles formation and stabilization on carbon supports through in situ Joule heating method. We find that the formation of metallic nanoparticles is associated with the simultaneous phase transition of amorphous carbon to a highly defective turbostratic graphite (T-graphite). Molecular dynamic (MD) simulations suggest that the defective T-graphite provide numerous nucleation sites for the nanoparticles to form. Furthermore, the nanoparticles partially intercalate and take root on edge planes, leading to high binding energy on support. This interaction between nanoparticles and T-graphite substrate strengthens the anchoring and provides excellent thermal stability to the nanoparticles. These findings provide mechanistic understanding of rapid high temperature synthesis of metal nanoparticles on carbon supports and the origin of their stability.
Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway
Authors: Dai Enyong , Han Leng , Liu Jiao , Xie Yangchun , Zeh Herbert J. , Kang Rui , Bai Lulu , Tang Daolin
Published: December 2020

Ferroptosis is a more recently recognized form of cell death that relies on iron-mediated oxidative damage. Here, we evaluate the impact of high-iron diets or depletion of Gpx4, an antioxidant enzyme reported as an important ferroptosis suppressor, in the pancreas of mice with cerulean- or L-arginine-induced pancreatitis, and in an oncogenic Kras murine model of spontaneous pancreatic ductal adenocarcinoma (PDAC). We find that either high-iron diets or Gpx4 depletion promotes 8-OHG release and thus activates the TMEM173/STING-dependent DNA sensor pathway, which results in macrophage infiltration and activation during Kras-driven PDAC in mice. Consequently, the administration of liproxstatin-1 (a ferroptosis inhibitor), clophosome-mediated macrophage depletion, or pharmacological and genetic inhibition of the 8-OHG-TMEM173 pathway suppresses Kras-driven pancreatic tumorigenesis in mice. GPX4 is also a prognostic marker in patients with PDAC. These findings provide pathological and mechanistic insights into ferroptotic damage in PDAC tumorigenesis in mice.
D-mannose suppresses macrophage IL-1β production
Authors: Torretta Simone , Scagliola Alessandra , Ricci Luisa , Mainini Francesco , Di Marco Sabrina , Cuccovillo Ivan , Kajaste-Rudnitski Anna , Sumpton David , Ryan Kevin M. , Cardaci Simone
Published: December 2020

D-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.
A partially self-regenerating synthetic cell
Authors: Lavickova Barbora , Laohakunakorn Nadanai , Maerkl Sebastian J.
Published: December 2020

Self-regeneration is a fundamental function of all living systems. Here we demonstrate partial molecular self-regeneration in a synthetic cell. By implementing a minimal transcription-translation system within microfluidic reactors, the system is able to regenerate essential protein components from DNA templates and sustain synthesis activity for over a day. By quantitating genotype-phenotype relationships combined with computational modeling we find that minimizing resource competition and optimizing resource allocation are both critically important for achieving robust system function. With this understanding, we achieve simultaneous regeneration of multiple proteins by determining the required DNA ratios necessary for sustained self-regeneration. This work introduces a conceptual and experimental framework for the development of a self-replicating synthetic cell.
Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis
Authors: Jutzi Daniel , Campagne Sébastien , Schmidt Ralf , Reber Stefan , Mechtersheimer Jonas , Gypas Foivos , Schweingruber Christoph , Colombo Martino , von Schroetter Christine , Loughlin Fionna E. , Devoy Anny , Hedlund Eva , Zavolan Mihaela , Allain Frédéric H.-T. , Ruepp Marc-David
Published: December 2020

Mutations in the RNA-binding protein Fused in Sarcoma (FUS) cause early-onset amyotrophic lateral sclerosis (ALS). However, a detailed understanding of central RNA targets of FUS and their implications for disease remain elusive. Here, we use a unique blend of crosslinking and immunoprecipitation (CLIP) and NMR spectroscopy to identify and characterise physiological and pathological RNA targets of FUS. We find that U1 snRNA is the primary RNA target of FUS via its interaction with stem-loop 3 and provide atomic details of this RNA-mediated mode of interaction with the U1 snRNP. Furthermore, we show that ALS-associated FUS aberrantly contacts U1 snRNA at the Sm site with its zinc finger and traps snRNP biogenesis intermediates in human and murine motor neurons. Altogether, we present molecular insights into a FUS toxic gain-of-function involving direct and aberrant RNA-binding and strengthen the link between two motor neuron diseases, ALS and spinal muscular atrophy (SMA).
Depth-dependent valence stratification driven by oxygen redox in lithium-rich layered oxide
Authors: Zhang Jin , Wang Qinchao , Li Shaofeng , Jiang Zhisen , Tan Sha , Wang Xuelong , Zhang Kai , Yuan Qingxi , Lee Sang-Jun , Titus Charles J. , Irwin Kent D. , Nordlund Dennis , Lee Jun-Sik , Pianetta Piero , Yu Xiqian , Xiao Xianghui , Yang Xiao-Qing , Hu Enyuan , Liu Yijin
Published: December 2020

Lithium-rich nickel-manganese-cobalt (LirNMC) layered material is a promising cathode for lithium-ion batteries thanks to its large energy density enabled by coexisting cation and anion redox activities. It however suffers from a voltage decay upon cycling, urging for an in-depth understanding of the particle-level structure and chemical complexity. In this work, we investigate the Li1.2Ni0.13Mn0.54Co0.13O2 particles morphologically, compositionally, and chemically in three-dimensions. While the composition is generally uniform throughout the particle, the charging induces a strong depth dependency in transition metal valence. Such a valence stratification phenomenon is attributed to the nature of oxygen redox which is very likely mostly associated with Mn. The depth-dependent chemistry could be modulated by the particles’ core-multi-shell morphology, suggesting a structural-chemical interplay. These findings highlight the possibility of introducing a chemical gradient to address the oxygen-loss-induced voltage fade in LirNMC layered materials.
Receptor-targeted engineered probiotics mitigate lethal Listeria infection
Authors: Drolia Rishi , Amalaradjou Mary Anne Roshni , Ryan Valerie , Tenguria Shivendra , Liu Dongqi , Bai Xingjian , Xu Luping , Singh Atul K. , Cox Abigail D. , Bernal-Crespo Victor , Schaber James A. , Applegate Bruce M. , Vemulapalli Ramesh , Bhunia Arun K.
Published: December 2020

Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillusprobiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-κB and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.
A social engineering model for poverty alleviation
Authors: Chattopadhyay Amit K. , Kumar T. Krishna , Rice Iain
Published: December 2020

Poverty, the quintessential denominator of a developing nation, has been traditionally defined against an arbitrary poverty line; individuals (or countries) below this line are deemed poor and those above it, not so! This has two pitfalls. First, absolute reliance on a single poverty line, based on basic food consumption, and not on total consumption distribution, is only a partial poverty index at best. Second, a single expense descriptor is an exogenous quantity that does not evolve from income-expenditure statistics. Using extensive income-expenditure statistics from India, here we show how a self-consistent endogenous poverty line can be derived from an agent-based stochastic model of market exchange, combining all expenditure modes (basic food, other food and non-food), whose parameters are probabilistically estimated using advanced Machine Learning tools. Our mathematical study establishes a consumption based poverty measure that combines labor, commodity, and asset market outcomes, delivering an excellent tool for economic policy formulation.
The erosion of biodiversity and biomass in the Atlantic Forest biodiversity hotspot
Authors: de Lima Renato A. F. , Oliveira Alexandre A. , Pitta Gregory R. , de Gasper André L. , Vibrans Alexander C. , Chave Jérôme , ter Steege Hans , Prado Paulo I.
Published: December 2020

Tropical forests are being deforested worldwide, and the remaining fragments are suffering from biomass and biodiversity erosion. Quantifying this erosion is challenging because ground data on tropical biodiversity and biomass are often sparse. Here, we use an unprecedented dataset of 1819 field surveys covering the entire Atlantic Forest biodiversity hotspot. We show that 83−85% of the surveys presented losses in forest biomass and tree species richness, functional traits, and conservation value. On average, forest fragments have 25−32% less biomass, 23−31% fewer species, and 33, 36, and 42% fewer individuals of late-successional, large-seeded, and endemic species, respectively. Biodiversity and biomass erosion are lower inside strictly protected conservation units, particularly in large ones. We estimate that biomass erosion across the Atlantic Forest remnants is equivalent to the loss of 55−70 thousand km2of forests or US$2.3−2.6 billion in carbon credits. These figures have direct implications on mechanisms of climate change mitigation.
Dietary carbohydrates influence muscle texture of olive flounder Paralichthys olivaceus through impacting mitochondria function and metabolism of glycogen and protein
Authors: Liu Jiahuan , Deng Kangyu , Pan Mingzhu , Liu Guangxia , Wu Jing , Yang Mengxi , Huang Dong , Zhang Wenbing , Mai Kangsen
Published: December 2020

The present study was conducted to estimate the effects of dietary carbohydrates on muscle quality and the underlying mechanisms. Six isonitrogenous and isolipidic diets were formulated to contain graded levels of carbohydrates (0%, 8%, 12%, 16%, 20% and 24%, respectively). These diets were named as C0, C8, C12, C16, C20 and C24, respectively. After a 10-week feeding trial, results showed that the muscle pH, liquid holding capacity (LHC) and hardness were significantly decreased by the increasing dietary carbohydrate levels. Dietary carbohydrates significantly decreased the muscle fibre diameter, and the highest value was found in the C0 group. Accumulated glycogen and degenerated mitochondrial cristae were observed in the C24 group. Significantly higher contents of protein carbonyls were observed in the C20 group and C24 group (P < 0.05). There was a significant decrease of mtDNA copy number in the C24 group compared with that in the C0 and C8 groups. The AMP/ATP ratio in muscle decreased first and then increased with the increasing dietary carbohydrate levels. The dietary incorporation of carbohydrate significantly reduced the expression of opa1, pygm and genes involved in myogenesis (myf5 and myog). Meanwhile, proteolysis-related genes (murf-1, mafbx, capn2 and ctsl), pro-inflammatory cytokines (il-6 and tnf-α) and mstn were significantly up-regulated. In the C24 group, significant increase of phosphorylation of AMPK (Thr172), up-regulation of PGC-1α and GLUT4 were observed, while the phosphorylation level of S6 (Ser235/236) was significantly decreased. It was concluded that excessive dietary carbohydrate level (24%) had negative impacts on mitochondria function and promoted glycogen accumulation, and thereafter influenced the muscle quality of olive flounder. The activation of AMPK as well as the upregulation of PGC-1α and GLUT4 was the key mechanism.
Symmetry prediction and knowledge discovery from X-ray diffraction patterns using an interpretable machine learning approach
Authors: Suzuki Yuta , Hino Hideitsu , Hawai Takafumi , Saito Kotaro , Kotsugi Masato , Ono Kanta
Published: December 2020

Determination of crystal system and space group in the initial stages of crystal structure analysis forms a bottleneck in material science workflow that often requires manual tuning. Herein we propose a machine-learning (ML)-based approach for crystal system and space group classification based on powder X-ray diffraction (XRD) patterns as a proof of concept using simulated patterns. Our tree-ensemble-based ML model works with nearly or over 90% accuracy for crystal system classification, except for triclinic cases, and with 88% accuracy for space group classification with five candidates. We also succeeded in quantifying empirical knowledge vaguely shared among experts, showing the possibility for data-driven discovery of unrecognised characteristics embedded in experimental data by using an interpretable ML approach.
Shorebirds wintering in Southeast Asia demonstrate trans-Himalayan flights
Authors: Li David , Davison Geoffrey , Lisovski Simeon , Battley Phil F. , Ma Zhijun , Yang Shufen , How Choon Beng , Watkins Doug , Round Philip , Yee Alex , Srinivasan Vupasana , Teo Clarice , Teo Robert , Loo Adrian , Leong Chee Chiew , Er Kenneth
Published: December 2020

Many birds wintering in the Indian subcontinent fly across the Himalayas during migration, including Bar-headed Geese (Anser indicus), Demoiselle Cranes (Anthropoides virgo) and Ruddy Shelducks (Tadorna ferruginea). However, little is known about whether shorebirds migrate across the Himalayas from wintering grounds beyond the Indian subcontinent. Using geolocators and satellite tracking devices, we demonstrate for the first time that Common Redshanks (Tringa totanus) and Whimbrels (Numenius phaeopus) wintering in Singapore can directly fly over the Himalayas to reach breeding grounds in the Qinghai-Tibet Plateau and north-central Russia respectively. The results also show that migratory shorebirds wintering in Southeast Asia can use both the Central Asian Flyway and the East Asian-Australasian Flyway. For Redshanks, westerly-breeding birds crossed the Himalayas while more easterly breeders on the Plateau migrated east of the Himalayas. For Whimbrels, an individual that crossed the Himalayas was probably from a breeding population that was different from the others that migrated along the coast up the East Asian-Australasian Flyway. The minimum required altitude of routes of trans-Himalayan Redshanks were no higher on average than those of eastern migrants, but geolocator temperature data indicate that birds departing Singapore flew at high elevations even when not required to by topography, suggesting that the Himalayan mountain range may be less of a barrier than assumed.
Defective membrane repair machinery impairs survival of invasive cancer cells
Authors: Bouvet F. , Ros M. , Bonedeau E. , Croissant C. , Frelin L. , Saltel F. , Moreau V. , Bouter A.
Published: December 2020

Cancer cells are able to reach distant tissues by migration and invasion processes. Enhanced ability to cope with physical stresses leading to cell membrane damages may offer to cancer cells high survival rate during metastasis. Consequently, down-regulation of the membrane repair machinery may lead to metastasis inhibition. We show that migration of MDA-MB-231 cells on collagen I fibrils induces disruptions of plasma membrane and pullout of membrane fragments in the wake of cells. These cells are able to reseal membrane damages thanks to annexins (Anx) that are highly expressed in invasive cancer cells. In vitro membrane repair assays reveal that MDA-MB-231 cells respond heterogeneously to membrane injury and some of them possess a very efficient repair machinery. Finally, we show that silencing of AnxA5 and AnxA6 leads to the death of migrating MDA-MB-231 cells due to major defect of the membrane repair machinery. Disturbance of the membrane repair process may therefore provide a new avenue for inhibiting cancer metastasis.
Segregation distortion: high genetic load suggested by a Chinese shrimp family under high-intensity selection
Authors: Fu Qiang , Meng Xianhong , Luan Sheng , Chen Baolong , Cao Jiawang , Li Xupeng , Kong Jie
Published: December 2020

Segregation distortion is a common phenomenon found in most genetic mapping studies and is an important resource to dissect the mechanism of action in gene loci that cause deviation. Marine animals possess high genetic diversity and genomic heterozygosity, they therefore are ideal model organisms to study segregation distortion induced by selection. In the present study, we constructed a full-sib family of Fenneropenaeus chinensis and exerted high-intensity selection on 10,000 incipient progenies. 2b-RAD method was employed in remaining 273 individuals to develop genome-wide SNPs for segregating analysis and 41,612 SNPs were developed. 50.77% of 32,229 high-quality representative markers deviated from the expected Mendelian ratio. Results showed that most of these distorted markers (91.57%) were influenced at zygotic level. Heterozygote excess (53.07%) and homozygous deletions (41.96%) may both play an important role, sum of which explained 95.03% of distortion after fertilization. However, further results identified highly probable linkage among deleterious alleles, which may account for a considerable portion of heterozygote excess rather than single locus with heterozygote advantage. Results of this study support a major role of deleterious alleles in genetic load, thus in favor of partial dominance hypothesis. It would also offer necessary recommendations for the formulation of breeding strategy in shrimps.
The inhibitory effect of word neighborhood size when reading with central field loss is modulated by word predictability and reading proficiency
Authors: Sauvan Lauren , Stolowy Natacha , Aguilar Carlos , François Thomas , Gala Núria , Matonti Frédéric , Castet Eric , Calabrèse Aurélie
Published: December 2020

For normally sighted readers, word neighborhood size (i.e., the total number of words that can be formed from a single word by changing only one letter) has a facilitator effect on word recognition. When reading with central field loss (CFL) however, individual letters may not be correctly identified, leading to possible misidentifications and a reverse neighborhood size effect. Here we investigate this inhibitory effect of word neighborhood size on reading performance and whether it is modulated by word predictability and reading proficiency. Nineteen patients with binocular CFL from 32 to 89 years old (mean ± SD = 75 ± 15) read short sentences presented with the self-paced reading paradigm. Accuracy and reading time were measured for each target word read, along with its predictability, i.e., its probability of occurrence following the two preceding words in the sentence using a trigram analysis. Linear mixed effects models were then fit to estimate the individual contributions of word neighborhood size, predictability, frequency and length on accuracy and reading time, while taking patients’ reading proficiency into account. For the less proficient readers, who have given up daily reading as a consequence of their visual impairment, we found that the effect of neighborhood size was reversed compared to normally sighted readers and of higher amplitude than the effect of frequency. Furthermore, this inhibitory effect is of greater amplitude (up to 50% decrease in reading speed) when a word is not easily predictable because its chances to occur after the two preceding words in a specific sentence are rather low. Severely impaired patients with CFL often quit reading on a daily basis because this task becomes simply too exhausting. Based on our results, we envision lexical text simplification as a new alternative to promote effective rehabilitation in these patients. By increasing reading accessibility for those who struggle the most, text simplification might be used as an efficient rehabilitation tool and daily reading assistive technology, fostering overall reading ability and fluency through increased practice.
Structural and functional comparison of SARS-CoV-2-spike receptor binding domain produced in Pichia pastoris and mammalian cells
Authors:   Argentinian AntiCovid Consortium, Arbeitman Claudia R. , Auge Gabriela , Blaustein Matías , Bredeston Luis , Corapi Enrique S. , Craig Patricio O. , Cossio Leandro A. , Dain Liliana , D’Alessio Cecilia , Elias Fernanda , Fernández Natalia B. , Gándola Yamila B. , Gasulla Javier , Gorojovsky Natalia , Gudesblat Gustavo E. , Herrera María G. , Ibañez Lorena I. , Idrovo Tommy , Rando Matías Iglesias , Kamenetzky Laura , Nadra Alejandro D. , Noseda Diego G. , Paván Carlos H. , Pavan María F. , Pignataro María F. , Roman Ernesto , Ruberto Lucas A. M. , Rubinstein Natalia , Santos Javier , Velazquez Francisco , Zelada Alicia M.
Published: December 2020

The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cells was properly folded, as indicated by UV-absorption, circular dichroism and tryptophan fluorescence. They also had similar stability, as indicated by temperature-induced unfolding (observed Tm were 50 °C and 52 °C for RBD produced in P. pastoris and HEK-293T cells, respectively). Moreover, the stability of both variants was similarly reduced when the ionic strength was increased, in agreement with a computational analysis predicting that a set of ionic interactions may stabilize RBD structure. Further characterization by high-performance liquid chromatography, size-exclusion chromatography and mass spectrometry revealed a higher heterogeneity of RBD expressed in P. pastoris relative to that produced in HEK-293T cells, which disappeared after enzymatic removal of glycans. The production of RBD in P. pastoris was scaled-up in a bioreactor, with yields above 45 mg/L of 90% pure protein, thus potentially allowing large scale immunizations to produce neutralizing antibodies, as well as the large scale production of serological tests for SARS-CoV-2.
Model-size reduction for reservoir computing by concatenating internal states through time
Authors: Sakemi Yusuke , Morino Kai , Leleu Timothée , Aihara Kazuyuki
Published: December 2020

Reservoir computing (RC) is a machine learning algorithm that can learn complex time series from data very rapidly based on the use of high-dimensional dynamical systems, such as random networks of neurons, called “reservoirs.” To implement RC in edge computing, it is highly important to reduce the amount of computational resources that RC requires. In this study, we propose methods that reduce the size of the reservoir by inputting the past or drifting states of the reservoir to the output layer at the current time step. To elucidate the mechanism of model-size reduction, the proposed methods are analyzed based on information processing capacity proposed by Dambre et al. (Sci Rep 2:514, 2012). In addition, we evaluate the effectiveness of the proposed methods on time-series prediction tasks: the generalized Hénon-map and NARMA. On these tasks, we found that the proposed methods were able to reduce the size of the reservoir up to one tenth without a substantial increase in regression error.
Synthesis, characterization and catalytic testing of MCM-22 derived catalysts for n-hexane cracking
Authors: Ahmad Ali , Naqvi Salman Raza , Rafique Muhammad , Nasir Habib , Sarosh Ali
Published: December 2020

Layered zeolites and their delaminated structures are novel materials that enhance the catalytic performance of catalysts by addressing diffusion limitations of the reactant molecules. n-Hexane catalytic cracking was observed over MCM-22 layered zeolite and its derivative structures over the temperature range of 450–650 °C for the production of olefins. MCM-22, H-MCM-22, and ITQ-2 zeolites were prepared by the hydrothermal method. Oxalic acid was used as a dealuminating reagent to obtain H-MCM-22 with various Si/Al ratios ranging from 09–65. The prepared samples were characterized by XRD, SEM, TGA, and BET. The cracking of n-hexane was carried out by Pyro/GC–MS. It was observed that the selectivity for olefins was improved by increasing the Si/Al ratio. H-MCM-22–10% produced the highest relative olefinic concentration of 68% as compared to other dealuminated structures. Moreover, the product distribution showed that higher reaction temperature is favorable to produce more olefins. Furthermore, a comparison between ITQ-2 and MCM-22 derived structures showed that ITQ-2 is more favorable for olefins production at high temperatures. The concentration of relative olefins was increased up to 80% over ITQ-2 at 650 °C.
Large global variations in measured airborne metal concentrations driven by anthropogenic sources
Authors: McNeill Jacob , Snider Graydon , Weagle Crystal L. , Walsh Brenna , Bissonnette Paul , Stone Emily , Abboud Ihab , Akoshile Clement , Anh Nguyen Xuan , Balasubramanian Rajasekhar , Brook Jeffrey R. , Coburn Craig , Cohen Aaron , Dong Jinlu , Gagnon Graham , Garland Rebecca M. , He Kebin , Holben Brent N. , Kahn Ralph , Kim Jong Sung , Lagrosas Nofel , Lestari Puji , Liu Yang , Jeba Farah , Joy Khaled Shaifullah , Martins J. Vanderlei , Misra Amit , Norford Leslie K. , Quel Eduardo J. , Salam Abdus , Schichtel Bret , Tripathi S. N. , Wang Chien , Zhang Qiang , Brauer Michael , Gibson Mark D. , Rudich Yinon , Martin Randall V.
Published: December 2020

Globally consistent measurements of airborne metal concentrations in fine particulate matter (PM2.5) are important for understanding potential health impacts, prioritizing air pollution mitigation strategies, and enabling global chemical transport model development. PM2.5 filter samples (N ~ 800 from 19 locations) collected from a globally distributed surface particulate matter sampling network (SPARTAN) between January 2013 and April 2019 were analyzed for particulate mass and trace metals content. Metal concentrations exhibited pronounced spatial variation, primarily driven by anthropogenic activities. PM2.5 levels of lead, arsenic, chromium, and zinc were significantly enriched at some locations by factors of 100–3000 compared to crustal concentrations. Levels of metals in PM2.5 and PM10 exceeded health guidelines at multiple sites. For example, Dhaka and Kanpur sites exceeded the US National Ambient Air 3-month Quality Standard for lead (150 ng m−3). Kanpur, Hanoi, Beijing and Dhaka sites had annual mean arsenic concentrations that approached or exceeded the World Health Organization’s risk level for arsenic (6.6 ng m−3). The high concentrations of several potentially harmful metals in densely populated cites worldwide motivates expanded measurements and analyses.
Difference of ecological half-life and transfer coefficient in aquatic invertebrates between high and low radiocesium contaminated streams
Authors: Yoshimura Mayumi , Akama Akio
Published: December 2020

The Fukushima accident emitted radioactive substances into the environment, contaminating litter, algae, sand substrate, aquatic invertebrates, and fish in freshwater streams. Because these substances have substantial effects on stream ecology over many years, it is necessary to clarify the diffusion and decay mechanisms of radiocesium. The transfer coefficient differed among aquatic invertebrate groups, likely due to the differences in habitat. The ecological half-life of cesium was longer where the air dose rate was lower. The transfer coefficient was also higher in areas with lower air dose rate. The radiocesium concentration in algae was inversely related to stream current velocity in the radiocesium-contaminated area. However, this relationship was not observed in the lower air dose rate area: the radiocesium concentration in algae in the rapid-velocity areas tended to be higher than that in the slow-velocity areas. This reverse trend would lead to a longer period of freshwater contamination. The radiocesium concentration would continue to decrease in highly contaminated areas, but it would be difficult to reduce the radiocesium concentration in less-contaminated areas because different contamination mechanisms are at work. Controlling the water flow is key to regulating radiocesium concentration in freshwater ecosystems.
Tree rings reveal signs of Europe’s sustainable forest management long before the first historical evidence
Authors: Muigg Bernhard , Skiadaresis Georgios , Tegel Willy , Herzig Franz , Krusic Paul J. , Schmidt Uwe E. , Büntgen Ulf
Published: December 2020

To satisfy the increasing demand for wood in central Europe during medieval times, a new system of forest management was developed, one far superior to simple coppicing. The adoption of a sophisticated, Coppice-with-Standards (CWS) management practice created a two-storey forest structure that could provide fuelwood as well as construction timber. Here we present a dendrochronological study of actively managed CWS forests in northern Bavaria to detect the radial growth response to cyclical understorey harvesting in overstorey oaks (Quercussp.), so-calledstandards. All modernstandardsexhibit rapid growth releases every circa 30 years, most likely caused by regular understorey management. We further analyse tree-ring width patterns in 2120 oak timbers from historical buildings and archaeological excavations in southern Germany and north-eastern France, dating between 300 and 2015 CE, and succeeded in identifying CWS growth patterns throughout the medieval period. Several potential CWSstandardseven date to the first millennium CE, suggesting CWS management has been in practice long before its first mention in historical documents. Our dendrochronological approach should be expanded routinely to indentify the signature of past forest management practices in archaeological and historical oak wood.