bluuebunny/crossref_metadata_2025_split huggingface dataset:
Termination of Solar Cycles and Correlated Tropospheric Variability
Authors: Leamon Robert J. , McIntosh Scott W. , Marsh Daniel R. 
Published: February 2021

AbstractThe Sun provides the energy required to sustain life on Earth and drive our planet's atmospheric circulation. However, establishing a solid physical connection between solar and tropospheric variability has posed a considerable challenge. The canon of solar variability is derived from the 400 years of observations that demonstrates the waxing and waning number of sunspots over an 11(‐ish) year period. Recent research has demonstrated the significance of the underlying 22 years magnetic polarity cycle in establishing the shorter sunspot cycle. Integral to the manifestation of the latter is the spatiotemporal overlapping and migration of oppositely polarized magnetic bands. We demonstrate the impact of “terminators”—the end of Hale magnetic cycles—on the Sun's radiative output and particulate shielding of our atmosphere through the rapid global reconfiguration of solar magnetism. Using direct observation and proxies of solar activity going back some six decades we can, with high statistical significance, demonstrate a correlation between the occurrence of terminators and the largest swings of Earth's oceanic indices: the transition from El Niño to La Niña states of the central Pacific. This empirical relationship is a potential source of increased predictive skill for the understanding of El Niño climate variations, a high‐stakes societal imperative given that El Niño impacts lives, property, and economic activity around the globe. A forecast of the Sun's global behavior places the next solar cycle termination in mid‐2020; should a major oceanic swing follow, then the challenge becomes: when does correlation become causation and how does the process work?
Hyporheic Exchange in Sand Dunes Under a Freely Deforming River Water Surface
Authors: Lee Anzy , Aubeneau Antoine , Liu Xiaofeng , Cardenas M. Bayani 
Published: February 2021

AbstractBedform‐driven hyporheic exchange is conditioned by the head gradients at the sediment‐water interface. Local exchange phenomena between the surface and the subsurface are often driven by the dynamic forces related to the velocity distributions around sediment waves. In open channels, the static forces are represented by the water depth, yet most computational fluid dynamics models use a rigid‐lid approximation. We investigated whether and when the deformation of the river’s free‐surface influences bedform‐driven hyporheic exchange. This was done through simulations of coupled open channel and hyporheic flows with the air‐water interface modeled either as a free‐surface or a rigid‐lid across increasing subcritical Froude numbers from ∼0.05 to ∼0.95. The normalized hyporheic flux was higher when considering free‐surface deformation across most of the range of Froude numbers considered. When the Froude number was larger than 0.6 and smaller than 0.85, both hydrostatic and nonhydrostatic‐driven fluxes increased significantly compared to the rigid‐lid approach and the total flux was about five times that predicted with the rigid‐lid. These results indicate that bedform‐driven hyporheic fluxes are underestimated in most studies that use a rigid‐lid assumption in subcritical flows.
The application of BH3 mimetics in myeloid leukemias
Authors: Parry Narissa , Wheadon Helen , Copland Mhairi 
Published: February 2021

AbstractExecution of the intrinsic apoptotic pathway is controlled by the BCL-2 proteins at the level of the mitochondrial outer membrane (MOM). This family of proteins consists of prosurvival (e.g., BCL-2, MCL-1) and proapoptotic (e.g., BIM, BAD, HRK) members, the functional balance of which dictates the activation of BAX and BAK. Once activated, BAX/BAK form pores in the MOM, resulting in cytochrome c release from the mitochondrial intermembrane space, leading to apoptosome formation, caspase activation, and cleavage of intracellular targets. This pathway is induced by cellular stress including DNA damage, cytokine and growth factor withdrawal, and chemotherapy/drug treatment. A well-documented defense of leukemia cells is to shift the balance of the BCL-2 family in favor of the prosurvival proteins to protect against such intra- and extracellular stimuli. Small molecule inhibitors targeting the prosurvival proteins, named ‘BH3 mimetics’, have come to the fore in recent years to treat hematological malignancies, both as single agents and in combination with standard-of-care therapies. The most significant example of these is the BCL-2-specific inhibitor venetoclax, given in combination with standard-of-care therapies with great success in AML in clinical trials. As the number and variety of available BH3 mimetics increases, and investigations into applying these novel inhibitors to treat myeloid leukemias continue apace the need to evaluate where we currently stand in this rapidly expanding field is clear.
Targeted de-repression of neuronal Nrf2 inhibits α-synuclein accumulation
Authors: Baxter Paul S. , Márkus Nóra M. , Dando Owen , He Xin , Al-Mubarak Bashayer R. , Qiu Jing , Hardingham Giles E. 
Published: February 2021

AbstractMany neurodegenerative diseases are associated with neuronal misfolded protein accumulation, indicating a need for proteostasis-promoting strategies. Here we show that de-repressing the transcription factor Nrf2, epigenetically shut-off in early neuronal development, can prevent protein aggregate accumulation. Using a paradigm of α-synuclein accumulation and clearance, we find that the classical electrophilic Nrf2 activator tBHQ promotes endogenous Nrf2-dependent α-synuclein clearance in astrocytes, but not cortical neurons, which mount no Nrf2-dependent transcriptional response. Moreover, due to neuronal Nrf2 shut-off and consequent weak antioxidant defences, electrophilic tBHQ actually induces oxidative neurotoxicity, via Nrf2-independent Jun induction. However, we find that epigenetic de-repression of neuronal Nrf2 enables them to respond to Nrf2 activators to drive α-synuclein clearance. Moreover, activation of neuronal Nrf2 expression using gRNA-targeted dCas9-based transcriptional activation complexes is sufficient to trigger Nrf2-dependent α-synuclein clearance. Thus, targeting reversal of the developmental shut-off of Nrf2 in forebrain neurons may alter neurodegenerative disease trajectory by boosting proteostasis.
SARS-CoV-2 nsp12 attenuates type I interferon production by inhibiting IRF3 nuclear translocation
Authors: Wang Wenjing , Zhou Zhuo , Xiao Xia , Tian Zhongqin , Dong Xiaojing , Wang Conghui , Li Li , Ren Lili , Lei Xiaobo , Xiang Zichun , Wang Jianwei 
Published: February 2021

AbstractSARS-CoV-2 is the pathogenic agent of COVID-19, which has evolved into a global pandemic. Compared with some other respiratory RNA viruses, SARS-CoV-2 is a poor inducer of type I interferon (IFN). Here, we report that SARS-CoV-2 nsp12, the viral RNA-dependent RNA polymerase (RdRp), suppresses host antiviral responses. SARS-CoV-2 nsp12 attenuated Sendai virus (SeV)- or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner. It also inhibited IFN promoter activation triggered by RIG-I, MDA5, MAVS, and IRF3 overexpression. Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3. Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12. Given these findings, our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.
Impairment of novelty-related theta oscillations and P3a in never medicated first-episode psychosis patients
Authors: Solís-Vivanco Rodolfo , Mondragón-Maya Alejandra , Reyes-Madrigal Francisco , de la Fuente-Sandoval Camilo 
Published: February 2021

AbstractWe explored the neurophysiological activity underlying auditory novelty detection in antipsychotic-naive patients with a first episode of psychosis (FEP). Fifteen patients with a non-affective FEP and 13 healthy controls underwent an active involuntary attention task along with an EEG acquisition. Time-frequency representations of power, phase locking, and fronto-parietal connectivity were calculated. The P3a event-related potential was extracted as well. Compared to controls, the FEP group showed reduced theta phase-locking and fronto-parietal connectivity evoked by deviant stimuli. Also, the P3a amplitude was significantly reduced. Moreover, reduced theta connectivity was associated with more severe negative symptoms within the FEP group. Reduced activity (phase-locking and connectivity) of novelty-related theta oscillations, along with P3a reduction, may represent a failure to synchronize large-scale neural populations closely related to fronto-parietal attentional networks, and might be explored as a potential biomarker of disease severity in patients with emerging psychosis, given its association with negative symptoms.
A DNA barcode-based survey of wild urban bees in the Loire Valley, France
Authors: Villalta Irene , Ledet Romain , Baude Mathilde , Genoud David , Bouget Christophe , Cornillon Maxime , Moreau Sébastien , Courtial Béatrice , Lopez-Vaamonde Carlos 
Published: February 2021

AbstractThe current decline of wild bees puts important ecosystem services such as pollination at risk. Both inventory and monitoring programs are needed to understand the causes of wild bee decline. Effective insect monitoring relies on both mass-trapping methods coupled with rapid and accurate identifications. Identifying wild bees using only morphology can be challenging, in particular, specimens from mass-trapped samples which are often in poor condition. We generated DNA barcodes for 2931 specimens representing 157 species (156 named and one unnamed species) and 28 genera. Automated cluster delineation reveals 172 BINs (Barcodes Index Numbers). A total of 36 species (22.93%) were found in highly urbanized areas. The majority of specimens, representing 96.17% of the species barcoded form reciprocally exclusive groups, allowing their unambiguous identification. This includes several closely related species notoriously difficult to identify. A total of 137 species (87.26%) show a “one-to-one” match between a named species and the BIN assignment. Fourteen species (8.92%) show deep conspecific lineages with no apparent morphological differentiation. Only two species pairs shared the same BIN making their identification with DNA barcodes alone uncertain. Therefore, our DNA barcoding reference library allows reliable identification by non-experts for the vast majority of wild bee species in the Loire Valley.
Evaluation of indigenous aromatic rice cultivars from sub-Himalayan Terai region of India for nutritional attributes and blast resistance
Authors: Mondal Debayan , Kantamraju Prudveesh , Jha Susmita , Sundarrao Gadge Sushant , Bhowmik Arpan , Chakdar Hillol , Mandal Somnath , Sahana Nandita , Roy Bidhan , Bhattacharya Prateek Madhab , Chowdhury Apurba Kr , Choudhury Ashok 
Published: February 2021

AbstractIndigenous folk rice cultivars often possess remarkable but unrevealed potential in terms of nutritional attributes and biotic stress tolerance. The unique cooking qualities and blissful aroma of many of these landraces make it an attractive low-cost alternative to high priced Basmati rice. Sub-Himalayan Terai region is bestowed with great agrobiodiversity in traditional heirloom rice cultivars. In the present study, ninety-nine folk rice cultivars from these regions were collected, purified and characterized for morphological and yield traits. Based on traditional importance and presence of aroma, thirty-five genotypes were selected and analyzed for genetic diversity using micro-satellite marker system. The genotypes were found to be genetically distinct and of high nutritive value. The resistant starch content, amylose content, glycemic index and antioxidant potential of these genotypes represented wide variability and ‘Kataribhog’, ‘Sadanunia’, ‘Chakhao’ etc. were identified as promising genotypes in terms of different nutritional attributes. These cultivars were screened further for resistance against blast disease in field trials and cultivars like ‘Sadanunia’, ‘T4M-3-5’, ‘Chakhao Sampark’ were found to be highly resistant to the blast disease whereas ‘Kalonunia’, ‘Gobindabhog’, ‘Konkanijoha’ were found to be highly susceptible. Principal Component analysis divided the genotypes in distinct groups for nutritional potential and blast tolerance. The resistant and susceptible genotypes were screened for the presence of the blast resistantpigenes and association analysis was performed with disease tolerance. Finally, a logistic model based on phenotypic traits for prediction of the blast susceptibility of the genotypes is proposed with more than 80% accuracy.
The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
Authors: Ikeda Yayoi , Tagami Ayako , Maekawa Mamiko , Nagai Akiko 
Published: February 2021

AbstractSteroidogenic factor 1 (NR5A1) is essential for gonadal development. To study the importance of NR5A1 during early gonadal sex differentiation, we generated Sox9-Cre-Nr5a1 conditional knockout (cKO) mice: Sox9-Cre;Nr5a1flox/flox and Sox9-Cre;Nr5a1flox/− mice. Double-immunostaining for NR5A1 and AMH revealed silenced NR5A1 in Sertoli cells and reduced AMH+ cells in the gonads of XY Sox9-Cre-Nr5a1 cKO mice between embryonic days 12.5 (E12.5) and E14.5. Double-immunostaining for SOX9 and FOXL2 further indicated an early block in Sertoli cells and ectopic granulosa cell differentiation. The number of cells expressing the Leydig cell marker 3βHSD obviously reduced in the gonads of XY Sox9-Cre;Nr5a1flox/− but not Sox9-Cre;Nr5a1flox/flox mice at E15.5. The presence of STRA8+ cells indicated that germ cells entered meiosis in the gonads of XY Sox9-Cre-Nr5a1 cKO mice. The results of qRT-PCR revealed remarkably reduced and elevated levels of testis and ovary markers, respectively, in the gonads of XY Sox9-Cre-Nr5a1 cKO mice at E12.5‒E13.5. These data suggested that the loss of Nr5a1 abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial/complete male-to-female gonadal sex reversal. Our findings provide evidence for the critical role of NR5A1 in murine gonadal sex determination in vivo.
Gharial nesting in a reservoir is limited by reduced river flow and by increased bank vegetation
Authors: Vashistha Gaurav , Mungi Ninad Avinash , Lang Jeffrey W. , Ranjan Vivek , Dhakate Parag Madhukar , Khudsar Faiyaz Ahmad , Kothamasi David 
Published: February 2021

AbstractThe gharial (Gavialis gangeticusGmelin) is a fish-eating specialist crocodylian, endemic to south Asia, and critically endangered in its few remaining wild localities. A secondary gharial population resides in riverine-reservoir habitat adjacent to the Nepal border, within the Katerniaghat Wildlife Sanctuary (KWS), and nests along a 10 km riverbank of the Girwa River. A natural channel shift in the mainstream Karnali River (upstream in Nepal) has reduced seasonal flow in the Girwa stretch where gharials nest, coincident with a gradual loss of nest sites, which in turn was related to an overall shift to woody vegetation at these sites. To understand how these changes in riparian vegetation on riverbanks were related to gharial nesting, we sampled vegetation at these sites from 2017 to 2019, and derived an Enhanced Vegetation Index (EVI) from LANDSAT 8 satellite data to quantify riverside vegetation from 1988 through 2019. We found that sampled sites transitioned to woody cover, the number of nesting sites declined, and the number of nests were reduced by > 40%. At these sites, after the channel shift, woody vegetation replaced open sites that predominated prior to the channel shift. Our findings indicate that the lack of open riverbanks and the increase in woody vegetation at potential nesting sites threatens the reproductive success of the KWS gharial population. This population persists today in a regulated river ecosystem, and nests in an altered riparian habitat which appears to be increasingly unsuitable for the continued successful recruitment of breeding adults. This second-ranking, critically endangered remnant population may have incurred an "extinction debt" by living in a reservoir that will lead to its eventual extirpation.
Tuning flavin environment to detect and control light-induced conformational switching in Drosophila cryptochrome
Authors: Chandrasekaran Siddarth , Schneps Connor M. , Dunleavy Robert , Lin Changfan , DeOliveira Cristina C. , Ganguly Abir , Crane Brian R. 
Published: February 2021

AbstractLight-induction of an anionic semiquinone (SQ) flavin radical in Drosophila cryptochrome (dCRY) alters the dCRY conformation to promote binding and degradation of the circadian clock protein Timeless (TIM). Specific peptide ligation with sortase A attaches a nitroxide spin-probe to the dCRY C-terminal tail (CTT) while avoiding deleterious side reactions. Pulse dipolar electron-spin resonance spectroscopy from the CTT nitroxide to the SQ shows that flavin photoreduction shifts the CTT ~1 nm and increases its motion, without causing full displacement from the protein. dCRY engineered to form the neutral SQ serves as a dark-state proxy to reveal that the CTT remains docked when the flavin ring is reduced but uncharged. Substitutions of flavin-proximal His378 promote CTT undocking in the dark or diminish undocking in the light, consistent with molecular dynamics simulations and TIM degradation activity. The His378 variants inform on recognition motifs for dCRY cellular turnover and strategies for developing optogenetic tools.
A versatile microfluidic platform measures hyphal interactions between Fusarium graminearum and Clonostachys rosea in real-time
Authors: Gimeno Alejandro , Stanley Claire E. , Ngamenie Zacharie , Hsung Ming-Hui , Walder Florian , Schmieder Stefanie S. , Bindschedler Saskia , Junier Pilar , Keller Beat , Vogelgsang Susanne 
Published: February 2021

AbstractRoutinely, fungal–fungal interactions (FFI) are studied on agar surfaces. However, this format restricts high-resolution dynamic imaging. To gain experimental access to FFI at the hyphal level in real-time, we developed a microfluidic platform, a FFI device. This device utilises microchannel geometry to enhance the visibility of hyphal growth and provides control channels to allow comparisons between localised and systemic effects. We demonstrate its function by investigating the FFI between the biological control agent (BCA) Clonostachys rosea and the plant pathogen Fusarium graminearum. Microscope image analyses confirm the inhibitory effect of the necrotrophic BCA and we show that a loss of fluorescence in parasitised hyphae of GFP-tagged F. graminearum coincides with the detection of GFP in mycelium of C. rosea. The versatility of our device to operate under both water-saturated and nutrient-rich as well as dry and nutrient-deficient conditions, coupled with its spatio-temporal output, opens new opportunities to study relationships between fungi.
Dexamethasone and lactoferrin induced PMN-MDSCs relieved inflammatory adverse events of anti-cancer therapy without tumor promotion
Authors: Li Xing , Chen Jie , Chen Yong-Jian , Qiao Yi-Dan , Zhao Li-Yun , Jiang Nan , Wu Xiang-Yuan , Xing Yan-Fang 
Published: February 2021

AbstractIn this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies.
Sociality sculpts similar patterns of molecular evolution in two independently evolved lineages of eusocial bees
Authors: Shell Wyatt A. , Steffen Michael A. , Pare Hannah K. , Seetharam Arun S. , Severin Andrew J. , Toth Amy L. , Rehan Sandra M. 
Published: February 2021

AbstractWhile it is well known that the genome can affect social behavior, recent models posit that social lifestyles can, in turn, influence genome evolution. Here, we perform the most phylogenetically comprehensive comparative analysis of 16 bee genomes to date: incorporating two published and four new carpenter bee genomes (Apidae: Xylocopinae) for a first-ever genomic comparison with a monophyletic clade containing solitary through advanced eusocial taxa. We find that eusocial lineages have undergone more gene family expansions, feature more signatures of positive selection, and have higher counts of taxonomically restricted genes than solitary and weakly social lineages. Transcriptomic data reveal that caste-affiliated genes are deeply-conserved; gene regulatory and functional elements are more closely tied to social phenotype than phylogenetic lineage; and regulatory complexity increases steadily with social complexity. Overall, our study provides robust empirical evidence that social evolution can act as a major and surprisingly consistent driver of macroevolutionary genomic change.
Bundle sheath suberisation is required for C4 photosynthesis in a Setaria viridis mutant
Authors: Danila Florence R. , Thakur Vivek , Chatterjee Jolly , Bala Soumi , Coe Robert A. , Acebron Kelvin , Furbank Robert T. , von Caemmerer Susanne , Quick William Paul 
Published: February 2021

AbstractC4 photosynthesis provides an effective solution for overcoming the catalytic inefficiency of Rubisco. The pathway is characterised by a biochemical CO2 concentrating mechanism that operates across mesophyll and bundle sheath (BS) cells and relies on a gas tight BS compartment. A screen of a mutant population of Setaria viridis, an NADP-malic enzyme type C4 monocot, generated using N-nitroso-N-methylurea identified a mutant with an amino acid change in the gene coding region of the ABCG transporter, a step in the suberin synthesis pathway. Here, Nile red staining, TEM, and GC/MS confirmed the alteration in suberin deposition in the BS cell wall of the mutant. We show that this has disrupted the suberin lamellae of BS cell wall and increased BS conductance to CO2 diffusion more than two-fold in the mutant. Consequently, BS CO2 partial pressure is reduced and CO2 assimilation was impaired in the mutant. Our findings provide experimental evidence that a functional suberin lamellae is an essential anatomical feature for efficient C4 photosynthesis in NADP-ME plants like S. viridis and have implications for engineering strategies to ensure future food security.