bluuebunny/crossref_metadata_2025_split huggingface dataset:
Buried but unsafe – defoliation depletes the underground storage organ (USO) of the mesic grassland geophyte,Hypoxis hemerocallidea
Authors: Morris Craig D. 
Published: March 2021

AbstractMesic grasslands in South Africa (> 650 mm a-1MAP) are rich in herbaceous forbs, which outnumber grass species by more than 5 to 1. Many of these forbs have underground storage units (USOs), such as thickened rootstocks, rhizomes, bulbs, or corms, that provide resources (non-structural carbohydrates, minerals, and water) enabling them to resprout after dry, frosty winters, and fire. However, despite their extensive biomass and reserves ostensibly protected underground, geophytic mesic grassland forbs can be severely depleted or extirpated by chronic trampling and grazing of their aerial parts by livestock. This study examined a possible explanation for forb demise in overgrazed grassland by investigating, in a pot trial, whether the growth of forbs and the size of their USOs are negatively affected by simulated green leaf loss. In a 2×2 factorial (clipped vs. unclipped x spring regrowth in the dark vs. light), five replicate plants ofHypoxis hemerocallidea, a common mesic grassland forb that resprouts from a corm, were subject to six severe (clipped to 80 mm) defoliations during the growing season and regrown in spring under full or restricted light to measure stored reserve contribution to regrowth. Defoliated plants were resilient to defoliation during the growing season, matching the total biomass production of unclipped plants, though cutting reduced the number of leaves by ¬60% and flowers by almost 85%. Spring regrowth on stored reserves equalled that from reserves plus concurrent photosynthesis, indicating the value of USOs for regrowth. However, there was a marked carry-over effect of previous season defoliation, resulting in a one-third reduction in shoot growth and 40% fewer inflorescence in spring. Crucially, corm mass was more than halved by clipping. Above-ground spring growth was linearly related to corm mass. It was concluded that buried stored reserves are not protected by recurrent disturbance to aerial plant parts and that continued diminishment of USOs under chronic disturbance by overgrazing or frequent mowing would weaken and likely eventually kill plants, reducing forb species richness. Lenient management by infrequent summer mowing or grazing at moderate stocking rates combined with periodic rotational full season resting and dormant-season burning is recommend to maintain the USOs and vigour of forbs in mesic grassland.
An fMRI-based brain marker predicts individual differences in delay discounting
Authors: Koban Leonie , Lee Sangil , Schelski Daniela S. , Simon Marie-Christine , Lerman Caryn , Weber Bernd , Kable Joseph W. , Plassmann Hilke 
Published: March 2021

ABSTRACTIndividual differences in impatience—how much we discount future compared to immediate rewards—are associated with general life outcomes and related to substance use, psychiatric diseases, and obesity. Here, we use machine-learning on fMRI activity during an intertemporal choice task to develop a brain marker of individual differences in delay discounting. Study 1 (N=110) was used as a training and cross-validation set, resulting in significant prediction accuracy (r= 0.49) and suggesting an interplay between brain regions associated with affect, value, and cognitive control. The validity of the brain marker was replicated in an independent data set (Study 2, N=145,r= 0.45). In both studies, responses of the marker significantly differed between overweight and lean individuals. This pattern is a first step towards a generalizable neuromarker of delay discounting and a potentially transdiagnostic phenotype, which can be used as a brain-based target measure in future studies.
Type II alveolar cells with constitutive expression of MHCII and limited antigen presentation capacity contribute to improved respiratory viral disease outcomes
Authors: Toulmin Sushila A. , Bhadiadra Chaitali , Paris Andrew J. , Lin Jeffrey H. , Katzen Jeremy , Basil Maria C. , Morrisey Edward E. , Worthen G. Scott , Eisenlohr Laurence C. 
Published: March 2021

AbstractType II alveolar cells (AT2s) are critical for basic respiratory homeostasis and tissue repair after lung injury. Prior studies indicate that AT2s also express major histocompatibility complex II (MHCII) molecules, but how MHCII expression by AT2s is regulated and how it contributes to host defense remain unclear. Here we show that AT2s express high levels of MHCII independent of conventional inflammatory stimuli, and that selective loss of MHCII from AT2s in mice results in the worsening of respiratory virus disease following influenza and Sendai virus infections. We also find that AT2s exhibit MHCII presentation capacity that is substantially limited in comparison to professional antigen presenting cells. The combination of constitutive MHCII expression and restrained presentation may position AT2s to contribute to lung adaptive immune responses in a measured fashion, without over-amplifying damaging inflammation.
Agricultural pressures impair trophic link between aquatic microorganisms and invertebrates
Authors: Blom Rody , Barmentlo S. Henrik , Schrama Maarten J.J. , Hunting Ellard R. 
Published: March 2021

AbstractDecadal declines in aquatic ecosystem health prompted monitoring efforts and studies on effects of human practices on aquatic biodiversity, yet a consideration of ecological processes and trophic linkages is increasingly required to develop an in-depth understanding of aquatic food webs and its vulnerability to human activities. Here, we test in laboratory incubations using natural organic matter whether agricultural practices have an effect on two interacting ecological processes (i.e., decomposition and invertebrate growth) as the relevant temporal components of the trophic linkage between aquatic microbial communities and aquatic invertebrates. We further assess whether these altered trophic interactions are visible on ecologically relevant scales. We observed clear patterns in agricultural constraints on microbial decomposition, which coincided with reduced invertebrate growth and an unexpected increase in invertebrate consumption of organic matter. Similar differences in invertebrate length depending on land use were observed in our field survey, thereby providing important clues on the relevance and vulnerability of interdependent processes that can serve to improve future forays in monitoring ecosystem health.
Behavioral context shapes vocal sequences in two anuran species with different repertoire sizes
Authors: Bhat Ananda Shikhara , Sane Varun Aniruddha , S Seshadri K , Krishnan Anand 
Published: March 2021

AbstractAcoustic signals in animals serve to convey context-dependent information to receivers. Birds and mammals combine diverse sounds into complex sequences to communicate, but these sequences largely remain understudied in other taxa. Anuran vocalizations are a prominent feature of their life history, and function in defense of territories and to attract mates. However, despite the spectacular diversity of anurans in tropical regions of the world, vocal diversity and communication strategies remain relatively poorly studied. Specifically, studies of vocal sequences and context-dependent vocal patterns in frogs remain few. Here, we investigated the context-dependent vocal repertoire and the use of vocal sequences by two anuran species belonging to different lineages, both endemic to the hyper-diverse Western Ghats of India. By recording vocal sequences both when frogs were alone and in the presence of a territorial rival, we present evidence that both species modify their vocal repertoire according to context. Specifically, one species appends notes to generate more complex sequences, whereas the other shifts to different note types, resulting in different sequences for different contexts. Thus, despite differences in repertoire size, both frog species are capable of adjusting the temporal sequence of vocalizations to communicate in different contexts. This study highlights the need for further studies of insular frogs, to understand how diversification across these continental islands has influenced the evolution of vocal repertoires, vocal sequence patterns and communication systems.Lay SummaryAnimals employ complex sequences of acoustic signals to communicate in diverse behavioral contexts. Here, we demonstrate that two frog species with different vocal repertoires both modify the sequence of note emissions in the presence of a territorial rival. These patterns demonstrate that anurans are capable of complex shifts in the patterns of their vocalization, to communicate different messages to different receivers. Our findings demonstrate the value of studying behavioral diversity in tropical regions.
Transcriptomic analysis reveals that severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammationin vivoand more rapid induction of pro-inflammatory responses in primary bursal cells stimulatedex vivo
Authors: Asfor Amin S. , Nazki Salik , Reddy Vishwanatha RAP , Campbell Elle , Dulwich Katherine L. , Giotis Efstathios S. , Skinner Michael A. , Broadbent Andrew J. 
Published: March 2021

AbstractIn order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p<0.01) and, when stimulatedex vivowith LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.
Momelotinib is a highly potent inhibitor of FLT3-mutant AML
Authors: Azhar Mohammad , Kincaid Zachary , Kesarwani Meenu , Latif Tahir , Starczynowski Daniel , Azam Mohammad 
Published: March 2021

AbstractKinase activating mutation in FLT3 is the most frequent genetic lesion associated with poor prognosis in acute myeloid leukemia (AML). Therapeutic response to FLT3 tyrosine kinase inhibitor (TKI) therapy is dismal, and many patients relapse even after allogenic stem cell transplantation. Despite the introduction of more selective FLT3 inhibitors, remissions are short-lived, and patients show progressive disease after an initial response. Acquisition of resistance-conferring genetic mutations and growth factor signaling are two principal mechanisms that drive relapse. FLT3 inhibitors targeting both escape mechanisms could lead to a more profound and lasting clinical responses. Here we show that the JAK2 inhibitor, momelotinib, is an equipotent type-1 FLT3 inhibitor. Momelotinib showed potent inhibitory activity on both mouse and human cells expressing FLT3-ITD, including clinically relevant resistant mutations within the activation loop at residues, D835, D839, and Y842. Additionally, momelotinib efficiently suppressed the resistance mediated by FLT3 ligand (FL) and hematopoietic cytokine activated JAK2 signaling. Interestingly, unlike gilteritinib, momelotinib inhibits the expression of MYC in leukemic cells. Consequently, concomitant inhibition of FLT3 and downregulation of MYC by momelotinib treatment showed better efficacy in suppressing the leukemia in a preclinical murine model of AML. Altogether, these data provide evidence that momelotinib is an effective type-1 dual JAK2/FLT3 inhibitor and may offer an alternative to gilteritinib. Its ability to impede the resistance conferred by growth factor signaling and activation loop mutants suggests that momelotinib treatment could provide a deeper and durable response; thus, warrants its clinical evaluation.Key pointsMomelotinib shows high efficacy against FLT3 mutated AML cells including quizartinib-resistant activation loop variants.Momelotinib effectively suppresses intrinsic resistance conferred by FLT3 ligand and hematopoietic cytokines (GM-CSF and IL3).
A Circuit for Secretion-coupled Cellular Autonomy in Multicellular Eukaryotes
Authors: Qiao Lingxia , Sinha Saptarshi , El-Hafeez Amer Ali Abd , Lo I-Chung , Midde Krishna K. , Ngo Tony , Aznar Nicolas , Lopez-Sanchez Inmaculada , Gupta Vijay , Farquhar Marilyn G. , Rangamani Padmini , Ghosh Pradipta 
Published: March 2021

ABSTRACTCancers represent complex autonomous systems, displaying self-sufficiency in growth signaling. Autonomous growth is fueled by a cancer cell’s ability to ‘secrete-and-sense’ growth factors: a poorly understood phenomenon. Using an integrated systems and experimental approach, here we dissect the impact of a feedback-coupled GTPase circuit within the secretory pathway that imparts secretion-coupled autonomy. The circuit is assembled when the Ras-superfamily monomeric GTPase Arf1, and the heterotrimeric GTPase Giαβγ and their corresponding GAPs and GEFs are coupled by GIV/Girdin, a protein that is known to fuel aggressive traits in diverse cancers. One forward and two key negative feedback loops within the circuit create closed-loop control (CLC), allow the two GTPases to coregulate each other, and convert the expected switch-like behavior of Arf1-dependent secretion into an unexpected dose response alignment behavior of sensing and secretion. Such behavior translates into cell survival that is self-sustained by stimulus-proportionate secretion. Proteomic studies and protein-protein interaction network analyses pinpoint growth factors (e.g., the epidermal growth factor; EGF) as a key stimuli for such self-sustenance. Findings highlight how enhanced coupling of two biological switches in cancer cells is critical for multiscale feedback control to achieve secretion-coupled autonomy of growth factors.SYNOPSIS IMAGESTANDFIRST TEXTThis work defines the inner workings of a Golgi-localized molecular circuitry comprised of coupled GTPases, which empowers cells to achieve self-sufficiency in growth factor signaling by creating a secrete-and-sense autocrine loop.HIGHLIGHTS/MAIN FINDINGSModeling and experimental approaches were used to dissect a coupled GTPase circuit.Coupling enables closed loop feedback and mutual control of GTPases.Coupling generates dose response alignment behavior of sensing and secretion of growth factors.Coupling is critical for multiscale feedback control to achieve secretion-coupled autonomy.
Reverse Transcriptase Real-Time PCR Assay for the Rapid Enumeration of LiveCandida aurisfrom the Healthcare Environment
Authors: Freitas Bryanna Lexus , Leach Lynn , Chaturvedi Vishnu , Chaturvedi Sudha 
Published: March 2021

ABSTRACTOngoing healthcare-associated outbreaks of multidrug-resistant yeastCandida aurishave prompted development of several rapid DNA-based molecular diagnostic tests. These tests do not distinguish between live and deadC. auriscells, limiting their use for environmental surveillance and containment efforts. We addressed this critical gap by developing a reverse transcriptase (RT) real-time PCR assay for rapid detection of liveC. aurisin healthcare environments. The assay targets the internal transcribed spacer 2 (ITS2) cDNA ofC. auris, amplified by obtaining pure RNA followed by reverse transcription and real-time PCR assay. The assay was highly sensitive, with the detection limit of ten colony-forming units (CFU) per RT real-time PCR reaction. InC. aurisviability studies, ITS2 cDNA was detectable in heat- and ethanol-killedC. auriscells, but not bleach-killed cells. Validation studies showed no cycle threshold (Ct) values were obtained from samples on a sponge matrix spiked with either deadC. auris(105/ml) or otherCandidaspecies (105/ml), while most environmental samples spiked with 102to 105CFU of liveC. aurisyielded positive Ct values. Finally, 33 environmental samples positive forC. aurisDNA but negative by culture were all negative by RT real-time PCR assay, confirming concordance between culture and the assay. The RT real-time PCR assay appears highly reproducible, robust, and specific for detecting liveC. aurisfrom environmental samples, and could be an invaluable tool in surveillance efforts to control the spread of liveC. aurisin healthcare environments.
Does the Zebra Finch Mating Song Circuit Use Spike Times Efficiently?
Authors: Nicola Wilten , Newton Thomas Robert , Clopath Claudia 
Published: March 2021

AbstractPrecise and reliable spike times are thought to subserve multiple possible functions, including improving the accuracy of encoding stimuli or behaviours relative to other coding schemes. Indeed, repeating sequences of spikes with sub-millisecond precision exist in nature, such as the synfire chain of spikes in area HVC of the zebra-finch mating-song circuit. Here, we analyzed what impact precise and reliable spikes have on the encoding accuracy for both the zebra-finch and more generic neural circuits using computational modelling. Our results show that neural circuits can use precisely timed spikes to encode signals with a higher-order accuracy than a conventional rate code. Circuits with precisely timed and reliably emitted spikes increase their encoding accuracy linearly with network size, which is the hallmark signature of an efficient code. This qualitatively differs from circuits that employ a rate code which increase their encoding accuracy with the square-root of network size. However, this improved scaling is dependent on the spikes becoming more accurate and more reliable with larger networks. Finally, we discuss how to test this scaling relationship in the zebra mating song circuit using both neural data and song-spectrogram-based recordings while taking advantage of the natural fluctuation in HVC network size due to neurogenesis. The zebra-finch mating-song circuit may represent the most likely candidate system for the use of spike-timing-based, efficient coding strategies in nature.
Limited effects of m6A modification on mRNA partitioning into stress granules
Authors: Khong Anthony , Matheny Tyler , Huynh Thao Ngoc , Babl Vincent , Parker Roy 
Published: March 2021

ABSTRACTRecent studies have argued that the m6A modification of mRNAs promotes mRNA recruitment to stress granules through the interaction with YTHDF proteins (Anders et al., 2018; Ries et al., 2019). However, mRNAs that contain multiple m6A modified sites partition similarly into stress granules in both wild-type and m6A-deficient cells by single-molecule FISH suggesting m6A modifications play a minor role in mRNA partitioning into stress granules. Moreover, multiple linear regression analysis suggests m6A modification plays a minimal role in stress granule recruitment. Finally, the artificial tethering of 25 YTHDF proteins on reporter mRNAs leads to only a modest increase in mRNA partitioning to stress granules. These results indicate m6A modification makes a small, but measurable, contribution to recruiting specific mRNAs to stress granules.
Fibrinogen and Complement Factor H are promising CSF protein biomarker(s) for Parkinson’s disease with cognitive impairment- A Proteomics and ELISA based study
Authors: Naskar Aditi , Stezin Albert , Dharmappa Arpitha , Hegde Shantala , Philip Mariamma , Kamble Nitish , Saini Jitender , Sandhya K , Tatu Utpal , Yadav Ravi , Pal Pramod Kumar , Alladi Phalguni Anand 
Published: March 2021

AbstractCognitive impairment is a debilitating non-motor symptom of Parkinson’s disease (PD). The diagnosis of PD with cognitive impairment (PDCI) is essentially through clinical and neuropsychological examinations. There is an emerging need to identify biomarker(s) to foresee cognitive decline in PD patients, at an early stage. We performed label-free unbiased nontargeted proteomics (Q-TOF LC/MS-MS) in CSF of non-neurological control (NNC); PDCI; PD and normal pressure hydrocephalus (NPH), followed by targeted ELISA for validation. The diagnosis was confirmed by neuropsychological and MRI assessments prior to CSF collection. Of the 282 proteins identified by mass spectrometry, 42 were differentially altered in PD, PDCI and NPH. Further, 28 proteins were altered in PDCI and 25 in NPH. An interesting overlap of certain proteins was noted both in PDCI and NPH. Five significantly upregulated proteins in PDCI were fibrinogen, gelsolin, complement factor-H, apolipoprotein A-IV and apolipoprotein A-I. Whereas carnosine dipeptidase 1, carboxypeptidase E, dickkpof 3 and secretogranin 3 precursor proteins were down-regulated. NPH also had few uniquely altered proteins viz. insulin-like growth factor-binding protein, ceruloplasmin, α-1 antitrypsin, VGF nerve growth factor, neural cell adhesion molecule L1 like protein. Interestingly, the ELISA-derived protein concentrations correlated well with the neuropsychological scores of certain cognitive domains. Executive function was affected both in PDCI and NPH. In PD, Wisconsin card sorting test (WCST) percentile correlated positively with ApoA-IV and negatively with the ratio of ApoAI: ApoA-IV. Thus assessment of a battery of proteins like fibrinogen-α-chain, CFAH and ApoAI: ApoA-IV ratio alongside neuropsychological could be reliable biomarkers to distinguish PDCI and NPH.
Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization
Authors: Sha Zhiqiang , Schijven Dick , Francks Clyde 
Published: March 2021

AbstractAutism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing versus empathizing cognitive styles, with resemblances to male versus female average sex differences. Left-right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes, and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores (PRS) for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness and subcortical volume measures in 32,256 participants from the UK Biobank. PRS for the two disorders were positively correlated (r=0.08, p=7.13×10−50), and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each PRS was associated with multivariate brain asymmetry after adjusting for sex, ASD PRS r=0.03, p=2.17×10−9, schizophrenia PRS r=0.04, p=2.61×10−11, but the multivariate patterns were mostly distinct for the two PRS, and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both PRS were associated with asymmetries of regions important for language and executive functions, consistent with behavioural associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risk for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.