Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrating remote sensing and jurisdictional observation networks to improve the resolution of ecological management

The emergence of citizen science, passive sensors (e.g., trail cameras and acoustic monitoring), and satellite remote sensing have enabled biological data to be collected at unprecedented spatial and temporal scales. There is growing interest in networking these datastreams to expedite the collection and synthesis of environmental and biological data to improve broad-scale ecological monitoring, but there are no examples of such networks being developed to directly inform decision-making by managing agencies. Here, we present the implementation of one such jurisdictional observation network (JON), Snapshot Wisconsin (SW), that links satellite remote sensing (RS) with a volunteer-based trail camera network to generate new insights into wildlife distributions and improve their management by the state agency. SW relies on citizen scientists to deploy trail cameras across the state and classify images of wildlife. As of early 2020 SW comprises nearly 1800 volunteers hosting >2100 active cameras recording >37 million images across a sampling effort of >2000 combined trap-years at >3300 distinct camera locations. We use a set of case studies to demonstrate the potential power of a JON to monitor wildlife with unprecedented combinations of spatial, temporal, and biological resolution and extent. Specifically, we demonstrate that SW markedly improves the spatial and temporal resolution with which black bear distributions can be monitored or forecast, in turn improving the resolution of decision-making. Enhancing the biological resolution of monitoring (e.g., monitoring the distribution of species traits or behaviors) may provide new insights into population drivers, such as the connection between vegetation productivity and white-tailed deer foraging behaviors. Enhanced taxonomic extent provided by trail cameras and other passive sensor networks provide managers new information for a wide range of species and communities that are not otherwise monitored. Our cases further show that JONs synergize existing monitoring practices by serving as a complementary and independent line of evidence or as a tool to enhance the extent and precision of existing models through integrated modeling approaches. SW and other JONS are a powerful new tool for agencies to better achieve their missions and reshape the nature of environmental decision-making.
Myosin-X and talin modulate integrin activity at filopodia tips

Filopodia assemble unique integrin-adhesion complexes to sense the extracellular matrix. However, the mechanisms of integrin localization and regulation in filopodia are poorly defined. Here, we observed that active integrins accumulate at the tip of myosin-X(MYO10)-positive filopodia while inactive integrins are uniformly distributed. RNAi depletion of 10 integrin activity modulators identified talin as the principal integrin activator in filopodia. Deletion of the MYO10-FERM domain, or mutation of the β1-integrin-binding residues within, revealed MYO10 as facilitating integrin activation but not transport in filopodia. However, MYO10-FERM alone could not activate integrins, potentially due to dual binding to both a- and β-integrin tails. As swapping MYO10-FERM with talin-FERM enabled integrin activation in filopodia, our data indicate that an integrin-binding FERM domain coupled to a myosin motor is a core requirement for integrin activation in filopodia. Therefore, we propose a two-step integrin activation model in filopodia: receptor tethering by MYO10 followed by talin-mediated integrin activation.
SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species

There are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.
Transcription Terminator-Mediated Enhancement in Transgene Expression in Maize: Preponderance of the AUGAAU Motif Overlapping With Poly(A) Signals

The selection of transcription terminators (TTs) for pairing with high expressing constitutive promoters in chimeric constructs is crucial to deliver optimal transgene expression in plants. In this study, the use of the native combinations of four polyubiquitin gene promoters and corresponding TTs resulted in up to >3-fold increase in transgene expression in maize. Of the eight polyubiquitin promoter and TT regulatory elements utilized, seven were novel and identified from the polyubiquitin genes of Brachypodium distachyon, Setaria italica, and Zea mays. Furthermore, gene expression driven by the Cassava mosaic virus promoter was studied by pairing the promoter with distinct TTs derived from the high expressing genes of Arabidopsis. Of the three TTs studied, the polyubiquitin10 gene TT produced the highest transgene expression in maize. Polyadenylation patterns and mRNA abundance from eight distinct TTs were analyzed using 3’-RACE and next-generation sequencing. The results exhibited one to three unique polyadenylation sites in the TTs. The poly(A) site patterns for the StPinII TT were consistent when the same TT was deployed in chimeric constructs irrespective of the reporter gene and promoter used. Distal to the poly(A) sites, putative polyadenylation signals were identified in the near-upstream regions of the TTs based on previously reported mutagenesis and bioinformatics studies in rice and Arabidopsis. The putative polyadenylation signals were 9 to 11 nucleotides in length. Six of the eight TTs contained the putative polyadenylation signals that were overlaps of either canonical AAUAAA or AAUAAA-like polyadenylation signals and AUGAAU, a top-ranking-hexamer of rice and Arabidopsis gene near-upstream regions. Three of the polyubiquitin gene TTs contained the identical 9-nucleotide overlap, AUGAAUAAG, underscoring the functional significance of such overlaps in mRNA 3’ end processing. In addition to identifying new combinations of regulatory elements for high constitutive trait gene expression in maize, this study demonstrated the importance of TTs for optimizing gene expression in plants. Learning from this study could be applied to other dicotyledonous and monocotyledonous plant species for transgene expression.
Single Cell-type Integrative Network Modeling Identified Novel Microglial-specific Targets for the Phagosome in Alzheimer’s disease

Late-Onset Alzheimer’s Disease (LOAD) results from a complex pathological process influenced by genetic variation, aging and environment factors. Genetic susceptibility factors indicate that myeloid cells such as microglia play a significant role in the onset of LOAD. Here, we developed a computational systems biology approach to construct probabilistic causal and predictive network models of genetic regulatory programs of microglial cells under LOAD diagnosis by integrating two independent brain transcriptome and genome-wide genotype datasets from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) and Mayo Clinic (MAYO) studies in the AMP-AD consortium. From this network model, we identified and replicated novel microglial-specific master regulators predicted to modulate network states associated with LOAD. We experimentally validated three microglial master regulators (FCER1G, HCK and LAPTM5) in primary human microglia-like cells (MDMi) by demonstrating the molecular impact these master regulators have on modulating downstream genomic targets identified by our top-down/bottom-up method and the causal relations among the three key drivers. These master regulators are involved in phagocytosis, a process associated with LOAD. Thus, we propose three new master regulator (key driver) genes that emerged from our network analyses as robust candidates for further evaluation in LOAD therapeutic development efforts.
Synchronization, stochasticity and phase waves in neuronal networks with spatially-structured connectivity

Oscillations in the beta/low gamma range (10-45 Hz) are recorded in diverse neural structures. They have successfully been modeled as sparsely synchronized oscillations arising from reciprocal interactions between randomly connected excitatory (E) pyramidal cells and local interneurons (I). The synchronization of spatially distant oscillatory spiking E-I modules has been well studied in the rate model framework but less so for modules of spiking neurons. Here, we first show that previously proposed modifications of rate models provide a quantitative description of spiking E-I modules of Exponential Integrate-and-Fire (EIF) neurons. This allows us to analyze the dynamical regimes of sparsely synchronized oscillatory E-I modules connected by long-range excitatory interactions, for two modules, as well as for a chain of such modules. For modules with a large number of neurons (> 105), we obtain results similar to previously obtained ones based on the classic deterministic Wilson-Cowan rate model, with the added bonus that the results quantitatively describe simulations of spiking EIF neurons. However, for modules with a moderate (~ 104) number of neurons, stochastic variations in the spike emission of neurons are important and need to be taken into account. On the one hand, they modify the oscillations in a way that tends to promote synchronization between different modules. On the other hand, independent fluctuations on different modules tend to disrupt synchronization. The correlations between distant oscillatory modules can be described by stochastic equations for the oscillator phases that have been intensely studied in other contexts. On shorter distances, we develop a description that also takes into account amplitude modes and that quantitatively accounts for our simulation data. Stochastic dephasing of neighboring modules produces transient phase gradients and the transient appearance of phase waves. We propose that these stochastically-induced phase waves provide an explanative framework for the observations of traveling waves in the cortex during beta oscillations.
An ABA-GA bistable switch can account for natural variation in the variability of Arabidopsis seed germination time

Genetically identical plants growing in the same conditions can display heterogeneous phenotypes. Whether this phenotypic variability is functional and the mechanisms behind it are unclear. Here we use Arabidopsis seed germination time as a model system to examine phenotypic variability. We show extensive variation in seed germination time variability between Arabidopsis accessions, and use a multi-parent recombinant inbred population to identify two loci involved in this trait. Both loci include genes implicated in ABA signalling that could contribute to seed germination variability. Modelling reveals that the GA/ABA bistable switch underlying germination can amplify variability and account for the effects of these two loci on germination distributions. The model predicts the effects of modulating ABA and GA levels, which we validate genetically and by exogenous addition of hormones. We confirm that germination variability could act as a bet hedging strategy, by allowing a fraction of seeds to survive lethal stress.
The Drosophila Individual Activity Monitoring and Detection System (DIAMonDS)

Here, we have developed DIAMonDS (Drosophila Individual Activity Monitoring and Detection System) comprising time-lapse imaging by a charge-coupled device (CCD) flatbed scanner and Sapphire, a novel algorithm and web application. DIAMonDS automatically and sequentially identified the transition time points of multiple life cycle events such as pupariation, eclosion, and death in individual flies at high temporal resolution and on a large scale. DIAMonDS performed simultaneous multiple scans to measure individual deaths (≤ 1,152 flies per scanner) and pupariation and eclosion timings (≤ 288 flies per scanner) under various chemical exposures, environmental conditions, and genetic backgrounds. DIAMonDS correctly identified 74–85% of the pupariation and eclosion events and ∼92% of the death events within ±10 scanning frames. This system is a powerful tool for studying the influences of genetic and environmental factors on fruit flies and efficient, high-throughput genetic and chemical screening in drug discovery.
A single N6-methyladenosine site in lncRNA HOTAIR regulates its function in breast cancer cells

N6-methyladenosine (m6A) modification of RNA plays important roles in normal and cancer biology, but knowledge of its function on long noncoding RNAs (lncRNAs) remains limited. Here, we investigate whether m6A regulates the function of the human HOTAIR lncRNA, which contributes to multiple pro-tumor phenotypes in triple-negative breast cancer (TNBC) cells. We identify at least 8 individual m6A sites within HOTAIR, with a single site (A783) consistently methylated. Mutation of A783 impairs cellular proliferation and invasion in HOTAIR-overexpressing TNBC cells. m6A at A783 regulates HOTAIR’s ability to localize to chromatin and induce gene pathways that affect tumor progression. In contrast, A783U mutant HOTAIR demonstrates loss-of-function and antimorph behaviors by impairing gene expression changes induced by WT HOTAIR and, in some cases, inducing opposite changes in gene expression. HOTAIR interacts with nuclear m6A reader YTHDC1 and high HOTAIR is significantly associated with shorter overall patient survival, particularly in the context of high YTHDC1. At the molecular level, YTHDC1-HOTAIR interactions are required for chromatin localization and regulation of gene repression. Our work demonstrates how modification of one base in a lncRNA can elicit a distinct gene regulation mechanism and drive disease-associated phenotypic changes such as proliferation and invasion.
Asymmetry of Auditory-Motor Speech Processing is Determined by Language Experience

Speech processing relies on interactions between auditory and motor systems and is asymmetrically organized in the human brain. The left auditory system is specialized for processing of phonemes, whereas the right is specialized for processing of pitch changes in speech affecting prosody. In speakers of tonal languages, however, processing of pitch (i.e., tone) changes that alter word meaning is left-lateralized indicating that linguistic function and language experience shape speech processing asymmetries. Here, we investigated the asymmetry of motor contributions to auditory speech processing in male and female speakers of tonal and non-tonal languages. We temporarily disrupted the right or left speech motor cortex using transcranial magnetic stimulation (TMS) and measured the impact of these disruptions on auditory discrimination (mismatch negativity; MMN) responses to phoneme and tone changes in sequences of syllables using electroencephalography (EEG). We found that the effect of motor disruptions on processing of tone changes differed between language groups: disruption of the right speech motor cortex suppressed responses to tone changes in non-tonal language speakers, whereas disruption of the left speech motor cortex suppressed responses to tone changes in tonal language speakers. In non-tonal language speakers, the effects of disruption of left speech motor cortex on responses to tone changes were inconclusive. For phoneme changes, disruption of left but not right speech motor cortex suppressed responses in both language groups. We conclude that the contributions of the right and left speech motor cortex to auditory speech processing are determined by the functional roles of acoustic cues in the listener's native language. SIGNIFICANCE STATEMENT The principles underlying hemispheric asymmetries of auditory speech processing remain debated. The asymmetry of processing of speech sounds is affected by low-level acoustic cues, but also by their linguistic function. By combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG), we investigated the asymmetry of motor contributions to auditory speech processing in tonal and non-tonal language speakers. We provide causal evidence that the functional role of the acoustic cues in the listener's native language affects the asymmetry of motor influences on auditory speech discrimination ability [indexed by mismatch negativity (MMN) responses]. Lateralized top-down motor influences can affect asymmetry of speech processing in the auditory system.
The Identification of A ROS Responsive Motif that is regulated by snoRNP in Arabidopsis

A GGGCC motif (site II like motif) was identified from the upstream sequences of reactive oxygen species (ROS) and light induced genes in Arabidopsis. This motif is highly enriched within the −50 to −250 bp region of the induced genes, and it is also specifically distributed in the same region in mouse and human genome. EMSA experiments revealed that several nuclear factors (NFs) bind to this motif, and the binding activities altered under H2O2 treatment. Two C/D family snoRNP proteins, namely fibrillarin 2 and NOP56, were identified from the site II like motif binding NFs. Several C/D family snoRNA, including R63, U24a and Z15, were also cloned from the motif binding NFs. These data suggest new regulatory roles of snoRNP in Arabidopsis.
Antimetabolic effects of plant lectins towards nymphal stages of the planthoppers Tarophagous proserpina and Nilaparvata lugens

Taro Colocasia esculenta (L. Schott) and rice (Oryza sativa L.) form a major part of the staple diet of pacific islanders. Pest constraints hamper the sustainability of taro and rice production in the Pacific region. Insect feeding trials were conducted in vitro to determine the effects of plant lectins against planthopper pests of taro and rice. Lectins were incorporated into artificial diet at 0.1% (w/v) level. The lectins Galanthus nivalis agglutinin (GNA) and concanavalin A (Con A) showed significant antimetabolic effects towards third instar nymphs of taro planthopper (Tarophagous proserpina Kirkaldy) whilst Pisum sativum agglutinin (PSA) showed no significant effects toward the insect. Psophocarpus tetragonolobus agglutinin (PTA) showed significant antimetabolic effects towards third instar nymphs of rice brown planthopper (Nilaparvata lugens Stål). PTA also reduced honeydew excretion levels of rice brown planthopper, over a 24‐hour period, demonstrating antifeedant properties of the protein.
Mms19 promotes spindle microtubule assembly in neural stem cells through two distinct pathways

Mitotic divisions depend on the timely assembly and proper orientation of the mitotic spindle. Malfunctioning of these processes can considerably delay mitosis, thereby compromising tissue growth and homeostasis, and leading to chromosomal instability. Here we identified Mms19 as an important player in these processes as it promotes spindle and astral microtubule (MT) growth and consequently regulates spindle orientation and mitosis duration in Drosophila neural stem cells. Loss of functional Mms19 drastically affects the growth and development of mitotic tissues in Drosophila larvae. We found that Mms19 performs its mitotic activities through two different pathways. By stimulating the mitotic kinase cascade, it triggers the localization of the MT regulatory complex TACC/Msps (Transforming Acidic Coiled Coil/Minispindles, the homolog of human ch-TOG) to the centrosome. In addition, we present evidence that Mms19 stimulates MT stability and bundling by binding directly to MTs.
Development of a Nested-MultiLocus Sequence Typing approach for a highly sensitive and specific identification of Xylella fastidiosa subspecies directly from plant samples

Different sequence types (ST) of Xylella fastidiosa were already identified in France and Spain based on direct MultiLocus Sequence Typing (MLST) of plant DNA samples. However, direct typing of plant DNA is partly efficient. In order to improve the sensitivity of X. fastidiosa identification, we developed a direct nested-MLST assay on plant extracted DNA. This method was performed based on a largely used scheme targeting seven housekeeping gene (HKG) loci (cysG, gltT, holC, leuA, malF, nuoL, petC). Nested primers were designed from multi-sequence alignments of 38 genomes representing all subspecies and one genome of Xylella taiwanensis. Sequences obtained were long enough to be used for BLAST comparison in PubMLST database. No nonspecific amplification products were observed in these samples. Efficiency of the nested-MLST was tested on extracted DNA from 106 samples proven positive (Cq<35) or equivocal (35≤Cq≤40) using the Harper’s qPCR test. Samples analyzed included 49 plant species and two insect species (Philaenus spumarius, Neophilaenus campestris) that were collected in 2017 (106 plant samples in France), in 2018 (162 plant samples in France, 40 plant samples and 26 insect samples in Spain), and in 2019 (30 plant samples in Spain). With the conventional-MLST assay, no complete MLST profile was obtained for any of the samples from France and for most samples (59/66) from Spain. Conversely, with the nested approach, complete profiles were obtained for six French plant samples, 55 Spanish plant samples and nine Spanish insect samples. The threshold was improved by 100 to 1000 times compared to conventional PCR and was between 22 pg.mL−1 to 2.2 pg.mL−1 depending on the HKG. Using nested-MLST assay, plants that were not yet considered hosts tested positive and revealed novel alleles in France, whereas for Spanish samples it was possible to assign the subspecies or ST to samples considered as new hosts in Europe. Direct typing by nested-MLST from plant material has an increased sensitivity and may be useful for epidemiological purposes.