Miracle-dz/UniFAR-FTUs huggingface dataset:
Large-scale identification of viral quorum sensing systems reveals density-dependent sporulation-hijacking mechanisms in bacteriophages

Communication between viruses supported by quorum sensing systems (QSSs) were found to optimize the fitness of temperate bacteriophages of Bacilli by guiding the transition from the host-destructive lytic cycle to the host-protective lysogenic cycle in a density-dependent manner. All known phage-encoded QSSs consist of a communication propeptide and a cognate intracellular receptor that regulates the expression of adjacent target genes upon recognition of the matured peptide, a signature known as RRNPP and found in chromosomes, plasmids and phages of Firmicutes bacteria. Recently, we have introduced the RRNPP_detector software to detect novel genetic systems matching the RRNPP signature, which unearthed many novel phage-encoded candidate QSSs. Here, by looking at the adjacent genes likely regulated by these viral candidate QSSs, we identified an unsuspected clustering of viral QSSs with viral genes whose bacterial homologs are key regulators of the last-resort bacterial sporulation initiation pathway (rap, spo0E or abrB). Consistently, we found evidence in published data that certain of these QSSs encoded by prophages (phage genomes inserted within a bacterial genome) dynamically manipulate the timing of sporulation in the host. Because these viral QSSs are genetically diverse and are found associated with different sporulation regulators, this suggests a convergent evolution in bacteriophages of density-dependent sporulation-hijacking mechanisms. SIGNIFICANCE Communication between viruses supported by quorum sensing systems (QSSs) is a brand new research area that has transformed our views of viral adaptation and virus-host co-evolution. The viral QSSs discovered so far were found to guide the lysis-lysogeny decision in temperate bacteriophages as a function of phage density. Here, we identified that quorum sensing-mediated communication between phages can not only guide the regulation of viral processes but also the manipulation of the bacterial sporulation pathway. Our finding introduces the new view that not only bacteria decide when it is time to sporulate, some bacteriophages are also key stakeholders in this dynamical decision-making process. Considering that spores are the transmissive form of many pathogens, these new insights have important applied implications.
Ciliary and extraciliary Gpr161 pools repress hedgehog signaling in a tissue-specific manner

The role of compartmentalized cAMP signaling in primary cilia is not well understood. The cilia-localized G-protein-coupled receptor—Gpr161 represses hedgehog pathway via cAMP signaling. Here, by generating knock-in mutant mouse at endogenous Gpr161 locus (mut1), we show that ciliary and extraciliary receptor pools repress hedgehog signaling in a tissue-specific manner. Gpr161mut1 was competent in generating cAMP but did not transit through cilia. Compared to knockout, Gpr161mut1 had delayed embryonic lethality, less upregulation of hedgehog targets and partially down-regulated Gli3-repressor. Ventral-most progenitor expansion in neural tube of Gpr161 knockout occurred in a Gli2-activator-dependent manner but was not seen in Gpr161mut1. Intermediate-level ventralization occurred from Gpr161 lack specifically in cilia but was restored by increased extraciliary mutant generating Gli3-repressor. Morphogenesis in limb buds and midface that require Gli-repressor manifested hedgehog hyperactivation phenotypes— polydactyly and midfacial widening—in Gpr161mut1. Thus, ciliary and extraciliary cAMP signaling establishes tissue-specific Gli-repressor thresholds in dictating morpho-phenotypic outcomes. Impact statement Signaling by Cilia Signaling by cAMP specifically in cilia directs tissue-specific morphogenesis
An Omic and Multidimensional Spatial Atlas from Serial Biopsies of an Evolving Metastatic Breast Cancer

Mechanisms of therapeutic resistance manifest in metastatic cancers as tumor cell intrinsic alterations and extrinsic microenvironmental influences that can change during treatment. To support the development of methods for the identification of these mechanisms in individual patients, we present here an Omic and Multidimensional Spatial (OMS) Atlas generated from four serial biopsies of a metastatic breast cancer patient during 3.5 years of therapy. This resource links detailed, longitudinal clinical metadata including treatment times and doses, anatomic imaging, and blood-based response measurements to exploratory analytics including comprehensive DNA, RNA, and protein profiles, images of multiplexed immunostaining, and 2- and 3-dimensional scanning electron micrographs. These data reveal aspects of therapy-associated heterogeneity and evolution of the cancer’s genome, signaling pathways, immune microenvironment, cellular composition and organization, and ultrastructure. We present illustrative examples showing how integrative analyses of these data provide insights into potential mechanisms of response and resistance, and suggest novel therapeutic vulnerabilities.
Thanks for Your Recognition, Boss! a Study of How and When Voice Endorsement Promotes Job Performance and Voice

Existing studies mainly explore the antecedents and distal outcomes of voice behavior of employees. Less is known about what may occur after supervisors endorse ideas of employees. Based on the conservation of resources theory, we explored how and when voice endorsement affects job performance and voice behavior of employees. With the sample of 444 matched supervisor–subordinate pairs from a large organization, we found that voice endorsement of supervisors positively influences voice behavior and job performance of employees through the mediating effects of positive mood and work engagement. Additionally, we found that the voice commitment of employees strengthens the influence of voice endorsement of supervisors on positive mood of employees. Theoretical and practical implications of these findings are discussed.
Fruit Herbivory Alters Plant Electrome: Evidence for Fruit-Shoot Long-Distance Electrical Signaling in Tomato Plants

The electrical activity of tomato plants subjected to fruit herbivory was investigated. The study aimed to test the hypothesis that tomato fruits transmit long-distance electrical signals to the shoot when subjected to herbivory. For such, time series classification by machine learning techniques and analyses related to the oxidative response were employed. Tomato plants (cv. “Micro-Tom”) were placed into a Faraday's cage and an electrode pair was inserted in the fruit's peduncle. Helicoverpa armigera caterpillars were placed on the fruit (either green and ripe) for 24 h. The time series were recorded before and after the fruit's exposure of the caterpillars. The plant material for chemical analyses was collected 24 and 48 h after the end of the acquisition of electrophysiological data. The time series were analyzed by the following techniques: Fast Fourier Transform (FFT), Wavelet Transform, Power Spectral Density (PSD), and Approximate Entropy. The following features from FFT, PSD, and Wavelet Transform were used for PCA (Principal Component Analysis): average, maximum and minimum value, variance, skewness, and kurtosis. Additionally, these features were used in Machine Learning (ML) analyses for looking for classifiable patterns between tomato plants before and after fruit herbivory. Also, we compared the electrome before and after herbivory in the green and ripe fruits. To evaluate an oxidative response in different organs, hydrogen peroxide, superoxide anion, catalase, ascorbate peroxidase, guaiacol peroxidase, and superoxide dismutase activity were evaluated in fruit and leaves. The results show with 90% of accuracy that the electrome registered in the fruit's peduncle before herbivory is different from the electrome during predation on the fruits. Interestingly, there was also a sharp difference in the electrome of the green and ripe fruits' peduncles before, but not during, the herbivory, which demonstrates that the signals generated by the herbivory stand over the others. Biochemical analysis showed that herbivory in the fruit triggered an oxidative response in other parts of the plant. Here, we demonstrate that the fruit perceives biotic stimuli and transmits electrical signals to the shoot of tomato plants. This study raises new possibilities for studies involving electrical signals in signaling and systemic response, as well as for the applicability of ML to classify electrophysiological data and its use in early diagnosis.
M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

Background Endometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis. Methods M1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis. Results M1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs. Conclusions M1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.
Multimodal Neuroimaging Predictors of Learning Performance of Sensorimotor Rhythm Up-Regulation Neurofeedback

Electroencephalographic (EEG) neurofeedback (NFB) is a popular neuromodulation method to help one selectively enhance or inhibit his/her brain activities by means of real-time visual or auditory feedback of EEG signals. Sensory motor rhythm (SMR) NFB protocol has been applied to improve cognitive performance, but a large proportion of participants failed to self-regulate their brain activities and could not benefit from NFB training. Therefore, it is important to identify the neural predictors of SMR up-regulation NFB training performance for a better understanding the mechanisms of individual difference in SMR NFB. Twenty-seven healthy participants (12 males, age: 23.1 ± 2.36) were enrolled to complete three sessions of SMR up-regulation NFB training and collection of multimodal neuroimaging data [resting-state EEG, structural magnetic resonance imaging (MRI), and resting-state functional MRI (fMRI)]. Correlation analyses were performed between within-session NFB learning index and anatomical and functional brain features extracted from multimodal neuroimaging data, in order to identify the neuroanatomical and neurophysiological predictors for NFB learning performance. Lastly, machine learning models were trained to predict NFB learning performance using features from each modality as well as multimodal features. According to our results, most participants were able to successfully increase the SMR power and the NFB learning performance was significantly correlated with a set of neuroimaging features, including resting-state EEG powers, gray/white matter volumes from MRI, regional and functional connectivity (FC) of resting-state fMRI. Importantly, results of prediction analysis indicate that NFB learning index can be better predicted using multimodal features compared with features of single modality. In conclusion, this study highlights the importance of multimodal neuroimaging technique as a tool to explain the individual difference in within-session NFB learning performance, and could provide a theoretical framework for early identification of individuals who cannot benefit from NFB training.
Molecular Mechanisms of Coral Persistence Within Highly Urbanized Locations in the Port of Miami, Florida

Healthy coral communities can be found on artificial structures (concrete walls and riprap) within the Port of Miami (PoM), Florida. These communities feature an unusually high abundance of brain corals, which have almost entirely vanished from nearby offshore reefs. These corals appear to be thriving in very low-quality waters influenced by dense ship and boat traffic, dredging, and numerous residential and industrial developments. The PoM basin is part of Biscayne Bay, an estuarine environment that experiences frequent freshwater input, high nutrient loading, hypoxia, and acidification. To investigate if there is a molecular basis behind the ability of these corals to persist within these highly “urbanized” waters, we compared whole transcriptome expression profiles from 25 PoM Pseudodiploria strigosa colonies against six conspecifics from a nearby offshore reef. We found that the urban corals exhibited higher expression of (1) transcripts encoding pattern-recognition receptors which may allow these corals to better sense and detect food particles and pathogenic invaders; (2) digestive and degradation-associated enzymes, which may suggest an elevated capacity for heterotrophy and pathogen digestion; and (3) transcripts related to innate immunity, defense, and cellular detoxification, which may collectively protect against pathogenic organisms and water pollution impacts. Large ribosomal subunit rRNA gene mapping revealed that P. strigosa colonies from the PoM sites predominantly hosted heat-tolerant endosymbionts from the genus Durusdinium while offshore conspecifics’ communities were dominated by symbionts in the genus Breviolum. These findings reveal transcriptomic plasticity and molecular mechanisms contributing to the persistence of these corals within a highly urbanized habitat.
Drought and Competition With Ivyleaf Morningglory (Ipomoea hederacea) Inhibit Corn and Soybean Growth

Agricultural impacts of climate change include direct effects on crop plants and indirect effects, such as changes to the distributions and competitiveness of weed species. In the northeastern United States, warming temperatures are likely to result in periods of soil moisture deficit and changes to weed communities. Ivyleaf morningglory (IMG, Ipomoea hederacea Jacq.) is a summer annual vine that competes with field crops and interferes with harvesting. Climate change may increase the competitive effects of IMG on northeastern U.S. field crops. We conducted a greenhouse study to evaluate the effects of IMG on corn (Zea mays L.) and soybean [Glycine max (L.) Merr. ] under drought and non-drought conditions. The drought treatment was crossed against an IMG competition treatment with five levels: one crop plant without IMG plants, one crop plant with one, two, or three IMG plants, and one IMG plant without crop plants. Both drought and IMG (presence or biomass) reduced the biomass of corn and soybean (P < 0.05). Drought and IMG (presence) reduced soybean pod production (P < 0.001). IMG biomass was reduced by drought and the presence of corn (P < 0.001). Across all competition treatments, drought reduced IMG biomass by 71% in the corn experiment and 79% in the soybean experiment, compared with a corn biomass reduction of 50% and a soybean biomass reduction of 58%. Well-designed management programs should mitigate the risks associated with stressors such as IMG and drought, which may threaten northeastern U.S. field crop production under climate change.
A Neural Network Reveals Motoric Effects of Maternal Preconception Exposure to Nicotine on Rat Pup Behavior: A New Approach for Movement Disorders Diagnosis

Neurodevelopmental disorders can stem from pharmacological, genetic, or environmental causes and early diagnosis is often a key to successful treatment. To improve early detection of neurological motor impairments, we developed a deep neural network for data-driven analyses. The network was applied to study the effect of maternal nicotine exposure prior to conception on 10-day-old rat pup motor behavior in an open field task. Female Long-Evans rats were administered nicotine (15 mg/L) in sweetened drinking water (1% sucralose) for seven consecutive weeks immediately prior to mating. The neural network outperformed human expert designed animal locomotion measures in distinguishing rat pups born to nicotine exposed dams vs. control dams (87 vs. 64% classification accuracy). Notably, the network discovered novel movement alterations in posture, movement initiation and a stereotypy in “warm-up” behavior (repeated movements along specific body dimensions) that were predictive of nicotine exposure. The results suggest novel findings that maternal preconception nicotine exposure delays and alters offspring motor development. Similar behavioral symptoms are associated with drug-related causes of disorders such as autism spectrum disorder and attention-deficit/hyperactivity disorder in human children. Thus, the identification of motor impairments in at-risk offspring here shows how neuronal networks can guide the development of more accurate behavioral tests to earlier diagnose symptoms of neurodevelopmental disorders in infants and children.
Inhibition of Lipoxygenases Showed No Benefit for the Musculoskeletal System in Estrogen Deficient Rats

Background In previous studies, we reported the beneficial impact of two lipoxygenase-inhibitors, Baicalein and Zileuton, on osteoporotic bone in a postmenopausal rat model. Whereas subcutaneous Baicalein predominantly improved cortical bone, Zileuton enhanced vertebral and femoral trabecular bone. In this study, we aimed to reveal whether the oral administration of Baicalein caused similar effects on bone and whether a combined administration of Baicalein and Zileuton could act synergistically to ameliorate the formerly reported effects in the musculoskeletal system. Methods We treated ovariectomized (OVX) female Sprague-Dawley rats either with Baicalein (10mg/kg BW), Zileuton (10mg/kg BW) or a combination of both (each 10mg/kg BW) for 13 weeks and compared with untreated OVX and NON-OVX groups (n=12-16 rats per group). Lumbar vertebral bodies and femora were analyzed. Tibiae were osteotomized, plate-stabilized (at week 8 after OVX) and likewise analyzed by biomechanical, histological, micro-computed tomographical and ashing tests. The skeletal muscle structure was analyzed. Results Oral administration of Baicalein did not confirm the reported favorable cortical effects in neither vertebra nor femur. Zileuton showed a beneficial effect on trabecular vertebra, while the femur was negatively affected. Callus formation was enhanced by all treatments; however, its density and biomechanical properties were unaltered. Lipoxygenase inhibition did not show a beneficial effect on skeletal muscle. The combination therapy did not ameliorate OVX-induced osteoporosis but induced even more bone loss. Conclusions The preventive anti-osteoporotic treatments with two lipoxygenase inhibitors applied either alone or in combination showed no benefit for the musculoskeletal system in estrogen deficient rats.
Decipering the Molecular Mechanism of ACE2 Regulating A549 Cells

Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.
An Association Between Phonetic Complexity of Infant Vocalizations and Parent Vowel Hyperarticulation

Extreme or exaggerated articulation of vowels, or vowel hyperarticulation, is a characteristic commonly found in infant-directed speech (IDS). High degrees of vowel hyperarticulation in parent IDS has been tied to better speech sound category development and bigger vocabulary size in infants. In the present study, the relationship between vowel hyperarticulation in Swedish IDS to 12-month-old and phonetic complexity of infant vocalizations is investigated. Articulatory adaptation toward hyperarticulation is quantified as difference in vowel space area between IDS and adult-directed speech (ADS). Phonetic complexity is estimated using the Word Complexity Measure for Swedish (WCM-SE). The results show that vowels in IDS was more hyperarticulated than vowels in ADS, and that parents’ articulatory adaptation in terms of hyperarticulation correlates with phonetic complexity of infant vocalizations. This can be explained either by the parents’ articulatory behavior impacting the infants’ vocalization behavior, the infants’ social and communicative cues eliciting hyperarticulation in the parents’ speech, or the two variables being impacted by a third, underlying variable such as parents’ general communicative adaptiveness.