Miracle-dz/UniFAR-FTUs huggingface dataset:
The Earth BioGenome Project 2020: Starting the clock

Harris A. Lewin , Stephen Richards , Erez Lieberman Aiden, Miguel L. Allende , John M. Archibald, Mikl os B alint, Katharine B. Barker, Bridget Baumgartner, Katherine Belov, Giorgio Bertorelle, Mark L. Blaxter , Jing Cai, Nicolette D. Caperello, Keith Carlson, Juan Carlos Castilla-Rubio, Shu-Miaw Chaw, Lei Chen, Anna K. Childers, Jonathan A. Coddington , Dalia A. Conde , Montserrat Corominas , Keith A. Crandall , Andrew J. Crawford, Federica DiPalma, Richard Durbin , ThankGod E. Ebenezer, Scott V. Edwards , Olivier Fedrigo, Paul Flicek, Giulio Formenti, Richard A. Gibbs, M. Thomas P. Gilbert , Melissa M. Goldstein, Jennifer Marshall Graves , Henry T. Greely , Igor V. Grigoriev , Kevin J. Hackett, Neil Hall, David Haussler, Kristofer M. Helgen, Carolyn J. Hogg , Sachiko Isobe, Kjetill Sigurd Jakobsen , Axel Janke , Erich D. Jarvis, Warren E. Johnson , Steven J. M. Jones, Elinor K. Karlsson , Paul J. Kersey, Jin-Hyoung Kim, W. John Kress , Shigehiro Kuraku, Mara K. N. Lawniczak, James H. Leebens-Mack , Xueyan Li, Kerstin Lindblad-Toh , Xin Liu, Jose V. Lopez, Tomas Marques-Bonet , Sophie Mazard, Jonna A. K. Mazet , Camila J. Mazzoni, Eugene W. Myers , Rachel J. O’Neill, Sadye Paez, Hyun Park, Gene E. Robinson , Cristina Roquet , Oliver A. Ryder , Jamal S. M. Sabir , H. Bradley Shaffer , Timothy M. Shank, Jacob S. Sherkow , Pamela S. Soltis , Boping Tang , Leho Tedersoo, Marcela Uliano-Silva, Kun Wang, Xiaofeng Wei, Regina Wetzer, Julia L. Wilson, Xun Xu, Huanming Yang, Anne D. Yoder , and Guojie Zhang
Cryptochrome proteins regulate the circadian intracellular behavior and localization of PER2 in mouse suprachiasmatic nucleus neurons

Significance The suprachiasmatic nucleus (SCN), the master circadian clock of the mammalian brain, coordinates cellular clocks across the organism to regulate daily rhythms of physiology and behavior. SCN timekeeping pivots around transcriptional/translational feedback loops whereby PERIOD (PER) and CRYPTOCHROME (CRY) proteins associate and enter the nucleus to inhibit their own expression. The individual and interactive behaviors of PER and CRY and the mechanisms that regulate them are poorly understood. We combined fluorescence imaging of endogenous PER2 and viral vector–expressed CRY in SCN slices and show how CRYs, acting via their C terminus, control nuclear localization and mobility of PER2 to dose-dependently initiate SCN timekeeping and control its period. Our results reveal PER and CRY interactions central to the SCN clockwork. The ∼20,000 cells of the suprachiasmatic nucleus (SCN), the master circadian clock of the mammalian brain, coordinate subordinate cellular clocks across the organism, driving adaptive daily rhythms of physiology and behavior. The canonical model for SCN timekeeping pivots around transcriptional/translational feedback loops (TTFL) whereby PERIOD (PER) and CRYPTOCHROME (CRY) clock proteins associate and translocate to the nucleus to inhibit their own expression. The fundamental individual and interactive behaviors of PER and CRY in the SCN cellular environment and the mechanisms that regulate them are poorly understood. We therefore used confocal imaging to explore the behavior of endogenous PER2 in the SCN of PER2::Venus reporter mice, transduced with viral vectors expressing various forms of CRY1 and CRY2. In contrast to nuclear localization in wild-type SCN, in the absence of CRY proteins, PER2 was predominantly cytoplasmic and more mobile, as measured by fluorescence recovery after photobleaching. Virally expressed CRY1 or CRY2 relocalized PER2 to the nucleus, initiated SCN circadian rhythms, and determined their period. We used translational switching to control CRY1 cellular abundance and found that low levels of CRY1 resulted in minimal relocalization of PER2, but yet, remarkably, were sufficient to initiate and maintain circadian rhythmicity. Importantly, the C-terminal tail was necessary for CRY1 to localize PER2 to the nucleus and to initiate SCN rhythms. In CRY1-null SCN, CRY1Δtail opposed PER2 nuclear localization and correspondingly shortened SCN period. Through manipulation of CRY proteins, we have obtained insights into the spatiotemporal behaviors of PER and CRY sitting at the heart of the TTFL molecular mechanism.
Structure and function of an effector domain in antiviral factors and tumor suppressors SAMD9 and SAMD9L

Significance SAMD9 and SAMD9L (SAMD9/9L) are important innate immune defenders against viruses and the development of myeloid tumors. They form a crucial host barrier that poxviruses must overcome for successful infection. A myriad of human diseases including many pediatric myelodysplastic syndromes are caused by mutations in SAMD9/9L. However, the molecular functions of SAMD9/9L and how their functions are executed are unknown, hindering progress in developing effective therapies for SAMD9/9L-associated human diseases. Here, we identified the structure and function of a SAMD9/9L effector domain that is essential for their physiological functions as well as the pathogenic effects exerted by patient-derived mutations. Our study revealed a potential therapeutic target for SAMD9/9L-associated human diseases. SAMD9 and SAMD9L (SAMD9/9L) are antiviral factors and tumor suppressors, playing a critical role in innate immune defense against poxviruses and the development of myeloid tumors. SAMD9/9L mutations with a gain-of-function (GoF) in inhibiting cell growth cause multisystem developmental disorders including many pediatric myelodysplastic syndromes. Predicted to be multidomain proteins with an architecture like that of the NOD-like receptors, SAMD9/9L molecular functions and domain structures are largely unknown. Here, we identified a SAMD9/9L effector domain that functions by binding to double-stranded nucleic acids (dsNA) and determined the crystal structure of the domain in complex with DNA. Aided with precise mutations that differentially perturb dsNA binding, we demonstrated that the antiviral and antiproliferative functions of the wild-type and GoF SAMD9/9L variants rely on dsNA binding by the effector domain. Furthermore, we showed that GoF variants inhibit global protein synthesis, reduce translation elongation, and induce proteotoxic stress response, which all require dsNA binding by the effector domain. The identification of the structure and function of a SAMD9/9L effector domain provides a therapeutic target for SAMD9/9L-associated human diseases.
Skin-resident dendritic cells mediate postoperative pain via CCR4 on sensory neurons

Significance Interactions between the nervous and immune systems control the generation and maintenance of inflammatory pain. However, the immune cells and mediators controlling this response remain poorly characterized. We identified the cytokines CCL22 and CCL17 as secreted mediators that act directly on sensory neurons to mediate postoperative pain via their shared receptor, CCR4. We also show that skin-resident dendritic cells are key contributors to the inflammatory pain response. Blocking the interaction between these dendritic cell–derived ligands and their receptor can abrogate the pain response, highlighting CCR4 antagonists as potentially effective therapies for postoperative pain. Our findings identify functions for these tissue-resident myeloid cells and uncover mechanisms underlying pain pathophysiology. Inflammatory pain, such as hypersensitivity resulting from surgical tissue injury, occurs as a result of interactions between the immune and nervous systems with the orchestrated recruitment and activation of tissue-resident and circulating immune cells to the site of injury. Our previous studies identified a central role for Ly6Clow myeloid cells in the pathogenesis of postoperative pain. We now show that the chemokines CCL17 and CCL22, with their cognate receptor CCR4, are key mediators of this response. Both chemokines are up-regulated early after tissue injury by skin-resident dendritic and Langerhans cells to act on peripheral sensory neurons that express CCR4. CCL22, and to a lesser extent CCL17, elicit acute mechanical and thermal hypersensitivity when administered subcutaneously; this response abrogated by pharmacological blockade or genetic silencing of CCR4. Electrophysiological assessment of dissociated sensory neurons from naïve and postoperative mice showed that CCL22 was able to directly activate neurons and enhance their excitability after injury. These responses were blocked using C 021 and small interfering RNA (siRNA)-targeting CCR4. Finally, our data show that acute postoperative pain is significantly reduced in mice lacking CCR4, wild-type animals treated with CCR4 antagonist/siRNA, as well as transgenic mice depleted of dendritic cells. Together, these results suggest an essential role for the peripheral CCL17/22:CCR4 axis in the genesis of inflammatory pain via direct communication between skin-resident dendritic cells and sensory neurons, opening therapeutic avenues for its control.
A wireless inductive-capacitive (L-C) sensor for rotating component temperature monitoring

Abstract Temperature monitoring is critical in almost every type of machinery and application, especially in rotating components such as jet turbines, engines, and power plants, etc. These components involve harsh environments and where the physical connections for monitoring systems are impossible. This paper presents a resonant inductive-capacitive (L-C) circuit based wireless temperature sensor suitable for working in these harsh environments to monitor the temperature of rotating components. Design and performance analysis of the wireless temperature sensor has been conducted and the sensor prototype was successfully fabricated and calibrated up to 200°C with sensitivity of 30 kHz/°C. As a result it is confirmed that temperature monitoring of a rotating component can be carried out without requiring physical connection, power supplies or active elements in the sensor circuit.
DROSHA but not DICER is required for human haematopoietic stem cell function

DROSHA and DICER have central roles in the biogenesis of microRNAs (miRNAs). However, we previously showed that in the murine system, DROSHA has an alternate function where it directly recognises and cleaves protein‐coding messenger (m)RNAs and this is critical for safeguarding the pluripotency of haematopoietic stem cells (HSCs). Maintenance of murine HSC function is dependent on DROSHA‐mediated cleavage of two mRNAs, Myl9 and Todr1. The goal of this study is to determine whether this pathway is conserved in human HSCs.
Effects of Acute Moderate- and High-Intensity Aerobic Exercise on Oxygenation in Prefrontal Cortex of Male Methamphetamine-Dependent Patients

The aim of this study was to explore the influence of different intensities of acute aerobic exercise on brain activation in male methamphetamine (MA)-dependent patients during exercise. Twenty MA-dependent patients were divided randomly into two groups participating in 35 min of either moderate- or high-intensity aerobic exercise. Functional near-infrared spectral imaging (fNIRS) was used to detect hemodynamic changes in prefrontal cortex during the main 25-min exercise stage. The results revealed that high-intensity acute aerobic exercise aroused more cerebral oxygenation changes in the prefrontal cortex and left dorsolateral prefrontal cortex during exercise as compared with moderate-intensity exercise. Furthermore, there was a stronger positive connection observed between orbital frontal cortex and left dorsolateral prefrontal cortex in the high-intensity group than in the moderate-intensity group. Together these results suggest that for submaximal exercise intensities, high-intensity exercise may bring more benefits to male MA-dependent patients than moderate-intensity.
Indigenous and Traditional Management Creates and Maintains the Diversity of Ecosystems of South American Tropical Savannas

The tropical South American savannas have been occupied and manipulated by humans since the late Pleistocene. Ecologists consider that soils, hydrology, and seasonal precipitation influence the structure and composition of plants and the fire-proneness of savannas. However, the human influence on these dynamics remains uncertain. This is because little is known about human activities and what influence they have on the diversity of ecosystems. Considering this, our study sought to synthesize the management practices used by small-scale societies of the South American savannas, compile the species that are the focus of direct management, and demonstrate the role of this management in maintaining the diverse ecosystems that make up the savannas. We also set out to test the hypotheses that forms of management differ depending on the ecosystem and cultural matrices. To do so, we conducted a systematic review, in which we collected 51 articles with information about the management carried out by small-scale societies. From this, we categorized 10 management practices directed to ecosystems: protection of the ecosystem, enrichment of species, topographic changes, increased soil fertility, cleaning, prevention of fire, resource promotion, driving of game, swidden-fallow, and maintenance of ecosystem structure. We identified 19 native plant species whose populations are managed in-situ. These management practices have proven capable of keeping savanna and grassland ecosystems open and increasing the occurrence of forest ecosystems in the mosaic, as well as favoring plants of human interest in general. We note that there is a relationship between management practices with ecosystems and cultures, which suggests that both factors influence the management of landscapes. We conclude that management practices of small-scale societies are responsible for domesticating South American tropical savannas and that these savannas are composed of a mosaic of culturally constructed niches. The small-scale societies that inhabit these environments have important traditional ecological knowledge and strategies that enable the use, conservation, and restoration of savannas, extremely threatened by agribusiness today. Systematic Review Registration: [website], identifier [registration number].
Are There Postnatal Benefits to Prenatal Kick Counting? A Quasi-Experimental Longitudinal Study

Mild signs of postpartum depression or anxiety are present in up to half of all new mothers. However, the impact of having the “baby blues” on infant development remains largely unknown. The current study explores a potential relation between mother’s self-reported depression or anxiety symptoms and infant’s motor development in a longitudinal sample of 50 mother-infant dyads. Further, we examine whether engaging in fetal kick counting during pregnancy may reduce maternal psychopathology symptoms and thereby positively influence infant motor development and parent-child engagement during the first months of life. We hypothesized that subclinical maternal psychopathology would negatively impact infant motor development, and that completing a fetal kick count activity during the third trimester would reduce overall signs of maternal psychopathology. Results only partially support these hypotheses. Postpartum maternal anxiety seems to negatively affect the emergence of infants’ fine motor skills. However, engaging in fetal kick counting during pregnancy did not reduce maternal depression or anxiety symptoms. Nevertheless, preliminary evidence suggests that engaging in fetal kick counting may impact early child development by altering the mother’s attitudes toward the child. Future research is needed to examine the value of this low-cost intervention strategy more closely.
A Feasibility Test of a Brief Mobile Virtual Reality Meditation for Frontline Healthcare Workers in a Hospital Setting

The purpose of this study was to examine whether a virtual reality plus neurofeedback (VR+NF) meditation experience (experimental condition) was more effective than a standard guided audio-only meditation (control condition) in improving mood in one hundred healthcare workers. Data collection occurred in a hospital setting between October, 2020 and March, 2021 at the height of the COVID-19 pandemic. Participants were alternately assigned to one of the two conditions. Before and after the meditation experience, participants completed the Brunel Mood Scale. Results indicated that both groups showed a similar and significant decrease in Anger, Tension, and Depression. On scales measuring Vigor, Fatigue, and Confusion, the VR+NF group showed decreases, while the audio-only group showed no significant change. The VR+NF group showed significant increases on the Calmness and Happiness scales, which did not change significantly in the audio-only group. These results suggest that the addition of VR and neurofeedback may increase the positive outcomes associated with standard audio-guided meditation. These increased benefits may be due to the sense of presence intrinsic to VR, the inclusion of nature-based scenes in the VR experience, as well as the increased self-awareness created by the addition of neurofeedback. As the pre and post measures take place within one 50-min session, further studies assessing the longer-term changes are needed.
Orientation Invariant Sensorimotor Object Recognition Using Cortical Grid Cells

Grid cells enable efficient modeling of locations and movement through path integration. Recent work suggests that the brain might use similar mechanisms to learn the structure of objects and environments through sensorimotor processing. This work is extended in our network to support sensor orientations relative to learned allocentric object representations. The proposed mechanism enables object representations to be learned through sensorimotor sequences, and inference of these learned object representations from novel sensorimotor sequences produced by rotated objects through path integration. The model proposes that orientation-selective cells are present in each column in the neocortex, and provides a biologically plausible implementation that echoes experimental measurements and fits in with theoretical predictions of previous studies.
Seismic Imaging of Lithospheric Structure Beneath Central-East Java Region, Indonesia: Relation to Recent Earthquakes

The Central and East Java region, which is part of the Sunda Arc, has an important role in producing destructive earthquakes and volcanic complexes in Indonesia as a result of the convergence between the Indo-Australian plate that subducts under the Eurasian plate. In this study, the 3-D seismic velocity structure (Vp, Vs, and Vp/Vs) of the crust and upper mantle was determined to reveal the presence of the subducted slab, volcanic sources, and seismogenic features in the Central and East Java region. We have manually re-picked P- and S-arrivals of 1,488 events from January 2009 to September 2017 recorded at 27 stations of the BMKG network. An iterative damped least-squares inversion method was applied to simultaneously calculate both hypocenter relocations and velocity structure beneath this high-risk region to a depth of 200 km. We then compare the tomographic results and seismicity to interpret structural features in the seismic zones. The subducted slab is dipping toward the north, imaged by the high-velocity regions with low Vp/Vs at depths of about 50–100 km. Low-velocity anomalies with high Vp/Vs above the slab at a depth of ∼100 km, imply the possible location of partial melting from slab dehydration. Fluids and melts are ascending to feed the volcanoes i. e. , Merapi-Merbabu, Wilis, Pandan, Semeru, Bromo, and Ijen that also have similar low-velocity anomalies at 10–30 km depths, suggesting the presence of the sedimentary basin or magma reservoir. We also have redetermined the hypocenter location of the 2021 (Mw 6.1) Malang earthquake at 8.94oS, 112.45oE, with a depth of 59.7 km. The location error in the x, y, and z directions are 3.08, 6.39, and 11.91 km, respectively. This intraslab event with a thrusting mechanism is located in the high-velocity region and close to the intermediate-depth seismic clusters, which indicates the geometry of the oceanic slab. In the region of 1994 (Mw 7.8) Banyuwangi earthquake, we found a low-velocity anomaly at ∼ 50 km depth that might be associated with the presence of subducting seamount that is more hydrated than the surrounding slab. The slip over this subducting seamount caused the tsunamigenic earthquake.
Berberine Alleviate Cisplatin-Induced Peripheral Neuropathy by Modulating Inflammation Signal via TRPV1

Chemotherapy induced peripheral neuropathy (CIPN) is a severe neurodegenerative disorder caused by chemotherapy drugs. Berberine is a natural monomer compound of Coptis chinensis, which has anti-tumor effect and can improve neuropathy through anti-inflammatory mechanisms. Transient receptor potential vanilloid (TRPV1) can sense noxious thermal and chemical stimuli, which is an important target for the study of pathological pain. In both vivo and in vitro CIPN models, we found that berberine alleviated peripheral neuropathy associated with dorsal root ganglia inflammation induced by cisplatin. We confirmed that berberine mediated the neuroinflammatory reaction induced by cisplatin by inhibiting the overexpression of TRPV1 and NF-κB and activating the JNK/p38 MAPK pathways in early injury, which inhibited the expression of p-JNK and mediated the expression of p38 MAPK/ERK in late injury in vivo. Moreover, genetic deletion of TRPV1 significantly reduced the protective effects of berberine on mechanical and heat hyperalgesia in mice. In TRPV1 knockout mice, the expression of NF-κB increased in late stage, and berberine inhibited the overexpression of NF-κB and p-ERK in late injury. Our results support berberine can reverse neuropathic inflammatory pain response induced by cisplatin, TRPV1 may be involved in this process.
Assessment of Physiological Responses During Field Science Task Performance: Feasibility and Future Needs

Objective By understanding the physiological demands of different types of tasks that will be performed during extravehicular activity (EVA) on Mars, human performance safety risks can be mitigated. In addition, such understanding can assist in planning EVAs with an appropriate balance of human health and safety with scientific mission return. Background This paper describes the results of a study of technical feasibility performed within a Mars human research analog, with participants conducting scientifically relevant planetary science sample analysis and return tasks in two distinct field locations. Methods The authors collected heart rate, respiration rate, and heart rate variability (HRV) data, using commercial off-the-shelf hardware and software from study participants as they performed field science tasks within a concept of operations for a Mars science return human expedition mission. These data were remotely monitored, shared in real time, and later analyzed to identify different responses to different tasks in order to determine if there were any predictable or consistent patterns among participants. Results It was ultimately determined that, while differences exist between responses to tasks, they are highly subject to multiple sources of individual variability, dynamics of evolving field science tasks, and demands of a demanding physical environment. Further, distributional analyses of participants do not support parametric statistical analysis techniques. Conclusion The authors conclude that the physiology of individual astronauts should be extensively studied and modeled to support individualized automated monitoring tools for each crew member that is sent to Mars. Application: Physiological monitoring for specialized populations will require significant individual-level analysis, baselining, and bootstrap statistical methods to enable appropriate human performance determinations.