Miracle-dz/UniFAR-FTUs huggingface dataset:
Centriole-independent centrosome assembly in interphase mammalian cells

The major microtubule-organizing center (MTOC) in animal cells, the centrosome, comprises a pair of centrioles surrounded by pericentriolar material (PCM), which nucleates and anchors microtubules. Centrosome assembly depends on the interactions of PCM with centrioles, PCM self-association and dynein-mediated transport. Here, we show that if centrioles are lost due to PLK4 depletion or inhibition, PCM still forms a single centrally located MTOC when non-centrosomal microtubule minus-end organization pathways are disabled. Acentriolar MTOC assembly depends on dynein-driven coalescence of PCM clusters with attached microtubule minus ends and requires γ-tubulin, pericentrin, CDK5RAP2 and ninein, but not NEDD1, CEP152 or CEP192. PCM self-assembly is inhibited by AKAP450-dependent PCM recruitment to the Golgi and by CAMSAP2-mediated microtubule minus-end stabilization. However, if CAMSAP2 is linked to a minus-end-directed motor, a single MTOC containing PCM components can still form, and its organization depends on the presence of pericentrin. Our results reveal that the formation of a single central MTOC in interphase mammalian cells is not strictly centriole dependent but can be driven by self-organization of PCM and microtubule minus ends.
Comparative Study of Protein Aggregation Propensity and Mutation Tolerance Between Naked Mole-Rat and Mouse

The molecular mechanisms of aging and life expectancy have been studied in model organisms with short lifespans. However, long-lived species may provide insights into successful strategies of healthy aging, potentially opening the door for novel therapeutic interventions in age-related diseases. Notably, naked mole-rats, the longest-lived rodent, present attenuated aging phenotypes in comparison to mice. Their resistance toward oxidative stress has been proposed as one hallmark of their healthy aging, suggesting their ability to maintain cell homeostasis, and specifically their protein homeostasis. To identify the general principles behind their protein homeostasis robustness, we compared the aggregation propensity and mutation tolerance of naked mole-rat and mouse orthologous proteins. Our analysis showed no proteome-wide differential effects in aggregation propensity and mutation tolerance between these species, but several subsets of proteins with a significant difference in aggregation propensity. We found an enrichment of proteins with higher aggregation propensity in naked mole-rat involved the inflammasome complex, and in nucleic acid binding. On the other hand, proteins with lower aggregation propensity in naked mole-rat have a significantly higher mutation tolerance compared to the rest of the proteins. Among them, we identified proteins known to be associated with neurodegenerative and age-related diseases. These findings highlight the intriguing hypothesis about the capacity of the naked mole-rat proteome to delay aging through its proteomic intrinsic architecture. Significance statement The molecular mechanisms behind naked mole-rat longevity are still poorly understood. Here, we address how the proteome architecture can help delay the onset of aging in naked mole-rat by studying properties that modulate protein aggregation. We identify ∼1,000 proteins with significant differences in aggregation propensity and mutation tolerance involved in processes known to be dysfunctional during aging. These findings highlight how evolutionary adaptations in protein aggregation in distinct biological processes could explain naked mole-rat longevity.
Water pollution and administrative division adjustments: A quasi-natural experiment in Chaohu Lake, China

Administrative division adjustments, such as agglomerations, upgrading, and revocation, introduce a series of uncertain impacts on the social and economic development in administrative regions. Previous studies have focused more on the economic effects of administrative division adjustments, but in this paper, we also consider the environmental effects of such adjustments. In 2011, with the approval of the State Council, the prefecture-level Chaohu city was officially revoked, resulting in a county-level Chaohu city. One district and four counties under the jurisdiction of the original Chaohu city were placed under the jurisdiction of Hefei, Wuhu, and Ma’anshan. This adjustment made Chaohu Lake an inner lake of Hefei city. The administrative division adjustment of Chaohu Lake, China, is used as a quasi-natural experiment to explore the influence of such an adjustment on pollution control. The synthetic control method (SCM) is used in this study to evaluate the effect of the administrative division adjustment on the water quality indicators of Chaohu Lake. The following conclusions are drawn. First, after the administrative division adjustment, some water quality indicators, such as ammonia nitrogen, improved; however, other major pollution indicators, such as chemical oxygen demand (COD) and dissolved oxygen (DO), worsened to varying degrees. Second, the results reveal that improper development ideas, excessive industrial expansion, and the shift in economic growth and environmental goals were problems after the adjustment. Returning to the original intention of the administrative division adjustment, rationalizing the Chaohu Lake management system and designing a sound and feasible accountability mechanism are fundamental measures for reducing pollution.
Coupled small molecules target RNA interference and JAK/STAT signaling to reduce Zika virus infection in Aedes aegypti

The recent global Zika epidemics have revealed the significant threat that mosquito-borne viruses pose. There are currently no effective vaccines or prophylactics to prevent Zika virus (ZIKV) infection. Limiting exposure to infected mosquitoes is best way to reduce disease incidence. Recent studies have focused on targeting mosquito reproduction and immune responses to reduce transmission. In particular, previous work evaluated the effect of insulin signaling on antiviral JAK/STAT and RNAi in vector mosquitoes. In this work, we demonstrate that targeting insulin signaling through the repurposing of small molecule drugs results in the activation of both of these antiviral pathways. Activation of this coordinated response additively reduced ZIKV levels in Aedes aegypti mosquitoes. This effect included a quantitatively greater reduction in salivary gland ZIKV levels relative to single pathway activation, indicating the potential for field delivery of these small molecules to substantially reduce virus transmission.
The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines

mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity. Given the fact that a Delta variant with three similar RBD mutations has already emerged according to the GISAID database, it is necessary to develop vaccines that protect against such complete breakthrough variants.
Online self-evaluation of fMRI-based neurofeedback performance

This study explores the subjective evaluation of supplementary motor area (SMA) regulation performance in a real-time functional magnetic resonance imaging neurofeedback (fMRI-NF) task. In fMRI-NF, people learn how to self-regulate their brain activity by performing mental actions to achieve a certain target level of blood-oxygen-level-dependent (BOLD) activation. This setup offers the possibility to study performance monitoring in the absence of somatosensory feedback. Here, we studied two types of self-evaluation expressed before receiving neurofeedback: performance predictions and perceived confidence in the prediction judgement. We hypothesized that throughout learning, participants would (1) improve the precision of their performance predictions about the actual changes in their BOLD response, and (2) that reported confidence would progressively increase with improved metacognitive precision. Participants completed three sessions of SMA regulation in a 7T fMRI scanner, performing a drawing motor imagery task. During each trial, they modulated their mental drawing strategy to achieve one of two different levels of target fMRI signal change. They then reported a performance prediction and their confidence in the prediction before receiving delayed BOLD-activation feedback. Results show that participants’ performance predictions improved with learning throughout the three sessions, and that these improvements were not driven exclusively by their knowledge of previous performance. Confidence reports on the other hand showed no change throughout training and did not differentiate between the better and worse predictions. In addition to shedding light on mechanisms of internal monitoring during neurofeedback training, these results also point to a dissociation between self-evaluation of performance and corresponding reported confidence in the presence of feedback.
Time Evolution of the Stroke Symptom-Herb Networks Based on TCM Prescriptions

Traditional Chinese Medicine (TCM) has its origins in distant antiquity and has piled up over a long time with much knowledge about diseases, especially stroke. Different combinations of symptom variables yield different combinations of herbs to form a myriad of prescriptions, and they have undergone repeated confirmation and are worthy objects of excavation and analysis. Herbal studies on stroke have developed from genomics to transcriptomics, proteomics and metabolomics, yet more thought is needed on putting time in a wider perspective of the symptoms and herbs for stroke in Chinese medicine. Due to this, we studied the dynamic structure of TCM prescriptions on stroke, using over 270 TCM prescription books containing 2231 prescriptions related to stroke recorded from 341 to 2000 CE. We labeled the functions of the prescriptions with the symptoms based on subject terms in MESH Neurologic Manifestations, then standardized the herbs in the prescriptions, and finally connected the co-occurring symptoms and herbs in the prescriptions to build an undirected complex network. The Stroke Symptom-Herb Networks (SSHNs) can be seen from its network characteristics that it is not a random network and has small-world characteristics. It has experienced two peaks in its nearly 1700-year history, during the Song dynasty, the Ming and Qing dynasties. From 600 years onwards, the core herb cluster has been initially formed. The comparison of sub-network similarities allowed us to identify several symptoms with similar herb clusters. We divided the community based on modularity, and by analyzing the community evolution, we found a more fixed historical evolutionary trend with Hemiplegia and Sialorrhea nodes and their associated symptom and herb nodes. In the time series analysis, we found many symptom-herb combinations that were consistently closely related to historic time depends on assessing the similarity between the symptoms and the herbs. The complex network provides a distinctive perspective for understanding the symptom-herb relationships embedded in TCM prescriptions in remote antiquity.
A robust ex vivo system to study cellular dynamics underlying mouse peri-implantation development

Upon implantation, mammalian embryos undergo major morphogenesis and key developmental processes such as body axis specification and gastrulation. However, limited accessibility obscures study of these crucial processes. Here, we develop an ex vivo Matrigel-collagen-based culture to recapitulate mouse development from E4.5 to 6.0. Our system not only recapitulates embryonic growth, axis initiation, and overall 3D architecture in 49% of cases, its compatibility with light-sheet microscopy enables study of cellular dynamics through automatic cell segmentation. We find that upon implantation, release of the increasing tension in the polar trophectoderm is necessary for its constriction and invagination. The resulting extra-embryonic ectoderm plays a key role in growth, morphogenesis and patterning of the neighboring epiblast, which subsequently gives rise to all embryonic tissues. This 3D-ex vivo system thus offers an unprecedented access to peri-implantation development for in toto monitoring, measurement and spatio-temporally controlled perturbation, revealing a mechano-chemical interplay between extra-embryonic and embryonic tissues.
Reconstitution of surface lipoprotein translocation reveals Slam as an outer membrane translocon in Gram-negative bacteria

Surface lipoproteins (SLPs) are peripherally attached to the outer leaflet of the outer membrane in many Gram-negative bacteria, playing significant roles in nutrient acquisition and immune evasion in the host. While the factors that are involved in the synthesis and delivery of SLPs in the inner membrane are well characterized, the molecular machineries required for the movement of SLPs to the surface are still not fully elucidated. In this study, we investigated the translocation of a surface lipoprotein TbpB through a Slam1-dependent pathway. Using purified components, we developed an in vitro translocation assay where unfolded TbpB is transported through Slam1 containing proteoliposomes, confirming Slam1 as an outer membrane translocon. While looking to identify factors to increase translocation efficiency, we discovered the periplasmic chaperone Skp interacted with TbpB in the periplasm of Escherichia coli. The presence of Skp was found to increase the translocation efficiency of TbpB in the reconstituted translocation assays. A knockout of Skp in Neisseria meningitidis revealed that Skp is essential for functional translocation of TbpB to the bacterial surface. Taken together, we propose a pathway for surface destined lipoproteins, where Skp acts as a holdase for Slam-mediated TbpB translocation across the outer membrane.
Study of Main Solutes on Evaporation and Crystallization Processes of the Desulfurization Wastewater Droplet

In this study, the evaporation and crystallization processes of the desulfurization wastewater droplet with different concentrations of main solutes were analyzed by TGA and DSC methods. The drying crystals were scanned by a scanning electron microscope. The supersolubilities were measured by the laser intensity detecting method. A mathematic model was built to investigate the relationship between the evaporation and crystallization rates and the species and concentrations of the solutes. The results show that, comparing SO42– with Cl–, the higher concentration of SO42– gives higher evaporation rate (4.75 min of 0.006 mol NaCl, 4.5 min 0.003 mol Na2SO4) and lower crystallization rate (2.2 min of 0.006 mol NaCl, 2.5 min of 0.003 mol Na2SO4). This is because the vapor pressure is higher and the supersolubility is lower when the concentration of SO42– is higher. Comparing Mg2+ with Na+, the changing concentration hardly affects the evaporation rate because of similar vapor pressure. The higher concentration .
Regional COVID-19 Dynamics: Surrogate Synchrony in Case Infection Rates

As many jurisdictions consider in-person learning strategies (including at Institutions of Higher Education, IHE), implementing travel restrictions or quarantines, and/or establishing interstate pacts to reduce COVID-19 spread, this study explores the degree to which COVID-19 case infection rates in a group of neighboring, Southern and Midwestern U.S. states (namely, Arkansas and its contiguous neighbors) are patterned in a non-random way known as synchrony. Utilizing surrogate synchrony (SUSY) to estimate the dyadic coupling between the COVID-19 case infection rate processes in this region from March to December 2020, results indicate that significant synchrony is present between Arkansas and three of its neighbors. The highest level of instantaneous synchrony occurs between Arkansas and Tennessee, with the next highest level occurring between Arkansas and Missouri. There is evidence of directionality in the synchrony, indicating that Arkansas case infection rates lead Mississippi while rates in Missouri and Tennessee lead Arkansas. The lagged cross-correlations suggest the greatest synchrony to occur between 3 and 6 days. To explore the effect of IHE reopening on COVID-19, synchrony is compared between pre- and post-reopening windows. Results suggested that, following reopening, there are gains in detectable synchrony and that COVID-19 is in-flowing to Arkansas from all of its neighboring states. Taken together, results suggest that there is spatiality to COVID-19 with neighboring states having case infection rates that are significantly synchronous at a lag time that would be expected based on symptom onset. This synchrony is potentially strengthened by the in-flow and cross-border movement of IHE students.
900 MHz Radiofrequency Field Induces Mitochondrial Unfolded Protein Response in Mouse Bone Marrow Stem Cells

Objective: To examine whether exposure of mouse bone marrow stromal cells (BMSC) to 900 MHz radiofrequency fields used in mobile communication devices can induce mitochondrial unfolded protein response (UPRmt). Methods: BMSCs were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm2 power intensity for 4 h/d for 5 consecutive days. Cells in sham group (SH) were cultured in RF exposure system, but without RF radiation. The positive control cells were irradiated with 6 Gy X-ray at a dose rate of 1.103 Gy/min (XR). To inhibit the upstream molecular JNK2 of UPRmt, cells in siRNA + RF, and siRNA + XR group were also pretreated with 100 nM siRNA-JNK2 for 48 h before RF/XR exposure. Thirty minutes, 4 h, and 24 h post-RF/XR exposure, cells were collected, the level of ROS was measured with flow cytometry, the expression levels of UPRmt-related proteins were detected using western blot analysis. Results: Compared with Sham group, the level of ROS in RF and XR group was significantly increased 30 min and 4 h post-RF/XR exposure (P < 0.05), however, the RF/XR-induced increase of ROS level reversed 24 h post-RF/XR exposure. Compared with Sham group, the expression levels of HSP10/HSP60/ClpP proteins in cells of RF and XR group increased significantly 30 min and 4 h post-RF/XR exposure (P < 0.05), however, the RF/XR-induced increase of HSP10/HSP60/ClpP protein levels reversed 24 h post-RF exposure. After interfering with siRNA-JNK2, the RF/XR exposures could not induce the increase of HSP10/HSP60/ClpP protein levels any more. Conclusions: The exposure of 900 MHz RF at 120 μW/cm2 power flux density could increase ROS level and activate a transient UPRmt in BMSC cells. Mitochondrial homeostasis in term of protein folding ability is restored 24 h post-RF exposure. Exposure to RF in our experimental condition did not cause permanent and severe mitochondrial dysfunctions. However, the detailed underlying molecular mechanism of RF-induced UPRmt remains to be further studied.
From Click Chemistry to Cross-Coupling: Designer Polymers from One Efficient Reaction

Palladium-catalyzed Suzuki–Miyaura cross-coupling was demonstrated to be a versatile reaction platform to install functional groups onto well-defined polymers derived from reversible addition–fragmentation chain-transfer (RAFT) polymerization. Cross-coupled products were achieved utilizing a range of functional boronic acids including, but not limited to, furan, alkyloxyphenyl, methacrylamide, trifluorophenyl, anthracene, and dimethylaminophenyl. High to quantitative degrees of functionalization were obtained by employing convenient reaction conditions at low to moderate temperatures (23–60 °C), within short reaction times (2–16 h), while using air-stable reagents at 1.5–3.0 equiv. of boronic acid. Specifically, a custom monomer, N-[2-(4-bromophenyl)ethyl]acrylamide (BPEA), was synthesized bearing a reactive handle for subsequent cross-coupling, and its chemical structure was verified using nuclear magnetic resonance. RAFT polymerization of BPEA revealed attributes of a successful reversible-deactivation .
Daucus carota DcPSY2 and DcLCYB1 as Tools for Carotenoid Metabolic Engineering to Improve the Nutritional Value of Fruits

Carotenoids are pigments with important nutritional value in the human diet. As antioxidant molecules, they act as scavengers of free radicals enhancing immunity and preventing cancer and cardiovascular diseases. Moreover, α-carotene and β-carotene, the main carotenoids of carrots (Daucus carota) are precursors of vitamin A, whose deficiency in the diet can trigger night blindness and macular degeneration. With the aim of increasing the carotenoid content in fruit flesh, three key genes of the carotenoid pathway, phytoene synthase (DcPSY2) and lycopene cyclase (DcLCYB1) from carrots, and carotene desaturase (XdCrtI) from the yeast Xanthophyllomyces dendrorhous, were optimized for expression in apple and cloned under the Solanum chilense (tomatillo) polygalacturonase (PG) fruit specific promoter. A biotechnological platform was generated and functionally tested by subcellular localization, and single, double and triple combinations were both stably transformed in tomatoes (Solanum lycopersicum var. Microtom) and transiently transformed in Fuji apple fruit flesh (Malus domestica). We demonstrated the functionality of the S. chilense PG promoter by directing the expression of the transgenes specifically to fruits. Transgenic tomato fruits expressing DcPSY2, DcLCYB1, and DcPSY2-XdCRTI, produced 1.34, 2.0, and 1.99-fold more total carotenoids than wild-type fruits, respectively. Furthermore, transgenic tomatoes expressing DcLCYB1, DcPSY2-XdCRTI, and DcPSY2-XdCRTI-DcLCYB1 exhibited an increment in β-carotene levels of 2.5, 3.0, and 2.57-fold in comparison with wild-type fruits, respectively. Additionally, Fuji apple flesh agroinfiltrated with DcPSY2 and DcLCYB1 constructs showed a significant increase of 2.75 and 3.11-fold in total carotenoids and 5.11 and 5.84-fold in β-carotene, respectively whereas the expression of DcPSY2-XdCRTI and DcPSY2-XdCRTI-DcLCYB1 generated lower, but significant changes in the carotenoid profile of infiltrated apple flesh. The results in apple demonstrate that DcPSY2 and DcLCYB1 are suitable biotechnological genes to increase the carotenoid content in fruits of species with reduced amounts of these pigments.