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BioRxiv : the Preprint Server For... Jun 2024Severe invagination of the nuclear envelope is a hallmark of cancers, aging, neurodegeneration, and infections. However, the outcomes of nuclear invagination remain...
UNLABELLED
Severe invagination of the nuclear envelope is a hallmark of cancers, aging, neurodegeneration, and infections. However, the outcomes of nuclear invagination remain unclear. This work identified a new function of nuclear invagination: regulating ribosome biogenesis. With expansion microscopy, we observed frequent physical contact between nuclear invaginations and nucleoli. Surprisingly, the higher the invagination curvature, the more ribosomal RNA and pre-ribosomes are made in the contacted nucleolus. By growing cells on nanopillars that generate nuclear invaginations with desired curvatures, we can increase and decrease ribosome biogenesis. Based on this causation, we repressed the ribosome levels in breast cancer and progeria cells by growing cells on low-curvature nanopillars, indicating that overactivated ribosome biogenesis can be rescued by reshaping nuclei. Mechanistically, high-curvature nuclear invaginations reduce heterochromatin and enrich nuclear pore complexes, which promote ribosome biogenesis. We anticipate that our findings will serve as a foundation for further studies on nuclear deformation.
HIGHLIGHTS
Nuclear invaginations regulate ribosome biogenesis by physically contacting nucleoli.High-curvature nuclear tunnels increase ribosome biogenesis.Nanopillars reduce ribosome biogenesis by transforming high-curvature nuclear invaginations to low-curvature ones.
PubMed: 38948754
DOI: 10.1101/2024.06.21.597078 -
BioRxiv : the Preprint Server For... Jun 2024Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for...
UNLABELLED
Gram-negative bacteria harness the proton motive force (PMF) within their inner membrane (IM) to uphold the integrity of their cell envelope, an indispensable aspect for both division and survival. The IM TolQ-TolR complex is the essential part of the Tol-Pal system, serving as a conduit for PMF energy transfer to the outer membrane. Here we present cryo-EM reconstructions of TolQ in apo and TolR- bound forms at atomic resolution. The apo TolQ configuration manifests as a symmetric pentameric pore, featuring a trans-membrane funnel leading towards a cytoplasmic chamber. In contrast, the TolQ-TolR complex assumes a proton non-permeable stance, characterized by the TolQ pentamer's flexure to accommodate the TolR dimer, where two protomers undergo a translation-based relationship. Our structure-guided analysis and simulations support the rotor-stator mechanism of action, wherein the rotation of the TolQ pentamer harmonizes with the TolR protomers' interplay. These findings broaden our mechanistic comprehension of molecular stator units empowering critical functions within the Gram-negative bacterial cell envelope.
TEASER
Apo TolQ and TolQ-TolR structures depict structural rearrangements required for cell envelope organization in bacterial cell division.
PubMed: 38948712
DOI: 10.1101/2024.06.19.599759 -
BioRxiv : the Preprint Server For... Jun 2024Hairpin forming expanded CAG/CTG repeats pose significant challenges to DNA replication which can lead to replication fork collapse. Long CAG/CTG repeat tracts relocate...
UNLABELLED
Hairpin forming expanded CAG/CTG repeats pose significant challenges to DNA replication which can lead to replication fork collapse. Long CAG/CTG repeat tracts relocate to the nuclear pore complex to maintain their integrity. Forks impeded by DNA structures are known to activate the DNA damage checkpoint, thus we asked whether checkpoint proteins play a role in relocation of collapsed forks to the nuclear periphery in . We show that relocation of a (CAG/CTG) tract is dependent on activation of the Mrc1/Rad53 replication checkpoint. Further, checkpoint-mediated phosphorylation of the kinetochore protein Cep3 is required for relocation, implicating detachment of the centromere from the spindle pole body. Activation of this pathway leads to DNA damage-induced microtubule recruitment to the repeat. These data suggest a role for the DNA replication checkpoint in facilitating movement of collapsed replication forks to the nuclear periphery by centromere release and microtubule-directed motion.
HIGHLIGHTS
The DNA damage checkpoint is needed for relocation of a structure-forming CAG repeat tract to the nuclear pore complexThe importance of Mrc1 (hClaspin) implicates fork uncoupling as the initial checkpoint signalPhosphorylation of the Cep3 kinetochore protein by Dun1 kinase modulates centromere release, which is critical for collapsed fork repositioningDamage-inducible nuclear microtubules colocalize with the CAG repeat locus and are required for relocalizationEstablishes a new role for the DNA replication and DNA damage checkpoint response to trigger repositioning of collapsed forks within the nucleus.
PubMed: 38948692
DOI: 10.1101/2024.06.17.599319 -
Journal of Family Medicine and Primary... May 2024Skin pores (SPs) are normal and benign skin structures that are mostly located on the face (nose, cheeks, etc.) that cause many aesthetic concerns or complaints. One...
BACKGROUND AND PURPOSE
Skin pores (SPs) are normal and benign skin structures that are mostly located on the face (nose, cheeks, etc.) that cause many aesthetic concerns or complaints. One known effective treatment is botulinum toxin A (BTXA), which is also approved for the treatment of strabismus, blepharospasm, muscle spasm, cervical dystonia, glabella wrinkles, and primary axillary hyperhidrosis. Therefore, the aim of this study was to compare the effect of intra-dermal injection of botulinum toxin and normal saline serum (NSS) in the treatment of large facial pores.
METHODS
The study included 25 people who referred to the skin clinic of Imam Khomeini Hospital in Ahvaz from June 2021 to January 2022 for the treatment of large facial skin pores. Randomly, some subjects were injected with botulinum toxin at ten points, and each point was equivalent to 2.5 units of Masport (500 units vial of Masport diluted with 10 ml of NSS). Some other people were injected with 0.05 ml of NSS by intra-dermal injection at ten points. Finally, the data were analyzed using SPSS-Ver. 22 software.
RESULTS
Based on optical coherence tomography results, it was determined that the diameter of facial pores decreased significantly ( = 0.011). Dermoscopy showed a significant decrease in the average size of facial pores ( < 0.011), and also, the pore score decreased significantly ( = 0.021). In addition, the results showed that the size of skin pores and facial fat on both sides of the face did not decrease significantly from the patients' point of view ( = 0.71).
CONCLUSION
Based on the results of the present study, it can be concluded that intra-dermal injection of botulinum toxin is an effective and safe method to control facial pores, which showed acceptable results after 3 months.
PubMed: 38948607
DOI: 10.4103/jfmpc.jfmpc_1327_23 -
Regenerative Biomaterials 2024In recent years, bridging repair has emerged as an effective approach for the treatment of massive rotator cuff tears (MRCTs). The objective of this study was to develop...
In recent years, bridging repair has emerged as an effective approach for the treatment of massive rotator cuff tears (MRCTs). The objective of this study was to develop a composite patch that combines superior mechanical strength and biocompatibility and evaluate its potential for enhancing the outcomes of bridging repair for MRCTs. The composite patch, referred to as the PET-matrix patch (PM), was fabricated by immersing a plain-woven PET patch in decellularized matrix gel and utilizing the freeze-drying technique. The results demonstrated that the PM has reliable mechanical properties, with a maximum failure load of up to 480 N. The decellularized matrix sponge (DMS), present on the surface of the PM, displayed a loose and porous structure, with an average pore size of 62.51 μm and a porosity of 95.43%. experiments showed significant elongation of tenocytes on the DMS, with cells spanning across multiple pores and extending multiple protrusions as observed on SEM images. In contrast, tenocytes on the PET patch appeared smaller in size and lacked significant elongation. Additionally, the DMS facilitated the proliferation, migration and differentiation of tenocytes. In a rabbit model of chronic MRCTs, the PM group showed superior outcomes compared to the PET group at 4, 8 and 12 weeks after bridging repair. The PM group displayed significantly higher tendon maturing score, larger collagen diameter in the regenerated tendon and improved tendon-to-bone healing scores compared to the PET group (<0.05). Moreover, the maximum failure load of the tendon-bone complex in the PM group was significantly higher than that in the PET group (<0.05). In summary, the PM possesses reliable mechanical properties and excellent cytocompatibility, which can significantly improve the outcomes of bridging repair for chronic MRCTs in rabbits. Therefore, it holds great potential for clinical applications.
PubMed: 38948337
DOI: 10.1093/rb/rbae061 -
ACS Omega Jun 2024Coalfield fires represent a critical environmental and safety concern, warranting a comprehensive understanding of the factors influencing the reactivity of oxidized...
Coalfield fires represent a critical environmental and safety concern, warranting a comprehensive understanding of the factors influencing the reactivity of oxidized coal residues within fire zones. This study investigates the influence of the oxygen volume fraction and oxidation temperature on the residual structure of oxidized coal, elucidating the underlying mechanisms driving reduced coal reactivity. The representative oxidation conditions for coalfield fire zones were determined. Through industrial and elemental analyses, complemented by methods such as infrared diffuse reflection, specific surface area determination, and pore size analysis, results indicate that higher temperatures and oxygen levels decrease volatile matter and fixed carbon, notably above 400 °C due to oxygen-deficient combustion. Hydroxyl groups decrease with a rising temperature in high oxygen conditions, while carboxyl groups increase at lower temperatures with elevated oxygen. Oxygen-lean and high-temperature conditions reinforce the coal structure, evidenced by the reduced condensation index in aromatic hydrocarbon. Oxidation alters the pore morphology, progressing from micropores to larger irregular pores through various stages, including pore formation, expansion, and merging. Elevated oxygen levels intensify oxidation, consuming the coal carbon matrix and reducing micropores, hindering internal gas diffusion, which is the key to a reduced coal reactivity in fire zones.
PubMed: 38947841
DOI: 10.1021/acsomega.4c03605 -
ACS Omega Jun 2024Oligocene-Pliocene shale reservoirs in the Western Qaidam Depression represent typical mixed shale deposits characterized by moderate organic matter (OM) abundance and...
Oligocene-Pliocene shale reservoirs in the Western Qaidam Depression represent typical mixed shale deposits characterized by moderate organic matter (OM) abundance and sufficient OM maturity, indicating substantial shale-oil resource potential. Here, a comprehensive study was conducted to analyze the reservoir characteristics of different shale types, including the Upper Xiaganchaigou (late Oligocene), Shangganchaigou (Miocene), and Xiayoushashan (early Pliocene) Formations in the Western Qaidam Depression. Our analysis focused on the pore structural characteristics of shale reservoirs, employing X-ray diffraction, casting thin sections, scanning electron microscopy, low-temperature nitrogen adsorption, and nuclear magnetic resonance (NMR) as investigative techniques. Our results show that (1) the study area comprises five typical shale types: lime shale, argillaceous shale, limestone, argillaceous limestone, and mudstone. The best hydrocarbon source rock conditions are found in the lime shale and argillaceous shale. (2) Inorganic pores, including dissolution pores, intergranular pores, bedding fractures, structural fractures, and intraparticle pores in clay minerals, are the main pore types found in the studied samples and constitute the primary reservoir space for shale oil. On the basis of fractal dimensions obtained through NMR, the pores can be classified as micropores (<100 nm), mesopores (100-1000 nm), or macropores (>1000 nm). Mesopores are the main contributors to porosity. (3) The development of micropores is positively correlated with clay mineral content. The development of mesopores and macropores is influenced by the quartz, feldspar, dolomite, and calcite contents. Calcite content exhibits a negative correlation with porosity, suggesting that later-stage pore cementation hinders shale reservoir development. (4) The five typical shale reservoirs in the study area can be categorized into three types. Type I reservoir lithologies include lime shale and argillaceous shale; type II reservoir lithologies include limestone and argillaceous limestone; and type III reservoirs comprise mudstone. Type I and II reservoirs are of better quality than type III.
PubMed: 38947797
DOI: 10.1021/acsomega.4c03956 -
ACS Omega Jun 2024With the development of high-rise and large-scale modern structures, traditional concrete has become a design limitation due to its excessive dead weight. High-strength...
With the development of high-rise and large-scale modern structures, traditional concrete has become a design limitation due to its excessive dead weight. High-strength lightweight concrete is being emphasized. Lightweight concrete has low density and the characteristics of a brittle material. This is an important factor affecting the strength and ductility of the lightweight concrete. To improve these shortcomings and proffer solutions, a three-phase composite lightweight concrete was prepared using a combination of tumbling and molding methods. This paper investigates the various influencing factors such as the stacking volume fraction of GFR-EMS, the type of fiber, and the content and length of fiber in the matrix. Studies have shown that the addition of fibers significantly increases the compressive strength of the concrete. The compressive strength of concrete with a 12 mm basalt fiber (BF) (1.5%) admixture is 9.08 MPa, which is 62.43% higher than that of concrete without the fiber admixture. The compressive strength was increased by 27.53 and 21.88% compared to concrete containing 3 mm BF (1.5%) and 0.5% BF (12 mm), respectively. Fibers can fill the pore defects within the matrix. Mutually overlapping fibers easily form a network structure to improve the bond between the cement matrix and the aggregate particles. The compressive strength of lightweight concrete with the addition of BF was 16.71% higher than that with the addition of polypropylene fiber (PPF) with the same length and content of fibers. BF has been shown to be more effective in improving the mechanical properties of concrete. In this work, the compressive mechanism and optimum preparation parameters of a three-phase composite lightweight concrete were analyzed through compression tests. This provides some insights into the development of lightweight concrete.
PubMed: 38947776
DOI: 10.1021/acsomega.3c10076 -
IScience Jun 2024experiments and cryo-EM structures of p97 and its cofactor, Ufd1/Npl4 (UN), elucidated substrate processing. Yet, the structural transitions and the related ATPase...
experiments and cryo-EM structures of p97 and its cofactor, Ufd1/Npl4 (UN), elucidated substrate processing. Yet, the structural transitions and the related ATPase cycle upon UN binding remain unresolved. We captured two discrete conformations: One in which D1 protomers are ATP bound, while the D2 subunits are in the ADP state, presumably required for substrate engagement with the D2 pore; and a heterologous nucleotide state within the D1 ring in which only two NTDs are in the "up" ATP state that favors UN binding. Further analysis suggests that initially, UN binds p97's non-symmetrical conformation, this association promotes a structural transition upon which five NTDs shift to an "up" state and are poised to bind ATP. The UBXL domain of Npl4 was captured bound to an NTD in the ADP state, demonstrating a conformation that may provide directionality to incoming substrate and introduce the flexibility needed for substrate processing.
PubMed: 38947518
DOI: 10.1016/j.isci.2024.110061 -
IScience Jun 2024In recent years, vegetation plays a key role in landslide stability under extreme rainfall in the Three Gorges Reservoir area, so it is very important to identify the...
In recent years, vegetation plays a key role in landslide stability under extreme rainfall in the Three Gorges Reservoir area, so it is very important to identify the mechanism of vegetation slope protection. This study takes wildcat landslide in Three Gorges Reservoir area as the research object, using indoor landslide model test and building monitoring systems such as stress field, displacement field, and soil erosion, to illustrate the protective effect of typical vegetation. Furthermore, Bermuda cover effectively reduces pore water pressure, pore soil pressure, displacement, and turbidity. In particular, the three stages of interception and buffering of rainfall by stems and leaves, infiltration and absorption of rainfall by the root system, and the reinforcement of the slope against sliding forces by the root system have been divided. Moreover, these findings offer valuable preliminary insights for guiding landslide mitigation strategies in the Three Gorges Reservoir area.
PubMed: 38947505
DOI: 10.1016/j.isci.2024.110057