Growth Defects Research Articles

Growth disturbances of the temporomandibular joint: causes, diagnosis and treatment

Growth disturbances of the temporomandibular Joint are characterized by mandibular asymmetry, sometimes with secondary maxillar disturbances. Although the clinical symptoms are sometimes quite severe, patients usually have no pain. There are several growth disturbances, but in this article we discuss three particular causes of facial asymmetry, namely hemimandibular growth defects; overdevelopment, underdevelopment and neoplasms of the mandibular joint. Hemimandibular overdevelopment (hyperplasia) is a growth disorder characterized by progressive asymmetry of the mandibula. Hemimandibular hypoplasia, on the other hand, is a growth disorder involving underdevelopment of the condyle mandibulae due to impingement of the growth center and ankylosing. A pronounced asymmetrical face can cause aesthetic problems and always requires diagnostics, because in addition to the hyperplasia and hypoplasia mentioned above, other causes can explain the asymmetry such as, for example, an osteoarthritis or even a tumor emanating from the base of the skull, mandibula or soft tissues.

FgPfn participates in vegetative growth, sexual reproduction, pathogenicity, and fungicides sensitivity via affecting both microtubules and actin in the filamentous fungus Fusarium graminearum.

Fusarium head blight (FHB), caused by Fusarium graminearum species complexes (FGSG), is an epidemic disease in wheat and poses a serious threat to wheat production and security worldwide. Profilins are a class of actin-binding proteins that participate in actin depolymerization. However, the roles of profilins in plant fungal pathogens remain largely unexplored. Here, we identified FgPfn, a homolog to profilins in F. graminearum, and the deletion of FgPfn resulted in severe defects in mycelial growth, conidia production, and pathogenicity, accompanied by marked disruptions in toxisomes formation and deoxynivalenol (DON) transport, while sexual development was aborted. Additionally, FgPfn interacted with Fgα1 and Fgβ2, the significant components of microtubules. The organization of microtubules in the ΔFgPfn was strongly inhibited under the treatment of 0.4 μg/mL carbendazim, a well-known group of tubulin interferers, resulting in increased sensitivity to carbendazim. Moreover, FgPfn interacted with both myosin-5 (FgMyo5) and actin (FgAct), the targets of the fungicide phenamacril, and these interactions were reduced after phenamacril treatment. The deletion of FgPfn disrupted the normal organization of FgMyo5 and FgAct cytoskeleton, weakened the interaction between FgMyo5 and FgAct, and resulting in increased sensitivity to phenamacril. The core region of the interaction between FgPfn and FgAct was investigated, revealing that the integrity of both proteins was necessary for their interaction. Furthermore, mutations in R72, R77, R86, G91, I101, A112, G113, and D124 caused the non-interaction between FgPfn and FgAct. The R86K, I101E, and D124E mutants in FgPfn resulted in severe defects in actin organization, development, and pathogenicity. Taken together, this study revealed the role of FgPfn-dependent cytoskeleton in development, DON production and transport, fungicides sensitivity in F. graminearum.

Epithelial Skiv2l deletion promotes aberrant secretory cell differentiation in the small intestine

Background: Inflammatory bowel disease (IBD) remains a global concern, with millions affected and incidence increasing. The etiology of IBD is multifaceted, but gene variants in epithelial and immune cells can contribute to its onset. Trichohepatoenteric syndrome (THES) is a form of monogenic very early onset IBD (VEO-IBD) that arises due to variants in SKIV2L and TTC37, which are components of the cytoplasmic RNA exosome involved in mRNA quality control. Patients with THES experience a decreased quality of life characterized by poor growth, intractable diarrhea, and immune defects. There are limited drugs approved by the FDA for treatment of IBD in children and those that have been approved are geared towards suppressing the immune system and have side effects. Therefore, there is a need for the development of therapeutics that target epithelial regeneration and repair. Understanding how genetic variants, such as those observed in THES, are involved in epithelial function is one avenue to improved therapies. The objective of the current study is to understand how the RNA exosome contributes to intestinal epithelial homeostasis by studying deletion of SKIV2L. Preclinical studies in mice revealed that global Skiv2l deletion resulted in increased mTOR signaling, and overactivated T cells, while B cell specific deletion of Skiv2l led to impaired B cell development. Ex vivo studies from our lab revealed that colonoids from THES patients exhibit decreased organoid formation effciency (OFE), suggesting that SKIV2L may have important roles in the intestinal stem cell self-renewal. We hypothesize that SKIV2L is required for intestinal epithelial cell growth and tissue function. Methods: We generated VillinCre;Skiv2l ( Skiv2l KO) mice with Skiv2l deletion in intestinal epithelial cells. Skiv2l WT and KO mice weights were monitored weekly, starting from ~2 weeks of age. Between 4 and 6 weeks of age, intestines were harvested for immunofluorescence, flow cytometry and OFE assays. Results and conclusion: Skiv2l KO mice experienced failure to thrive, were significantly smaller, and had shorter colons and small intestines compared to their WT counterparts. Immunofluorescence and flow cytometry revealed increased secretory cells in the small intestine of Skiv2l KO compared to WT mice, with significant accumulation of goblet cells in the crypt region in KO mice. Furthermore, Skiv2l KO mice had reduced OFE. These findings suggest that SKIV2L is essential for intestinal homeostasis and that aberrant secretory cell differentiation may underlie the decreased stem cell self-renewal observed in Skiv2l KO mice and THES patients. More broadly, these studies suggest an essential role for mRNA quality control in normal intestinal homeostasis. University of Pennsylvania, Institution of Regenerative Medicine; NIH R01DK124369. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nodular defects aggravated tribocorrosion failure mechanism in Cr/GLC multilayer coatings for marine applications

Amorphous carbon coatings by various physical vapor deposition (PVD) have been widely attempted for enhancing both anti-wear and corrosion resistance of bulk materials used in harsh marine environments. However, PVD coatings are apt to be worn due to the existence of growth defects mostly like macro-size nodular particles. In this work, we deliberately fabricated the SiO2 nanoparticles with a size of 200 nm as nodular defects in Cr and graphite-like carbon (Cr/GLC) multilayer coatings, and the dependence of tribocorrosion behavior of coating on the nodular defects was focused by the comprehensively tribological and electrochemical tests. The results showed that introducing SiO2 nodular particles could not degrade the mechanical properties of Cr/GLC coating, but significantly accelerated both the abrasive wear in early sliding-stage under dry friction and the corrosive failure in chloride solution. Particularly, once the tribocorrosion tests in 3.5 wt.% NaCl solution were conducted for the Cr/GLC coating with nodular defects, the distinct ploughing damage originated from abrasive wear promoted the localized spallation of coatings, which thereafter enabled the easy water wedging along spallation for the substantial catastrophe of coatings. The present observations could evident the importance to fabricate the defect-free protective coatings required for harsh tribocorrosion applications.

Golgi-localized APYRASE 1 is critical for Arabidopsis growth by affecting cell wall integrity under boron deficiency.

Many nucleoside triphosphate-diphosphohydrolases (NTPDases/APYRASEs, APYs) play a key role in modulating extracellular nucleotide levels. However, the Golgi-localized APYs, which help control glycosylation, have rarely been studied. Here, we identified AtAPY1, a gene encoding an NTPDase in the Golgi apparatus, which is required for cell wall integrity and plant growth under boron (B) limited availability. Loss of function in AtAPY1 hindered cell elongation and division in root tips while increasing the number of cortical cell layers, leading to swelling of the root tip and abundant root hairs under low B stress. Further, expression pattern analysis revealed that B deficiency significantly induced AtAPY1, especially in the root meristem and stele. Fluorescent-labeled AtAPY1-GFP localized to the Golgi stack. Biochemical analysis showed that AtAPY1 exhibited a preference of UDP and GDP hydrolysis activities. Consequently, the loss of function in AtAPY1 might disturb the homoeostasis of NMP-driven NDP-sugar transport, which was closely related to the synthesis of cell wall polysaccharides. Further, cell wall-composition analysis showed that pectin content increased and borate-dimerized RG-II decreased in apy1 mutants, along with a decrease in cellulose content. Eventually, altered polysaccharide characteristics presumably cause growth defects in apy1 mutants under B deficiency. Altogether, these data strongly support a novel role for AtAPY1 in mediating responses to low B availability by regulating cell wall integrity.

The Transcription Factors AcuK and AcuM Influence Siderophore Biosynthesis of Aspergillus fumigatus.

The mold Aspergillus fumigatus employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the essential trace element iron. SIA has previously been shown to be crucial for virulence in mammalian hosts. Here, we show that a lack of AcuK or AcuM, transcription factors required for the activation of gluconeogenesis, decreases the production of both extra- and intracellular siderophores in A. fumigatus. The lack of AcuM or AcuK did not affect the expression of genes involved in RIA and SIA, suggesting that these regulators do not directly regulate iron homeostasis genes, but indirectly affect siderophore production through their influence on metabolism. Consistent with this, acetate supplementation reversed the intracellular siderophore production defect of ΔacuM and ΔacuK. Moreover, ΔacuM and ΔacuK displayed a similar growth defect under iron limitation and iron sufficiency, which suggests they have a general role in carbon metabolism apart from gluconeogenesis. In agreement with a potential role of the glyoxylate cycle in adaptation to iron starvation, transcript levels of the malate synthase-encoding acuE were found to be upregulated by iron limitation that is partially dependent on AcuK and AcuM. Together, these data demonstrate the influence of iron availability on carbon metabolism.

The ING protein Fng2 associated with RPD3 HDAC complex for the regulation of fungal development and pathogenesis in wheat head blight fungus

ING proteins display a high level of evolutionary conservation across various species, and play a crucial role in modulating histone acetylation levels, thus regulating various important biological processes in yeast and humans. Filamentous fungi possess distinct biological characteristics that differentiate them from yeasts and humans, and the specific roles of ING proteins in filamentous fungi remain largely unexplored. In this study, an ING protein, Fng2, orthologous to the yeast Pho23, has been identified in the wheat head blight fungus Fusarium graminearum. The deletion of the FNG2 gene resulted in defects in vegetative growth, conidiation, sexual reproduction, plant infection, and deoxynivalenol (DON) biosynthesis. Acting as a global regulator, Fng2 exerts negative control over histone H4 acetylation and governs the expression of over 4000 genes. Moreover, almost half of the differentially expressed genes in the fng3 mutant were found to be co-regulated by Fng2, emphasizing the functional association between these two ING proteins. Notably, the fng2 fng3 double mutant exhibits significantly increased H4 acetylation and severe defects in both fungal development and pathogenesis. Furthermore, Fng2 localizes within the nucleus and associates with the FgRpd3 histone deacetylase (HDAC) to modulate gene expression. Overall, Fng2's interaction with FgRpd3, along with its functional association with Fng3, underscores its crucial involvement in governing gene expression, thereby significantly influencing fungal growth, asexual and sexual development, pathogenicity, and secondary metabolism.

Boron modulates cell wall structure that alleviate aluminum toxicity-induced root growth defects in citrus

Based on the soil acidification situation in citrus plantation of southern China and even worldwide, it's essential to explore improved methods for resistant aluminum (Al) toxicity in plant. Trifoliate (Poncirus trifoliate (L) Raf.) is the most common rootstock in China. The ambition of this research was to illustrate the influence of boron (B) on Al bound in cell wall (CW) and the mechanism in trifoliate seedlings. Healthy seedlings were exposed to 0 or 300 µM AlCl3·6H2O with 10 µM B (H3BO3, control) and 50 µM B, respectively. The results displayed that Al accumulated in roots and root tips during Al exposure. However, Al content in root rips was reduced under B sufficient that reflected by lower morin fluorescence intensity compared to B10-treated roots. More specifically, B addition abates the Al content in root CW, manifested in lower Al content in pectin and hemicellulose 1 (HC1), with HC1 being more prominent. Moreover, B addition inhibited the pectin methyl-esterase (PME) activity to reduce pectin content, while increasing the xyloglucan endotransglucosylase (XET) and xyloglucan endotransglucosylase-hydrolase (XEH) activity. Thereby HC1 content was decreased, ultimately suppressing the bound site of Al in pectin and HC1, and diminished Al content in CW with B supply. Collectively, our results illustrate that B supply was attributed to the mitigation effect of B on Al toxicity by induced devaluation of Al accumulation in CW, which was associated with the reduction of binding Al with pectin and HC1 by regulating compounds of CW through adjusting CW enzymes (PME, XET, and XEH).

IL-6 promotes tumor growth through immune evasion but is dispensable for cachexia

Various cytokines have been implicated in cancer cachexia. One such cytokine is IL-6, deemed as a key cachectic factor in mice inoculated with colon carcinoma 26 (C26) cells, a widely used cancer cachexia model. Here we tested the causal role of IL-6 in cancer cachexia by knocking out the IL-6 gene in C26 cells. We found that the growth of IL-6 KO tumors was dramatically delayed. More strikingly, while IL-6 KO tumors eventually reached the similar size as wild-type tumors, cachexia still took place, despite no elevation in circulating IL-6. In addition, the knockout of leukemia inhibitory factor (LIF), another IL-6 family cytokine proposed as a cachectic factor in the model, also affected tumor growth but not cachexia. We further showed an increase in the infiltration of immune cell population in the IL-6 KO tumors compared with wild-type controls and the defective IL-6 KO tumor growth was rescued in immunodeficient mice while cachexia was not. Thus, IL-6 promotes tumor growth by facilitating immune evasion but is dispensable for cachexia.

Identification of a 1-acyl-glycerol-3-phosphate acyltransferase from Mycobacterium tuberculosis, a key enzyme involved in triacylglycerol biosynthesis.

Latent tuberculosis, caused by dormant Mycobacterium tuberculosis (Mtb), poses a threat to global health through the incubation of undiagnosed infections within the community. Dormant Mtb, which is phenotypically tolerant to antibiotics, accumulates triacylglycerol (TAG) utilizing fatty acids obtained from macrophage lipid droplets. TAG is vital to mycobacteria, serving as a cell envelope component and energy reservoir during latency. TAG synthesis occurs by sequential acylation of glycerol-3-phosphate, wherein the second acylation step is catalyzed by acylglycerol-3-phosphate acyltransferase (AGPAT), resulting in the production of phosphatidic acid (PA), a precursor for the synthesis of TAG and various phospholipids. Here, we have characterized a putative acyltransferase of Mtb encoded by Rv3816c. We found that Rv3816c has all four characteristic motifs of AGPAT, exists as a membrane-bound enzyme, and functions as 1-acylglycerol-3-phosphate acyltransferase. The enzyme could transfer the acyl group to acylglycerol-3-phosphate (LPA) from monounsaturated fatty acyl-coenzyme A of chain length 16 or 18 to produce PA. Complementation of Escherichia coli PlsC mutant invivo by Rv3816c confirmed that it functions as AGPAT. Its active site mutants, H43A and D48A, were incapable of transferring the acyl group to LPA invitro and were not able to rescue the growth defect of E. coli PlsC mutant invivo. Identifying Rv3816c as AGPAT and comparing its properties with other AGPAT homologs is not only a step toward understanding the TAG biosynthesis in mycobacteria but has the potential to explore it as a drug target.

Optimal nitrogen source for the recovery of phycoerythrin in discolored Rhodomonas sp.

Rhodomonas species are of interest as excellent aquaculture feed because of their ideal biochemical composition, especially their high protein content, resulting from the presence of intracellular phycoerythrin (PE). One of the most crucial issue with this species as a feed source is PE degradation under ambient nitrogen starvation, which leads to unpredictable growth defects and reduced nutritional value associated with cell discoloration. The aim of this study was to propose an optimal nitrogen source for the recovery of intracellular PE in discolored Rhodomonas sp. We supplied three different nitrogen sources, i.e., nitrate, ammonium, and urea, to PE-degraded cells and monitored changes in PE content and the expression of related genes. Supplementation with each nitrogen source increased cell density, with nitrate exhibiting the highest specific growth rate of 0.30 ± 0.02 day−1. The maximum PE content in each nitrogen group at 48 h after N supplementation was about 3.8 pg cell−1 with no major difference between groups. In contrast, the highest relative PE recovery rate of 5.73 ± 0.18-fold and the highest PE productivities of 0.32 ± 0.01 μg mL−1 h−1 were obtained in the nitrate group. Nitrogen transporter genes, including RhNrt2, RhAmt1, and RhDur3, were upregulated under nitrogen-starvation conditions, demonstrating the ability of this species to utilize each of the tested nitrogen sources. Furthermore, RhCpeb, which serves as a molecular indicator of PE biosynthesis, was significantly upregulated in all nitrogen-supplemented groups, with the strongest and fastest increase in expression in the nitrate group, emphasizing the potential of nitrate as the most favorable nitrogen source for PE recovery in this species. Our findings pave the way for informed strategies for the stable management and production of Rhodomonas species as high-protein feed in aquaculture.

Functional Differentiation of the Succinate Dehydrogenase Subunit SdhC Governs the Sensitivity to SDHI Fungicides, ROS Homeostasis, and Pathogenicity in Fusarium asiaticum.

Succinate dehydrogenase (SDH) is an integral component of the tricarboxylic acid cycle (TCA) and respiratory electron transport chain (ETC), targeted by succinate dehydrogenase inhibitors (SDHIs). Fusarium asiaticum is a prominent phytopathogen causing Fusarium head blight (FHB) on wheat. Here, we characterized the functions of the FaSdhA, FaSdhB, FaSdhC1, FaSdhC2, and FaSdhD subunits. Deletion of FaSdhA, FaSdhB, or FaSdhD resulted in significant growth defects in F. asiaticum. The FaSdhC1 or FaSdhC2 deletion mutants exhibited substantial reductions in fungal growth, conidiation, virulence, and reactive oxygen species (ROS). The FaSdhC1 expression was significantly induced by pydiflumetofen (PYD). The ΔFaSdhC1 mutant displayed hypersensitivity to SDHIs, whereas the ΔFaSdhC2 mutant exhibited resistance against most SDHIs. The transmembrane domains of FaSdhC1 are essential for regulating mycelial growth, virulence, and sensitivity to SDHIs. These findings provided valuable insights into how the two SdhC paralogues regulated the functional integrity of SDH, ROS homeostasis, and the sensitivity to SDHIs in phytopathogenic fungi.

SUMO protease FUG1, histone reader AL3 and chromodomain protein LHP1 are integral to repeat expansion-induced gene silencing in Arabidopsis thaliana.

Epigenetic gene silencing induced by expanded repeats can cause diverse phenotypes ranging from severe growth defects in plants to genetic diseases such as Friedreich's ataxia in humans. The molecular mechanisms underlying repeat expansion-induced epigenetic silencing remain largely unknown. Using a plant model with a temperature-sensitive phenotype, we have previously shown that expanded repeats can induce small RNAs, which in turn can lead to epigenetic silencing through the RNA-dependent DNA methylation pathway. Here, using a genetic suppressor screen and yeast two-hybrid assays, we identified novel components required for epigenetic silencing caused by expanded repeats. We show that FOURTH ULP GENE CLASS 1 (FUG1)-an uncharacterized SUMO protease with no known role in gene silencing-is required for epigenetic silencing caused by expanded repeats. In addition, we demonstrate that FUG1 physically interacts with ALFIN-LIKE 3 (AL3)-a histone reader that is known to bind to active histone mark H3K4me2/3. Loss of function of AL3 abolishes epigenetic silencing caused by expanded repeats. AL3 physically interacts with the chromodomain protein LIKE HETEROCHROMATIN 1 (LHP1)-known to be associated with the spread of the repressive histone mark H3K27me3 to cause repeat expansion-induced epigenetic silencing. Loss of any of these components suppresses repeat expansion-associated phenotypes coupled with an increase in IIL1 expression with the reversal of gene silencing and associated change in epigenetic marks. Our findings suggest that the FUG1-AL3-LHP1 module is essential to confer repeat expansion-associated epigenetic silencing and highlight the importance of post-translational modifiers and histone readers in epigenetic silencing.

Mistranslating the genetic code with leucine in yeast and mammalian cells

ABSTRACT Translation fidelity relies on accurate aminoacylation of transfer RNAs (tRNAs) by aminoacyl-tRNA synthetases (AARSs). AARSs specific for alanine (Ala), leucine (Leu), serine, and pyrrolysine do not recognize the anticodon bases. Single nucleotide anticodon variants in their cognate tRNAs can lead to mistranslation. Human genomes include both rare and more common mistranslating tRNA variants. We investigated three rare human tRNALeu variants that mis-incorporate Leu at phenylalanine or tryptophan codons. Expression of each tRNALeu anticodon variant in neuroblastoma cells caused defects in fluorescent protein production without significantly increased cytotoxicity under normal conditions or in the context of proteasome inhibition. Using tRNA sequencing and mass spectrometry we confirmed that each tRNALeu variant was expressed and generated mistranslation with Leu. To probe the flexibility of the entire genetic code towards Leu mis-incorporation, we created 64 yeast strains to express all possible tRNALeu anticodon variants in a doxycycline-inducible system. While some variants showed mild or no growth defects, many anticodon variants, enriched with G/C at positions 35 and 36, including those replacing Leu for proline, arginine, alanine, or glycine, caused dramatic reductions in growth. Differential phenotypic defects were observed for tRNALeu mutants with synonymous anticodons and for different tRNALeu isoacceptors with the same anticodon. A comparison to tRNAAla anticodon variants demonstrates that Ala mis-incorporation is more tolerable than Leu at nearly every codon. The data show that the nature of the amino acid substitution, the tRNA gene, and the anticodon are each important factors that influence the ability of cells to tolerate mistranslating tRNAs.

CPK10 protein kinase regulates Arabidopsis tolerance to borondeficiency through phosphorylation and activation of BOR1 transporter.

Boron (B) is crucial for plant growth and development. B deficiency can impair numerous physiological and metabolic processes, particularly in root development and pollen germination, seriously impeding crop growth and yield. However, the molecular mechanism underlying boron signal perception and signal transduction is rather limited. In this study, we discovered that CPK10, a calcium-dependent protein kinase in the CPK family, has the strongest interaction with the boron transporter BOR1. Mutations in CPK10 led to growth and root development defects under B-deficiency conditions, while constitutively active CPK10 enhanced plant tolerance to B deficiency. Furthermore, we found that CPK10 interacted with and phosphorylated BOR1 at the Ser689 residue. Through various biochemical analyses and complementation of B transport in yeast and plants, we revealed that Ser689 of BOR1 is important for its transport activity. In summary, these findings highlight the significance of the CPK10-BOR1 signaling pathway in maintaining B homeostasis in plants and provide targets for the genetic improvement of crop tolerance to B-deficiency stress.

FgFAD12 Regulates Vegetative Growth, Pathogenicity and Linoleic Acid Biosynthesis in Fusarium graminearum.

Polyunsaturated fatty acids (PUFAs), as important components of lipids, play indispensable roles in the development of all organisms. ∆12 fatty acid desaturase (FAD12) is a speed-determining step in the biosynthesis of PUFAs. Here, we report the characterization of FAD12 in Fusarium graminearum, which is the prevalent agent of Fusarium head blight, a destructive plant disease worldwide. The results demonstrated that deletion of the FgFAD12 gene resulted in defects in vegetative growth, conidial germination and plant pathogenesis but not sexual reproduction. A fatty acid analysis further proved that the deletion of FgFAD12 restrained the reaction of oleic acid to linoleic acid, and a large amount of oleic acid was detected in the cells. Moreover, the ∆Fgfad12 mutant showed increased resistance to osmotic stress and reduced tolerance to oxidative stress. The expression of FgFAD12 did show a temperature-dependent manner, which was not affected at a low temperature of 10 °C when compared to 25 °C. RNA-seq analysis further demonstrated that most genes enriched in fatty acid metabolism, the biosynthesis of unsaturated fatty acids, fatty acid biosynthesis, fatty acid degradation, steroid biosynthesis and fatty acid elongation pathways were significantly up-regulated in the ∆Fgfad12 mutants. Overall, our results indicate that FgFAD12 is essential for linoleic acid biosynthesis and plays an important role in the infection process of F. graminearum.

BmATAD3A mediates mitochondrial ribosomal protein expression to maintain the mitochondrial energy metabolism of the silkworm, Bombyx mori.

ATAD3A is a mitochondrial membrane protein belonging to the ATPase family that contains the AAA+ domain. It is widely involved in mitochondrial metabolism, protein transport, cell growth, development and other important life processes. It has previously been reported that the deletion of ATAD3A causes growth and development defects in humans, mice and Caenorhabditis elegans. To delve into the mechanism underlying ATAD3A defects and their impact on development, we constructed a Bombyx mori ATAD3A (BmATAD3A) defect model in silkworm larvae. We aim to offer a reference for understanding ATAD3A genetic defects and elucidating the molecular regulatory mechanisms. The results showed that knockout of the BmATAD3A gene significantly affected the weight, survival rate, ATPase production and mitochondrial metabolism of individuals after 24h of incubation. Combined metabolomics and transcriptomics analysis further demonstrated that BmATAD3A knockout inhibits amino acid biosynthesis through the regulation of mitochondrial ribosomal protein expression. Simultaneously, our findings indicate that BmATAD3A knockout impeded mitochondrial activity and ATPase synthesis and suppressed the mitochondrial oxidative phosphorylation pathway through B.mori mitochondrial ribosomal protein L11 (BmmRpL11). These results provide novel insights into the molecular mechanisms involved in the inhibition of development caused by ATAD3A deficiency, offering a potential direction for targeted therapy in diseases associated with abnormal ATAD3A expression.

Pps1, phosphatidylserine synthase, regulates the salt stress response in Schizosaccharomyces pombe.

Phosphatidylserine (PS) is important for maintaining growth, cytoskeleton, and various functions in yeast; however, its role in stress responses is poorly understood. In Schizosaccharomyces pombe, the PS synthase deletion (pps1∆) mutant shows defects in growth, morphology, cytokinesis, actin cytoskeleton, and cell wall integrity, and these phenotypes are rescued by ethanolamine supplementation. Here, we evaluated the role of Pps1 in the salt stress response in S. pombe. We found that pps1∆ cells are sensitive to salt stresses such as KCl and CaCl2 even in the presence of ethanolamine. Loss of the functional cAMP-dependent protein kinase (git3∆ or pka1∆) or phospholipase B Plb1 (plb1∆) enhanced the salt stress-sensitive phenotype in pps1∆ cells. Green fluorescent protein (GFP)-Pps1 was localized at the plasma membrane and endoplasmic reticulum regardless of the stress conditions. In pka1∆ cells, GFP-Pps1 was accumulated around the nucleus under the KCl stress. Pka1 was localized in the nucleus and the cytoplasm under normal conditions and transferred from the nucleus to the cytoplasm under salt-stress conditions. Pka1 translocated from the nucleus to the cytoplasm during CaCl2 stress in the wild-type cells, while it remained localized in the nucleus in pps1∆ cells. Expression and phosphorylation of Pka1-GFP were not changed in pps1∆ cells. Our results demonstrate that Pps1 plays an important role in the salt stress response in S. pombe.

Human AAA+ATPase FIGNL1 suppresses RAD51-mediated ultra-fine bridge formation.

RAD51 filament is crucial for the homology-dependent repair of DNA double-strand breaks and stalled DNA replication fork protection. Positive and negative regulators control RAD51 filament assembly and disassembly. RAD51 is vital for genome integrity but excessive accumulation of RAD51 on chromatin causes genome instability and growth defects. However, the detailed mechanism underlying RAD51 disassembly by negative regulators and the physiological consequence of abnormal RAD51 persistence remain largely unknown. Here, we report the role of the human AAA+ATPase FIGNL1 in suppressing a novel type of RAD51-mediated genome instability. FIGNL1 knockout human cells were defective in RAD51 dissociation after replication fork restart and accumulated ultra-fine chromosome bridges (UFBs), whose formation depends on RAD51 rather than replication fork stalling. FIGNL1 suppresses homologous recombination intermediate-like UFBs generated between sister chromatids at genomic loci with repeated sequences such as telomeres and centromeres. These data suggest that RAD51 persistence per se induces the formation of unresolved linkage between sister chromatids resulting in catastrophic genome instability. FIGNL1 facilitates post-replicative disassembly of RAD51 filament to suppress abnormal recombination intermediates and UFBs. These findings implicate FIGNL1 as a key factor required for active RAD51 removal after processing of stalled replication forks, which is essential to maintain genome stability.

Expanding the applications of the wear-resistant titanium aluminum nitride thin-film to include temperature sensing

This study investigates an approach to temperature sensing by integrating Titanium Aluminum Nitride (TiAlN), originally engineered for wear and corrosion applications, as a temperature sensor within a multilayered thin film system. A nitride multilayer system was developed by physical vapor deposition (PVD) using a single four-target magnetron sputtering chamber; intermediate vacuum interruption steps were employed for masking procedures. The multilayer architecture design aimed to provide the sensor layer with mechanical protection and electrical shielding. Structural and electrical characterization of the TiAlN single layer revealed semiconductor behavior and stable electrical resistance up to 750 °C, with minimal signal stabilization requirements. Despite the higher Al content, the TiAlN temperature sensor exhibited a cubic crystal structure characterized by diffuse nanolayers, resulting from a two-fold rotational deposition and target configuration. A detailed examination of the multilayer system cross-section containing the TiAlN sensor was conducted using scanning transmission electron microscopy (STEM). The analysis revealed its columnar morphology with the presence of typical PVD growth defects, including voids and droplets. While the presence of these defects may impact the electrical characteristics of the sensor, the selected experimental conditions effectively maintained the structural integrity of the multilayer system despite the vacuum interruptions caused by masking procedures. Validation experiments confirmed the functionality of the multilayer system for temperature measurements up to 400 °C. The signal acquisition system addressed room temperature resistance variations and low sensitivity (thermistor coefficient ∼100 K), resulting in a measured error of approximately 6%. This study demonstrates promising results of TiAlN as a temperature sensor within a multilayered system, expanding its range of potential applications.