Fatty Acid Biosynthesis Genes Research Articles

De novo transcriptome analysis and gene expression profiling of Conticribra weissflogii during low salinity reveals regulation of fatty acid biosynthesis genes

De novo transcriptome analysis and gene expression profiling of Conticribra weissflogii during low salinity reveals regulation of fatty acid biosynthesis genes

Rice Protein Peptides Alleviate Alcoholic Liver Disease via the PPARγ Signaling Pathway: Through Liver Metabolomics and Gut Microbiota Analysis.

Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of Alloprevotella and Alistipes, and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.

Metabolic changes in response to food intake in somatostatin 1.1 deficient zebrafish

Somatostatin is a multifunctional hormone with several genes in teleost fishes. A zebrafish CRISPR/Cas9 knockout of the somatostatin 1.1 (sst1.1) with persistent hyperglycaemia and hyperlipidaemia displayed reduced fecundity when fed brine shrimp ad libitum. Here, we investigated the effect of feeding brine shrimp one to three times a day on fecundity and liver transcriptomics of the sst1.1 mutant compared to their wild-type siblings to unravel molecular pathways associated with the phenotype. We find that the sst1.1 deficient zebrafish had high mortality when fed at the highest rate and that in both genotypes, growth and fecundity were proportional to food intake. Although glucose and cholesterol decreased substantially at the lowest level of feeding, they were still higher in the mutant than in the wild-type zebrafish. Furthermore, sst1.1 deficiency had a small but significant effect on the hepatic expression of protein, carbohydrate, and fatty acid biosynthesis genes, contributing to the mutant's diabetic phenotype.

Zinc nutrition at first feeding imprints a programming effect on growth and hepatic lipid metabolism in juvenile rainbow trout

The objective of this study was to determine whether supplementation with deficient zinc (Zn) or/and excess copper (Cu) in the first-feeding diet of rainbow trout fry influenced the growth and physiological regulation of juvenile fish subjected to similar challenge feeds again. The feeding trial lasted for 24 weeks and had three phases. In phase I, rainbow trout fry was treated with one of four different plant-based feeds containing or exempting Zn or Cu supplementation (coded Zn-Cu-, Zn+Cu-, Zn-Cu+, Zn+Cu+) for 6 weeks. Thereafter, all groups were fed a common commercial feed for the next 12 weeks (phase II). In phase III, all groups were fed with the “challenge diet” for another 6 weeks which was the basal diet (Zn-Cu-) except that the vegetable oils were replaced by fish oil. The results demonstrated that fish fed a Zn+ diet at first feeding increased larval growth (phase-I), but it had no effect on growth at the end of phase II when fed commercial feeds. In phase III, when re-introduced to a Zn- challenge diet, the feed intake and growth of juveniles with Zn+ history significantly increased, with reduced feed efficiency. Fish growth was neither influenced by dietary Cu levels or by the dietary Cu history in any of the growth phases, but dietary Cu excess (Cu+) reduced body lipid and energy content in fry. In phase I, lower whole-body Zn concentration was observed in the fry of Zn- group compared to Zn+, while the contrary was observed in the juvenile fish as affected by dietary Zn history (phase III). In addition, Zn- dietary history showed increased levels of PUFA and higher mRNA expression of fatty acid biosynthesis genes in the liver. To conclude, early-stage dietary Zn+ history improved growth of juvenile rainbow trout, while dietary Zn- history exhibited signs of improved fatty acid biosynthesis capacity in the liver.

AmiA and AliA peptide ligands, found in Klebsiella pneumoniae, are imported into pneumococci and alter the transcriptome

Klebsiella pneumoniae releases the peptides AKTIKITQTR and FNEMQPIVDRQ, which bind the pneumococcal proteins AmiA and AliA respectively, two substrate-binding proteins of the ABC transporter Ami-AliA/AliB oligopeptide permease. Exposure to these peptides alters pneumococcal phenotypes such as growth. Using a mutant in which a permease domain of the transporter was disrupted, by growth analysis and epifluorescence microscopy, we confirmed peptide uptake via the Ami permease and intracellular location in the pneumococcus. By RNA-sequencing we found that the peptides modulated expression of genes involved in metabolism, as pathways affected were mostly associated with energy or synthesis and transport of amino acids. Both peptides downregulated expression of genes involved in branched-chain amino acid metabolism and the Ami permease; and upregulated fatty acid biosynthesis genes but differed in their regulation of genes involved in purine and pyrimidine biosynthesis. The transcriptomic changes are consistent with growth suppression by peptide treatment. The peptides inhibited growth of pneumococcal isolates of serotypes 3, 8, 9N, 12F and 19A, currently prevalent in Switzerland, and caused no detectable toxic effect to primary human airway epithelial cells. We conclude that pneumococci take up K. pneumoniae peptides from the environment via binding and transport through the Ami permease. This changes gene expression resulting in altered phenotypes, particularly reduced growth.

Biocompatible silver nanoparticles as nanopriming mediators for improved rice germination and root growth: A transcriptomic perspective

Silver nanoparticles (AgNPs) have an important role in agriculture since they have several applications that are essential for the enhanced yield of crops. Furthermore, they act as nano-pesticides, delivering a proper dose to the target plants without releasing unwanted pesticides into the environment. Upholding the sustainable nano agriculture, biocompatible silver nanoparticles were synthesised utilising Piper colubrinum Link. leaf extract. Different characterization methods (TEM, EDX and XRD) revealed that AgNPs were successfully formed and coated with phytochemicals that constituted the plant extract. Enhanced root development during the early post-germination phase is crucial for the success of direct seeding in rice cultivation. The effects of AgNPs on the growth of plant roots are poorly understood. In this work, Piper colubrinum mediated AgNPs-primed Oryza sativa L. seeds, at various concentrations (0, 50, 80, 100, and 150 mg/L), exceeded typical hydro-primed controls in terms of germination and seedling growth. Oryza sativa L. treated with AgNPs at a concentration of 80 mg/L enhanced root elongation. Additionally, exposure to AgNPs significantly enhanced the content of chlorophyll. The Kyoto Encyclopedia of Genes and Genomes (KEGG) study revealed that the identified pathways like Aromatic amino acid biosynthesis genes, Fatty acid biosynthesis genes, and Carotenoid biosynthesis genes were the most enriched. Some of the genes associated with root growth and development like glucosyltransferases, Glutathione pathway genes, Calcium-ion binding pathway genes, Peroxidase precursor and Nitrilase-associated protein were up regulated. Overall, AgNPs treatments promoted seed germination, growth, chlorophyll content and gene expression patterns, which might be attributable to the beneficial effects of AgNPs on rice.

BZIP transcription factor FabR: Redox-dependent mechanism controlling docosahexaenoic acid biosynthesis and H2O2 stress response in Schizochytrium sp.

Schizochytrium sp. is an important industrial strain for commercial production of docosahexaenoic acid (DHA), which plays essential physiological roles in infant development and human health. The regulatory network for DHA biosynthesis and lipid accumulation in Schizochytrium remains poorly understood. FabR (fatty acid biosynthesis repressor), a basic leucine zipper (bZIP) transcription factor, was transcriptionally downregulated under low-nitrogen condition. Deletion of fabR gene (mutant ΔfabR) increased production of total lipids and DHA by 30.1% and 46.5%, respectively. ΔfabR displayed H2O2 stress resistance higher than that of parental strain or complementation strain CfabR. FabR bound specifically to 7-bp pseudo-palindromic sequence 5′-ATTSAAT-3′ in upstream regions and repressed transcription of fatty acid biosynthesis genes (acl, fas, pfa) and antioxidant defense genes (cat, sod1, sod2, gpx). DNA binding activity of FabR was regulated in a redox-dependent manner. Under oxidative condition, FabR forms intermolecular disulfide bonds between two Cys46 residues of dimers; its DNA binding activity is thereby lost, and the transcription of its target genes is enhanced through derepression. Our findings clarify the redox-dependent mechanism that modulates FabR activity governing lipid and DHA biosynthesis and H2O2 stress response in Schizochytrium.

Robust and high-efficient nitrogen removal from real sewage and waste activated sludge (WAS) reduction in zero-external carbon PN/A combined with in-situ fermentation-denitrification process under decreased temperatures

Despite the advantages of the combined anammox and fermentation-driven denitrification process in nitrogen removal and energy consumption, stable performance at decreased temperatures remains a challenge. In this study, a robust and high-efficient nitrogen removal efficiency (95.0–93.1 ∼ 86.8–93.4%) with desirable effluent quality (3.0–4.1 ∼ 7.9–4.9 mg/L) under long-term decreased temperatures (30 °C→25 °C→20 °C) was achieved in a zero-external carbon Partial Nitritation/Anammox combined with in-situ sludge Fermentation-Denitrification process treating sewage. Excellent sludge reduction averaged at 14.9% assuming no microbial growth. Increased hzsB mRNA (2.2-fold) and reduced Ea (80.9 kJ/mol) proved resilient anammox to lower temperature. RT-qPCR tests revealed increased NarG/NirK (5.1) and NarG/NirS (4.9) mRNA at 20 °C, suggesting higher NO3−→NO2− over NO2−→N2 pathway. Metagenomics unraveled dominant anammox bacteria (Candidatus_Brocadia, 2.27%), increased denitritation bacteria containing more NarG (Hyphomicrobium, 0.8%), fatty acid biosynthesis and CAZymes genes. Enhanced denitritation with recovered organics from sludge reserved nitrite for anammox and facilitated higher anammox contribution to N removal at 20 °C (42.4%) than 30 °C (39.5%). This study proposed an innovative low-temperature strategy for in-situ sludge fermentation, and demonstrated stability of advanced municipal wastewater treatment and sludge disposal through energy savings and carbon recovery under decreased temperatures.

Abstract B073: Inhibiting prostate cancer by targeting the metabolic mevalonate pathway

Abstract Background: A major challenge in the clinical management of prostate cancer (PCa) is inhibiting progression to lethal castrate-resistant PC (CRPC). Deregulated activity of mevalonate (MVA), cholesterol biosynthetic pathway is a recognized hallmark of PCa cells. Statins are potent inhibitors of this metabolic pathway that have been used for decades in the control of hypercholesterolemia. Statins have recently been shown to have anti-PCa activity, however statin treatment triggers a feedback response that restores the MVA pathway, which reduces statin efficacy and contributes to resistance. This restorative feedback loop is controlled by the transcriptional activity of sterol regulatory-element binding protein (SREBP), which primarily induces fatty acid biosynthesis and MVA pathway genes. We have recently identified the anti-platelet agent dipyridamole (DP) as an inhibitor of the statin-induced SREBP-mediated feedback response. However, DP is not SREBP-specific and given its anti-platelet activity, may not be suitable for every cancer patient. Thus, our goal was to identify additional drugs that potentiate the pro-apoptotic activity of statins, which can be used to treat PCa patients. Methods: Two independent, yet complimentary strategies were used. The first focused on performing an in silico analysis to identify drugs that had similar properties to DP at the level of drug structure, molecular perturbations and cell line sensitivity. The second strategy involved a high-content imaging analysis of 1508 FDA approved drugs, which was performed in LNCaP (relatively statin insensitive and feedback competent) and PC3 cells (statin sensitive and feedback incompetent). Cells were treated with a sub-lethal dose of fluvastatin, the drugs or the fluvastatin-drug combination, then treated with apoptotic stains (TMRE, Annexin, Draq 5). Captured images were analyzed using a machine learning approach. Results: Validation of hits from the in silico MVA-DNF approach and high-content screening has identified several drugs that fulfill our criteria of potentiating statin-induced cell death in a feedback-dependent or feedback-independent manner. Interestingly, many show higher Z-scores compared to DP indicating their superior statin potentiation activity to drive PCa cell death. Moreover, a sub-set of these drug significantly inhibit statin-triggered expression of MVA pathway genes HMGCS1 and INSIG1 (p < 0.001) more potently than DP. Conclusions: We have detailed two successful strategies to identify drugs that inhibit SREBP activation in response to statin treatment. These statin-drug combinations represent an effective ‘one-two punch’ to inhibit CRPC progression. These novel inhibitors of SREBP activation potentiate statin at clinically relevant concentrations more potently than DP and have no effect on the platelet activity. Excitingly, many of these agents are FDA-approved and can be immediately used in combination with statins for the treatment of PCa. Overall, our research will lead to novel therapies to improve patient outcome. Citation Format: Diandra Zipinotti dos Santos, Mohamad Elbaz, Emily Branchard, Wiebke Schormann, David W. Andrews, Linda Z. Penn. Inhibiting prostate cancer by targeting the metabolic mevalonate pathway [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B073.

Transcription factor bZIP52 modulates Arabidopsis seed oil biosynthesis through interaction with WRINKLED1.

Transcriptional regulation mediated by combinatorial interaction of transcription factors (TFs) is a key molecular mechanism modulating plant development and metabolism. Basic leucine zipper (bZIP) TFs play important roles in various plant developmental and physiological processes. However, their involvement in fatty acid biosynthesis is largely unknown. Arabidopsis (Arabidopsis thaliana) WRINKLED1 (WRI1) is a pivotal TF in regulation of plant oil biosynthesis and interacts with other positive and negative regulators. In this study, we identified two bZIP TFs, bZIP21 and bZIP52, as interacting partners of AtWRI1 by yeast-two-hybrid (Y2H)-based screening of an Arabidopsis TF library. We found that coexpression of bZIP52, but not bZIP21, with AtWRI1 reduced AtWRI1-mediated oil biosynthesis in Nicotiana benthamiana leaves. The AtWRI1-bZIP52 interaction was further verified by Y2H, in vitro pull-down, and bimolecular fluorescence complementation assays. Transgenic Arabidopsis plants overexpressing bZIP52 showed reduced seed oil accumulation, while the CRISPR/Cas9-edited bzip52 knockout mutant exhibited increased seed oil accumulation. Further analysis revealed that bZIP52 represses the transcriptional activity of AtWRI1 on the fatty acid biosynthetic gene promoters. Together, our findings suggest that bZIP52 represses fatty acid biosynthesis genes through interaction with AtWRI1, resulting in a reduction of oil production. Our work reports a previously uncharacterized regulatory mechanism that enables fine-tuning of seed oil biosynthesis.

Diversity of fatty acid biosynthesis genes across the soybean pangenome.

Soybean (Glycine max) is a major crop that contributes more than half of global oilseed production. Much research has been directed towards improvement of the fatty acid profile of soybean seeds through marker assisted breeding. Recently published soybean pangenomes, based on thousands of soybean lines, provide an opportunity to identify new alleles that may be involved in fatty acid biosynthesis. In this study, we identify fatty acid biosynthesis genes in soybean pangenomes based on sequence identity with known genes and examine their sequence diversity across diverse soybean collections. We find three possible instances of a gene missing in wild soybean, including FAD8 and FAD2-2D, which may be involved in oleic and linoleic acid desaturation, respectively, although we recommend follow-up research to verify the absence of these genes. More than half of the 53 fatty acid biosynthesis genes identified contained missense variants, including one linked with a previously identified QTL for oil quality. These variants were present in multiple studies based on either short read mappings or alignment of reference grade genomes. Missense variants were found in previously characterized genes including FAD2-1A and FAD2-1B, both of which are involved in desaturation of oleic acid, as well as uncharacterized candidate fatty acid biosynthesis genes. We find that the frequency of missense alleles in fatty acid biosynthesis genes has been reduced significantly more than the global average frequency of missense mutations during domestication, and missense variation in some genes is near absent in modern cultivars. This could be due to the selection for fatty acid profiles in seed, though future work should be conducted towards understanding the phenotypic impacts of these variants.

RNA Sequencing (RNA-Seq) Analysis Reveals Liver Lipid Metabolism Divergent Adaptive Response to Low- and High-Salinity Stress in Spotted Scat (Scatophagus argus).

Spotted scat (Scatophagus argus) can tolerate a wide range of salinity fluctuations. It is a good model for studying environmental salinity adaptation. Lipid metabolism plays an important role in salinity adaptation in fish. To elucidate the mechanism of lipid metabolism in the osmoregulation, the liver transcriptome was analyzed after 22 d culture with a salinity of 5 ppt (Low-salinity group: LS), 25 ppt (Control group: Ctrl), and 35 ppt (High-salinity group: HS) water by using RNA sequencing (RNA-seq) in spotted scat. RNA-seq analysis showed that 1276 and 2768 differentially expressed genes (DEGs) were identified in the LS vs. Ctrl and HS vs. Ctrl, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the pathways of steroid hormone biosynthesis, steroid biosynthesis, glycerophospholipid metabolism, glycerolipid metabolism, and lipid metabolism were significantly enriched in the LS vs. Ctrl. The genes of steroid biosynthesis (sqle, dhcr7, and cyp51a1), steroid hormone biosynthesis (ugt2a1, ugt2a2, ugt2b20, and ugt2b31), and glycerophospholipid metabolism (cept1, pla2g4a, and ptdss2) were significantly down-regulated in the LS vs. Ctrl. The pathways related to lipid metabolisms, such as fatty acid metabolism, fatty acid biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine signaling pathway, fatty acid degradation, and unsaturated fatty acid biosynthesis, were significantly enriched in the HS vs. Ctrl. The genes of unsaturated fatty acid biosynthesis (scd1, hacd3, fads2, pecr, and elovl1) and adipocytokine signaling pathway (g6pc1, socs1, socs3, adipor2, pck1, and pparα) were significantly up-regulated in the HS vs. Ctrl. These results suggest that the difference in liver lipid metabolism is important to adapt to low- and high-salinity stress in spotted scat, which clarifies the molecular regulatory mechanisms of salinity adaptation in euryhaline fish.

WRINKLED1 Positively Regulates Oil Biosynthesis in Carya cathayensis.

Hickory (Carya cathayensis Sarg.) is a kind of important woody oil tree species, and its nut has high nutritional value. Previous gene coexpression analysis showed that WRINKLED1 (WRI1) may be a core regulator during embryo oil accumulation in hickory. However, its specific regulatory mechanism on hickory oil biosynthesis has not been investigated. Herein, two hickory orthologs of WRI1 (CcWRI1A and CcWRI1B) containing two AP2 domains with AW-box binding sites and three intrinsically disordered regions (IDRs) but lacking the PEST motif in the C-terminus were characterized. They are nucleus-located and have self-activated ability. The expression of these two genes was tissue-specific and relatively high in the developing embryo. Notably, CcWRI1A and CcWRI1B can restore the low oil content, shrinkage phenotype, composition of fatty acid, and expression of oil biosynthesis pathway genes of Arabidopsis wri1-1 mutant seeds. Additionally, CcWRI1A/B were shown to modulate the expression of some fatty acid biosynthesis genes in the transient expression system of nonseed tissues. Transcriptional activation analysis further indicated that CcWRI1s directly activated the expression of SUCROSE SYNTHASE2 (SUS2), PYRUVATE KINASE β SUBUNIT 1 (PKP-β1), and BIOTIN CARBOXYL CARRIER PROTEIN2 (BCCP2) involved in oil biosynthesis. These results suggest that CcWRI1s can promote oil synthesis by upregulating some late glycolysis- and fatty acid biosynthesis-related genes. This work reveals the positive function of CcWRI1s in oil accumulation and provides a potential target for improving plant oil by bioengineering technology.

Guild-Level Microbiome Signature Associated with COVID-19 Severity and Prognosis.

Coronavirus disease 2019 (COVID-19) severity has been associated with alterations of the gut microbiota. However, the relationship between gut microbiome alterations and COVID-19 prognosis remains elusive. Here, we performed a genome-resolved metagenomic analysis on fecal samples from 300 in-hospital COVID-19 patients, collected at the time of admission. Among the 2,568 high quality metagenome-assembled genomes (HQMAGs), redundancy analysis identified 33 HQMAGs which showed differential distribution among mild, moderate, and severe/critical severity groups. Co-abundance network analysis determined that the 33 HQMAGs were organized as two competing guilds. Guild 1 harbored more genes for short-chain fatty acid biosynthesis, and fewer genes for virulence and antibiotic resistance, compared with Guild 2. Based on average abundance difference between the two guilds, the guild-level microbiome index (GMI) classified patients from different severity groups (average AUROC [area under the receiver operating curve] = 0.83). Moreover, age-adjusted partial Spearman's correlation showed that GMIs at admission were correlated with 8 clinical parameters, which are predictors for COVID-19 prognosis, on day 7 in hospital. In addition, GMI at admission was associated with death/discharge outcome of the critical patients. We further validated that GMI was able to consistently classify patients with different COVID-19 symptom severities in different countries and differentiated COVID-19 patients from healthy subjects and pneumonia controls in four independent data sets. Thus, this genome-based guild-level signature may facilitate early identification of hospitalized COVID-19 patients with high risk of more severe outcomes at time of admission. IMPORTANCE Previous reports on the associations between COVID-19 and gut microbiome have been constrained by taxonomic-level analysis and overlook the interaction between microbes. By applying a genome-resolved, reference-free, guild-based metagenomic analysis, we demonstrated that the relationship between gut microbiota and COVID-19 is genome-specific instead of taxon-specific or even species-specific. Moreover, the COVID-19-associated genomes were not independent but formed two competing guilds, with Guild 1 potentially beneficial and Guild 2 potentially more detrimental to the host based on comparative genomic analysis. The dominance of Guild 2 over Guild 1 at time of admission was associated with hospitalized COVID-19 patients at high risk for more severe outcomes. Moreover, the guild-level microbiome signature is not only correlated with the symptom severity of COVID-19 patients, but also differentiates COVID-19 patients from pneumonia controls and healthy subjects across different studies. Here, we showed the possibility of using genome-resolved and guild-level microbiome signatures to identify hospitalized COVID-19 patients with a high risk of more severe outcomes at the time of admission.

Anammox Bacterial S-Adenosyl-l-Methionine Dependent Methyltransferase Crystal Structure and Its Interaction with Acyl Carrier Proteins

Ladderane lipids (found in the membranes of anaerobic ammonium-oxidizing [anammox] bacteria) have unique ladder-like hydrophobic groups, and their highly strained exotic structure has attracted the attention of scientists. Although enzymes encoded in type II fatty acid biosynthesis (FASII) gene clusters in anammox bacteria, such as S-adenosyl-l-methionine (SAM)-dependent enzymes, have been proposed to construct a ladder-like structure using a substrate connected to acyl carrier protein from anammox bacteria (AmxACP), no experimental evidence to support this hypothesis was reported to date. Here, we report the crystal structure of a SAM-dependent methyltransferase from anammox bacteria (AmxMT1) that has a substrate and active site pocket between a class I SAM methyltransferase-like core domain and an additional α-helix inserted into the core domain. Structural comparisons with homologous SAM-dependent C-methyltransferases in polyketide synthase, AmxACP pull-down assays, AmxACP/AmxMT1 complex structure predictions by AlphaFold, and a substrate docking simulation suggested that a small compound connected to AmxACP could be inserted into the pocket of AmxMT1, and then the enzyme transfers a methyl group from SAM to the substrate to produce branched lipids. Although the enzymes responsible for constructing the ladder-like structure remain unknown, our study, for the first time, supports the hypothesis that biosynthetic intermediates connected to AmxACP are processed by SAM-dependent enzymes, which are not typically involved in the FASII system, to produce the ladder-like structure of ladderane lipids in anammox bacteria.

Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid.

Streptococcus pneumoniae (pneumococcus) is a leading cause of severe invasive infectious diseases such as sepsis and meningitis. Understanding how pneumococcus adapts and survive in the human bloodstream environment and cerebrospinal fluid (CSF) is important for development of future treatment strategies. This study investigates the global transcriptional response of pneumococcus to human blood components and CSF acquired from discarded and anonymized patient samples. Extensive transcriptional changes to human blood components were observed during early stages of interaction. Plasma-specific responses were primarily related to metabolic components and include strong downregulation of fatty acid biosynthesis genes, and upregulation of nucleotide biosynthesis genes. No transcriptional responses specific to the active plasma proteins (e.g., complement proteins) were observed during early stages of interaction as demonstrated by a differential expression analysis between plasma and heat-inactivated plasma. The red blood cell (RBC)-specific response was far more complex, and included activation of the competence system, differential expression of several two-component systems, phosphotransferase systems and transition metal transporter genes. Interestingly, most of the changes observed for CSF were also observed for plasma. One of the few CSF-specific responses, not observed for plasma, was a strong downregulation of the iron acquisition system piuBCDA. Intriguingly, this transcriptomic analysis also uncovers significant differential expression of more than 20 small non-coding RNAs, most of them in response to RBCs, including small RNAs from uncharacterized type I toxin-antitoxin systems. In summary, this transcriptomic study identifies key pneumococcal metabolic pathways and regulatory genes involved with adaptation to human blood and CSF. Future studies should uncover the potential involvement of these factors with virulence in-vivo.

Functional characterization reveals a diverse array of metazoan fatty acid biosynthesis genes.

Long-chain (≥C20 ) polyunsaturated fatty acids (LC-PUFAs) are physiologically important fatty acids for most animals, including humans. Although most LC-PUFA production occurs in aquatic primary producers such as microalgae, recent research indicates the ability of certain groups of (mainly marine) invertebrates for endogenous LC-PUFA biosynthesis and/or bioconversion from dietary precursors. The genetic pathways for and mechanisms behind LC-PUFA biosynthesis remain unknown in many invertebrates to date, especially in non-model species. However, the numerous genomic and transcriptomic resources currently available can contribute to our knowledge of the LC-PUFA biosynthetic capabilities of metazoans. Within our previously generated transcriptome of the benthic harpacticoid copepod Platychelipus littoralis, we detected expression of one methyl-end desaturase, one front-end desaturase, and seven elongases, key enzymes responsible for LC-PUFA biosynthesis. To demonstrate their functionality, we characterized eight of them using heterologous expression in yeast. The P. littoralis methyl-end desaturase has Δ15/17/19 desaturation activity, enabling biosynthesis of α-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid (DHA) from 18:2 n-6, 20:4 n-6 and 22:5 n-6, respectively. Its front-end desaturase has Δ4 desaturation activity from 22:5 n-3 to DHA, implying that P. littoralis has multiple pathways to produce this physiologically important fatty acid. All studied P. littoralis elongases possess varying degrees of elongation activity for saturated and unsaturated fatty acids, producing aliphatic hydrocarbon chains with lengths of up to 30 carbons. Our investigation revealed a functionally diverse range of fatty acid biosynthesis genes in copepods, which highlights the need to scrutinize the role that primary consumers could perform in providing essential nutrients to upper trophic levels.

Transcriptome and targeted metabolome analysis provide insights into bile acids' new roles and mechanisms on fat deposition and meat quality in lamb

Higher quality lamb carcasses with more muscle and less fat are crucial for consumer preference and healthy eating. This study evaluated bile acids' functional roles and mechanisms on fat deposition in lambs. Forty-five lambs were arranged into three groups with control (CON) and two types of bile acid treatments (BA1, mainly hyocholic acid; BA2, mainly hyodeoxycholic acid, ruminally protected). The BA1 treatment did not affect the dry matter intake, body weight, and the average daily gain but significantly decreased the body fat (assessed as GR value) compared to the CON (7.92 vs 5.55 mm). The BA2 decreased tail fat weight compared to CON (1.99 vs 1.51 kg). Both BA1 and BA2 significantly decreased the tail fat ratio (110 vs 89.8 vs 78.6 g/kg of carcass weight). No significant differences were found between the three groups' blood antioxidant capacity and immune characteristics. The RNA-sequencing analysis identified 46 differentially expressed genes between CON and BA2. Several pathways, including ferroptosis and fatty acid biosynthesis and core genes such as HSPA8, HIFIA, HEXB, ACSL6, and MAP1LC3B were changed mainly or significantly correlated with the tail fat weight or proportion phenotypes, can be selected as targeted gene markers related to regulating the tail fat. This study provided new insight into bile acids' roles and revealed their comprehensive mechanism in regulating fat distribution in ruminants and will facilitate improvements of lamb meat production with decreased subcutaneous and tail fat deposition.

Transcriptome Analysis and Gene Expression Profiling of the Peanut Small Seed Mutant Identified Genes Involved in Seed Size Control.

Seed size is a key factor affecting crop yield and a major agronomic trait concerned in peanut (Arachis hypogaea L.) breeding. However, little is known about the regulation mechanism of peanut seed size. In the present study, a peanut small seed mutant1 (ssm1) was identified through irradiating peanut cultivar Luhua11 (LH11) using 60Coγ ray. Since the globular embryo stage, the embryo size of ssm1 was significantly smaller than that of LH11. The dry seed weight of ssm1 was only 39.69% of the wild type LH14. The seeds were wrinkled with darker seed coat. The oil content of ssm1 seeds were also decreased significantly. Seeds of ssm1 and LH11 were sampled 10, 20, and 40 days after pegging (DAP) and were used for RNA-seq. The results revealed that genes involved in plant hormones and several transcription factors related to seed development were differentially expressed at all three stages, especially at DAP10 and DAP20. Genes of fatty acid biosynthesis and late embryogenesis abundant protein were significantly decreased to compare with LH11. Interestingly, the gene profiling data suggested that PKp2 and/or LEC1 could be the key candidate genes leading to the small seed phenotype of the mutant. Our results provide valuable clues for further understanding the mechanisms underlying seed size control in peanut.

Exploring the impact of paracetamol on the transcriptome of Streptococcus pneumoniae D39

IntroductionParacetamol (acetaminophen) is a medicine used for the treatment of fever, pain, and inflammation during pneumococcal infection. ObjectivesTo see how paracetamol affects the transcriptional profile of Streptococcus pneumonia across the genome. MethodsIn this study, microarray analysis was performed for transcriptional profiling. ResultsTranscriptome data showed differential expression of several genes in S. pneumoniae D39 wild-type incorporated with paracetamol in the growth medium. Furthermore, these genes were categorized using Clusters of Orthologous Groups (COG) functional categorization on the basis of the suspected functions of the respective proteins. The majority of differentially expressed genes are in COG categories E (Amino acid transport and metabolism) and I (Lipid transport and metabolism). Analysis of protein–protein interaction networks exhibited compactly connected networks between fatty acid transport/biosynthesis and antibiotic biosynthesis genes. Moreover, pathways enrichment analysis revealed that fatty acid metabolism and biosynthesis genes were significantly affected under the criteria we've established. ConclusionThese results suggest the fatty acid biosynthesis and metabolism genes to be potential target of paracetamol in S. pneumoniae D39 wild-type.