Complex Biochemical Changes Research Articles

Type I interferon signaling and peroxisomal dysfunction contribute to enhanced inflammatory cytokine production in IRGM1-deficient macrophages

The human IRGM gene has been linked to inflammatory diseases including sepsis and Crohn’s disease. Decreased expression of human IRGM, or of the mouse orthologues Irgm1 and Irgm2, leads to increased production of a number of inflammatory chemokines and cytokines in vivo and/or in cultured macrophages. Prior work has indicated that increased cytokine production is instigated by metabolic alterations and by changes in mitochondrial homeostasis; however, a comprehensive mechanism has not been elucidated. In the studies presented here, RNA deep sequencing and quantitative PCR were used to show that increases in cytokine production, as well as most changes in the transcriptional profile of Irgm1-/- bone marrow-derived macrophages (BMM), are dependent on increased type I IFN production seen in those cells. Metabolic alterations that drive increased cytokines in Irgm1-/- BMM - specifically increases in glycolysis and increased accumulation of acyl-carnitines - were unaffected by quenching type I IFN signaling. Dysregulation of peroxisomal homeostasis was identified as a novel upstream pathway that governs type I IFN production and inflammatory cytokine production. Collectively, these results enhance our understanding of the complex biochemical changes that are triggered by lack of Irgm1 and contribute to inflammatory disease seen with Irgm1-deficiency.

Metabolite perturbations in fermented legumes as elucidated using metabolomics: a review

SummaryLegumes are vital food sources in global diets, especially in developing nations, offering affordability, nutrition, and sustainability. Legumes are rich bioactive compounds as well as in macro‐ and micro‐nutrients and help combat protein‐energy malnutrition. Fermentation is a food processing technique that enhances nutritional content, digestibility and overall composition, rendering fermented legumes like dawadawa, natto, tempeh, and kinema dietary sources worldwide. This simple process leads to significant perturbations in the numerous metabolites contained in legumes and subsequent fermented products. Such metabolites including bioactive constituents, vitamins, minerals, volatile compounds, lipids, amino acids, among others contribute to the flavour, aroma, nutritional value and health beneficial properties of fermented legume products. Modifications in these complex constituents might be somewhat challenging to investigate and understand thus necessitating a robust technique such as metabolomics. Metabolomics as an analytical approach can elucidate how fermentation alters the composition of fermented legumes revealing compositional changes, nutritional enhancements, and impacts of fermentation conditions and microbial metabolism. This review emphasises fermented legumes' dietary importance, the transformative role of fermentation, and the effectiveness of metabolomics in unravelling complex biochemical changes during legume fermentation, providing insights into nutritional, sensory and safety aspects of fermented legumes.

Chemical Inhibition of Sterol Biosynthesis.

Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, and cardiovascular medications. These medications can interfere with various enzymes of the post-lanosterol biosynthetic pathway, giving rise to complex biochemical changes throughout the body. The consequences of these short- and long-term homeostatic disruptions are mostly unknown. We performed a comprehensive review of the literature and built a catalogue of chemical agents capable of inhibiting post-lanosterol biosynthesis. This process identified significant gaps in existing knowledge, which fall into two main areas: mechanisms by which sterol biosynthesis is altered and consequences that arise from the inhibitions of the different steps in the sterol biosynthesis pathway. The outcome of our review also reinforced that sterol inhibition is an often-overlooked mechanism that can result in adverse consequences and that there is a need to develop new safety guidelines for the use of (novel and already approved) medications with sterol biosynthesis inhibiting side effects, especially during pregnancy.

Interaction and tolerance to Alternaria brassicae in Indian mustard (Brassica juncea) genotypes

The biochemical changes were observed in leaves of Indian mustard tolerant (EC-399301, EC-399296, EC-399299, PHR-2) and susceptible (Varuna) genotypes infected with Alternaria blight (AB) caused by Alternaria brassicae at critical stage (75 days after sowing) of disease development. The presence of metabolites in infected B. juncea leaves such as glucosinolate (µ moles), phenol (mg/g), sugar (mg/g), protein (mg/g), carotenoids (µg/g) and chlorophyll (mg/g) were highly associated with the fungal infection. As compared to the susceptible check Varuna, level of glucosinolate, sugar, carotenoids and chlorophyll were decreased in tolerant hosts' leaves after pathogen infection. Although, the phenol and protein content in tolerant and susceptible genotypes were increased in AB infected leaves than healthy leaves. Our findings are discussed within the context of A. brassicae-B. junceainteraction and tolerance to this pathogen. The results indicated that factors conditioning the host response to A. brassicae might be the outcome of complex biochemical changes operated in host genotypes.

Metabolic effects of long-term cadmium exposure: an overview.

Cadmium (Cd) is a toxic non-essential heavy metal. Chronic low Cd exposure (CLCE) has been associated with distinct pathologies in many organ systems, including liver and kidney damage, osteoporosis, carcinogenicity, or reproductive toxicity. Currently, about 10% of the global population is at risk of CLCE. It is urgent to find robust and effective biomarkers for early diagnosis of Cd exposure and treatment. Metabolomics is a high-throughput method based on mass spectrometry to study the dynamic changes in a series of endogenous small molecular metabolites (typically < 1000Da) of tissues, cells, or biofluids. It can reflect the rich and complex biochemical changes in the body after exposure to heavy metals, which may be useful in screening biomarkers to monitor exposure to environmental pollutants and/or predict disease risk. Therefore, this review focuses on the changes in metabolic profiles of humans and rodents under long-term Cd exposure from the perspective of metabolomics. Furthermore, the relationship between the disturbance of metabolic pathways and the toxic mechanism of Cd is discussed. All these information will facilitate the development of reliable metabolic biomarkers for early detection and diagnosis of Cd-related diseases.

Transcriptomic and histochemical analysis reveal the complex regulatory networks in equine chorioallantois during spontaneous term labor†.

The equine chorioallantois (CA) undergoes complex physical and biochemical changes during labor. However, the molecular mechanisms controlling these changes are still unclear. Therefore, the current study aimed to characterize the transcriptome of equine CA during spontaneous labor and compare it with that of normal preterm CA. Placental samples were collected postpartum from mares with normal term labor (TL group, n = 4) and from preterm not in labor mares (330days GA; PTNL group, n = 4). Our study identified 4137 differentially expressed genes (1820 upregulated and 2317 downregulated) in CA during TL as compared with PTNL. TL was associated with the upregulation of several proinflammatory mediators (MHC-I, MHC-II, NLRP3, CXCL8, and MIF). Also, TL was associated with the upregulation of matrix metalloproteinase (MMP1, MMP2, MMP3, and MMP9) with subsequent extracellular matrix degradation and apoptosis, as reflected by upregulation of several apoptosis-related genes (ATF3, ATF4, FAS, FOS, and BIRC3). In addition, TL was associated with downregulation of 21 transcripts coding for collagens. The upregulation of proteases, along with the downregulation of collagens, is believed to be implicated in separation and rupture of the CA during TL. Additionally, TL was associated with downregulation of transcripts coding for proteins essential for progestin synthesis (SRD5A1 and AKR1C1) and angiogenesis (VEGFA and RTL1), as well as upregulation of prostaglandin synthesis-related genes (PTGS2 and PTGES), which could reflect the physiological switch in placental endocrinology and function during TL. In conclusion, our findings revealed the equine CA gene expression signature in spontaneous labor at term, which improves our understanding of the molecular mechanisms triggering labor.

Molecular feature of neutrophils in immune microenvironment of muscle atrophy.

Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments.

Metabolic characterization of hemolymph in Bombyx mori varieties after Bombyx mori nucleopolyhedrovirus infection by GC-MS-based metabolite profiling.

The "Huakang 2" silkworm variety, bred by the Sericulture ResearchInstitute of the Chinese Academy of Agricultural Sciences, is highly resistant to Bombyx mori nucleopolyhedrovirus (BmNPV) and effectively solves the issue of frequent Bombyx mori nuclear polyhedrosis in sericultural production. The molecular mechanism of its resistance to BmNPV, however, is still unknown. The purpose of the present study was therefore to identify these anti-BmNPV mechanisms by using metabolomics in combination with transcriptomics after subcutaneous injection of budded virus (BV) with high concentrations of BmNPV from specimens of the Baiyu N variety (which is highly resistant to BmNPV) and the Baiyu variety (which is sensitive to BmNPV). A total of 375 differential metabolites were identified, which mainly included sugars, acids, amines, alcohols, glycosides, and other small molecules. KEGG enrichment analysis and functional clustering of differential metabolites identified possible metabolic pathways, including tyrosine metabolism, oxidative phosphorylation, and alanine, aspartate, and glutamate metabolism. The differentially expressed genes (DEGs) identified by transcriptome analysis were annotated in KEGG. Association analysis showed that the metabolic pathways of different silkworm varieties are affected differently by BmNPV infection, triggering a series of complex physiological and biochemical changes in the organism. In particular, oxidative phosphorylation might be an essential pathway involved in regulation of disease resistance.

Community metabolomics provides insights into mechanisms of pollution-induced community tolerance of periphyton

Chemical pollution is a major concern for freshwater ecosystems, but the impact and mechanisms of chemical stressors on communities are barely understood. Pollution stress beyond natural homeostatic capacities can trigger succession of tolerant species within a community, enhancing the overall community tolerance. This process was operationalized in the Pollution-Induced Community Tolerance (PICT) concept and applied in many case studies, however, the molecular mechanisms of community tolerance and implications for ecological functions remain largely unexplored. Our study aimed to demonstrate that 1) community metabolomics can unravel potential mechanisms of PICT in periphyton and 2) induced tolerance helps to maintain primary production under re-occuring pollution. To this end, we grew periphyton for 5 weeks with and without the model herbicide diuron in microcosms, quantified PICT, and determined the related metabolic fingerprint of periphyton by GC–MS-based untargeted metabolomics. Further, we explored the autotrophic community based on pigment composition and functional parameters including photosynthesis and gross primary production. Chronic diuron exposure resulted in a shift in pigment composition, higher community tolerance and an individual metabolic fingerprint in the contaminated communities. Opposing responses of selected metabolites during a short-term exposure indicated differences in diuron pre-adaptation in the different communities. Metabolites (threonic acid and two sugar acid lactones) were found to be related to tolerance development, suggesting that ascorbate metabolism was induced in contaminated communities. Despite these compensating mechanism, contaminated communities were compromised in production-to-respiration ratio and biomass. A ranking of sensitivity thresholds of different biological endpoints revealed that metabolites were less sensitive than photosynthetic parameters, which reflects the mode-of-action of the herbicide. In conclusion, we could demonstrate that community metabolomics is able to unravel complex biochemical changes and allows mechanistic insights into community tolerance. Moreover, we were able to show that induced community tolerance was insufficient to safeguard functions like primary production.

Integrative iTRAQ-based proteomic and transcriptomic analysis reveals the accumulation patterns of key metabolites associated with oil quality during seed ripening of Camellia oleifera

Camellia oleifera (C. oleifera) is one of the four major woody oil-bearing crops in the world and has relatively high ecological, economic, and medicinal value. Its seeds undergo a series of complex physiological and biochemical changes during ripening, which is mainly manifested as the accumulation and transformation of certain metabolites closely related to oil quality, especially flavonoids and fatty acids. To obtain new insights into the underlying molecular mechanisms, a parallel analysis of the transcriptome and proteome profiles of C. oleifera seeds at different maturity levels was conducted using RNA sequencing (RNA-seq) and isobaric tags for relative and absolute quantification (iTRAQ) complemented with gas chromatography-mass spectrometry (GC-MS) data. A total of 16,530 transcripts and 1228 proteins were recognized with significant differential abundances in pairwise comparisons of samples at various developmental stages. Among these, 317 were coexpressed with a poor correlation, and most were involved in metabolic processes, including fatty acid metabolism, α-linolenic acid metabolism, and glutathione metabolism. In addition, the content of total flavonoids decreased gradually with seed maturity, and the levels of fatty acids generally peaked at the fat accumulation stage; these results basically agreed with the regulation patterns of genes or proteins in the corresponding pathways. The expression levels of proteins annotated as upstream candidates of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) as well as their cognate transcripts were positively correlated with the variation in the flavonoid content, while shikimate O-hydroxycinnamoyltransferase (HCT)-encoding genes had the opposite pattern. The increase in the abundance of proteins and mRNAs corresponding to alcohol dehydrogenase (ADH) was associated with a reduction in linoleic acid synthesis. Using weighted gene coexpression network analysis (WGCNA), we further identified six unique modules related to flavonoid, oil, and fatty acid anabolism that contained hub genes or proteins similar to transcription factors (TFs), such as MADS intervening keratin-like and C-terminal (MIKC_MADS), type-B authentic response regulator (ARR-B), and basic helix-loop-helix (bHLH). Finally, based on the known metabolic pathways and WGCNA combined with the correlation analysis, five coexpressed transcripts and proteins composed of cinnamyl-alcohol dehydrogenases (CADs), caffeic acid 3-O-methyltransferase (COMT), flavonol synthase (FLS), and 4-coumarate: CoA ligase (4CL) were screened out. With this exploratory multiomics dataset, our results presented a dynamic picture regarding the maturation process of C. oleifera seeds on Hainan Island, not only revealing the temporal specific expression of key candidate genes and proteins but also providing a scientific basis for the genetic improvement of this tree species.

Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process.

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD+, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD+ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD+ production through the NAD+ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD+ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD+ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD+ biosynthesis pathways in mammals, the NAD+ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD+, have been developed so far. In this review, we will focus on the importance of NAD+ and the possible application of an activator of NAMPT to promote successive aging.

The Extent and Rate of the Appearance of the Major 110 and 30 kDa Proteolytic Fragments during Post-Mortem Aging of Beef Depend on the Glycolysing Rate of the Muscle and Aging Time: An LC-MS/MS Approach to Decipher Their Proteome and Associated Pathways.

Post-mortem (p-m) muscle undergoes a myriad of complex physical and biochemical changes prior to its conversion to meat, which are influential on proteolysis and hence tenderization. A more in-depth understanding of the mechanisms underpinning these dynamics is a key to consistently providing tender beef. Using an LC-MS/MS approach, with state-of-art mass spectrometry Q Exactive HF-X, the proteome and associated pathways contributing to the appearance of the proteolytic breakdown products appearing over 14 days p-m, at two important molecular weights (110 and 30 kDa) on 1D SDS-PAGE gels, have been investigated in beef longissimus thoracis et lumborum muscles exhibiting four rates of pH decline differentiated on the basis of time at pH 6 (fast glycolysing, <3 h; medium, 3-5 h; slow, 5-8 h; and very slow, 8+ h). Both 110 and 30 kDa bands appeared during aging and increased in intensity as a function of p-m time in a pH decline-dependent manner. The 110 kDa band appeared as early as 3 h p-m and displayed an incremental increase in all groups through to 14 days p-m. From 2 days p-m, this increase in abundance during aging was significantly (P < 0.001) influenced by the glycolytic rate: fast > or = medium > slow > very slow. The day 2 p-m appearance of the 30 kDa band was most evident for the fast glycolysing muscle with little or no evidence of appearance in slow and very slow. For days 7 and 14 p-m, the strength of appearance was dependent on glycolysing groups fast > medium > or = slow > very slow. LC-MS/MS analysis yielded a total of 22 unique proteins for the 110 kDa fragment and 13 for the 30 kDa, with 4 common proteins related to both the actin and fibrinogen complex. The Gene Ontology analysis revealed that a myriad of biological pathways are influential with many related to proteins involved primarily in muscle contraction and structure. Other pathways of interest include energy metabolism, apoptotic mitochondrial changes, calcium and ion transport, and so on. Interestingly, most of the proteins composing the fragments were so far identified as biomarkers of beef tenderness and other quality traits.

RNA sequencing (RNA-seq) analysis of gene expression provides new insights into hindlimb unloading-induced skeletal muscle atrophy.

BackgroundWeightlessness-induced skeletal muscle atrophy, accompanied by complex biochemical and physiological changes, has potentially damaged consequences. However, there is still an insufficient effective strategy to treat skeletal muscle atrophy. Therefore, exploring the molecular mechanisms regulating skeletal muscle atrophy and effective protection is necessary.MethodsRNA sequencing (RNA-seq) analysis was used to detect differentially expressed genes (DEGs) in the soleus muscle at 12, 24, 36 hours, three days, and seven days after hindlimb unloading in rats. Pearson correlation heatmaps and principal component analysis (PCA) were applied to analyze DEGs’ expression profiles. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for cluster analysis of DEGs. Ingenuity pathway analysis (IPA) was used to analyze specific biological processes further.ResultsAt different time points (12, 24, 36 hours, three days, seven days) after hindlimb unloading, the expression levels of 712, 1,109, 1,433, 1,162, and 1,182 genes in rat soleus muscle were upregulated, respectively, whereas the expression levels of 1,186, 1,324, 1,632, 1,446, and 1,596 genes were downregulated, respectively. PCA revealed that rat soleus muscle showed three different transcriptional phases within seven days after hindlimb unloading. KEGG and GO annotation indicated that the first transcriptional phase primarily involved the activation of stress responses, including oxidative stress, and the inhibition of cell proliferation and angiogenesis; the second transcriptional phase primarily involved the activation of proteolytic systems and, to a certain degree, inflammatory responses; and the third transcriptional phase primarily involved extensive activation of the proteolytic system, significant inhibition of energy metabolism, and activation of the aging process and slow-to-fast muscle conversion.ConclusionsDifferent physiological processes in rat skeletal muscles were activated sequentially after unloading. From these activated biological processes, the three transcriptional phases after skeletal muscle unloading can be successively defined as the stress response phase, the atrophic initiation phase, and the atrophic phase. Our study not only helps in the understanding of the molecular mechanisms underlying weightlessness-induced muscle atrophy but may also provide an important time window for the treatment and prevention of weightlessness-induced muscle atrophy.

Mechanobiological evaluation of prostate cancer metastasis to bone using an in vitro prostate cancer testbed

Prostate cancer exhibits a propensity to metastasize to the bone, which often leads to fatality. Bone metastasis is characterized by complex biochemical, morphological, pathophysiological, and genetic changes to cancer cells as they colonize at bone sites. In this study, we report the evaluation of MDA PCa2b prostate cancer cells' nanomechanical properties during the mesenchymal-to-epithelial transition (MET) and during disease progression at the metastatic site. Bone-mimetic tissue-engineered 3D nanoclay scaffolds have been used to create in vitro metastatic site for prostate cancer. A significant softening of the prostate cancer cells during MET and further softening as disease progression occurs at metastasis is also reported. The significant reduction in elastic modulus of prostate cancer cells during MET was attributed to actin reorganization and depolymerization. This study provides input towards direct nanomechanical measurements to evaluate the time evolution of cells' mechanical behavior in tumors at bone metastasis site.

Biochemical changes during ripening of cheeses in an animal skin

A few types of cheeses ripened in an animal skin sack are produced around the world: Sir iz mišine (Croatia), Sir iz mijeha (Bosnia and Herzegovina and Montenegro), Tulum and Divle Cave (Turkey), Bouhezza (Algeria) and Darfiyeh (Lebanon). Pronounced and piquant taste, flavour and aroma of these cheeses originate from intensive lipolysis and proteolysis as a result of specific anaerobic conditions inside the skin sack, autochthonous microorganisms from raw milk and skin, as well as their manufacturing procedure. The specific and complex biochemical changes that occur during ripening of cheeses in animal skin sacks have become of great interest to researchers, and numerous studies have been conducted over the last decade. Therefore, the aim of this paper is to review the specificities of proteolytic and lipolytic changes that occur during ripening of cheese in the animal skin sack, which cause the characteristic volatile compounds profile. Moreover, the manufacturing procedures and physico-chemical properties of cheeses is shown due to their relationship with biochemical reactions during cheese ripening. As biochemical changes during ripening directly influence sensory attributes of cheese, which determine consumer preference, this review could provide practical data for cheesemakers to prevent negative consequences of overly intensive biochemical changes during cheese ripening, and so improve the quality of this kind of cheeses.

Nondestructive monitoring of polyphenols and caffeine during green tea processing using Vis-NIR spectroscopy.

Increasing consumption of green tea is attributed to the beneficial effects of its constituents, especially polyphenols, on human health, which can be varied during leaf processing. Processing technology has the most important effect on green tea quality. This study investigated the system dynamics of eight catechins, gallic acid, and caffeine in the processing of two varieties of tea, from fresh leaves to finished tea. It was found that complex biochemical changes can occur through hydrolysis under different humidity and heating conditions during the tea processing. This process had a significant effect on catechin composition in the finished tea. The potential application of visible and near‐infrared (Vis‐NIR) spectroscopy for fast monitoring polyphenol and caffeine contents in tea leaves during the processing procedure has been investigated. It was found that a combination of PCA (principal component analysis) and Vis‐NIR spectroscopy can successfully classify the two varieties of tea samples and the five tea processing procedures, while quantitative determination of the constituents was realized by combined regression analysis and Vis‐NIR spectra. Furthermore, successive projections algorithm (SPA) was proposed to extract and optimize spectral variables that reflected the molecular characteristics of the constituents for the development of determination models. Modeling results showed that the models had good predictability and robustness based on the extracted spectral characteristics. The coefficients of determination for all calibration sets and prediction sets were higher than 0.862 and 0.834, respectively, which indicated high capability of Vis‐NIR spectroscopy for the determination of the constituents during the leaf processing. Meanwhile, this analytical method could quickly monitor quality characteristics and provide feedback for real‐time controlling of tea processing machines. Furthermore, the study on complex biochemical changes that occurred during the tea processing would provide a theoretical basis for improving the content of quality components and effective controlling processes.

Innovative breeding technologies in lettuce for improved post-harvest quality.

Societal awareness of healthy eating is increasing alongside the market for processed bagged salads, which remain as one of the strongest growing food sectors internationally, including most recently from indoor growing systems. Lettuce represents a significant proportion of this ready-to-eat salad market. However, such products typically have a short shelf life, with decay of post-harvest quality occurring through complex biochemical and physiological changes in leaves and resulting in spoilage, food waste and risks to health. We review the functional and quantitative genetic understanding of lettuce post-harvest quality, revealing that few findings have translated into improved cultivar development. We identify (i) phytonutrient status (for enhanced antioxidant and vitamin status, aroma and flavour) (ii) leaf biophysical, cell wall and water relations traits (for longer shelf life) (iii) leaf surface traits (for enhanced food safety and reduced spoilage) and (iv) chlorophyll, other pigments and developmental senescence traits (for appearance and colour), as key targets for future post-harvest breeding. Lettuce is well-placed for rapid future exploitation to address postharvest quality traits with extensive genomic resources including the recent release of the lettuce genome and the development of innovative breeding technologies. Although technologies such as CRISPR/Cas genome editing are paving the way for accelerated crop improvement, other equally important resources available for lettuce include extensive germplasm collections, bi-parental mapping and wide populations with genotyping for genomic selection strategies and extensive multiomic datasets for candidate gene discovery. We discuss current progress towards post-harvest quality breeding for lettuce and how such resources may be utilised for future crop improvement.

FREE RADICAL LIPID OXIDATION AS A LEADING MECHANISM IN DEVELPOING PERIODONTITIS

Generalized periodontitis is a disease, which occurrence rate increases with age and manifests as a destructive inflammatory process based on the complex biochemical and pathophysiological changes. Active resorption of the alveolar ridge is influenced by both local factors and the overall body condition and systemic diseases. Development of generalized periodontitis is associated with loss of skeletal bone mass and characterized by predominance of resorption over osteosynthesis. Key moments in the pathogenesis of periodontal diseases are impairment of the dynamic balance of the prooxidate-antioxidant system that leads to the accumulation of reactive oxygen species and toxic metabolites. Along with the general mechanisms, local factors are involved into the pathogenesis of periodontitis. As a result of the "respiratory burst" of neutrophils, there is an effect of enzymatic lipid peroxidation burst with the following formation of superoxide anion radical and eicosanoids, damage to periodontal structures, immunological disorders. Generalized periodontitis is a polyetiological disease associated with the pathology of internal organs. The mechanisms of inflammatory and destructive periodontal lesions are mediated by genetic and local factors, chronic concomitant pathology, free radical aggression, and secondary immunodeficiency states. In the mechanism of local destruction of periodontal tissues, an important role is played by periodontopathogenic microflora, which triggers reactions accompanied by intensification of the processes of free radical oxidation of lipids and proteins of cell membrane structures.

Plasma creatinine and oxidative stress biomarkers in amyotrophic lateral sclerosis

Objective: To determine the associations between plasma creatinine (PCr), plasma uric acid (PUA), and urinary oxidative stress (OS) biomarkers with the ALSFRS-R at baseline and survival in a large epidemiological cohort study (ALS COSMOS) with a well-phenotyped patient population (N = 355).Methods: Fasting plasma and first void urine samples were obtained. PCr, PUA, urinary 8-oxo-deoxy guanosine (8-oxodG), and 15-F2t-isoprostane (IsoP) were analyzed at baseline, near the midpoint of follow-up, and at the final blood draw (before death or withdrawal from study). We estimated associations between these biomarkers and the ALSFRS-R at baseline and survival.Results: At baseline, PCr correlated with ALSFRS-R (Spearman r = 0.30), percent (%) FVC (r = 0.20), PUA (r = 0.37), and 8-oxodG (r = −0.13, all p < 0.05). Baseline PCr significantly predicted survival (adjusted hazard ratio 0.28, p < 0.001). Time to death from baseline was shortest for those in the lowest two PCr quartiles relative to the highest two quartiles. PCr and ALSFRS-R values were significantly correlated at all three time points (baseline: r = 0.29, midpoint: r = 0.23, final: r = 0.38, all p < 0.001). PCr and PUA significantly declined over time, whereas OS biomarkers significantly increased over time.Conclusions: To date, PCr predicted survival the best, compared to PUA, 8-oxodG, and IsoP. Although PCr represents the degree of muscle mass, it may also represent complex biochemical changes in ALS. Because the field has no reliable prognostic biomarkers, the importance of PCr warrants further investigation through clinical studies in ALS.

Differential gene expression during substrate probing in larvae of the Caribbean coral Porites astreoides.

The transition from larva to adult is a critical step in the life history strategy of most marine animals. However, the genetic basis of this life history change remains poorly understood in many taxa, including most coral species. Recent evidence suggests that coral planula larvae undergo significant changes at the physiological and molecular levels throughout the development. To investigate this, we characterized differential gene expression (DGE) during the transition from planula to adult polyp in the abundant Caribbean reef‐building coral Porites astreoides, that is from nonprobing to actively substrate‐probing larva, a stage required for colony initiation. This period is crucial for the coral, because it demonstrates preparedness to locate appropriate substrata for settlement based on vital environmental cues. Through RNA‐Seq, we identified 860 differentially expressed holobiont genes between probing and nonprobing larvae (p ≤ .01), the majority of which were upregulated in probing larvae. Surprisingly, differentially expressed genes of endosymbiotic dinoflagellate origin greatly outnumbered coral genes, compared with a nearly 1:1 ratio of coral‐to‐dinoflagellate gene representation in the holobiont transcriptome. This unanticipated result suggests that dinoflagellate endosymbionts may play a significant role in the transition from nonprobing to probing behaviour in dinoflagellate‐rich larvae. Putative holobiont genes were largely involved in protein and nucleotide binding, metabolism and transport. Genes were also linked to environmental sensing and response and integral signalling pathways. Our results thus provide detailed insight into molecular changes prior to larval settlement and highlight the complex physiological and biochemical changes that occur in early transition stages from pelagic to benthic stages in corals, and perhaps more importantly, in their endosymbionts.