Exploring the onset of B12-based mutualisms using a recently evolved Chlamydomonas auxotroph and B12-producing bacteria

Cobalamin (vitamin B12), is a cofactor for crucial metabolic reactions in multiple eukaryotic taxa, including major primary producers such as algae, and yet only prokaryotes can produce it. Many bacteria can colonise the algal phycosphere, forming stable communities that gain preferential access to exudates and in return provide compounds, such as B12. Extended coexistence can then drive gene loss, leading to greater algal-bacterial interdependence. In this study, we investigate how a recently evolved B12-dependent strain of Chlamydomonas reinhardtii, metE7, forms a mutualism with certain bacteria, including the rhizobium Mesorhizobium loti and even a strain of the gut bacterium E. coli engineered to produce cobalamin. Although metE7 was supported by B12 producers, its growth in co-culture was slower than the B12-independent wild-type, suggesting that high bacterial B12 provision may be necessary to favour B12 auxotrophs and their evolution. Moreover, we found that an E. coli strain that releases more B12 makes a better mutualistic partner, and although this trait may be more costly in isolation, greater B12 release provided an advantage in co-cultures. We hypothesise that, given the right conditions, bacteria that release more B12 may be selected for, particularly if they form close interactions with B12-dependent algae.

Age-Dependent Decline of NAD+ - Universal Truth or Confounded Consensus?

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with age. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to increase NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

Interaction of Nootropic Drugs with Neurotransmitter Enzyme Acetylcholinesterase: An Insilico Approach: A Review

Nootropic drugs are the class of drugs or supplements that are claimed to enhance cognitive functions, specifically executive functions, memory and creativity in healthy individual. They are sometime referred as cognitive enhancers or smart drugs as they are associated with memory improvement functioning. Some of them are well known drugs and clinically approved by the Food and Drug Administration (FDA). All metabolic reactions are purely dependent on enzymatic actions as they play a very important role in regulating and maintaining most of the biological responses and various processes. An enzyme Acetylcholinesterase (AChE) seems to play an essential role in the conduction of cholinergic brain synapses and neuromuscular junctions. There have been different nootropic drugs identified and approved for curing neurodegenerative disorders such as Alzheimer, Parkinson and Huntington's disease. Their binding efficiency and energy have been well studied an established by using the in-silico docking tools. There are different docking tools available today for analysis of molecules such as PyRx, Auto dock and schrodinger suite. The advent of these tools is being widely used by the pharmaceutical industries for the virtual screening of the formulated drugs against the desired target molecule. It has made the drug formulation process more time efficient and cost effective. Thus, an in-silico approach has been widely accepted for drug discovery and its design.

Proteome allocation and the evolution of metabolic cross-feeding

Metabolic cross-feeding (MCF) is a widespread type of ecological interaction where organisms share nutrients. In a common instance of MCF, an organism incompletely metabolizes sugars and releases metabolites that are used by another as a carbon source to produce energy. Why would the former waste edible food, and why does this preferentially occur at specific locations in the sugar metabolic pathway (acetate and glycerol are preferentially exchanged) have challenged evolutionary theory for decades. After showing that cells should in principle prioritise upstream reactions, we investigate how a special feature of these metabolites - their high diffusivity across the cell membrane - may trigger the emergence of cross feeding in a population. We explicitly model metabolic reactions, their enzyme-driven catalysis, and the cellular constraints on the proteome that may incur a cost to expressing all enzymes along the metabolic pathway. We find that up to high permeability coefficients of an intermediate metabolite, the expected evolutionary outcome is not a diversification that resembles cross-feeding but a single genotype that instead overexpresses the enzymes downstream the metabolite to limit its diffusion. Only at very high permeabilities and under restricted sets of parameters should the population diversify and MCF evolve.

DEVELOPMENT OF A MATHEMATICAL MODEL OF LIVER FILTRATION

Клетки печени занимают центральное место в реакциях промежуточного метаболизма. Печень принимает участие в метаболизме почти всех классов веществ. Основной структурной единицей печени является печеночная долька, которая представляет собой призму размером 1,5-2 мм с плоскими основанием и вершиной. По всей дольке также распределены лимфатические сосуды, которые активно поглощают интерстициальную жидкость и выводят ее с регулируемой скоростью, однако зависимость скорости поглощения от интерстициального давления и других параметров известна не полностью. В работе представлена математическая модель для оценки кровотока в печеночной дольке. Рассмотренная клеточная модель включает в себя производство и прохождение лимфы по двум основным путям: поглощение лимфатическими сосудами и выход из печени через поверхность дольки в интерстициальное пространство. Приведены геометрические и механические допущения модели и ее недостатки. В биологической модели исследовано влияние изменений кровяного давления в печени на выработку лимфы и оценивается скорость поглощения лимфы и поток жидкости (как лимфы, так и крови) по всей поверхности печени. В математической модели показана классификация: статическая (не зависящая от времени), пространственная, детерминированная, нелинейная, непрерывная. Результаты исследования показали, что предлагаемая клеточная модель микроциркуляции печени включает в себя производство и прохождение лимфы по двум основным путям: поглощение лимфатическими сосудами и выход из печени через поверхность дольки в интерстициальное пространство. Выявлены основные недостатки разрабатываемой модели Liver cells are central to intermediate metabolic reactions. The liver is involved in the metabolism of almost all classes of substances. The main structural unit of the liver is the hepatic lobule, which is a prism 1.5-2 mm in size with a flat base and apex. Lymphatic vessels are also distributed throughout the lobule, which actively absorb interstitial fluid and remove it at a controlled rate, however, the dependence of the rate of absorption on interstitial pressure and other parameters is not fully known. The paper presents a mathematical model for assessing blood flow in the hepatic lobule. The considered cellular model includes the production and passage of lymph through two main pathways: absorption by the lymphatic vessels and exit from the liver through the surface of the lobule into the interstitial space. Geometric and mechanical assumptions of the model and its disadvantages are presented. A biological model investigates the effect of changes in liver blood pressure on lymph production and estimates the rate of lymph absorption and fluid flow (both lymph and blood) over the entire surface of the liver. The mathematical model shows the classification: static (independent of time), spatial, deterministic, nonlinear, continuous. The results of the study showed that the proposed cellular model of liver microcirculation includes the production and passage of lymph through two main pathways: absorption by the lymphatic vessels and exit from the liver through the surface of the lobule into the interstitial space. The main shortcomings of the developed model are revealed

Quality Attributes of Chitosan-Coated Cornelian Cherry (Cornus mas L.) Fruits under Different Storage Temperatures

Temperature is the dominant environmental stimulus that influences the postharvest quality, visual appearance, and nutritional content of fruits. Temperature hastens fruit ripening and senescence by the impact on respiration rate and the acceleration of metabolic reactions. This study was conducted to select the optimized temperature for preserving the quality-related traits and antioxidant potential of cornelian cherry fruits after harvest. The fruits were treated with 1% chitosan and then kept under 0, 5, 10, and 21 °C for 21 days. The results revealed that fruits kept under lower than room temperature (21 °C) better retained antioxidant capacity and had higher levels of phenolics, flavonoids, and anthocyanins and even higher antioxidant enzyme activity, hence attaining prolonged postharvest life. Considering the quantity attributes and the shelf life, the temperature of choice was 0 °C. Zero temperature was also the best to keep the antioxidant capacity of cornelian cherry fruits. Overall, the results showed that low temperature and chitosan pretreatment provide an efficient method for maintaining the nutritional quality and antioxidant capacity of cornelian cherry fruits during storage time.

Age-Dependent Decline of NAD+ - Universal Truth or Confounded Consensus?

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with time. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to boost NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human) to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support it is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies aimed to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD+ during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

Genome and transcriptome architecture of allopolyploid okra (Abelmoschus esculentus)

We present the first annotated genome assembly of the allopolyploid okra (Abelmoschus esculentus). Analysis of telomeric repeats and gene rich regions suggested we obtained whole chromosome and chromosomal arm scaffolds. Besides long distal blocks we also detected short interstitial TTTAGGG telomeric repeats, possibly representing hallmarks of chromosomal speciation upon polyploidization of okra. Ribosomal RNA genes are organized in 5S clusters separated from the 18S-5.8S-28S units, clearly indicating an S-type rRNA gene arrangement. The assembly is consistent with cytogenetic and cytometry observations, identifying 65 chromosomes and 1.45Gb of expected genome size in a haploid sibling. Approximately 57% of the genome consists of repetitive sequence. BUSCO scores and A50 plot statistics indicated a nearly complete genome. Kmer distribution analysis suggests that approximately 75% has a diploid nature, and at least 15% of the genome is heterozygous. We did not observe aberrant meiotic configurations, suggesting there is no recombination among the sub-genomes. BUSCO configurations pointed to the presence of at least 3 sub-genomes. These observations are indicative for an allopolyploid nature of the okra genome. Structural annotation using gene models derived from mapped transcriptome data, generated over 130,000 putative genes. The discovered genes appeared to be located predominantly at the distal ends of scaffolds, gradually decreasing in abundance toward more centrally positioned scaffold domains. In contrast, LTR retrotransposons were more abundant in centrally located scaffold domains, while less frequently represented in the distal ends. This gene and LTR-retrotransposon distribution is consistent with the observed heterochromatin organization of pericentromeric heterochromatin and distal euchromatin. The derived amino acid queries of putative genes were subsequently used for phenol biosynthesis pathway annotation in okra. Comparison against manually curated reference KEGG pathways from related Malvaceae species revealed the genetic basis for putative enzyme coding genes that likely enable metabolic reactions involved in the biosynthesis of dietary and therapeutic compounds in okra.

Kinetic compartmentalization by unnatural reaction for itaconate production

Physical compartmentalization of metabolisms using membranous organelles in eukaryotes is helpful for chemical biosynthesis to ensure the availability of substrates from competitive metabolic reactions. Bacterial hosts lack such a membranous system, which is one of the major limitations for efficient metabolic engineering. Here, we introduced kinetic compartmentalization as an alternative strategy to enable substrate availability from competitive reactions. This method utilizes a non-natural biochemical reaction performed by an engineered enzyme to kinetically isolate the metabolic pathways and ensure substrate availability for the desired reaction. As a proof of concept, we could successfully demonstrate kinetic separation for efficient itaconate production from acetate in Escherichia coli, mimicking the native mitochondrial membrane system in Aspergillus species. Despite the utilization of the non-preferred carbon source, kinetic compartmentalization could lead to substantial increases of itaconate in both yield and titer, suggesting enough potential of our strategy for broad applications in diverse engineering.