Complex Organisms Research Articles

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network

BackgroundResearchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PurposeMDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. Study designAcute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. Methods/resultsHere, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. ConclusionBrain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

Biophysics and Quantum Limitation of Photoreceptive Processes

This entry paper is an attempt to explain how the discrete nature of light (energy discreteness in the form of photons) constrains the light detection process all along the evolutionary path, in the not-fully-understood photoreceptive systems of unicellular microorganisms (nonimaging systems) and in the complex and well-known visual system of higher organisms (imaging systems). All these systems are perfect examples of the interplay between physics and biology, i.e., they are the perfect topic of research for biophysicists. The paper describes how photoreceptive and visual systems achieve the goal of photon counting, which information is conveyed by a finite number of photons, and which noise factors limit light-detecting processes.

GC-MS Profiling and Pharmacological Potential of Physconia venusta (Ach.) Poelt.

Lichens are complex symbiotic organisms that generate various bioactive compounds with significant therapeutic value. We investigated the chemical composition and bioactivity of the acetone extract of the Algerian lichen Physconia venusta (Ach.) poet. Phytochemical screening was performed using gas chromatography-mass spectrometry (GC-MS). The antibacterial activity was assessed against Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis, Salmonella typhi, Staphylococcus aureus, Listeria monocytogenes, and Bacillus subtilis using an agar diffusion test with the determination of the minimal inhibition concentration (MIC), while the antioxidant activity was determined using different chemical methods (DPPH, ABTS, CUPRAC, reducing power, superoxide anion scavenging, β-carotene bleaching, and metal chelate). In addition, cytotoxic activity was tested using Artemia salina (Brine shrimp) bioassay. The studied extract exhibited intense antibacterial activity against E. coli and S. aureus with inhibition diameters of 28 ± 0.01 and 22 ± 0.01 mm, respectively, with a MIC value of 6.25 mg/mL and a selectivity index of 2.8. The obtained extract showed different antioxidant trends depending on the selected assay. GC-MS analysis revealed many secondary metabolites. P. venusta, a type of lichen, is a potential source of bioactive substances that could be used in pharmaceuticals.

Three kingdoms and one ceramide to rule them all. A comparison of the structural basis of ceramide-dependent regulation of sphingolipid biosynthesis in animals, plants, and fungi

Sphingolipids are a diverse class of lipids with essential functions as determinants of membrane physical properties and as intra- and intercellular signaling agents. Disruption of the normal biochemical processes that establish the levels of individual sphingolipids is associated with a variety of human diseases including cancer, cardiovascular disease, metabolic disease, skin diseases, and lysosomal storage diseases. A unique aspect of this metabolic network is that there is a single enzymatic step that initiates the biosynthetic pathway for all sphingolipids. This step is catalyzed by the enzyme serine palmitoyltranserase (SPT). Under most circumstances SPT condenses serine and the 16-carbon acyl-CoA, palmitoyl-CoA to produce the precursor of all sphingolipids. SPT, a four-subunit protein complex, is subject to classic feedback regulation: when cellular sphingolipids are elevated, SPT activity is inhibited. Ceramide is the sphingolipid sensed by this system and it regulates SPT by directly binding to the complex. The ceramide binding site in the SPT complex, and how ceramide binding results in SPT inhibition, has now been determined in vertebrates, plants, and yeast using molecular modeling and cryo-electron microscopy. Here we discuss the similarities and differences revealed by these resolved structures and the surprising result that ceramide binds at almost identical positions in the SPT complex of these divergent organisms, but accomplishes SPT regulation in very different ways.

Criticality Analysis: Bio-Inspired Nonlinear Data Representation.

The representation of arbitrary data in a biological system is one of the most elusive elements of biological information processing. The often logarithmic nature of information in amplitude and frequency presented to biosystems prevents simple encapsulation of the information contained in the input. Criticality Analysis (CA) is a bio-inspired method of information representation within a controlled Self-Organised Critical system that allows scale-free representation. This is based on the concept of a reservoir of dynamic behaviour in which self-similar data will create dynamic nonlinear representations. This unique projection of data preserves the similarity of data within a multidimensional neighbourhood. The input can be reduced dimensionally to a projection output that retains the features of the overall data, yet has a much simpler dynamic response. The method depends only on the Rate Control of Chaos applied to the underlying controlled models, which allows the encoding of arbitrary data and promises optimal encoding of data given biologically relevant networks of oscillators. The CA method allows for a biologically relevant encoding mechanism of arbitrary input to biosystems, creating a suitable model for information processing in varying complexity of organisms and scale-free data representation for machine learning.

VALIDATION OF A ZEBRAFISH DEVELOPMENTAL DEFECTS ASSAY AS A QUALIFIED ALTERNATIVE TEST FOR ITS REGULATORY USE FOLLOWING THE ICH S5(R3) GUIDELINE

Zebrafish is a popular toxicology model and provides an ethically acceptable small-scale analysis system with the complexity of a complete organism. Our goal is to further validate this model for its regulatory use for reproductive and developmental defects by testing the compounds indicated in the “Guideline on detection of reproductive and developmental toxicity for human pharmaceuticals” (ICH S5(R3) guideline.) To determine the embryotoxic and developmental risk of the 32 reference compounds listed in the ICH S5(R3) guideline, the presence of morphological alterations in zebrafish embryos was analyzed at two different stages to calculateLC50 and EC50 values for each stage. Teratogenic Indexes were established as the ratio between LC50 and EC50 critical for the proper compound classification as teratogenic when it is ≥ 2. A total of three biological replicates have been conducted to study the reproducibility of the assay. The chemicals’ concentration in the medium and internally in the zebrafish embryos was evaluated. In this study, the 3 negative compounds were properly categorized while 23 compounds out of the 29 reference ones (sensitivity of 79.31%) were classified as teratogenic in zebrafish. The 6 that had false-negative results were classified 4 as inconclusive, 1 as not toxic, and 1 compound resulted toxic for zebrafish embryos under testing conditions. After the bioavailability experiments, some of the obtained inconclusive results were refined. The developmental defects assay in zebrafish gives an accuracy of 89.66%, sensitivity of 88.46%, specificity and repeatability of 100% compared to mammals; therefore, this is a well-integrated strategy using New Alternative Methods, to minimize the use of animals in developmental toxicity studies.

Evaluating modularity in the hominine skull related to feeding biomechanics.

Modular architecture of traits in complex organisms can be important for morphological evolution at micro- and sometimes macroevolutionary scales as it may influence the tempo and direction of changes to groups of traits that are essential for particular functions, including food acquisition and processing. We tested several distinct hypotheses about craniofacial modularity in the hominine skull in relation to feeding biomechanics. First, we formulated hypothesized functional modules for craniofacial traits reflecting specific demands of feeding biomechanics (e.g., masseter leverage/gape or tooth crown mechanics) in Homo sapiens, Pan troglodytes, and Gorilla gorilla. Then, the pattern and strength of modular signal was quantified by the covariance ratio coefficient and compared across groups using covariance ratio effect size. Hierarchical clustering analysis was then conducted to examine whether a priori-defined functional modules correspond to empirically recovered clusters. There was statistical support for most a priori-defined functional modules in the cranium and half of the functional modules in the mandible. Modularity signal was similar in the cranium and mandible, and across the three taxa. Despite a similar strength of modularity, the empirically recovered clusters do not map perfectly onto our priori functional modules, indicating that further work is needed to refine our hypothesized functional modules. The results suggest that modular structure of traits in association with feeding biomechanics were mostly shared with humans and the two African apes. Thus, conserved patterns of functional modularity may have facilitated evolutionary changes to the skull during human evolution.

Titanium-doped PET nanoplastics, from opaque milk bottle degradation, as a model of environmental true-to-life nanoplastics. Hazardous effects on Drosophila

Micro and nanoplastics (MNPLs) are emergent environmental pollutants, resulting from the degradation of plastic waste, requiring urgent information on their potential risks to human health. To determine such risks, reliable true-to-life materials are essential. In this work, we have used titanium-doped PET NPLs [PET(Ti)NPLs], obtained by grinding opaque milk polyethylene terephthalate (PET) bottles, as a true-to-life MNPLs model. These opaque PET bottles, with an average size of 112 nm, contain about 3% Ti in the form of titanium dioxide rod nanoparticles. TEM investigation confirmed the mixed Ti/PET nature of the obtained true-to-life NPLs, and the rod shape of the embedded TiO2NPs. In the in vivo Drosophila model neither PET(Ti)NPLs nor TiO2NPs reduced the survival rates, although their internalization was confirmed in different compartments of the larval body by using confocal and transmission electron microscopies. The presence of Ti in the PET(Ti)NPLs permitted to quantify its presence both in larvae (2.1 ± 2.2 μg/g of Ti) and in the resulting adults (3.4 ± 3.2 μg/g of Ti) after treatment with 500 μg/g food of PET(Ti)NPL, suggesting its potential use to track their fate in more complex organisms such as mammals. PET(Ti)NPLs, as well as TiO2NPs, altered the expression of genes driving different response pathways, inducing significant oxidative stress levels (up to 10 folds), and genotoxicity. This last result on the genotoxic effects is remarkable in the frame of the hot topic discussion on the risk that titanium compounds, used as food additives, may pose to humans.

Modelling physical processes in higher plants using leaf replicas for space applications

In the future, higher plant cultivation will be a key component of Bioregenerative Life-Support Systems. This will require a deep understanding of phenomena that play an important role at the core of plant metabolism and of their interaction with the environment. Plants are complex organisms that must be studied with the use of leaf replicas. This enables the study of physical phenomena at the leaf surface, without biochemical or biological interactions nor genetic variability. To assess the influence of gravity, it is a necessary step to develop precise mechanistic models of plant behaviour in space. This review article presents the state-of-the-art of leaf replicas and concomitant phenomena, with a space gaze.

Naphthylamine-based ratiometric fluorescence probe with a large Stokes shift for monitoring mitochondrial peroxynitrite

The design of ratiometric fluorescence probes with large Stokes shift is greatly significant in addressing the major challenges of detecting and imaging target substances in complex organisms. Such probes with a self-calibration function can minimize the interference of probe concentration and excitation light. In this study, a novel fluorophore of NA-Py with large Stokes shift of 158 nm, was easily obtained in one step. As a proof of concept, based on NA-Py, a fluorescence probe NA-BOH with strong intramolecular charge transfer (ICT) structural characteristics is designed for detecting peroxynitrite (ONOO−). NA-BOH exhibits red emission (627 nm) and a larger Stokes shift of 178 nm. Furthermore, it demonstrats rapid response (within 20 min) and high selectivity towards ONOO−, with ratiometric quantitative response (0–20 μM), and high sensitivity (182 nM). Alongside excellent biocompatibility and remarkable mitochondrial targeting ability, NA-BOH is successfully utilized for the proportional imaging of ONOO− in living cells and zebrafish.

The Role of mRNA Quality Control in the Aging of Caenorhabditis elegans.

The proper maintenance of mRNA quality that is regulated by diverse surveillance pathways is essential for cellular homeostasis and is highly conserved among eukaryotes. Here, we review findings regarding the role of mRNA quality control in the aging and longevity of Caenorhabditis elegans, an outstanding model for aging research. We discuss the recently discovered functions of the proper regulation of nonsense-mediated mRNA decay, ribosome-associated quality control, and mRNA splicing in the aging of C. elegans. We describe how mRNA quality control contributes to longevity conferred by various regimens, including inhibition of insulin/insulin-like growth factor 1 (IGF-1) signaling, dietary restriction, and reduced mechanistic target of rapamycin signaling. This review provides valuable information regarding the relationship between the mRNA quality control and aging in C. elegans, which may lead to insights into healthy longevity in complex organisms, including humans.

Why an animal needs a brain.

In Principles of Neural Design (2015, MIT Press), inspired by Charles Darwin, Sterling and Laughlin undertook the unfashionable task of distilling principles from facts in the technique-driven, data-saturated domain of neuroscience. Their starting point for deriving the organizing principles of brains are two brainless single-celled organisms, Escherichia coli and Paramecium, and the 302-neuron brain of the nematode Caenorhabditis elegans. The book is an exemplar in how to connect the dots between simpler and (much) more complex organisms in a particular area. Here, they have generously agreed to republish an abridged version of Chapter 2 (Why an Animal Needs a Brain), in which many of their principles are first described.

Polymerase chain reaction: a powerful analytical tool in the field of food safety

Abstract The polymerase chain reaction (PCR) is the canonical DNA analysis technique that has enabled the understanding of the complexity of organisms and significantly advanced achievements in the field of biological sciences. Today, the method is still widely used in basic science research, but PCR-based diagnostics are becoming increasingly important in industries such as food and agriculture. This method provides high sensitivity because it requires trace amounts of template DNA to generate enough copies for detection. Using primers specific to the DNA sequence ensures the high specificity of the test. The advantages of the method are time – and cost-effectiveness and reproducibility. PCR-based techniques have found favor in areas where food traceability is important, whether from an economic, legal, health, or religious-cultural point of view. This review outlines the most important aspects in which the PCR method has been successfully applied, namely in the protection of human health by enabling the identification of foodborne pathogens or allergens. Furthermore, the use of PCR in the so-called green criminology, a branch that deals with tracking illegal practices such as food adulteration, compliance with the labeling rules, and detection of food products containing GMO material or other undeclared food ingredients, was also described.

Research progress of single-cell sequencing in tuberculosis.

Tuberculosis is a major infectious disease caused by Mycobacterium tuberculosis infection. The pathogenesis and immune mechanism of tuberculosis are not clear, and it is urgent to find new drugs, diagnosis, and treatment targets. A useful tool in the quest to reveal the enigmas related to Mycobacterium tuberculosis infection and disease is the single-cell sequencing technique. By clarifying cell heterogeneity, identifying pathogenic cell groups, and finding key gene targets, the map at the single cell level enables people to better understand the cell diversity of complex organisms and the immune state of hosts during infection. Here, we briefly reviewed the development of single-cell sequencing, and emphasized the different applications and limitations of various technologies. Single-cell sequencing has been widely used in the study of the pathogenesis and immune response of tuberculosis. We review these works summarizing the most influential findings. Combined with the multi-molecular level and multi-dimensional analysis, we aim to deeply understand the blank and potential future development of the research on Mycobacterium tuberculosis infection using single-cell sequencing technology.

Direct observation of triplet energy transfer between chlorophylls and carotenoids in the core antenna of photosystem I from Thermosynechococcus elongatus

Quenching of chlorophyll triplet states by carotenoids is an essential photoprotective process, which prevents formation of reactive singlet oxygen in photosynthetic light-harvesting complexes. The process is usually very efficient in oxygenic organisms under physiological conditions, thus preventing any observable accumulation of chlorophyll triplets. However, it subsequently prevents also the determination of the triplet transfer rate. Here we report results of nanosecond transient absorption spectroscopy on photosystem I core complexes, where a major part of chlorophyll a triplet states (~60 %) accumulates on a nanosecond time scale at ambient temperature. As a consequence, the triplet energy transfer could be resolved and the transfer time was determined to be about 24 ns. A smaller fraction of chlorophyll a triplet states (~40 %) is quenched with a faster rate, which could not be determined. Our analysis indicates that these chlorophylls are in direct contact with carotenoids. The overall chlorophyll triplet yield in the core antenna was estimated to be ~0.3 %, which is a value two orders of magnitude smaller than in most other photosynthetic light-harvesting complexes. This explains why slower quenching of chlorophyll triplet states is sufficient for photoprotection of photosystem I. Nevertheless, the core antenna of photosystem I represents one of only few photosynthetic complexes of oxygenic organisms in which the quenching rate of the majority of chlorophyll triplets can be directly monitored under physiological temperature.

Editorial Preface to Special Issue: The radiations within the Great Ordovician Biodiversification Event

In order to improve our understanding of the biodiversification of marine life that took place during the early Palaeozoic, we present this special issue focused on the Ordovician radiations. The Great Ordovician Biodiversification Event (GOBE) is a conceptual term that is today largely used to refer to the most significant increase of marine biodiversity of the Phanerozoic that occurred during the Ordovician Period between 485 and 444 Ma. Some authors, focusing on taxonomic diversity counts of selected groups, understand the GOBE to be related to a single dramatic biodiversification event of short duration in the Darriwilian Stage of the Middle Ordovician Series between 470 and 455 Ma, whereas others follow the more traditional view and consider the Ordovician biodiversification as an aggregation of radiation events capturing a large and complex increase of taxonomic diversity but also ecological complexity of marine organisms covering the entire Ordovician. This special issue features 16 selected papers that provide different perspectives on these Ordovician biodiversification events, illustrating a variety of radiations occurring during the Ordovician Period. Several papers focus on the available biodiversity datasets and their biases, and the difficulty to distinguish and interpret the various regional and global scales. It becomes clear that the Cambrian and Ordovician radiations are artificially separated by a late Cambrian ‘Furongian Biodiversity Gap’ and that a single long-term early Palaeozoic radiation is more and more visible. A few papers provide additional data on this crucial interval across the Cambrian-Ordovician boundary displaying a much higher ecological complexity than previously assumed. Both the diversification of the plankton and the evolution of nektonic groups during the Ordovician are investigated, in papers including Computational Fluid Dynamic simulations. The virtual special issue closes with papers documenting the development of reefs during the Late Ordovician.

Multichannel measurements of C. elegans largest Lyapunov exponents using optical diffraction.

Dynamic diffraction (DOD) is a form of microscopy that allows the dynamic tracking of changing shapes in a 1D time series. DOD can capture the locomotion of a nematode while swimming freely in a 3D space, allowing the locomotion of the worm to more closely mimic natural behavior than in some other laboratory environments. More importantly, we are able to see markers of chaos as DOD covers dynamics on multiple length scales. This work introduces a multichannel method to measure the dynamic complexity of microscopic organisms. We show that parameters associated with chaos, such as the largest Lyapunov exponent (LLE), the mean frequency, mutual information (MI), and the embedding dimension, are independent of the specific point sampled in the diffraction pattern, thus demonstrating experimentally the consistency of our dynamic parameters sampled at various locations (channels) in the associated optical far-field pattern.

Common Post-translational Modifications (PTMs) of Proteins: Analysis by Up-to-Date Analytical Techniques with an Emphasis on Barley.

Post-translational modifications (PTMs) of biomacromolecules can be useful for understanding the processes by which a relatively small number of individual genes in a particular genome can generate enormous biological complexity in different organisms. The proteomes of barley and the brewing process were investigated by different techniques. However, their diverse and complex PTMs remain understudied. As standard analytical approaches have limitations, innovative analytical approaches need to be developed and applied in PTM studies. To make further progress in this field, it is necessary to specify the sites of modification, as well as to characterize individual isoforms with increased selectivity and sensitivity. This review summarizes advances in the PTM analysis of barley proteins, particularly those involving mass spectrometric detection. Our focus is on monitoring phosphorylation, glycation, and glycosylation, which critically influence functional behavior in metabolism and regulation in organisms.

Inductively Coupled Electrical Stimulation - Part 6: Duration of PEMF-induced enhanced seed germination

The objective of this study was to directly answer the practical question: how long lasting are the observed effects of pulsed electro-magnetic fields (PEMF) on seed germination? Earlier studies have shown that the effect of PEMF treatment on seed germination can be positive, neutral, or negative, exhibiting a tri-phasic inverse hormesis behavior as a function of total PEMF dosage during a single treatment session. This allows an optimal dosage range to be determined for maximum progerminative effect. Dosages in this range were found in earlier studies to increase the germination rate of pepper seeds to ~ 85%, from the baseline germination rate of ~56%, amounting to an increased germination rate of ~150% of baseline. 
 One major practical consideration of this observation is whether the PEMF treatment is durable enough to allow central processing and long-term storage of the seeds for later use, or whether seeds treated by PEMF need to be planted shortly after treatment due to rapid loss of effect over time. If the latter, what is the allowable time between PEMF treatment and planting? In addition to their practical value, these observations will have considerable theoretical value as well. As the underlying biophysical mechanism of PEMF remains to be elucidated, quantitative assessments of the durability of the effect of PEMF treatment will give important clues as to the potential mechanisms involved; for example, whether they involve the activation of enzyme systems that remain activated or taper off, whether they initiate the release or activation of substances in reserve in the germ that are exhausted upon a single use, whether multiple mechanisms are involved as evidenced by multi-phasic decay over time, or whether the progerminative effect can be repeated more than one time in any given seed.
 For this study, the duration of the progerminative effect was measured by applying a previously-determined “optimal” dose of PEMF to pepper seeds, then storing the seeds in their original paper envelopes in a darkened room at 50% RH and room temperature for a period of up to one year post-treatment before planting, and determination of germination rate at two weeks (14 days). Finally, we study whether the lost progerminative effect can be recovered in stored seeds by reapplication of PEMF at the same dose immediately before planting. 
 Our findings were that (1) the progerminative effect lasted only about 2 days after PEMF exposure, then returned about half way back to baseline and began a slow decline thereafter, but remained at approximately half-way, never returning to baseline even for periods of storage as long as 1 year, (2) a second application of PEMF restored almost all of the progerminative effect even after storage periods of up to one year. Storage periods longer than 1 year were not studied.
 These results add to the discussion of the mechanisms of PEMF across the span of complex organisms by suggesting the involvement of multiple mechanisms, some durable while others are semi-permanent.

Identification of herpesvirus transcripts from genomic regions around the replication origins

Long-read sequencing (LRS) techniques enable the identification of full-length RNA molecules in a single run eliminating the need for additional assembly steps. LRS research has exposed unanticipated transcriptomic complexity in various organisms, including viruses. Herpesviruses are known to produce a range of transcripts, either close to or overlapping replication origins (Oris) and neighboring genes related to transcription or replication, which possess confirmed or potential regulatory roles. In our research, we employed both new and previously published LRS and short-read sequencing datasets to uncover additional Ori-proximal transcripts in nine herpesviruses from all three subfamilies (alpha, beta and gamma). We discovered novel long non-coding RNAs, as well as splice and length isoforms of mRNAs. Moreover, our analysis uncovered an intricate network of transcriptional overlaps within the examined genomic regions. We demonstrated that herpesviruses display distinct patterns of transcriptional overlaps in the vicinity of or at the Oris. Our findings suggest the existence of a ‘super regulatory center’ in the genome of alphaherpesviruses that governs the initiation of both DNA replication and global transcription through multilayered interactions among the molecular machineries.