Biology Mechanisms Research Articles

Susceptibility of Rosaceous Pome and Stone Fruits to Postharvest Rot by Paecilomyces niveus.

Paecilomyces rot of apples is a postharvest disease caused by Paecilomyces niveus, a problematic spoiling agent of fruit juices and derivatives. Processing fruits infected with Paecilomyces rot can lead to juices contaminated with P. niveus ascospores. These ascospores are heat resistant and may survive food processing and germinate in finished products. Because the fungus produces the mycotoxin patulin, juice spoilage by P. niveus is an important health hazard. Little is known about the disease biology and control mechanisms of this recently described postharvest disease. The range of fruit products contaminated by P. niveus and patulin led us to hypothesize that the host range of Paecilomyces rot is broader than previously thought. Following Koch's postulates, we determined that multiple untested rosaceous fruits and popular apple cultivars are susceptible to Paecilomyces rot infection and that these infected fruits contain significant levels of patulin. We also observed that two closely related food spoiling fungi, Paecilomyces fulvus and Paecilomyces variotti, were unable to infect, cause symptoms in, or grow in wounded fruits. Therefore, we challenge the assumption that P. niveus spoilage inoculum is introduced to foods solely through environmental sources, and we show that other economically important rosaceous fruits, peaches, pears, sweet cherries, and sour cherries, are susceptible to infection and can also be sources of spoilage inoculum. Our results highlight the unique abilities of P. niveus to infect a variety of fruits, produce patulin, and form resistant spores capable of spoiling normally shelf-stable products.

Toward a Logic of the Organism: A Process Philosophical Consideration.

Mathematical models applied in contemporary theoretical and systems biology are based on some implicit ontological assumptions about the nature of organisms. This article aims to show that real organisms reveal a logic of internal causality transcending the tacit logic of biological modeling. Systems biology has focused on models consisting of static systems of differential equations operating with fixed control parameters that are measured or fitted to experimental data. However, the structure of real organisms is a highly dynamic process, the internal causality of which can only be captured by continuously changing systems of equations. In addition, in real physiological settings kinetic parameters can vary by orders of magnitude, i.e., organisms vary the value of internal quantities that in models are represented by fixed control parameters. Both the plasticity of organisms and the state dependence of kinetic parameters adds indeterminacy to the picture and asks for a new statistical perspective. This requirement could be met by the arising Biological Statistical Mechanics project, which promises to do more justice to the nature of real organisms than contemporary modeling. This article concludes that Biological Statistical Mechanics allows for a wider range of organismic ontologies than does the tacitly followed ontology of contemporary theoretical and systems biology, which are implicitly and explicitly based on systems theory.

Molecular Pathogenesis in Myeloid Neoplasms with Germline Predisposition.

Myeloid neoplasms with germline predisposition have recently been added as distinct provisional entities in the 2017 revision of the World Health Organization’s classification of tumors of hematopoietic and lymphatic tissue. Individuals with germline predisposition have increased risk of developing myeloid neoplasms—mainly acute myeloid leukemia and myelodysplastic syndrome. Although the incidence of myeloid neoplasms with germline predisposition remains poorly defined, these cases provide unique and important insights into the biology and molecular mechanisms of myeloid neoplasms. Knowledge of the regulation of the germline genes and their interactions with other genes, proteins, and the environment, the penetrance and clinical presentation of inherited mutations, and the longitudinal dynamics during the process of disease progression offer models and tools that can further our understanding of myeloid neoplasms. This knowledge will eventually translate to improved disease sub-classification, risk assessment, and development of more effective therapy. In this review, we will use examples of these disorders to illustrate the key molecular pathways of myeloid neoplasms.

The speciation view: Disentangling multiple causes of adaptive and non‐adaptive radiation in terms of speciation

AbstractBiological diversification often includes burst of lineage splitting. Such “radiation” has been known to act as evolutionary arenas with the potential to generate unique phylogenetic clusters and further novel groups. Although these radiations when accompanied by ecological diversification, so‐called “adaptive radiation” have persisted as a central premise in evolutionary biology, the ecological and genetic mechanism of such rapid diversification has remained unclear. There are several critical definitions for the pattern of adaptive radiation, and those provide delimitation of adaptive and non‐adaptive radiation. That being said, only a few studies have provided any clear demarcations in our understanding of the adaptive and non‐adaptive causes of radiation from the mechanism of speciation. Here, we review the current consensus for the causes of adaptive radiation, especially along with the recent theoretical synthesis of “ecological speciation.” Further, we suggest the signature of adaptive and non‐adaptive radiation in the earliest stages of diversification from the viewpoint of speciation. These criteria from the speciation view are useful to find the cases with the signatures of adaptive/non‐adaptive radiation.

Impact of radiation absorption on Caputo fractional fluid flow over an exponentially accelerated plate

With the advancement of nuclear energy as one of the top clean energy sources, studies on radiation effects are becoming more popular. Radiation absorption is an exothermic phenomenon where radiative energy is released to the surrounding environment. This occurrence can be seen widely in the field of manufacturing, biology, medicine and fluid mechanics. In this study, the impact of radiation absorption of fluid flow over a vertical plate that is exponentially accelerating will be investigated. Heat and mass transfer flowing vertically over the

A high-continuity and annotated tomato reference genome

BackgroundGenetic and functional genomics studies require a high-quality genome assembly. Tomato (Solanum lycopersicum), an important horticultural crop, is an ideal model species for the study of fruit development.ResultsHere, we assembled an updated reference genome of S. lycopersicum cv. Heinz 1706 that was 799.09 Mb in length, containing 34,384 predicted protein-coding genes and 65.66% repetitive sequences. By comparing the genomes of S. lycopersicum and S. pimpinellifolium LA2093, we found a large number of genomic fragments probably associated with human selection, which may have had crucial roles in the domestication of tomato. We also used a recombinant inbred line (RIL) population to generate a high-density genetic map with high resolution and accuracy. Using these resources, we identified a number of candidate genes that were likely to be related to important agronomic traits in tomato.ConclusionOur results offer opportunities for understanding the evolution of the tomato genome and will facilitate the study of genetic mechanisms in tomato biology.

Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation

BackgroundChromatin state provides a clear decipherable blueprint for maintenance of transcriptional patterns, exemplifying a mitotically stable form of cellular programming in dividing cells. In this regard, genomic studies of chromatin states within cancerous tissues have the potential to uncover novel aspects of tumor biology and unique mechanisms associated with disease phenotypes and outcomes. The degree to which chromatin state differences occur in accordance with breast cancer features has not been established.MethodsWe applied a series of unsupervised computational methods to identify chromatin and molecular differences associated with discrete physiologies across human breast cancer tumors.ResultsChromatin patterns alone are capable of stratifying tumors in association with cancer subtype and disease progression. Major differences occur at DNA motifs for the transcription factor FOXA1, in hormone receptor-positive tumors, and motifs for SOX9 in Basal-like tumors. We find that one potential driver of this effect, the histone chaperone ANP32E, is inversely correlated with tumor progression and relaxation of chromatin at FOXA1 binding sites. Tumors with high levels of ANP32E exhibit an immune response and proliferative gene expression signature, whereas tumors with low ANP32E levels appear programmed for differentiation.ConclusionsOur results indicate that ANP32E may function through chromatin state regulation to control breast cancer differentiation and tumor plasticity. This study sets a precedent for future computational studies of chromatin changes in carcinogenesis.

Redox biology mechanisms involved in muscle and neuronal functions: an overview

Redox biology mechanisms involved in muscle and neuronal functions: an overview

Partially Coherent Illumination Based Point-Diffraction Digital Holographic Microscopy Study Dynamics of Live Cells

This paper presents a partially coherent point-diffraction digital holographic microscopy (PC-pDHM) prototype and demonstrates its application in label-free imaging of the dynamic processes of live cells. In PC-pDHM, the light scattered by a rotating diffuser is coupled into a multi-mode fiber, and the output light is used as the partially coherent illumination (PCI), which reduces the speckle noise significantly in PC-pDHM. A polarization-grating is used to remold the object and the reference waves, and the fringe contrast of the generated hologram can be adjusted by changing the polarization of the illumination wave. Using the PC-pDHM prototype, transparent samples and notably the dynamic processes of live cells were imaged with high contrast and in a label-free manner, discovering the pathological mechanisms of biology in the cellular and sub-cellular levels.

Chromosome-level assembly reveals a putative Y-autosomal fusion in the sex determination system of the Greenland Halibut (Reinhardtius hippoglossoides).

Despite the commercial importance of Greenland Halibut (Reinhardtius hippoglossoides), important gaps still persist in our knowledge of this species, including its reproductive biology and sex determination mechanism. Here, we combined single-molecule sequencing of long reads (Pacific Sciences) with chromatin conformation capture sequencing (Hi-C) data to assemble the first chromosome-level reference genome for this species. The high-quality assembly encompassed more than 598 Megabases (Mb) assigned to 1594 scaffolds (scaffold N50 = 25 Mb) with 96% of its total length distributed among 24 chromosomes. Investigation of the syntenic relationship with other economically important flatfish species revealed a high conservation of synteny blocks among members of this phylogenetic clade. Sex determination analysis revealed that similar to other teleost fishes, flatfishes also exhibit a high level of plasticity and turnover in sex determination mechanisms. A low-coverage whole-genome sequence analysis of 198 individuals revealed that Greenland Halibut possesses a male heterogametic XY system and several putative candidate genes implied in the sex determination of this species. Our study also suggests for the first time in flatfishes that a putative Y-autosomal fusion could be associated with a reduction of recombination typical of the early steps of sex chromosome evolution.

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death. This review discusses the impact of NSCLC therapy strategies based on a meta-analysis of clinical studies. In addition, possible therapeutic strategies for repression when standard methods fail, such as the administration of low-toxicity natural anticancer agents targeting these phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in the context of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis (mechanisms related to tumour-associated and -infiltrating cells, epithelial–mesenchymal transition, and migration of cancer cells).

Serious consequences of Epstein-Barr virus infection: Hemophagocytic lymphohistocytosis.

Human is the host of the Epstein-Barr virus (EBV) especially in childhood and adolescence. Most of them are asymptomatic infection and self-limiting. However, for those patients who suffer from immune dysfunction, EBV infection will be life-threatening. Epstein-Barr virus-associated hemophagocytic lymphohistocytosis (EBV-HLH) is one of the severe effects. The diagnosis and differential diagnosis of EBV-HLH and other EBV infectious diseases are mentioned in this paper. The molecular biology mechanism and complications of EBV-HLH are equally briefly presented. It also provides a practical method for the genetic diagnosis of such diseases and the differential diagnosis with other human immunodeficiency diseases for medical scientists in routine clinical practice.

AACR Cancer Progress Report 2021: Discovery Science Driving Clinical Breakthroughs.

AACR Cancer Progress Report 2021: Discovery Science Driving Clinical Breakthroughs.

Brain Mechanisms of Conscious Awareness: Detect, Pulse, Switch, and Wave

Consciousness is a fascinating field of neuroscience research where questions often outnumber the answers. We advocate an open and optimistic approach where converging mechanisms in neuroscience may eventually provide a satisfactory understanding of consciousness. We first review several characteristics of conscious neural activity, including the involvement of dedicated systems for content and levels of consciousness, the distinction and overlap of mechanisms contributing to conscious states and conscious awareness of transient events, nonlinear transitions and involvement of large-scale networks, and finally the temporal nexus where conscious awareness of discrete events occurs when mechanisms of attention and memory meet. These considerations and recent new experimental findings lead us to propose an inclusive hypothesis involving four phases initiated shortly after an external sensory stimulus: (1) Detect—primary and higher cortical and subcortical circuits detect the stimulus and select it for conscious perception. (2) Pulse—a transient and massive neuromodulatory surge in subcortical-cortical arousal and salience networks amplifies signals enabling conscious perception to proceed. (3) Switch—networks that may interfere with conscious processing are switched off. (4) Wave—sequential processing through hierarchical lower to higher cortical regions produces a fully formed percept, encoded in frontoparietal working memory and medial temporal episodic memory systems for subsequent report of experience. The framework hypothesized here is intended to be nonexclusive and encourages the addition of other mechanisms with further progress. Ultimately, just as many mechanisms in biology together distinguish living from nonliving things, many mechanisms in neuroscience synergistically may separate conscious from nonconscious neural activity.

Resolved CFD-DEM simulation of blood flow with a reduced-order RBC model

Mathematical modeling of the blood flow with a resolved description of biological cells mechanics such as red blood cell (RBC) has been a challenge in the past decades as it involves physical complexities and demands high computational costs. In the present study, we propose an approach for efficient simulation of blood flow with several suspended RBCs. In this approach, we employ our previously proposed reduced-order model for deformable particles (Nair et al. in Comput Part Mech 7:593–601, 2020) to mimic the mechanical behavior of an individual RBC as a cluster of overlapping spheres interconnected by flexible mathematical bonds. This discrete element method-based model is then coupled with a fluid flow solver using the immersed boundary method with continuous forcing in the context of computational fluid dynamics-discrete element method (CFD-DEM) coupling. The present computational method is tested with a couple of validation cases in which the single RBC dynamics, as well as the blood flow with several RBCs, were tested in comparison with existing literature date. First, the RBC deformation index in shear flow at different shear rates is studied with a good accuracy. Then, the blood flow in micro-tubes of different diameters and hematocrits was simulated. The key characteristics of blood flow such as cell-free layer (CFL) thickness, Fahraeus effect and the relative apparent viscosity are used as the validation metrics. The proposed approach can predict the formation of the migration of RBC toward the tube center-line and the CFL thickness in good agreement with previous measurement and simulations. Furthermore, the model is employed to study the CFL enhancement for plasma separation based on channel constriction. The simulation results compute the CFL thickness downstream of the channel constriction in good agreement with the experiments in a wide range of flow rates and constriction lengths. The original contribution of this study lies in proposing an efficient resolved CFD-DEM simulation method for blood flows with many RBCs which can be employed for numerical investigation of bio-microfluidic applications.

Tick gut barriers impacting tick-microbe interactions and pathogen persistence.

Ticks are regarded as one of the most ancient, unique, and highly evolved ectoparasites. They can parasitize diverse vertebrates and transmit a number of widespread infections. Once acquired from infected hosts, many tick-borne pathogens, like Borrelia burgdorferi, are confined within the tick gut lumen and are surrounded by discrete gut barriers. Such barriers include the peritrophic membrane (PM) and the dityrosine network (DTN), which are in close contact with resident microbiota and invading pathogens, influencing their survival within the vector. Herein, we review our current state of knowledge about tick-microbe interactions involving the PM and DTN structures. As a model, we will focus on Ixodes ticks, their microbiome, and the pathogen of Lyme disease. We will address the most salient findings on the structural and physiological roles of these Ixodes gut barriers on microbial interactions, with a comparison to analogous functions in other model vectors, such as mosquitoes. We will distill how this information could be leveraged towards a better understanding of the basic mechanisms of gut biology and tick-microbial interactions, which could contribute to potential therapeutic strategies in response to ticks and tick-borne infections.

A propósito del tránsito intracelular de los virus. Comic ilustrativo.

Introduction. The mechanism of how viruses cross intracellular structures is the model that exemplifies the intracellular transit through the endomembrane system, the same that is used in the teaching and description of the different intracellular apparatus and organelles. Objective. Develop a didactic method that explains a mechanism of molecular biology, such as the comic strip in the transit and intracellular signaling of viruses. Methodology. A comic-illustrative story was designed where a viral structure is personified by an undercover spy, the fundamental axis of the plot is obtaining the genetic information molecules at the nucleus level, for this it has to go through the various departments of the cell representing the intracellular and intracytoplasmic organelles with their functional characteristics, the sequence obeys the communication that the different organelles have from the cell membrane to the nucleus. Results. The development of comics or comics can recreate events and phenomena studied in medical sciences such as biology, having the following results: increase interest, understanding, creativity, the need for knowledge and generation of new ideas in students. Conclusion. The comic is a useful didactic tool in teaching intracellular transit from the graphic narration of a viral model that is transported inside the cell.

Expanding the horizon of research into thepathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition.

White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target ( Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [1] . To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting was held virtually on March 3–4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust–sponsored workshops (Barone et al. in J Transl Med 14:1–14, [2]; Sorond et al. in GeroScience 42:81–96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop.

Through the Synergetic Union of Linguistics and Other Sciences - to New Challenges and Directions

In recent decades linguistics is less interested in the structure of language and the systemic relationships between its units, which are generally well described. At the turn of the century, we observe sharply increased interest in the problems of the relationship between language, consciousness, culture, mentality, national character and behavior. The language itself is understood as a mirror (though a crooked one) of reality, of a person, of his external and internal world. Such a broad approach supposes the impossibility of solving emerging problems as part of linguistics only; it needs the help of a whole range of related sciences about man - from psychology, anthropology, sociology, cultural studies to biology, neurosciences and quantum mechanics. Thus, we can see the interest in the integration of sciences. The purpose of this article is to conceptualize theoretically this new phenomenon and to show that modern linguistics must meet the requirements of the time and therefore it should be interdisciplinary and integrative; we tried to establish the relationship between tradition and new ideas in linguistics of the third millennium and showed that the problems arising in the language can be solved by the joint efforts of representatives of a number of sciences. The results obtained in this article allow us to put forward the issues that demand, in our view, immediate attention and show the importance of combining an objective linguistic analysis and the results of their research in semiotics, theology, psychology. These are such phenomena as 1) deep semantic processes; 2) language is a means of expressing Divine Truth; 3) language and national character. The obtained integrative knowledge can reveal non-causal relationships in the world, discover deeper laws of being, for example, the fact that consciousness is not rigidly connected with language, therefore it can hardly be researched by an associative experiment, although psycholinguists have long hoped for this. Physicist John Wheeler, taking into account experiments in quantum physics, proved that even if we just look at an object, it is changing under the influence of the gaze. How much stronger is the influence of a word? This is to be inquired in the near future as the part of an integrative approach.

The Versatile Roles of Cancer-Associated Fibroblasts in Colorectal Cancer and Therapeutic Implications.

The tumor microenvironment (TME) is populated by abundant cancer-associated fibroblasts (CAFs) that radically influence the disease progression across many cancers, including the colorectal cancer (CRC). In theory, targeting CAFs holds great potential in optimizing CRC treatment. However, attempts to translate the therapeutic benefit of CAFs into clinic practice face many obstacles, largely due to our limited understanding of the heterogeneity in their origins, functions, and mechanisms. In recent years, accumulating evidence has uncovered some cellular precursors and molecular markers of CAFs and also revealed their versatility in impacting various hallmarks of CRC, together helping us to better define the population of CAFs and also paving the way toward their future therapeutic targeting for CRC treatment. In this review, we outline the emerging concept of CAFs in CRC, with an emphasis on their origins, biomarkers, prognostic significance, as well as their functional roles and underlying mechanisms in CRC biology. At last, we discuss the prospect of harnessing CAFs as promising therapeutic targets for the treatment of patients with CRC.