Systems Biology

The microbiome of two strategies for ammonia removal with the sequencing batch moving bed biofilm reactor treating cheese production wastewater

Mon, 2023-11-27 06:00

Appl Environ Microbiol. 2023 Nov 27:e0150723. doi: 10.1128/aem.01507-23. Online ahead of print.

ABSTRACT

Cheese production facilities must abide by sewage discharge bylaws that prevent overloading municipal water resource recovery facilities, eutrophication, and toxicity to aquatic life. Compact treatment systems can permit on-site treatment of cheese production wastewater; however, competition between heterotrophs and nitrifiers impedes the implementation of the sequencing batch moving bed biofilm reactor (SB-MBBR) for nitrification from high-carbon wastewaters. This study demonstrates that a single SB-MBBR is not feasible for nitrification when operated with anerobic and aerobic cycling for carbon and phosphorous removal from cheese production wastewater, as nitrification does not occur in a single reactor. Thus, two reactors in series are recommended to achieve nitrification from cheese production wastewater in SB-MBBRs. These findings can be applied to pilot and full-scale SB-MBBR operations. By demonstrating the potential to implement partial nitrification in the SB-MBBR system, this study presents the possibility of implementing partial nitrification in the SB-MBBR, resulting in the potential for more sustainable treatment of nitrogen from cheese production wastewater.

PMID:38009922 | DOI:10.1128/aem.01507-23

Categories: Literature Watch

Resurgence of influenza during COVID-19 in Chongqing, China: A retrospective analysis

Mon, 2023-11-27 06:00

J Med Virol. 2023 Nov;95(11):e29249. doi: 10.1002/jmv.29249.

ABSTRACT

To better understand the trends of influenza and the impact of public health and social measures (PHSMs) implemented during the coronavirus disease 2019 (COVID-19) period in Chongqing, China. Data from the China Influenza Surveillance Information System from January 2017 to June 2022 were extracted. Epidemiological characteristics (influenza-like illness [ILI] and ILI%) and virological characteristics (influenza positive rate and circulating (sub)types) of influenza were described and compared between the pre-COVID-19 period and the COVID-19 period. Our survey showed that the implementation of PHSMs during the COVID-19 period had a positive impact on reducing influenza transmission. However, influenza activity resurged in 2021-2022 as the PHSMs were eased. Children under 5 years old constituted the highest proportion of ILI cases. The overall influenza positive rate was 23.70%, with a higher rate observed during the pre-COVID-19 period (31.55%) compared to the COVID-19 period (13.68%). Influenza virus subtypes co-circulated and the predominant subtype varied each year, with influenza A subtypes predominated in 2018/2019, while influenza B/Victoria lineage dominated in 2020/2021. PHSMs are effective measures to mitigate the spread of influenza. The findings underscore the need for bolstering monitoring systems, advocating influenza vaccination, and implementing practical PHSMs to strengthen prevention and control measures against influenza.

PMID:38009822 | DOI:10.1002/jmv.29249

Categories: Literature Watch

Application of Monolayer Graphene to Cryo-Electron Microscopy Grids for High-resolution Structure Determination

Mon, 2023-11-27 06:00

J Vis Exp. 2023 Nov 10;(201). doi: 10.3791/66023.

ABSTRACT

In cryogenic electron microscopy (cryoEM), purified macromolecules are applied to a grid bearing a holey carbon foil; the molecules are then blotted to remove excess liquid and rapidly frozen in a roughly 20-100 nm thick layer of vitreous ice, suspended across roughly 1 µm wide foil holes. The resulting sample is imaged using cryogenic transmission electron microscopy, and after image processing using suitable software, near-atomic resolution structures can be determined. Despite cryoEM's widespread adoption, sample preparation remains a severe bottleneck in cryoEM workflows, with users often encountering challenges related to samples behaving poorly in the suspended vitreous ice. Recently, methods have been developed to modify cryoEM grids with a single continuous layer of graphene, which acts as a support surface that often increases particle density in the imaged area and can reduce interactions between particles and the air-water interface. Here, we provide detailed protocols for the application of graphene to cryoEM grids and for rapidly assessing the relative hydrophilicity of the resulting grids. Additionally, we describe an EM-based method to confirm the presence of graphene by visualizing its characteristic diffraction pattern. Finally, we demonstrate the utility of these graphene supports by rapidly reconstructing a 2.7 Å resolution density map of a Cas9 complex using a pure sample at a relatively low concentration.

PMID:38009744 | DOI:10.3791/66023

Categories: Literature Watch

Cell-Matrix Elastocapillary Interactions Drive Pressure-based Wetting of Cell Aggregates

Mon, 2023-11-27 06:00

Phys Rev X. 2022 Jul-Sep;12(3):031027. doi: 10.1103/physrevx.12.031027. Epub 2022 Aug 17.

ABSTRACT

Cell-matrix interfacial energies and the energies of matrix deformations may be comparable on cellular length-scales, yet how capillary effects influence tis sue shape and motion are unknown. In this work, we induce wetting (spreading and migration) of cell aggregates, as models of active droplets onto adhesive substrates of varying elasticity and correlate the dynamics of wetting to the balance of interfacial tensions. Upon wetting rigid substrates, cell-substrate tension drives outward expansion of the monolayer. By contrast, upon wetting compliant substrates, cell substrate tension is attenuated and aggregate capillary forces contribute to internal pressures that drive expansion. Thus, we show by experiments, data-driven modeling and computational simulations that myosin-driven 'active elasto-capillary' effects enable adaptation of wetting mechanisms to substrate rigidity and introduce a novel, pressure-based mechanism for guiding collective cell motion.

PMID:38009085 | PMC:PMC10673637 | DOI:10.1103/physrevx.12.031027

Categories: Literature Watch

Bioinformatic Analysis of the Mechanism of Action of COL3A1 in Pan-Cancer and Design of Specific Inhibitors for Its Conformation

Sun, 2023-11-26 06:00

Stud Health Technol Inform. 2023 Nov 23;308:199-206. doi: 10.3233/SHTI230840.

ABSTRACT

In this study, we investigated the mechanism of action of COL3A1 in various types of cancers by bioinformatics analysis and designed some specific inhibitors aimed at the treatment of this gene. We found that COL3A1 was highly expressed in several cancer types and correlated with tumor progression and prognosis. Through systems biology analysis, we identified a central role for COL3A1 in cancer development, including cell proliferation, metastasis and invasion. We also used molecular dynamics simulations and drug screening techniques to design anticancer drugs with potential COL3A1 inhibitory functions. These results provide a strong rationale for the development and use of COL3A1 as a therapeutic target.

PMID:38007741 | DOI:10.3233/SHTI230840

Categories: Literature Watch

Pour some sugar on me: The diverse functions of phenylpropanoid glycosylation

Sat, 2023-11-25 06:00

J Plant Physiol. 2023 Nov 11;291:154138. doi: 10.1016/j.jplph.2023.154138. Online ahead of print.

ABSTRACT

The phenylpropanoid metabolism is the source of a vast array of specialized metabolites that play diverse functions in plant growth and development and contribute to all aspects of plant interactions with their surrounding environment. These compounds protect plants from damaging ultraviolet radiation and reactive oxygen species, provide mechanical support for the plants to stand upright, and mediate plant-plant and plant-microorganism communications. The enormous metabolic diversity of phenylpropanoids is further expanded by chemical modifications known as "decorative reactions", including hydroxylation, methylation, glycosylation, and acylation. Among these modifications, glycosylation is the major driving force of phenylpropanoid structural diversification, also contributing to the expansion of their properties. Phenylpropanoid glycosylation is catalyzed by regioselective uridine diphosphate (UDP)-dependent glycosyltransferases (UGTs), whereas glycosyl hydrolases known as β-glucosidases are the major players in deglycosylation. In this article, we review how the glycosylation process affects key physicochemical properties of phenylpropanoids, such as molecular stability and solubility, as well as metabolite compartmentalization/storage and biological activity/toxicity. We also summarize the recent knowledge on the functional implications of glycosylation of different classes of phenylpropanoid compounds. A balance of glycosylation/deglycosylation might represent an essential molecular mechanism to regulate phenylpropanoid homeostasis, allowing plants to dynamically respond to diverse environmental signals.

PMID:38006622 | DOI:10.1016/j.jplph.2023.154138

Categories: Literature Watch

Antibody Profiling of Microbial Antigens in the Blood of COVID-19 mRNA Vaccine Recipients Using Microbial Protein Microarrays

Sat, 2023-11-25 06:00

Vaccines (Basel). 2023 Nov 7;11(11):1694. doi: 10.3390/vaccines11111694.

ABSTRACT

Although studies have demonstrated that infections with various viruses, bacteria, and parasites can modulate the immune system, no study has investigated changes in antibodies against microbial antigens after the COVID-19 mRNA vaccination. IgG antibodies against microbial antigens in the blood of vaccinees were comprehensively analyzed using microbial protein microarrays that carried approximately 5000 microbe-derived proteins. Changes in antibodies against microbial antigens were scrutinized in healthy participants enrolled in the Fukushima Vaccination Community Survey conducted in Fukushima Prefecture, Japan, after their second and third COVID-19 mRNA vaccinations. Antibody profiling of six groups stratified by antibody titer and the remaining neutralizing antibodies was also performed to study the dynamics of neutralizing antibodies against SARS-CoV-2 and the changes in antibodies against microbial antigens. The results showed that changes in antibodies against microbial antigens other than SARS-CoV-2 antigens were extremely limited after COVID-19 vaccination. In addition, antibodies against a staphylococcal complement inhibitor have been identified as microbial antigens that are associated with increased levels of neutralizing antibodies against SARS-CoV-2. These antibodies may be a predictor of the maintenance of neutralizing antibodies following the administration of a COVID-19 mRNA vaccine.

PMID:38006026 | DOI:10.3390/vaccines11111694

Categories: Literature Watch

Plant-Associated Representatives of the <em>Bacillus cereus</em> Group Are a Rich Source of Antimicrobial Compounds

Sat, 2023-11-25 06:00

Microorganisms. 2023 Oct 31;11(11):2677. doi: 10.3390/microorganisms11112677.

ABSTRACT

Seventeen bacterial strains able to suppress plant pathogens have been isolated from healthy Vietnamese crop plants and taxonomically assigned as members of the Bacillus cereus group. In order to prove their potential as biocontrol agents, we perform a comprehensive analysis that included the whole-genome sequencing of selected strains and the mining for genes and gene clusters involved in the synthesis of endo- and exotoxins and secondary metabolites, such as antimicrobial peptides (AMPs). Kurstakin, thumolycin, and other AMPs were detected and characterized by different mass spectrometric methods, such as MALDI-TOF-MS and LIFT-MALDI-TOF/TOF fragment analysis. Based on their whole-genome sequences, the plant-associated isolates were assigned to the following species and subspecies: B. cereus subsp. cereus (6), B. cereus subsp. bombysepticus (5), Bacillus tropicus (2), and Bacillus pacificus. These three isolates represent novel genomospecies. Genes encoding entomopathogenic crystal and vegetative proteins were detected in B. cereus subsp. bombysepticus TK1. The in vitro assays revealed that many plant-associated isolates enhanced plant growth and suppressed plant pathogens. Our findings indicate that the plant-associated representatives of the B. cereus group are a rich source of putative antimicrobial compounds with potential in sustainable agriculture. However, the presence of virulence genes might restrict their application as biologicals in agriculture.

PMID:38004689 | DOI:10.3390/microorganisms11112677

Categories: Literature Watch

Biochemical, Catabolic, and PGP Activity of Microbial Communities and Bacterial Strains from the Root Zone of <em>Baccharis linearis</em> in a Mediterranean Mine Tailing

Sat, 2023-11-25 06:00

Microorganisms. 2023 Oct 26;11(11):2639. doi: 10.3390/microorganisms11112639.

ABSTRACT

The management of mine tailings (MT) is commonly workload heavy, intrusive, and expensive. Phytostabilization offers a promising approach for MT management; however, it poses challenges due to the unfavorable physicochemical properties of these wastes. Nevertheless, native microorganisms capable of supporting plant growth and development could enhance the efficacy of phytostabilization. This study assesses the biological activity of microbial communities from the root zone of Baccharis linearis, which is naturally present in MT, in order to evaluate their biotechnological potential for phytostabilization. The root zone and bulk samples were collected from B. linearis plants located within a MT in the Mediterranean zone of Chile. Enzyme activities related to the cycling of C, N, and P were assessed. The community-level physiological profile was evaluated using the MicroRespTM system. Bacterial plant growth-promoting (PGP) traits and colony forming units (CFU) were evaluated through qualitative and microbiological methods, respectively. CFU, enzyme activities, and CLPP were higher in the root zone compared with the bulk samples. Five bacterial strains from the root zone exhibited PGP traits such as P solubilization and N acquisition, among others. The presence of microbial communities in the root zone of B. linearis with PGP traits suggests their potential to enhance the ecological management of MT through phytostabilization programs.

PMID:38004650 | DOI:10.3390/microorganisms11112639

Categories: Literature Watch

Microbial Ecosystems in Movile Cave: An Environment of Extreme Life

Sat, 2023-11-25 06:00

Life (Basel). 2023 Oct 26;13(11):2120. doi: 10.3390/life13112120.

ABSTRACT

Movile Cave, situated in Romania close to the Black Sea, constitutes a distinct and challenging environment for life. Its partially submerged ecosystem depends on chemolithotrophic processes for its energetics, which are fed by a continuous hypogenic inflow of mesothermal waters rich in reduced chemicals such as hydrogen sulfide and methane. We sampled a variety of cave sublocations over the course of three years. Furthermore, in a microcosm experiment, minerals were incubated in the cave waters for one year. Both endemic cave samples and extracts from the minerals were subjected to 16S rRNA amplicon sequencing. The sequence data show specific community profiles in the different subenvironments, indicating that specialized prokaryotic communities inhabit the different zones in the cave. Already after one year, the different incubated minerals had been colonized by specific microbial communities, indicating that microbes in Movile Cave can adapt in a relatively short timescale to environmental opportunities in terms of energy and nutrients. Life can thrive, diversify and adapt in remote and isolated subterranean environments such as Movile Cave.

PMID:38004260 | DOI:10.3390/life13112120

Categories: Literature Watch

Influence of Prolonged Whole Egg Supplementation on Insulin-like Growth Factor 1 and Short-Chain Fatty Acids Product: Implications for Human Health and Gut Microbiota

Sat, 2023-11-25 06:00

Nutrients. 2023 Nov 16;15(22):4804. doi: 10.3390/nu15224804.

ABSTRACT

The gut microbiota exert a profound influence on human health and metabolism, with microbial metabolites playing a pivotal role in shaping host physiology. This study investigated the impact of prolonged egg supplementation on insulin-like growth factor 1 (IGF-1) and circulating short-chain fatty acids (SCFAs). In a subset of a cluster-randomized trial, participants aged 8-14 years were randomly assigned into three groups: (1) Whole Egg (WE)-consuming 10 additional eggs per week [n = 24], (2) Protein Substitute (PS)-consuming yolk-free egg substitute equivalent to 10 eggs per week [n = 25], and (3) Control Group (C) [n = 26]. At week 35, IGF-1 levels in WE significantly increased (66.6 ± 27.7 ng/mL, p < 0.05) compared to C, with positive SCFA correlations, except acetate. Acetate was stable in WE, increasing in PS and C. Significant propionate differences occurred between WE and PS (14.8 ± 5.6 μmol/L, p = 0.010). WE exhibited notable changes in the relative abundance of the Bifidobacterium and Prevotella genera. Strong positive SCFA correlations were observed with MAT-CR-H4-C10 and Libanicoccus, while Roseburia, Terrisporobacter, Clostridia_UCG-014, and Coprococcus showed negative correlations. In conclusion, whole egg supplementation improves growth factors that may be related to bone formation and growth; it may also promote benefits to gut microbiota but may not affect SCFAs.

PMID:38004198 | DOI:10.3390/nu15224804

Categories: Literature Watch

Systems Biology in Cancer Diagnosis Integrating Omics Technologies and Artificial Intelligence to Support Physician Decision Making

Sat, 2023-11-25 06:00

J Pers Med. 2023 Nov 10;13(11):1590. doi: 10.3390/jpm13111590.

ABSTRACT

Cancer is the second major cause of disease-related death worldwide, and its accurate early diagnosis and therapeutic intervention are fundamental for saving the patient's life. Cancer, as a complex and heterogeneous disorder, results from the disruption and alteration of a wide variety of biological entities, including genes, proteins, mRNAs, miRNAs, and metabolites, that eventually emerge as clinical symptoms. Traditionally, diagnosis is based on clinical examination, blood tests for biomarkers, the histopathology of a biopsy, and imaging (MRI, CT, PET, and US). Additionally, omics biotechnologies help to further characterize the genome, metabolome, microbiome traits of the patient that could have an impact on the prognosis and patient's response to the therapy. The integration of all these data relies on gathering of several experts and may require considerable time, and, unfortunately, it is not without the risk of error in the interpretation and therefore in the decision. Systems biology algorithms exploit Artificial Intelligence (AI) combined with omics technologies to perform a rapid and accurate analysis and integration of patient's big data, and support the physician in making diagnosis and tailoring the most appropriate therapeutic intervention. However, AI is not free from possible diagnostic and prognostic errors in the interpretation of images or biochemical-clinical data. Here, we first describe the methods used by systems biology for combining AI with omics and then discuss the potential, challenges, limitations, and critical issues in using AI in cancer research.

PMID:38003905 | DOI:10.3390/jpm13111590

Categories: Literature Watch

miRNA-Based Technologies in Cancer Therapy

Sat, 2023-11-25 06:00

J Pers Med. 2023 Nov 9;13(11):1586. doi: 10.3390/jpm13111586.

ABSTRACT

The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy.

PMID:38003902 | DOI:10.3390/jpm13111586

Categories: Literature Watch

An Epidemiological Update on <em>Anisakis</em> Nematode Larvae in Red Mullet (<em>Mullus barbatus</em>) from the Ligurian Sea

Sat, 2023-11-25 06:00

Pathogens. 2023 Nov 18;12(11):1366. doi: 10.3390/pathogens12111366.

ABSTRACT

Red mullet (Mullus barbatus) is a commercially relevant fish species, yet epidemiological data on anisakid nematode infestation in M. barbatus are scarce. To fill this gap, we report the occurrence of Anisakis larvae in red mullet in the Ligurian Sea (western Mediterranean). This survey was performed between 2018 and 2020 on fresh specimens of M. barbatus (n = 838) from two commercial fishing areas (Imperia, n = 190; Savona, n = 648) in the Ligurian Sea. Larvae morphologically identified as Anisakis spp. (n = 544) were characterized using PCR-RFLP as Anisakis pegreffii. The overall prevalence of A. pegreffii was 24.46%; the prevalence at each sampling site was 6.32% for Imperia and 29.78% for Savona. Furthermore, 3300 larvae of Hysterothylacium spp. were detected in the visceral organs of fish coinfected with A. pegreffii, showing that coinfection with two parasitic species is not rare. This study provides a timely update on the prevalence of ascaridoid nematodes in red mullet of the Ligurian Sea, an important commercial fishing area in the Mediterranean.

PMID:38003830 | DOI:10.3390/pathogens12111366

Categories: Literature Watch

A New Era of Sustainability: Plant Biostimulants

Sat, 2023-11-25 06:00

Int J Mol Sci. 2023 Nov 15;24(22):16329. doi: 10.3390/ijms242216329.

ABSTRACT

Today, environmental sustainability has become a fundamental concern in nearly every aspect of our daily lives, including the food sector [...].

PMID:38003519 | DOI:10.3390/ijms242216329

Categories: Literature Watch

Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia

Sat, 2023-11-25 06:00

Int J Mol Sci. 2023 Nov 10;24(22):16154. doi: 10.3390/ijms242216154.

ABSTRACT

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

PMID:38003344 | DOI:10.3390/ijms242216154

Categories: Literature Watch

Transboundary Monitoring of the Wolf Alpine Population over 21 Years and Seven Countries

Sat, 2023-11-25 06:00

Animals (Basel). 2023 Nov 17;13(22):3551. doi: 10.3390/ani13223551.

ABSTRACT

Wolves have large spatial requirements and their expansion in Europe is occurring over national boundaries, hence the need to develop monitoring programs at the population level. Wolves in the Alps are defined as a functional population and management unit. The range of this wolf Alpine population now covers seven countries: Italy, France, Austria, Switzerland, Slovenia, Liechtenstein and Germany, making the development of a joint and coordinated monitoring program particularly challenging. In the framework of the Wolf Alpine Group (WAG), researchers developed uniform criteria for the assessment and interpretation of field data collected in the frame of different national monitoring programs. This standardization allowed for data comparability across borders and the joint evaluation of distribution and consistency at the population level. We documented the increase in the number of wolf reproductive units (packs and pairs) over 21 years, from 1 in 1993-1994 up to 243 units in 2020-2021, and examined the pattern of expansion over the Alps. This long-term and large-scale approach is a successful example of transboundary monitoring of a large carnivore population that, despite administrative fragmentation, provides robust indexes of population size and distribution that are of relevance for wolf conservation and management at the transnational Alpine scale.

PMID:38003168 | DOI:10.3390/ani13223551

Categories: Literature Watch

Identification of microRNAs Derived from Transposable Elements in the <em>Macaca mulatta</em> (Rhesus Monkey) Genome

Sat, 2023-11-25 06:00

Genes (Basel). 2023 Oct 24;14(11):1984. doi: 10.3390/genes14111984.

ABSTRACT

Transposable elements (TEs) are mobile DNA entities that can move within the host genome. Over long periods of evolutionary time, TEs are typically silenced via the accumulation of mutations in the genome, ultimately resulting in their immobilization. However, they still play an important role in the host genome by acting as regulatory elements. They influence host transcription in various ways, one of which as the origin of the generation of microRNAs (miRNAs), which are so-called miRNAs derived from TEs (MDTEs). miRNAs are small non-coding RNAs that are involved in many biological processes by regulating gene expression at the post-transcriptional level. Here, we identified MDTEs in the Macaca mulatta (rhesus monkey) genome, which is phylogenetically close species to humans, based on the genome coordinates of miRNAs and TEs. The expression of 5 out of 17 MDTEs that were exclusively registered in M. mulatta from the miRBase database (v22) was examined via quantitative polymerase chain reaction (qPCR). Moreover, Gene Ontology analysis was performed to examine the functional implications of the putative target genes of the five MDTEs.

PMID:38002927 | DOI:10.3390/genes14111984

Categories: Literature Watch

Protein Biomarkers Shared by Multiple Neurodegenerative Diseases Are Calmodulin-Binding Proteins Offering Novel and Potentially Universal Therapeutic Targets

Sat, 2023-11-25 06:00

J Clin Med. 2023 Nov 11;12(22):7045. doi: 10.3390/jcm12227045.

ABSTRACT

Seven major neurodegenerative diseases and their variants share many overlapping biomarkers that are calmodulin-binding proteins: Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal lobar dementia (FTD), Huntington's disease (HD), Lewy body disease (LBD), multiple sclerosis (MS), and Parkinson's disease (PD). Calcium dysregulation is an early and persistent event in each of these diseases, with calmodulin serving as an initial and primary target of increased cytosolic calcium. Considering the central role of calcium dysregulation and its downstream impact on calcium signaling, calmodulin has gained interest as a major regulator of neurodegenerative events. Here, we show that calmodulin serves a critical role in neurodegenerative diseases via binding to and regulating an abundance of biomarkers, many of which are involved in multiple neurodegenerative diseases. Of special interest are the shared functions of calmodulin in the generation of protein biomarker aggregates in AD, HD, LBD, and PD, where calmodulin not only binds to amyloid beta, pTau, alpha-synuclein, and mutant huntingtin but also, via its regulation of transglutaminase 2, converts them into toxic protein aggregates. It is suggested that several calmodulin binding proteins could immediately serve as primary drug targets, while combinations of calmodulin binding proteins could provide simultaneous insight into the onset and progression of multiple neurodegenerative diseases.

PMID:38002659 | DOI:10.3390/jcm12227045

Categories: Literature Watch

Screening of Crucial Cytosolicproteins Interconnecting the Endoplasmic Reticulum and Mitochondria in Parkinson's Disease and the Impact of Anti-Parkinson Drugs in the Preservation of Organelle Connectivity

Sat, 2023-11-25 06:00

Brain Sci. 2023 Nov 5;13(11):1551. doi: 10.3390/brainsci13111551.

ABSTRACT

Mitochondrial dysfunction is well-established in Parkinson's disease (PD); however, its dysfunctions associating with cell organelle connectivity remain unknown. We aimed to establish the crucial cytosolic protein involved in organelle connectivity between mitochondria and the endopalmic reticulum (ER) through a computational approach by constructing an organelle protein network to extract functional clusters presenting the crucial PD protein connecting organelles. Then, we assessed the influence of anti-parkinsonism drugs (n = 35) on the crucial protein through molecular docking and molecular dynamic simulation and further validated its gene expression in PD participants under, istradefylline (n = 25) and amantadine (n = 25) treatment. Based on our investigation, D-aspartate oxidase (DDO )protein was found to be the critical that connects both mitochondria and the ER. Further, molecular docking showed that istradefylline has a high affinity (-9.073 kcal/mol) against DDO protein, which may disrupt mitochondrial-ER connectivity. While amantadine (-4.53 kcal/mol) shows negligible effects against DDO that contribute to conformational changes in drug binding, Successively, DDO gene expression was downregulated in istradefylline-treated PD participants, which elucidated the likelihood of an istradefylline off-target mechanism. Overall, our findings illuminate the off-target effects of anti-parkinsonism medications on DDO protein, enabling the recommendation of off-target-free PD treatments.

PMID:38002511 | DOI:10.3390/brainsci13111551

Categories: Literature Watch

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