The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity.

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs.

Roles and Sources of Calcium in Synaptic Exocytosis.

Calcium ions (Ca2+) play a critical role in triggering neurotransmitter release. The rate of release is directly related to the concentration of Ca2+ at the presynaptic site, with a supralinear relationship. There are two main sources of Ca2+ that trigger synaptic vesicle fusion: influx through voltage-gated Ca2+ channels in the plasma membrane and release from the endoplasmic reticulum via ryanodine receptors. This chapter will cover the sources of Ca2+ at the presynaptic nerve terminal, the relationship between neurotransmitter release rate and Ca2+ concentration, and the mechanisms that achieve the necessary Ca2+ concentrations for triggering synaptic exocytosis at the presynaptic site.

Regulation of Ryanodine Receptor-Dependent Neurotransmitter Release by AIP, Calstabins, and Presenilins.

Ryanodine receptors (RyRs) are Ca2+ release channels located in the endoplasmic reticulum membrane. Presynaptic RyRs play important roles in neurotransmitter release and synaptic plasticity. Recent studies suggest that the proper function of presynaptic RyRs relies on several regulatory proteins, including aryl hydrocarbon receptor-interacting protein, calstabins, and presenilins. Dysfunctions of these regulatory proteins can greatly impact neurotransmitter release and synaptic plasticity by altering the function or expression of RyRs. This chapter aims to describe the interaction between these proteins and RyRs, elucidating their crucial role in regulating synaptic function.

Construction of an artificial consortium of Escherichia coli and cyanobacteria for clean indirect production of volatile platform hydrocarbons from CO2.

Ethylene and isoprene are essential platform chemicals necessary to produce polymers and materials. However, their current production methods based on fossil fuels are not very efficient and result in significant environmental pollution. For a successful transition more sustainable economic model, producing these key polymeric building blocks from renewable and sustainable resources such as biomass or CO2 is essential. Here, inspired by the symbiotic relationship of natural microbial communities, artificial consortia composed of E. coli strains producing volatile platform chemicals: ethylene and isoprene and two strains of cyanobacteria phototrophically synthesizing and exporting sucrose to feed these heterotrophs were developed. Disaccharide produced by transgenic cyanobacteria was used as a carbon and electron shuttle between the two community components. The E. coli cscB gene responsible for sucrose transport was inserted into two cyanobacterial strains, Thermosynechococcus elongatus PKUAC-SCTE542 and Synechococcus elongatus PCC7942, resulting in a maximal sucrose yield of 0.14 and 0.07 g/L, respectively. These organisms were co-cultured with E. coli BL21 expressing ethylene-forming enzyme or isoprene synthase and successfully synthesized volatile hydrocarbons. Productivity parameters of these co-cultures were higher than respective transgenic cultures of E. coli grown individually at similar sucrose concentrations, highlighting the positive impact of the artificial consortia on the production of these platform chemicals.

Generation of miniploid cells and improved natural transformation procedure for a model cyanobacterium Synechococcus elongatus PCC 7942.

The biotechnologically important and naturally transformable cyanobacterium, Synechococcus elongatus PCC 7942, possesses multiple genome copies irrespective of its growth rate or condition. Hence, segregating mutations across all genome copies typically takes several weeks. In this study, Synechococcus 7942 cultivation on a solid growth medium was optimised using different concentrations of agar, the addition of antioxidants, and overexpression of the catalase gene to facilitate the rapid acquisition of colonies and fully segregated lines. Synechococcus 7942 was grown at different temperatures and nutritional conditions. The miniploid cells were identified using flow cytometry and fluorimetry. The natural transformation was carried out using miniploid cells and validated with PCR and high performance liquid chromatography (HPLC). We identified that 0.35% agar concentration and 200 IU of catalase could improve the growth of Synechococcus 7942 on a solid growth medium. Furthermore, overexpression of a catalase gene enhanced the growth rate and supported diluted culture to grow on a solid medium. Our results reveal that high temperature and phosphate-depleted cells contain the lowest genome copies (2.4 ± 0.3 and 1.9 ± 0.2) and showed the potential to rapidly produce fully segregated mutants. In addition, higher antibiotic concentrations improve the selection of homozygous transformants while maintaining similar genome copies at a constant temperature. Based on our observation, we have an improved cultivation and natural transformation protocol for Synechococcus 7942 by optimising solid media culturing, generating low-ploidy cells that ultimately reduced the time required for the complete segregation of engineered lines.

The design and implementation of an undergraduate health professional degree elective course on scientific writing, peer assessment, and critical appraisal.

BACKGROUND AND PURPOSE: Strong writing skills are critical to the pharmacy profession. This paper describes the design, delivery, and impact of a course intended to develop pharmacy students' scientific writing, peer assessment, and critical appraisal skills. EDUCATIONAL ACTIVITY AND SETTING: The course was offered in the final year of an undergraduate pharmacy program with students whose first language is not English. In this course, students write two structured pharmacy review articles (PRA) based on assigned scientific research articles and peer assess each others' written PRAs. Students also critically appraise scientific research articles on a weekly basis, complete one pre-journal club written reflective critique based on a assigned scientific research article, and moderate one journal club session. FINDINGS: Course rubrics were developed and validated by the course coordinators. A survey administered to students enrolled in the course identified that 85% of the students perceived that they gained adequate writing skills in the course. More than 70% of the students indicated they had the necessary skills to evaluate their peers' written assessments, and 93% felt comfortable providing and receiving feedback from peers. More than 90% of the students indicated that writing PRAs and the peer assessment improved their critical and analytical skills. SUMMARY: This course improved students' scientific writing, peer assessment, and critical appraisal skills. Further practice is required to reinforce the skills learned and to strengthen the writing skills of students.

Clozapine prescribing practice and trends in Qatar: First national observational study.

BACKGROUND: Clozapine is the gold standard in the management of treatment-resistant schizophrenia. Despite its clinically proven efficacy clozapine utilization is variable globally and published evidence is suggestive of its underutilization. Research from the Arab region on clozapine utilization is limited. The aim of our descriptive observational study was to evaluate the prescribing practice of clozapine and its sociodemographic and clinical corelates in the State of Qatar. METHODS: The study is a retrospective case-note review of all patients maintained on clozapine, in the calendar year 2020. Data were collected on sociodemographic characteristics of the patients; antipsychotic trials before initiating clozapine; and clinical characteristics of the patients, including their diagnoses leading to prescription of clozapine, duration of illness, psychiatric hospitalizations, and co-morbidities. RESULTS: During the study period, 100 patients were maintained on clozapine. Patients were mostly Qatari and non-Qatari Arab males. Prescription rates were significantly different for Qatari patients when compared to non-Qatari patients. Most patients had a chronic illness with the age of onset of illness in early adulthood and were diagnosed with schizophrenia or schizoaffective disorder. The mean daily dose of clozapine was 325 mg. Eighty percent of the patients received two or more antipsychotic trials before initiating clozapine. Sixty-eight percent of the patients had more than two antipsychotic trials before initiating Clozapine. One third of patients had no history of psychiatric hospitalizations, and one quarter had five or more previous psychiatric hospitalizations. Of the psychiatric comorbidities, mood and substance use disorders were common. Of medical comorbidities, endocrine and metabolic disorders were common. CONCLUSION: Despite apparent underutilization, the Clozapine prescribing rates in Qatar are comparable to countries with plasma monitoring systems when framed within Qatar's unique demographic context. However, there still is a significant delay in Clozapine initiation despite its clinical superiority. STRENGTHS AND LIMITATIONS OF THIS STUDY: First study on Clozapine utilization from the Middle-East and North-Africa region. This study examined prescribing of clozapine in a national cohort of patients in Qatar. Provides insight into sociodemographic and clinical correlates of clozapine prescribing in a country with 90% migrants. Limited by the completeness of the information contained in the patients' medical charts.

Discovery of Five New Ethylene-Forming Enzymes for Clean Production of Ethylene in E. coli.

Ethylene is an essential platform chemical with a conjugated double bond, which can produce many secondary chemical products through copolymerisation. At present, ethylene production is mainly from petroleum fractionation and cracking, which are unsustainable in the long term, and harmful to our environment. Therefore, a hot research field is seeking a cleaner method for ethylene production. Based on the model ethylene-forming enzyme (Efe) AAD16440.1 (6vp4.1.A) from Pseudomonas syringae pv. phaseolicol, we evaluated five putative Efe protein sequences using the data derived from phylogenetic analyses and the conservation of their catalytic structures. Then, pBAD expression frameworks were constructed, and relevant enzymes were expressed in E. coli BL21. Finally, enzymatic activity in vitro and in vivo was detected to demonstrate their catalytic activity. Our results show that the activity in vitro measured by the conversion of α-ketoglutarate was from 0.21-0.72 µmol ethylene/mg/min, which varied across the temperatures. In cells, the activity of the new Efes was 12.28-147.43 µmol/gDCW/h (DCW, dry cellular weight). Both results prove that all the five putative Efes could produce ethylene.

Comparative Genomic Analysis Revealed Distinct Molecular Components and Organization of CO2-Concentrating Mechanism in Thermophilic Cyanobacteria.

Cyanobacteria evolved an inorganic carbon-concentrating mechanism (CCM) to perform effective oxygenic photosynthesis and prevent photorespiratory carbon losses. This process facilitates the acclimation of cyanobacteria to various habitats, particularly in CO2-limited environments. To date, there is limited information on the CCM of thermophilic cyanobacteria whose habitats limit the solubility of inorganic carbon. Here, genome-based approaches were used to identify the molecular components of CCM in 17 well-described thermophilic cyanobacteria. These cyanobacteria were from the genus Leptodesmis, Leptolyngbya, Leptothermofonsia, Thermoleptolyngbya, Thermostichus, and Thermosynechococcus. All the strains belong to ß-cyanobacteria based on their ß-carboxysome shell proteins with 1B form of Rubisco. The diversity in the Ci uptake systems and carboxysome composition of these thermophiles were analyzed based on their genomic information. For Ci uptake systems, two CO2 uptake systems (NDH-13 and NDH-14) and BicA for HCO3 - transport were present in all the thermophilic cyanobacteria, while most strains did not have the Na+/HCO3 - Sbt symporter and HCO3 - transporter BCT1 were absent in four strains. As for carboxysome, the ß-carboxysomal shell protein, ccmK2, was absent only in Thermoleptolyngbya strains, whereas ccmK3/K4 were absent in all Thermostichus and Thermosynechococcus strains. Besides, all Thermostichus and Thermosynechococcus strains lacked carboxysomal ß-CA, ccaA, the carbonic anhydrase activity of which may be replaced by ccmM proteins as indicated by comparative domain analysis. The genomic distribution of CCM-related genes was different among the thermophiles, suggesting probably distinct expression regulation. Overall, the comparative genomic analysis revealed distinct molecular components and organization of CCM in thermophilic cyanobacteria. These findings provided insights into the CCM components of thermophilic cyanobacteria and fundamental knowledge for further research regarding photosynthetic improvement and biomass yield of thermophilic cyanobacteria with biotechnological potentials.

Burnout among pharmacy professionals in Qatar: A cross-sectional study.

BACKGROUND: Pharmacists' roles and responsibilities have expanded in the modern pharmacy profession, and the expectations from pharmacists have increased. This has been associated with new psychological challenges and emotional stress that can induce burnout. OBJECTIVE: To determine the prevalence of burnout syndrome and factors associated with burnout among pharmacy professionals in the healthcare system in Qatar. METHODS: This institutional-based cross-sectional study was conducted on 850 pharmacy professionals within Hamad Medical Corporation (HMC) in Qatar. Convenience sampling was followed. The survey utilized the Maslach Burnout Inventory (MBI) Toolkit™ for Medical Personnel and a modified version of the Astudillo and Mendinueta questionnaire. Statistical analyses were performed using Stata version 16 for Windows and SAS Studio 3.8 (Enterprise Edition). P-value of less than 0.05 was considered significant. RESULTS: One hundred ninety-four pharmacy professionals (23%) responded to the survey. The prevalence of burnout was 19.7% [95% Confidence interval (CI); 13.8% - 26.8%] among 142 respondents who completed MBI questionnaire and 17.3% [95% CI; 11.7%-24.2%] among 139 respondents who completed Astudillo Mendinueta questionnaire. The most commonly reported factors that may lead to burnout were: tension and lack of organization in teamwork (59.6%), lack of recognition of or indifference to effort from patients, superiors, and colleagues (58.2%), and demanding and challenging patients and family members (56.7%). Multiple regression analysis showed that overtime working hours per month is independently associated with a higher risk of burnout [odds ratio (OR), 1.57; 95% CI, 1.15-2.14 for each 10-hours increase in monthly overtime, P = 0.005], while non-Arab ethnicity is associated with lower risk of burnout [OR, 0.27; 95% CI, 0.1-0.75; P = 0.012]. CONCLUSIONS: There is a relatively low prevalence of burnout syndrome among health-system pharmacy professionals in Qatar. Overtime working hours and Arab ethnicity are independently associated with burnout.

The Genome Copy Number of the Thermophilic Cyanobacterium Thermosynechococcus elongatus E542 Is Controlled by Growth Phase and Nutrient Availability.

The recently isolated thermophilic cyanobacterium Thermosynechococcus elongatus PKUAC-SCTE542 (here Thermosynechococcus E542) is a promising strain for fundamental and applied research. Here, we used several improved ploidy estimation approaches, which include quantitative PCR (qPCR), spectrofluorometry, and flow cytometry, to precisely determine the ploidy level in Thermosynechococcus E542 across different growth stages and nutritional and stress conditions. The distribution of genome copies per cell among the populations of Thermosynechococcus E542 was also analyzed. The strain tends to maintain 3 or 4 genome copies per cell in lag phase, early growth phase, or stationary phase under standard conditions. Increased ploidy (5.5 ± 0.3) was observed in exponential phase; hence, the ploidy level is growth phase regulated. Nearly no monoploid cells were detected in all growth phases, and prolonged stationary phase could not yield ploidy levels lower than 3 under standard conditions. During the late growth phase, a significantly higher ploidy level was observed in the presence of bicarbonate (7.6 ± 0.7) and high phosphate (6.9 ± 0.2) at the expense of reduced percentages of di- and triploid cells. Meanwhile, the reduction in phosphates decreased the average ploidy level by increasing the percentages of mono- and diploid cells. In contrast, temperature and antibiotic stresses reduced the percentages of mono-, di-, and triploid cells yet maintained average ploidy. The results indicate a possible causality between growth rate, stress, and genome copy number across the conditions tested, but the exact mechanism is yet to be elucidated. Furthermore, the spectrofluorometric approach presented here is a quick and straightforward ploidy estimation method with reasonable accuracy.IMPORTANCE The present study revealed that the genome copy number (ploidy) status in the thermophilic cyanobacterium Thermosynechococcus E542 is regulated by growth phase and various environmental parameters to give us a window into understanding the role of polyploidy. An increased ploidy level is found to be associated with higher metabolic activity and increased vigor by acting as backup genetic information to compensate for damage to the other chromosomal copies. Several improved ploidy estimation approaches that may upgrade the ploidy estimation procedure for cyanobacteria in the future are presented in this work. Furthermore, the new spectrofluorometric method presented here is a rapid and straightforward method of ploidy estimation with reasonable accuracy compared to other laborious methods.

Prevalence, median time, and associated factors with the likelihood of initial antidepressant change: a cross-sectional study in Qatar.

BACKGROUND: Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4-12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. METHODS: This was a retrospective study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using several cox regression models. RESULTS: A total of 487 patients met the inclusion criteria of the study, 431 (88%) of them had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44-53%]) had their IAD changed less than or equal to 30 days. The median time to IAD change was 43 days with 95% CI [33.2-52.7]. The factors statistically associated with higher hazard of IAD change were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. CONCLUSIONS: Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. Our findings offered some clues to help clinicians identify the high-risk predictors of short survival and subsequent failure of IAD.

Calmodulin and Its Interactive Proteins Participate in Regulating the Explosive Growth of Alexandrium pacificum (Dinoflagellate).

Alexandrium pacificum is a typical dinoflagellate that can cause harmful algal blooms, resulting in negative impacts on ecology and human health. The calcium (Ca2+) signal transduction pathway plays an important role in cell proliferation. Calmodulin (CaM) and CaM-related proteins are the main cellular Ca2+ sensors, and can act as an intermediate in the Ca2+ signal transduction pathway. In this study, the proteins that interacted with CaM of A. pacificum were screened by two-dimensional electrophoresis analysis and far western blots under different growth conditions including lag phase and high phosphorus and manganese induced log phase (HPM). The interactive proteins were then identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Four proteins were identified, including Ca2+/CaM-dependent protein kinase, serine/threonine kinase, annexin, and inositol-3-phosphate synthase, which all showed high expression levels under HPM. The gene expression levels encoding these four proteins were also up-regulated under HPM, as revealed by quantitative polymerase chain reaction, suggesting that the identified proteins participate in the Ca2+ transport channel and cell cycle regulation to promote cell division. A network of proteins interacting with CaM and their target proteins involved in the regulation of cell proliferation was raised, which provided new insights into the mechanisms behind the explosive growth of A. pacificum.

Anti-hypertrophic effect of Na+/H+ exchanger-1 inhibition is mediated by reduced cathepsin B.

Previous studies have established the role of Na+/H+ exchanger isoform-1 (NHE1) and cathepsin B (Cat B) in the development of cardiomyocyte hypertrophy (CH). Both NHE1 and Cat B are activated under acidic conditions suggesting that their activities might be interrelated. The inhibition of NHE1 has been demonstrated to reduce cardiac hypertrophy but the mechanism that contributes to the anti-hypertrophic effect of NHE1 inhibition still remains unclear. H9c2 cardiomyoblasts were stimulated with Angiotensin (Ang) II in the presence and absence of N-[2-methyl-4,5-bis(methylsulphonyl)-benzoyl]-guanidine, hydrochloride (EMD, EMD 87580), an NHE1 inhibitor or CA-074Me, a Cat B inhibitor, and various cardiac hypertrophic parameters, namely cell surface area, protein content and atrial natriuretic peptide (ANP) mRNA were analyzed. EMD significantly suppressed markers of cardiomyocyte hypertrophy and inhibited Ang II stimulated Cat B protein and gene expression. Cat B is located within the acidic environment of lysosomes. Cat B proteases are released into the cytoplasm upon disintegration of the lysosomes. EMD or CA-074Me prevented the dispersal of the lysosomes induced by Ang II and reduced the ratio of LC3-II to LC3-I, a marker of autophagy. Moreover, Cat B protein expression and MMP-9 activity in the extracellular space were significantly attenuated in the presence of EMD or CA-074Me. Our study demonstrates a novel mechanism for attenuation of the hypertrophic phenotype by NHE1 inhibition that is mediated by a regression in Cat B. The inhibition of Cat B via EMD or CA-074Me attenuates the autosomal-lysosomal pathway and MMP-9 activation.

Detection, characterization and expression dynamics of histone proteins in the dinoflagellate Alexandrium pacificum during growth regulation.

Histones are the most abundant proteins associated with eukaryotic nuclear DNA. The exception is dinoflagellates, which have histone protein expression that is mostly reported to be below detectable levels. In this study, we investigated the presence of histone proteins and their functions in the dinoflagellate, Alexandrium pacificum. Histone protein sequences were analyzed, focusing on phylogenetic analysis and histone code. Histone expression was analyzed during the cell cycle and under nutritionally enhanced conditions using quantitative-PCR and western blots. Acid-soluble proteins were subjected to mass spectrometry analysis. To our knowledge, this is the first report of immunological detection of histone proteins (H2B and H4) in any dinoflagellate species. Absolute quantification of histone transcript in activily dividing cells revealed significant transcription in cells. The stable expression of histones during the cell cycle suggested that the histone genes in A. pacificum belonged to a replication-independent class and appeared to have a limited role in DNA packaging. The conservation of numerous post-translationally modified residues of multiple histone variants and differential expression of histones under nutritionally enhanced conditions suggested their functional significance in dinoflagellates. However, we detected histone H2B protein only via mass spectrometry. Histone-like protein was identified as most abundant acid-soluble protein of the cells.

Lead induces DNA damage and alteration of ALAD and antioxidant genes mRNA expression in construction site workers.

Oxidative stress and DNA damage are considered as possible mechanisms involved in lead toxicity. To test this hypothesis, DNA damage and expression variations of aminolevulinic acid dehydratase (ALAD), superoxide dismutase 2 (SOD2), and 8-oxoguanine DNA glycosylase 2a (OGG1-2a) genes was studied in a cohort of 100 exposed workers and 100 controls with comet assay and real-time polymerse chain reaction (PCR). Results indicated that increased number of comets was observed in exposed workers versus controls (p < 0.001). After qPCR analysis, significant down-regulation in ALAD (p < 0.0001), SOD2 (p < 0.0001), and OGG1-2a (p < 0.0001) level was observed in exposed workers versus controls. Additionally, a positive spearmen correlation was observed between ALAD versus SOD2 (r = 0.402**, p < 0.001), ALAD versus OGG1-2a (r = 0.235*, p < 0.05), and SOD2 versus OGG1-2a (r = 0.292*, p < 0.05). This study showed that lead exposure induces DNA damage, which is accompanied by an elevated intensity of oxidative stress and expression variation of lead-related gene.

The use of Socrative and Yammer online tools to promote interactive learning in pharmacy education.

BACKGROUND AND PURPOSE: Engagement of students in the didactic classroom setting restricts students' time spent towards active learning, which in turn, adversely affects the retention of concepts taught through traditional teaching methods. Thus, interactive learning is used as an alternative to engage students in the classroom and to enrich their learning experience. Integrating interactive learning activities has been shown to facilitate student learning and improve the learning outcomes. The objectives of this study are to assess the perceptions of students on the benefits and appropriateness of using online tools (e.g., Socrative and Yammer) to promote interaction of students with the instructor and other students in the classroom setting. EDUCATIONAL ACTIVITY AND SETTING: Students enrolled in the second and third professional years of the bachelor of pharmacy program at Qatar University were introduced to various interactive learning tools in two Pharmaceutical Sciences courses. Students were then surveyed to assess their perceptions about the benefits and appropriateness of the respective interactive learning tools introduced in the courses. FINDINGS: Our survey results indicate that the students are in favor of using online educational tools and believe that the use of interactive learning tools enhances their learning experience. SUMMARY: Pharmacy students at Qatar University perceive that the incorporation of online technology in Pharmaceutical Sciences courses enhances interactive learning in the classroom setting.

Distinctive Nuclear Features of Dinoflagellates with A Particular Focus on Histone and Histone-Replacement Proteins.

Dinoflagellates are important eukaryotic microorganisms that play critical roles as producers and grazers, and cause harmful algal blooms. The unusual nuclei of dinoflagellates "dinokaryon" have led researchers to investigate their enigmatic nuclear features. Their nuclei are unusual in terms of their permanently condensed nucleosome-less chromatin, immense genome, low protein to DNA ratio, guanine-cytosine rich methylated DNA, and unique mitosis process. Furthermore, dinoflagellates are the only known group of eukaryotes that apparently lack histone proteins. Over the course of evolution, dinoflagellates have recruited other proteins, e.g., histone-like proteins (HLPs), from bacteria and dinoflagellates/viral nucleoproteins (DVNPs) from viruses as histone substitutes. Expression diversity of these nucleoproteins has greatly influenced the chromatin structure and gene expression regulation in dinoflagellates. Histone replacement proteins (HLPs and DVNPs) are hypothesized to perform a few similar roles as histone proteins do in other eukaryotes, i.e., gene expression regulation and repairing DNA. However, their role in bulk packaging of DNA is not significant as low amounts of proteins are associated with the gigantic genome. This review intends to summarize the discoveries encompassing unique nuclear features of dinoflagellates, particularly focusing on histone and histone replacement proteins. In addition, a comprehensive view of the evolution of dinoflagellate nuclei is presented.

Identification of proteins responding to pathogen-infection in the red alga Pyropia yezoensis using iTRAQ quantitative proteomics.

BACKGROUND: Pyropia yezoensis is an important marine crop which, due to its high protein content, is widely used as a seafood in China. Unfortunately, red rot disease, caused by Pythium porphyrae, seriously damages P. yezoensis farms every year in China, Japan, and Korea. Proteomic methods are often used to study the interactions between hosts and pathogens. Therefore, an iTRAQ-based proteomic analysis was used to identify pathogen-responsive proteins following the artificial infection of P. yezoensis with P. porphyrae spores. RESULTS: A total of 762 differentially expressed proteins were identified, of which 378 were up-regulated and 384 were down-regulated following infection. A large amount of these proteins were involved in disease stress, carbohydrate metabolism, cell signaling, chaperone activity, photosynthesis, and energy metabolism, as annotated in the KEGG database. Overall, the data showed that P. yezoensis resists infection by inhibiting photosynthesis, and energy and carbohydrate metabolism pathways, as supported by changes in the expression levels of related proteins. The expression data are available via ProteomeXchange with the identifier PXD009363. CONCLUSIONS: The current data provide an overall summary of the red algae responses to pathogen infection. This study improves our understanding of infection resistance in P. yezoensis, and may help in increasing the breeding of P. porphyrae-infection tolerant macroalgae.