Smaug regulates germ plasm assembly and primordial germ cell number in Drosophila embryos.

During Drosophila oogenesis, the Oskar (OSK) RNA binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here, we identify mechanisms that subsequently regulate germ plasm assembly in the early embryo. We show that the Smaug (SMG) RBP is transported into the germ plasm of the early embryo where it accumulates in the germ granules. SMG binds to and represses translation of the osk messenger RNA (mRNA) as well as the bruno 1 (bru1) mRNA, which encodes an RBP that we show promotes germ plasm production. Loss of SMG or mutation of SMG's binding sites in the osk or bru1 mRNA results in excess translation of these transcripts in the germ plasm, accumulation of excess germ plasm, and budding of excess primordial germ cells (PGCs). Therefore, SMG triggers a posttranscriptional regulatory pathway that attenuates the amount of germ plasm in embryos to modulate the number of PGCs.

New flavonoids with multiple bronchodilator activity pathways from Tephrosia purpurea L. (Pers.) growing in Saudi Arabia.

Total extract of Tephrosia purpurea (T. purpurea) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of T. purpurea total extract (TPTE) using liquid-liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl3) soluble fraction. Phytochemical study of the CHCl3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 (epi-Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4''-Dehydroxytephroapollin E), and 5 (epi-Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1, 3, 4 and lanceolatin A (6) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K+)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G (2) selectively inhibited CCh-mediated contractions but was not found active against high K+. epi-Tephroapollin F (5) and (-)-Pseudosemiglabrin (7) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K+ similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca++ inhibitory effect of 1 and 3-7 was confirmed by the rightward deflection of Ca++ concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

In silico Screening and Validation of Achyranthes aspera as a Potential Inhibitor of BRAF and NRAS in Controlling Thyroid Cancer.

BACKGROUND: Thyroid carcinoma (THCA) is one of the most prevalent endocrine tumors, accounting for 3.4% of all cancers diagnosed annually. Single Nucleotide Polymorphisms (SNPs) are the most prevalent genetic variation associated with thyroid cancer. Understanding thyroid cancer genetics will enhance diagnosis, prognosis, and treatment. METHODS: This TCGA-based study analyzes thyroid cancer-associated highly mutated genes through highly robust in silico techniques. Pathway, gene expression, and survival studies were performed on the top 10 highly mutated genes (BRAF, NRAS, TG, TTN, HRAS, MUC16, ZFHX3, CSMD2, EIFIAX, SPTA1). Novel natural compounds from Achyranthes aspera Linn were discovered to target two highly mutated genes. The natural compounds and synthetic drugs used to treat thyroid cancer were subjected to comparative molecular docking against BRAF and NRAS targets. The ADME characteristics of Achyranthes aspera Linn compounds were also investigated. RESULTS: The gene expression analysis revealed that the expression of ZFHX3, MCU16, EIF1AX, HRAS, and NRAS was up-regulated in tumor cells while BRAF, TTN, TG, CSMD2, and SPTA1 were down-regulated in tumor cells. In addition, the protein-protein interaction network demonstrated that HRAS, BRAF, NRAS, SPTA1, and TG proteins have strong interactions with each other as compared to other genes. The ADMET analysis shows that seven compounds have druglike properties. These compounds were further studied for molecular docking studies. The compounds MPHY012847, IMPHY005295, and IMPHY000939 show higher binding affinity with BRAF than pimasertib. In addition, IMPHY000939, IMPHY000303, IMPHY012847, and IMPHY005295 showed a better binding affinity with NRAS than Guanosine Triphosphate. CONCLUSION: The outcomes of docking experiments conducted on BRAF and NRAS provide insight into natural compounds with pharmacological characteristics. These findings indicate that natural compounds derived from plants as a more promising cancer treatment option. Thus, the results of docking investigations conducted on BRAF and NRAS substantiate the conclusions that the molecule possesses the most suited drug-like qualities. Compared to other compounds, natural compounds are superior, and they are also druggable. This demonstrates that natural plant compounds can be an excellent source of potential anti-cancer agents. The preclinical research will pave the road for a possible anti-cancer agent.

Smaug regulates germ plasm synthesis and primordial germ cell number in Drosophila embryos by repressing the oskar and bruno 1 mRNAs.

During Drosophila oogenesis, the Oskar (OSK) RNA-binding protein (RBP) determines the amount of germ plasm that assembles at the posterior pole of the oocyte. Here we identify the mechanisms that regulate the osk mRNA in the early embryo. We show that the Smaug (SMG) RBP is transported into the germ plasm of the early embryo where it accumulates in the germ granules. SMG binds to and represses translation of the osk mRNA itself as well as the bruno 1 (bru1) mRNA, which encodes an RBP that we show promotes germ plasm production. Loss of SMG or mutation of SMG's binding sites in the osk or bru1 mRNAs results in ectopic translation of these transcripts in the germ plasm and excess PGCs. SMG therefore triggers a post-transcriptional regulatory pathway that attenuates germ plasm synthesis in embryos, thus modulating the number of PGCs.

Assessment of the Left Atrial Reservoir Function and Left Atrial Volume After Percutaneous Balloon Mitral Valvuloplasty Using Peak Atrial Longitudinal Strain.

Objective To evaluate the impact of successful percutaneous balloon mitral valvuloplasty (BMV) on left atrial (LA) reservoir function and LA volume in patients with severe mitral stenosis (MS) using peak atrial longitudinal strain (PALS). Method This was a prospective, non-randomized observational study conducted at the Laxmipat Singhania (LPS) Institute of Cardiology, Kanpur from August 2018 to February 2020 among patients with severe rheumatic MS undergoing BMV to assess LA reservoir function and its volume after BMV using PALS. Inclusion criteria were symptomatic severe rheumatic MS (NYHA ≥II), normal ventricular systolic function, and suitable valve morphology. Exclusion criteria were the coexistence of aortic valve involvement, left atrial appendage clot, mitral leak more than mild, pregnancy, hypertension, diabetes, and coronary artery disease. To assess LA reservoir function and its volume after BMV, PALS was used. LA was divided into six regions of interest and longitudinal strain curves of individual segments together with global strain were recorded. PALS was calculated at baseline 24 hours following the intervention, and at three months of follow-up. Result Successful BMV was performed in 260 patients (109 or 41.9% males and 151 or 58.1% females), resulting in significant improvement in mitral valve area (MVA) (0.89±0.11 cm2 vs. 1.83±0.3 cm2; p<0.001). The mean age of patients was 26.7±4.7 years; 214 (82.3%) patients were in normal sinus rhythm (NSR) while 46 (17.7%) had atrial fibrillation (AF). Significant improvement in PALS was noted immediately following the procedure (6.5±11.6% vs. 7.7±10.5%; p< 0.001) and it continued to improve at three months of follow-up (6.5±11.6% vs. 11.3±12.5%; p<0.001), which was 24% and 74% improvement from baseline respectively. Significant reduction in indexed left atrial (LA) volume was observed immediately following the procedure (56.8±14.3 ml/m2 vs 48.4±12.5 ml/m2; p=0.003), and at three months of follow-up (56.8±14.3 ml/m2 vs. 45.4±13.3 ml/m2; p=0.002). Those with AF had lesser improvement in PALS in comparison to those with NSR (60% vs. 84%; p=0.044) at three months of follow-up. At three months, the increase in PALS was also lower in patients with a history of stroke as compared to those without it (55% vs 80%; p=0.039). Both LA volume and indexed LA volume reduced significantly immediately at 24 hours and during follow-up. Conclusion LA reservoir function, as assessed by PALS, is reduced in patients with severe MS. It improved significantly within 24 hours following BMV and continued to improve at three months of follow-up. It is an underutilized modality among patients of MS for decision-making prior to intervention and to assess the effect of the intervention.

Protective effect of rosuvastatin pretreatment against acute myocardial injury by regulating Nrf2, Bcl-2/Bax, iNOS, and TNF-α expressions affecting oxidative/nitrosative stress and inflammation.

Cardiovascular disorders are the leading cause of death globally. Rosuvastatin is a member of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) with many pleiotropic properties. This study investigated cardioprotective effects of rosuvastatin in isoprenaline-induced myocardial injury. Male rats were given rosuvastatin (1, 5, or 10 mg/kg, oral) daily for 1 week and on seventh and eighth day isoprenaline (150 mg/kg, subcutaneous) was given to induce cardiac injury. On ninth day, rats were euthanized and different samples were harvested for analysis. Isoprenaline administration resulted in increased cardiac mass, increased cardiac injury marker levels (cTnI, CK-MB, ALT, and AST), increased lipid/protein oxidation, and increased cardiac nitrite levels. It also decreased superoxide dismutase, CAT, GST, and glutathione reductase activities, and total antioxidant activity. Isoprenaline also increased TNF-α and IL-6 levels. Decreased mRNA expression of Nrf2 and Bcl-2 along with increased mRNA expression of Bax, eNOS and iNOS genes was observed in isoprenaline treated animals. Histopathological evaluations of rosuvastatin pre-treated groups showed reduction of myocardial necrosis. Pretreatment with rosuvastatin (5 and 10 mg/kg) reduced many of these pathological changes. The current study showed that rosuvastatin significantly reduces myocardial injury induced by isoprenaline.

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS).

BACKGROUND: Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. METHODS: In BARNARDS, consenting mother-neonates aged 0-60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic-pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. FINDINGS: Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin-gentamicin, ceftazidime-amikacin, piperacillin-tazobactam-amikacin, and amoxicillin clavulanate-amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime-amikacin than for neonates treated with ampicillin-gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14-0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin-gentamicin; 286 (73·3%) to amoxicillin clavulanate-amikacin; 301 (77·2%) to ceftazidime-amikacin; and 312 (80·0%) to piperacillin-tazobactam-amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin-gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate-amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime-amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin-tazobactam-amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis. INTERPRETATION: Our data raise questions about the empirical use of combined ampicillin-gentamicin for neonatal sepsis in LMICs because of its high resistance and high rates of frequency of resistance and low probability of target attainment. Accessibility and affordability need to be considered when advocating antibiotic treatments with variance in economic health structures across LMICs. FUNDING: The Bill & Melinda Gates Foundation.

Pyrethroid-Induced Organ Toxicity and Anti-Oxidant-Supplemented Amelioration of Toxicity and Organ Damage: The Protective Roles of Ascorbic Acid and α-Tocopherol.

The pyrethroid toxicants, fatal at high doses, are found as remnants of crop pesticides and ingredients of commercially available insecticides. The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g, 1.17 g, and 0.04 g pyrethroid-instilled products, namely burning coils, pyrethroid-soaked mats, and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating. They provided 5.46 g/kg, 21.15 g/kg, and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os (p.o.) administration, producing necrosis, hyperemia, and fatty changes in the liver; fiber separation in cardiac muscles; atrophy, lymphatic infiltration, blood vessel congestion, and hyperemia in the heart tissues of the experimental animals. The glomerular tuft necrosis, cytoplasmic degeneration of renal tubular cells, necrotic tubules, congestion, and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals. Air-space enlargement, interstitial inflammation, lymphocyte infiltration aggregates, connective tissue infiltration by inflammatory cells, and hyperemia were found in the lung tissues. The pyrethroid toxicants also produced nervous tissue degeneration and decreased neurons in the brain, which were observed through histopathological examinations of the brain, lungs, heart, kidneys, and liver. The protective effects of ascorbic acid (AA/vitamin C) and α-tocopherol (E307/vitamin E) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice, aged between 3-4 months and weighing ≈30 g, ameliorated the tissue damage, as observed through the histopathological examinations. The ascorbic acid caused recovery of the liver, kidney, brain, and heart tissue damage, while α-tocopherol was effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups. The high levels of tissue damage recovery suggested a prophylactic effect of the concurrent use of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids.

Neutropenic Enterocolitis and Rapid Spontaneous Resolution of Portal Venous Gas: A Non-Respiratory Manifestation of COVID-19.

The COVID-19 pandemic is affecting millions across the globe. The population of immunosuppressed individuals are at greatest risk of morbidity and mortality. Data on COVID-19 induced illness in the immunocompromised host are sparse. We aim to highlight the possibility of atypical and non-respiratory presentations of COVID-19 (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) in immunosuppressed individuals as our case reveals a rare COVID-19 associated GI presentation of neutropenic enterocolitis with bloody diarrhea.

Precordial ECG Lead Mispositioning: Its Incidence and Estimated Cost to Healthcare.

BACKGROUND: The study was performed to estimate the incidence and economic burden of electrocardiogram (ECG) precordial lead mispositioning, in an effort to highlight the need for quality improvement. Lead mispositioning may result in further cardiovascular testing to rule out significant cardiac disease, thus adding to the national healthcare financial burden. METHODS: All consecutive adult ECGs done during 2018, were reviewed. ECGs with acute anterior myocardial infarction (AMI), bundle branch blocks, left ventricular hypertrophy (LVH), left anterior fascicular block (LAFB), pre-excitation, left axis deviation, ventricular pacing and low voltage QRS were excluded. Septal infarcts identified automatically by the computerized software or identified manually using the criteria of QS composite in V2 were not excluded. Computer interpreted ECGs as "cannot rule-out anterior infarct" were also not excluded from this data. Reimbursement of various stress test types was used to estimate the cost burden of misdiagnosed ECGs. RESULTS: A total of 9424 adult ECGs were evaluated. Poor R-wave progression (PRWP) or reversed R-wave progression (RRWP) accounted for 497 (5.27%) and 102 (1.08%) ECGs, respectively. A total of 335 septal infarct interpretations constituted about 3.55% of all ECGs. ECGs categorized as "cannot rule-out AMI" due to PRWP constituted about 0.89%. Therefore, a total of 1018 ECGs (10.8%) could be possibly falsely labelled as some type of myocardial infarction. CONCLUSION: Precordial ECG lead mispositioning can lead to significantly abnormal ECG patterns, leading to false diagnoses and further unnecessary cardiovascular testing. This not only increases risk and cost to the patient, but also adds to the national healthcare financial burden.

Determination of mutations in iron regulating genes of beta thalassemia major patients of Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Hepcidin and hemochromatosis (HFE) are iron regulatory proteins that are encoded by HAMP and HFE genes. Mutation in either HAMP gene or HFE gene causes Hepcidin protein deficiency that can lead to iron overload in beta thalassemia patients. The aim of this research work was to study the presence of G71D mutation of HAMP gene and H63D mutation of HFE gene in beta thalassemia major and minor group to check the association of these mutations with serum ferritin level of beta thalassemia patients. METHODS: The study was conducted on 42 beta thalassemia major and 20 beta thalassemia minor samples along with 20 control samples. The genotyping of both mutations has done by ARM-PCR technique with specific set of primers. RESULTS: Significant effect of G71D and H63D mutations was observed on serum ferritin level of thalassemia major group. The risk allele of HAMP G71D and HFE H63D was found with high frequency (48% and 49%, respectively) in beta thalassemia major than in control group. High genotypic frequency of HAMP and HFE gene mutation gene mutation was observed in beta thalassemia major than beta thalassemia minor and control group (7% and 9%, respectively). CONCLUSION: It can be concluded that both HAMP and HFE gene mutations show high frequency in beta thalassemia major patients and mean significant association between mutations and high serum ferritin level of beta thalassemia major patients but the nonsignificant results of Odd ratios showed that both mutations do not act as major risk factor in beta thalassemia major.

Atypical Manifestation of COVID-19-Induced Myocarditis.

We present a case of a 39-year-old male who presented with chest pain without fever or respiratory symptoms. Troponins were elevated and electrocardiogram (ECG) was inconclusive for ST-elevation myocardial infarction (STEMI). Angiography revealed normal coronaries and the patient was found to be coronavirus disease 2019 (COVID-19) positive; he was diagnosed with COVID-19 myocarditis. With the global pandemic, more cases are emerging regarding myocardial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although COVID-19 manifests primarily as respiratory disease, few cases of cardiac injury without respiratory involvement or febrile illness have been reported. This case illustrates that COVID-19 can present atypically and affect an isolated non-respiratory organ system.

Precise Temporal Regulation of Post-transcriptional Repressors Is Required for an Orderly Drosophila Maternal-to-Zygotic Transition.

In animal embryos, the maternal-to-zygotic transition (MZT) hands developmental control from maternal to zygotic gene products. We show that the maternal proteome represents more than half of the protein-coding capacity of Drosophila melanogaster's genome, and that 2% of this proteome is rapidly degraded during the MZT. Cleared proteins include the post-transcriptional repressors Cup, Trailer hitch (TRAL), Maternal expression at 31B (ME31B), and Smaug (SMG). Although the ubiquitin-proteasome system is necessary for clearance of these repressors, distinct E3 ligase complexes target them: the C-terminal to Lis1 Homology (CTLH) complex targets Cup, TRAL, and ME31B for degradation early in the MZT and the Skp/Cullin/F-box-containing (SCF) complex targets SMG at the end of the MZT. Deleting the C-terminal 233 amino acids of SMG abrogates F-box protein interaction and confers immunity to degradation. Persistent SMG downregulates zygotic re-expression of mRNAs whose maternal contribution is degraded by SMG. Thus, clearance of SMG permits an orderly MZT.

Global regulation of mRNA translation and stability in the early Drosophila embryo by the Smaug RNA-binding protein.

BACKGROUND: Smaug is an RNA-binding protein that induces the degradation and represses the translation of mRNAs in the early Drosophila embryo. Smaug has two identified direct target mRNAs that it differentially regulates: nanos and Hsp83. Smaug represses the translation of nanos mRNA but has only a modest effect on its stability, whereas it destabilizes Hsp83 mRNA but has no detectable effect on Hsp83 translation. Smaug is required to destabilize more than one thousand mRNAs in the early embryo, but whether these transcripts represent direct targets of Smaug is unclear and the extent of Smaug-mediated translational repression is unknown. RESULTS: To gain a panoramic view of Smaug function in the early embryo, we identified mRNAs that are bound to Smaug using RNA co-immunoprecipitation followed by hybridization to DNA microarrays. We also identified mRNAs that are translationally repressed by Smaug using polysome gradients and microarrays. Comparison of the bound mRNAs to those that are translationally repressed by Smaug and those that require Smaug for their degradation suggests that a large fraction of Smaug's target mRNAs are both translationally repressed and degraded by Smaug. Smaug directly regulates components of the TRiC/CCT chaperonin, the proteasome regulatory particle and lipid droplets, as well as many metabolic enzymes, including several glycolytic enzymes. CONCLUSIONS: Smaug plays a direct and global role in regulating the translation and stability of a large fraction of the mRNAs in the early Drosophila embryo, and has unanticipated functions in control of protein folding and degradation, lipid droplet function and metabolism.

Genome-wide analysis of the maternal-to-zygotic transition in Drosophila primordial germ cells.

BACKGROUND: During the maternal-to-zygotic transition (MZT) vast changes in the embryonic transcriptome are produced by a combination of two processes: elimination of maternally provided mRNAs and synthesis of new transcripts from the zygotic genome. Previous genome-wide analyses of the MZT have been restricted to whole embryos. Here we report the first such analysis for primordial germ cells (PGCs), the progenitors of the germ-line stem cells. RESULTS: We purified PGCs from Drosophila embryos, defined their proteome and transcriptome, and assessed the content, scale and dynamics of their MZT. Transcripts encoding proteins that implement particular types of biological functions group into nine distinct expression profiles, reflecting coordinate control at the transcriptional and posttranscriptional levels. mRNAs encoding germ-plasm components and cell-cell signaling molecules are rapidly degraded while new transcription produces mRNAs encoding the core transcriptional and protein synthetic machineries. The RNA-binding protein Smaug is essential for the PGC MZT, clearing transcripts encoding proteins that regulate stem cell behavior, transcriptional and posttranscriptional processes. Computational analyses suggest that Smaug and AU-rich element binding proteins function independently to control transcript elimination. CONCLUSIONS: The scale of the MZT is similar in the soma and PGCs. However, the timing and content of their MZTs differ, reflecting the distinct developmental imperatives of these cell types. The PGC MZT is delayed relative to that in the soma, likely because relief of PGC-specific transcriptional silencing is required for zygotic genome activation as well as for efficient maternal transcript clearance.

Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract.

BACKGROUND: This study was undertaken to provide pharmacological basis for the medicinal use of Viola odorata Linn. in hypertension and dyslipidemia using the in vivo and in vitro assays. RESULTS: Viola odorata leaves extract (Vo.Cr), which tested positive for alkaloids, saponins, tannins, phenolics, coumarins and flavonoids, caused a dose-dependent (0.1-1.0 mg/kg) decrease in mean arterial blood pressure in anaesthetized rats. In isolated guinea-pig atria, Vo.Cr equally inhibited force and rate of spontaneous atrial contractions. On the baseline of rat thoracic aortae (endothelium-intact and denuded), the plant extract caused phentolamine-sensitive vasoconstriction. When tested on phenylephrine (PE, 1 µM) and K(+) (80 mM)-induced vasoconstriction, Vo.Cr caused a concentration-dependent relaxation and also caused a rightward shift of Ca(++) concentration-response curves as well as suppression of PE (1 µM) control peaks in Ca(++)-free medium, similar to that caused by verapamil. In the presence of L-NAME, the relaxation curve of Vo.Cr was partially inhibited showing involvement of Nitric oxide (NO) mediated pathway. In Tyloxapol-induced dyslipidemia, Vo.Cr caused reduction in total cholesterol and triglyceride levels. In high-fat diet-induced dyslipidemia model, the plant extract caused a significant decrease in total cholesterol, LDL-C, atherogenic index and prevented the increase in average body weights, while it increased HDL-C. CONCLUSIONS: These data indicate that the vasodilator effect of the plant extract is mediated through multiple pathways like inhibition of Ca(++) influx via membranous Ca(++) channels, its release from intracellular stores and NO-mediated pathways, which possibly explain the fall in BP. The plant also showed reduction in body weight and antidyslipidemic effect which may be due to the inhibition of synthesis and absorption of lipids and antioxidant activities. Thus, this study provides a pharmacologic rationale to the medicinal use of Viola odorata in hypertension and dyslipidemia.

Chemical constituents of Nepeta distans.

Phytochemical investigation of Nepeta distans Raul resulted in the isolation of a new phenolic compound, nepatanol (1), and eight known compounds, markhamioside F, netidiol, nepedinol, thymoquinone, eugenol, oleanolic acid, ursolic acid, and beta-sitosterol, which have been isolated for the first time from this source. Structures of all the isolates were established on the basis of MS, and 1D and 2D NMR spectral data and by comparison with reported data.

Citric acid enhances the phytoextraction of manganese and plant growth by alleviating the ultrastructural damages in Juncus effusus L.

Chelate-assisted phytoextraction by high biomass producing plant species enhances the removal of heavy metals from polluted environments. In this regard, Juncus effusus a wetland plant has great potential. This study evaluated the effects of elevated levels of manganese (Mn) on the vegetative growth, Mn uptake and antioxidant enzymes in J. effusus. We also studied the role of citric acid and EDTA on improving metal accumulation, plant growth and Mn toxicity stress alleviation. Three-week-old plantlets of J. effusus were subjected to various treatments in the hydroponics as: Mn (50, 100 and 500 microM) alone, Mn (500 microM) + citric acid (5 mM), and Mn (500 microM) + EDTA (5 mM). After 2 weeks of treatment, higher Mn concentrations significantly reduced the plant biomass and height. Both citric acid and EDTA restored the plant height as it was reduced at the highest Mn level. Only the citric acid (but not EDTA) was able to recover the plant biomass weight, which was also obvious from the microscopic visualization of mesophyll cells. There was a concentration dependent increase in Mn uptake in J. effusus plants, and relatively more deposition in roots compared to aerial parts. Although both EDTA and citric acid caused significant increase in Mn accumulation; however, the Mn translocation was enhanced markedly by EDTA. Elevated levels of Mn augmented the oxidative stress, which was evident from changes in the activities of antioxidative enzymes in plant shoots. Raised levels of lipid peroxidation and variable changes in the activities of antioxidant enzymes were recorded under Mn stress. Electron microscopic images revealed several modifications in the plants at cellular and sub-cellular level due to the oxidative damage induced by Mn. Changes in cell shape and size, chloroplast swelling, increased number of plastoglobuli and disruption of thylakoid were noticed. However, these plants showed a high degree of tolerance against Mn toxicity stress, and it removed substantial amounts of Mn from the media. The EDTA best enhanced the Mn uptake and translocation, while citric acid best recovered the plant growth.

Cadmium-induced ultramorphological and physiological changes in leaves of two transgenic cotton cultivars and their wild relative.

The present study describes cadmium-induced alterations in the leaves as well as at the whole plant level in two transgenic cotton cultivars (BR001 and GK30) and their wild relative (Coker 312) using both ultramorphological and physiological indices. With elevated levels of Cd (i.e. 10, 100, 1000 microM), the mean lengths of root, stem and leaf and leaf width as well as their fresh and dry biomasses linearly decreased over their respective controls. Moreover, root, stem and leaf water absorption capacities progressively stimulated, which were high in leaves followed by roots and stems. BR001 accumulated more cadmium followed by GK30 and Coker 312. Root and shoot cadmium uptakes were significantly and directly correlated with each other as well as with leaf, stem and root water absorption capacities. The ultrastructural modifications in leaf mesophyll cells were triggered with increase in Cd stress regime. They were more obvious in BR001 followed by GK30 and Coker 312. Changes in morphology of chloroplast, increase in number and size of starch grains as well as increase in number of plastoglobuli were the noticed qualitative effects of Cd on photosynthetic organ. Cd in the form of electron dense granules could be seen inside the vacuoles and attached to the cell walls in all these cultivars. From the present experiment, it can be well established that both apoplastic and symplastic bindings are involved in Cd detoxification in these cultivars. Absence of tonoplast invagination reveals that Cd toxic levels did not cause water stress in any cultivars. Additionally, these cultivars possess differential capabilities towards Cd accumulation and its sequestration.

Congenitally corrected transposition of great arteries with ischemic symptoms in middle age.

Congenitally corrected transposition of the great arteries CCTGA is a rare congenital disease first described by Von Rokitansky in 1875. Transposition of the great arteries comprises 2.6 - 7.8% of all cases of congenital heart disease, and if uncorrected, is commonly fatal in the first year of life. Patients with corrected transposition of the great arteries without associated defects may remain undiagnosed until adult life. Symptoms occur rarely before the fourth and fifth decades, when rhythm disturbance, left atrioventricular valve regurgitation, and moderately impaired systemic ventricular function cause congestive cardiac failure. We report here a case of drug overdose with ischemic symptoms, and CCTGA without associated anomalies in a 40-year-old male.