Primary Tubercular Chorioretinitis Without a Pulmonary Focus: A Case Report.

Ocular tuberculosis (TB) can affect various eye structures and may manifest independently of systemic TB. Typically, it arises from hematogenous dissemination from a primary focus; however, in exceptional instances, it may originate as a primary infection after epithelial injury. Diagnosing TB in an extrapulmonary site presents a significant clinical challenge. We present the case of a 33-year-old Bangladeshi female who presented with a deteriorating loss of vision in her left eye. A thorough neurologic examination and serological tests, the tuberculin skin test, a CT scan of the chest, ocular fundus photography, and optical coherence tomography were performed. Based on the clinical features and the outcome of appropriate tests, a presumptive diagnosis of ocular TB was made and later confirmed after initiating antitubercular therapy, which resulted in a marked improvement in the patient's vision a week later. This case is an illustration of the rare nature and unusual presentation of extrapulmonary TB in the form of tubercular chorioretinitis, diagnosed in a resource-limited setting. Tubercular chorioretinitis, characterized by inflammation of the choroid and retina due to TB infection, presents a diagnostic challenge, especially in resource-limited environments where access to advanced diagnostic tools may be restricted. Therefore, this case highlights the importance of considering TB as a potential cause of ocular manifestations, even in settings where TB prevalence might not be high, and underscores the need for increased awareness and diagnostic capacity for extrapulmonary TB in resource-limited areas. This case exemplifies the infrequent occurrence and atypical manifestation, presenting a learning opportunity for future clinicians.

Epigenetic control of adaptive or homeostatic splicing during interval-training activities.

Interval-training activities induce adaptive cellular changes without altering their fundamental identity, but the precise underlying molecular mechanisms are not fully understood. In this study, we demonstrate that interval-training depolarization (ITD) of pituitary cells triggers distinct adaptive or homeostatic splicing responses of alternative exons. This occurs while preserving the steady-state expression of the Prolactin and other hormone genes. The nature of these splicing responses depends on the exon's DNA methylation status, the methyl-C-binding protein MeCP2 and its associated CA-rich motif-binding hnRNP L. Interestingly, the steady expression of the Prolactin gene is also reliant on MeCP2, whose disruption leads to exacerbated multi-exon aberrant splicing and overexpression of the hormone gene transcripts upon ITD, similar to the observed hyperprolactinemia or activity-dependent aberrant splicing in Rett Syndrome. Therefore, epigenetic control is crucial for both adaptive and homeostatic splicing and particularly the steady expression of the Prolactin hormone gene during ITD. Disruption in this regulation may have significant implications for the development of progressive diseases.

Quality of Life in Children and Young People With Congenital Adrenal Hyperplasia-UK Nationwide Multicenter Assessment.

CONTEXT: Quality of life (QoL) has been inconsistently reported in children and young people (CYP) with congenital adrenal hyperplasia (CAH). OBJECTIVE: Assess QoL in CYP with CAH in the UK alongside biometric and androgen profiles. DESIGN: To define the evidence base for health care delivery, we conducted a cross-sectional study in CYP with CAH in the UK. Questionnaire results were compared with normative data and between groups, and modelled for association with sex, height, weight, body mass index, or steroid biomarkers of CAH control. SETTING: Tertiary care in 14 UK centers. PATIENTS: Results from 104 patients, 55% female, mean age 12.7 years (SD 3.0), paired responses from parents. INTERVENTIONS: Strengths and Difficulties questionnaire (SDQ) and pediatric QoL questionnaire. MAIN OUTCOME MEASURE: Total QoL scores as assessed by SDQ and a pediatric QoL questionnaire in comparison to normative data. RESULTS: Total scores were worse in parents than normative data, but similar in patients. Patient QoL was rated better in social functioning but worse in emotional, school, and peer domains by patients, and worse in total scores and domains of peer problems, and psychosocial, emotional, and school functioning by parents. Parents consistently scored QoL of their children lower than their child. Larger height-SD score and lower weight-SD score were associated with better QoL. Girls with lower steroid biomarkers had worse SDQ scores. CONCLUSIONS: In CYP with CAH, reduced height, increased weight, and hormonal biomarkers consistent with overtreatment were associated with worse QoL; addressing these problems should be prioritized in clinical management.Clinical Trials Registration Number: SCH/15/088.

Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers.

Background: Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries. Methods: This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable. Findings: MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations. Interpretation: The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies. Funding: Swedish Research Council (Vetenskapsrådet, award D0886501 to PFS), US National Institutes of Mental HealthR01 MH123724 (to PFS), European Union's Horizon 2020 Research and Innovation Program (847776 and 964874, to OA) and European Research Council grant (grant agreement ID 101042183, to YL).

Transcriptome-Wide Detection of Intron/Exon Definition in the Endogenous Pre-mRNA Transcripts of Mammalian Cells and Its Regulation by Depolarization.

Pairing of splice sites across an intron or exon is the central point of intron or exon definition in pre-mRNA splicing with the latter mode proposed for most mammalian exons. However, transcriptome-wide pairing within endogenous transcripts has not been examined for the prevalence of each mode in mammalian cells. Here we report such pairings in rat GH3 pituitary cells by measuring the relative abundance of nuclear RNA-Seq reads at the intron start or end (RISE). Interestingly, RISE indexes are positively correlated between 5' and 3' splice sites specifically across introns or exons but inversely correlated with the usage of adjacent exons. Moreover, the ratios between the paired indexes were globally modulated by depolarization, which was disruptible by 5-aza-Cytidine. The nucleotide matrices of the RISE-positive splice sites deviate significantly from the rat consensus, and short introns or exons are enriched with the cross-intron or -exon RISE pairs, respectively. Functionally, the RISE-positive genes cluster for basic cellular processes including RNA binding/splicing, or more specifically, hormone production if regulated by depolarization. Together, the RISE analysis identified the transcriptome-wide regulation of either intron or exon definition between weak splice sites of short introns/exons in mammalian cells. The analysis also provides a way to further track the splicing intermediates and intron/exon definition during the dynamic regulation of alternative splicing by extracellular factors.

Forming cytoplasmic stress granules PURα suppresses mRNA translation initiation of IGFBP3 to promote esophageal squamous cell carcinoma progression.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies worldwide. Recently, our group identified purine-rich element binding protein alpha (PURα), a single-stranded DNA/RNA-binding protein, to be significantly associated with the progression of ESCC. Additional immunofluorescence staining demonstrated that PURα forms cytoplasmic stress granules to suppress mRNA translation initiation. The expression level of cytoplasmic PURα in ESCC tumor tissues was significantly higher than that in adjacent epithelia and correlated with a worse patient survival rate by immunohistochemistry. Functionally, PURα strongly preferred to bind to UG-/U-rich motifs and mRNA 3´UTR by CLIP-seq analysis. Moreover, PURα knockout significantly increased the protein level of insulin-like growth factor binding protein 3 (IGFBP3). In addition, it was further demonstrated that PURα-interacting proteins are remarkably associated with translation initiation factors and ribosome-related proteins and that PURα regulates protein expression by interacting with translation initiation factors, such as PABPC1, eIF3B and eIF3F, in an RNA-independent manner, while the interaction with ribosome-related proteins is significantly dependent on RNA. Specifically, PURα was shown to interact with the mRNA 3´UTR of IGFBP3 and inhibit its expression by suppressing mRNA translation initiation. Together, this study identifies cytoplasmic PURα as a modulator of IGFBP3, which could be a promising therapeutic target for ESCC treatment.

Health status of children and young persons with congenital adrenal hyperplasia in the UK (CAH-UK): a cross-sectional multi-centre study.

Objective: There is limited knowledge on the onset of comorbidities in congenital adrenal hyperplasia (CAH) during childhood. We aimed to establish the health status of children with CAH in the UK. Design and methods: This cross-sectional multicentre study involved 14 tertiary endocrine UK units, recruiting 101 patients aged 8-18 years with classic 21-hydroxylase deficiency and 83 controls. We analysed demographic, clinical and metabolic data, as well as psychological questionnaires (Strengths and Difficulties (SDQ), Paediatric Quality of Life (PedsQL)). Results: Patient height SDS in relation to mid-parental height decreased with age, indicating the discrepancy between height achieved and genetic potential height. Bone age was advanced in 40.5% patients, with a mean difference from the chronological age of 1.8 (±2.3) years. Patients were more frequently overweight (27%) or obese (22%) compared to controls (10.8% and 10.8%, respectively, P < 0.001). No consistent relationship between glucocorticoid dose and anthropometric measurements or hormonal biomarkers was detected. A small number of patients had raised total cholesterol (3.0%), low HDL (3.0%), raised LDL (7.0%) and triglycerides (5.0%). SDQ scores were within the 'high' and 'very high' categories of concern for 16.3% of patients. 'School functioning' was the lowest PedsQL scoring dimension with a median (interquartile range) of 70 (55-80), followed by 'emotional functioning' with a median of 75 (65-85). Conclusions: Our results show an increased prevalence of problems with growth and weight gain in CAH children and suggest reduced quality of life. This highlights the urgent need to optimise management and monitoring strategies to improve long-term health outcomes.

Baseline and Peak Cortisol Response to the Low-Dose Short Synacthen Test Relates to Indication for Testing, Age, and Sex.

Context: Meta-analyses report that the low dose short Synacthen test (LDSST) is more sensitive but less specific than the standard dose test for the diagnosis of adrenal insufficiency, and there are concerns regarding the accuracy of dosing in the LDSST. Objective: Perform a retrospective, observational study to review the outcomes of LDSSTs performed in a tertiary endocrine service from 2008 to 2014 (N = 335) and 2016 to 2020 (N = 160), and examine for relationships between cortisol measurements and indication for testing, age and sex. Methods: LDSST were performed by endocrine nurses. Synacthen 500 ng/1.73m2 administered as IV bolus, sampling at 0, 15, 25, and 35 minutes. Results: Mean (± 1SD) baseline cortisol was 221 ± 120 nmol/L, peak 510 ± 166 nmol/L and increment 210 ± 116 nmol/L. 336 (70%) patients had a normal response (baseline cortisol >100 nmol/L, peak >450 nmol/L), 78 (16%) a suboptimal response (peak cortisol 350-450 nmol/L) and were prescribed hydrocortisone to during periods of stress only, 67 (14%) an abnormal response (baseline <100nmol/L or peak <350nmol/L) and were prescribed daily hydrocortisone. Basal, peak, and incremental increases in cortisol were higher in females (P = .03, P < .001, P = .03, respectively). Abnormal results occurred most frequently in patients treated previously with pharmacological doses of glucocorticoids or structural brain abnormalities (P < .001). Conclusion: The low prevalence and strong association of abnormal results with indication for testing, suggests that over diagnosis occurred infrequently in this clinical setting.

Changes in physiological responses and MTP (metal tolerance protein) transcripts in soybean (Glycine max) exposed to differential iron availability.

Members of MTP (metal tolerance protein) family are potential metal ion transporters, but little is known about how their responses and expression are altered in response to the deficiency and excess of Fe in soybean. In this study, root and shoot length and biomass in addition to leaf chlorophyll score, PSII efficiency and photosynthetic performance index were adversely affected by Fe-deficiency and excess Fe. Fe and S concentrations in the root and shoot, as well as the increased root FCR activity, consistently decreased and increased, respectively, accompanied by elevated Zn levels under Fe deficiency and Fe toxicity. This implies that Fe-uptake of plants subjected to differential Fe availability are likely determined by S and Zn nutritional status. In qPCR analysis, GmMTP5, GmMTP7, GmMTP8, and GmMTP10 genes showed downregulation under Fe shortage, whereas GmMTP6 and GmMTP11 were significantly upregulated due to Fe-toxicity. Further, GmMTP1, GmMTP3, GmMTP6, GmMTP7, and GmMTP10 were significantly induced in response to Fe toxicity, indicating their potential role in metal tolerance. Bioinformatics analysis showed that soybean MTP genes possessed a close relationship with certain Arabidopsis genes (i.e. ZAT, MTPB1) involved in solute transport and metal sequestration. Furthermore, top five motifs of soybean MTP protein correspond to the cation efflux family exhibited strong amino acid and evolutionary similarities with Arabidopsisthaliana. These findings shed light on Fe homeostasis mechanisms in soybean and could be used to regulate Fe uptake through breeding or transgenic manipulations of MTP genes.

Silicon induces metallochaperone-driven cadmium binding to the cell wall and restores redox status through elevated glutathione in Cd-stressed sugar beet.

Cadmium (Cd) is toxic; however, whether silicon (Si) alleviates Cd toxicity was never studied in sugar beet. The study was conducted on 2-week-old sugar beet cultivated in the presence or absence of Cd (10 µM CdSO4 ) and Si (1 mM Na2 SiO3 ) in hydroponic conditions. The morphological impairment and cellular damages observed in sugar beet upon Cd toxicity were entirely reversed due to Si. Si substantially restored the energy-providing ability, absorbed energy flux, and electron transport toward PSII, which might be correlated with the upregulation of BvIRT1 and ferric chelate reductase activity leading to the restoration of Fe status in Cd-stressed sugar beet. Although Si caused a reduction of shoot Cd, the root Cd substantially increased under Cd stress, a significant part of which was retained in the cell wall rather than in the root vacuole. While the concentration of phytochelatin and the expression of BvPCS3 (PHYTOCHELATIN SYNTHASE 3) showed no changes upon Si exposure, Si induced the expression of BvHIPP32 (HEAVY METAL-ASSOCIATED ISOPRENYLATED PLANT PROTEIN 32) in the Cd-exposed root. The BvHIPP32 and AtHIPP32 metallochaperone proteins are localized in the cell wall and they share similar sequence alignment, physiochemical properties, secondary structure, cellular localization, motif locations, domain association, and metal-binding site (cd00371) linked to the metallochaperone-like protein. It suggests that Si reduces the Cd level in shoot by retaining the excess Cd in the cell wall of roots due to the induction of BvHIPP32 gene. Also, Si stimulates glutathione-related antioxidants along with the BvGST23 expression, inferring an ascorbate-glutathione ROS detoxification pathway in Cd-exposed plants.

Downregulation of Zn-transporters along with Fe and redox imbalance causes growth and photosynthetic disturbance in Zn-deficient tomato.

Zinc (Zn) deficiency hinders growth and development in tomato. This study unveils the responses of how Zn starvation affects physiological and molecular processes in tomato. Zn deficiency negatively affected the biomass, cellular integrity, and chlorophyll synthesis in tomato. Also, Zn deficiency decreased the maximum yield of PSII, photosynthesis performance index and dissipation energy per active reaction center, although the antenna size, trapping energy efficiency and electron transport flux were stable in Zn-starved leaves. Further, Zn shortage caused a substantial reduction in Zn and Fe concentrations in both roots and shoots along with decreased root Fe-reductase activity accompanied by the downregulation of Fe-regulated transporter 1, Zn transporter-like (LOC100037509), and Zn transporter (LOC101255999) genes predicted to be localized in the root plasma membrane. The interactome partners of these Zn transporters are predominantly associated with root-specific metal transporter, ferric-chelate reductase, BHLH transcriptional regulator, and Zn metal ion transporters, suggesting that Zn homeostasis may be tightly linked to the Fe status along with BHLH transcription factor in Zn-deficient tomato. We also noticed elevated O2.- and H2O2 due to Zn deficiency which was consistent with the inefficient antioxidant properties. These findings will be useful in the downstream approach to improve vegetable crops sensitive to Zn-deficiency.

Sulfur triggers glutathione and phytochelatin accumulation causing excess Cd bound to the cell wall of roots in alleviating Cd-toxicity in alfalfa.

Although Cd is threatening to the environment, animal, and human, the eco-friendly approach to mitigate the Cd-toxicity in alfalfa was barely studied. Therefore, this study aims at elucidating the role of S, a crucial macroelement, in alleviating Cd toxicity in alfalfa plants. The supplementation of S in Cd-stressed alfalfa reversed the detrimental effect on plant biomass, chlorophyll synthesis, and protein concentration. Interestingly, S surplus restored the photosynthetic kinetics, such as Fv/Fm, Pi_ABS, and Mo values in leaves of Cd-stressed alfalfa. Further, Cd-induced adverse effect on membrane stability, cell viability, and redox status was restored due to S under Cd stress. The exogenous S not only increased S status and the expression of sulfate transporters (MsSULRT1;2 and MsSULTR1;3), but also decreased the Cd concentration in the shoot by retaining elevated Cd in root tissue. Further analysis revealed the upregulation of MsGS (glutathione synthetase) and MsPCS1 (phytochelatin synthase) genes along with the increased concentration of glutathione and phytochelatin, predominantly in roots subjected to S surplus under Cd stress. The subcellular Cd analysis showed elevated Cd in the cell wall but not in the vacuole. It suggests that S-induced elevated glutathione enables the phytochelatin to bind with excess Cd leading to subcellular sequestration in the cell wall of roots. Also, S stimulates the S-metabolites and GR enzyme that coordinately counteracts Cd-induced oxidative damage. These findings can be utilized to popularize the application of S and to perform breeding/transgenic experiments to develop Cd-free forage crops.

Morpho-physiological retardations due to iron toxicity involve redox imbalance rather than photosynthetic damages in tomato.

Iron (Fe) toxicity is a major nutritional disorder that affects growth and yield in plants. Understanding the responses or damages due to Fe-toxicity may provide useful knowledge to improve tomato varieties. This study investigates the physiological and molecular responses in Fe-toxic tomato plants. The tomato plants were grown in separate hydroponic containers with two concentrations of Fe-EDTA (25 µM and 5 mM) in addition to the other nutrient elements. Fe-toxicity showed a severe reduction in growth parameters, which was accompanied by the increased electrolyte leakage and cell death in tomato. However, the SPAD score, quantum efficiency of PSII, and photosynthesis performance index did not show any changes in leaves, suggesting that damages due to Fe-toxicity are not related to the photosynthetic disturbance in tomato. The FCR (ferric chelate reductase) activity in root along with the Fe concentration in root and shoot significantly increased, being consistent with the upregulation of Fe-related genes (SlNramp1 and SlFRO1) in roots. It suggests that inefficiency to cope with elevated Fe is closely linked to Fe mobilization and uptake in roots of tomato. Consequently, this sensitive genotype was more prone to oxidative damages because of the inefficient antioxidant defense linked to antioxidant enzymes and metabolites. In conclusion, the growth retardation in Fe-toxic tomato is not related to photosynthetic inefficiency but highly associated with oxidative injuries in cells. These findings could be targeted in breeding or transgenic program to improve tomato plants sensitive to Fe toxicity.

Arbuscular mycorrhizal fungi mitigate Fe deficiency symptoms in sorghum through phytosiderophore-mediated Fe mobilization and restoration of redox status.

Sustainable management of iron (Fe) deficiency through the microbial association is highly desirable to ensure crop yield. This study elucidates whether and how arbuscular mycorrhizal fungi (AMF) ameliorate Fe deficiency symptoms in sorghum. AMF inoculation showed a significant improvement in plant biomass, chlorophyll score, Fv/Fm (quantum efficiency of photosystem II), and Pi_ABS (photosynthesis performance index), suggesting its potentiality to diminish Fe deficiency symptoms in sorghum. This AMF-driven prevention of Fe deficiency was further supported by the improvement of biochemical stress indicators, such as cell death, electrolyte leakage, hydrogen peroxide, and superoxide anion. In this study, AMF showed a significant increase in phytosiderophore (PS) release as well as Fe and S concentrations in sorghum under Fe deficiency. Quantitative real-time PCR analysis demonstrated the consistent upregulation of SbDMAS2 (deoxymugineic acid synthase 2), SbNAS2 (nicotianamine synthase 2), and SbYS1 (Fe-phytosiderophore transporter yellow stripe) in roots due to AMF with Fe deficiency. It suggests that the enhancement of Fe due to AMF is related to the mobilization of Fe(III)-PS in the rhizosphere supported by the long-distance transport of Fe by SbYS1 transporter in sorghum. Our study further showed that the elevation of S mainly in the presence of AMF possibly enhances the S-containing antioxidant metabolites (Met, Cys, and GSH) as well as enzymes (CAT, SOD, and GR) to counteract H2O2 and O2- for the restoration of redox status in Fe-deprived sorghum. Moreover, S possibly participates in Strategy II responses revealing its crucial role as a signaling molecule for Fe homeostasis in sorghum.

Arbuscular Mycorrhizal Symbiosis Mitigates Iron (Fe)-Deficiency Retardation in Alfalfa (Medicago sativa L.) Through the Enhancement of Fe Accumulation and Sulfur-Assisted Antioxidant Defense.

Iron (Fe)-deficiency is one of the major constraints affecting growth, yield and nutritional quality in plants. This study was performed to elucidate how arbuscular mycorrhizal fungi (AMF) alleviate Fe-deficiency retardation in alfalfa (Medicago sativa L.). AMF supplementation improved plant biomass, chlorophyll score, Fv/Fm (quantum efficiency of photosystem II), and Pi_ABS (photosynthesis performance index), and reduced cell death, electrolyte leakage, and hydrogen peroxide accumulation in alfalfa. Moreover, AMF enhanced ferric chelate reductase activity as well as Fe, Zn, S and P in alfalfa under Fe-deficiency. Although Fe-transporters (MsIRT1 and MsNramp1) did not induce in root but MsFRO1 significantly induced by AMF under Fe deficiency in roots, suggesting that AMF-mediated Fe enhancement is related to the bioavailability of Fe at rhizosphere/root apoplast rather than the upregulation of Fe transporters under Fe deficiency in alfalfa. Several S-transporters (MsSULTR1;1, MsSULTR1;2, MsSULTR1;3, and MsSULTR3;1) markedly increased following AMF supplementation with or without Fe-deficiency alfalfa. Our study further suggests that Fe uptake system is independently influenced by AMF regardless of the S status in alfalfa. However, the increase of S in alfalfa is correlated with the elevation of GR and S-metabolites (glutathione and cysteine) associated with antioxidant defense under Fe deficiency.

Arbuscular mycorrhizal fungi alleviate Fe-deficiency symptoms in sunflower by increasing iron uptake and its availability along with antioxidant defense.

Iron (Fe)-deficiency causes chlorosis and growth inhibition in sunflower, an important commercial crop. This study examines whether and how arbuscular mycorrhizal fungi (AMF) ameliorate Fe-deficiency symptoms in Fe-deficiency sensitive sunflower plants. AMF supplementation showed a significant improvement in plant biomass, chlorophyll score, Fv/Fm (quantum efficiency of photosystem II), and Pi_ABS (photosynthesis performance index), suggesting its beneficial effect under Fe deficiency. This AM-driven amelioration of Fe deficiency was further supported by the improvement of biochemical stress indicators, such as cell death, electrolyte leakage, superoxide anion, and hydrogen peroxide. In this study, the AMF supplementations resulted in significant improvement in Fe as well as Zn concentrations in root and shoot of sunflower under Fe deficiency. One of the primary Strategy-I responses, ferric reductase activity along with the expression of its respective gene (HaFRO1), significantly increased in roots due to AMF ensuring Fe availability in the rhizosphere under Fe deficiency. Our qPCR analysis also showed a significant upregulation of HaIRT1, HaNramp1, and HaZIP1 in roots of sunflower in the presence of AMF, suggesting that Fe and Zn transporters are concurrently involved with AMF-mediated alleviation of Fe deficiency. Further, AMF accelerates the activities of CAT and SOD, predominantly in roots to protect sunflower plants from Fe-deficiency reactive oxygen species (ROS). This study unveils the mechanistic basis of AMF to limit Fe deficiency retardation in sunflower.

Effect of Growth Hormone Therapy in Patients with Noonan Syndrome: A Retrospective Study.

BACKGROUND: Noonan syndrome is an autosomal dominant condition with an incidence of 1:1000 to 1:2500. The disorder is associated with distinct dysmorphic features, cardiac anomalies, developmental delay and delayed puberty. Short stature is a recognised feature of Noonan syndrome. OBJECTIVES: The aim of this study is to assess the effect of growth hormone treatment in patients with Noonan syndrome. METHODS: Retrospective data was collected from patients with Noonan syndrome treated with growth hormone. The results were analysed with variables expressed as mean values and standard deviation scores. RESULTS: Twelve Noonan syndrome patients (M: F = 10:2) treated with growth hormone were identified. The mean age of starting growth hormone was 8 years, with baseline height standard deviation score of -2.96 (range: -1.64 to -5.54). The height standard deviation score significantly improved to -2.50 (P = 0.0035) and then -2.22 (P = 0.0025), following one and two years of treatment, respectively. The average height velocity for the patients prior to starting treatment was 5.16cm/year (range: 2.4 - 8.2 cm/year), which significantly improved to 7.76cm/year (ranging from 4.1 to 12.8 cm/year) after one year of growth hormone treatment (P = 0.020) and to 6.51cm/year at the end of two years. CONCLUSIONS: Our study has shown that growth hormone treatment significantly improves the height standard deviation score of patients with Noonan syndrome over a two-year course of growth hormone therapy without any side effects. Further research is required to analyse the long-term effect of growth hormone therapy in patients with Noonan syndrome, including the impact on final adult height.

Genome-wide evolution of wobble base-pairing nucleotides of branchpoint motifs with increasing organismal complexity.

How have the branchpoint motifs evolved in organisms of different complexity? Here we identified and examined the consensus motifs (R1C2T3R4A5Y6, R: A or G, Y: C or T) of 898 fungal genomes. In Ascomycota unicellular yeasts, the G4/A4 ratio is mostly (98%) below 0.125 but increases sharply in multicellular species by about 40 times on average, and in the more complex Basidiomycota, it increases further by about 7 times. The global G4 increase is consistent with A4 to G4 transitions in evolution. Of the G4/A4-interacting amino acids of the branchpoint binding protein MSL5 (SF1) and the HSH155 (SF3B1), as well as the 5' splice sites (SS) and U2 snRNA genes, the 5' SS G3/A3 co-vary with the G4 to some extent. However, corresponding increase of the G4-complementary GCAGTA-U2 gene is rare, suggesting wobble-base pairing between the G4-containing branchpoint motif and GTAGTA-U2 in most of these species. Interestingly, the G4/A4 ratio correlates well with the abundance of alternative splicing in the two phyla, and G4 enriched significantly at the alternative 3' SS of genes in RNA metabolism, kinases and membrane proteins. Similar wobble nucleotides also enriched at the 3' SS of multicellular fungi with only thousands of protein-coding genes. Thus, branchpoint motifs have evolved U2-complementarity in unicellular Ascomycota yeasts, but have gradually gained more wobble base-pairing nucleotides in fungi of higher complexity, likely to destabilize branchpoint motif-U2 interaction and/or branchpoint A protrusion for alternative splicing. This implies an important role of relaxing the branchpoint signals in the multicellularity and further complexity of fungi.

Obesity is common at diagnosis of childhood pituitary adenoma and may persist following successful treatment.

OBJECTIVE: There is a paucity of data describing long-term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort. DESIGN: Retrospective cohort study. PATIENTS: Twenty-four white Caucasian patients aged <16 years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7-8.4 years. MEASUREMENTS: Clinical and radiological data at diagnosis and follow-up. RESULTS: Thirteen patients had prolactinomas (54.1%, age: 15.2 years, 13.2-15.8 years; all females), including ten macroadenomas (11.0-35.0 mm). Patients presented with menstrual disorders (91%), headache (46%), galactorrhoea (46%) and obesity (body mass index [BMI] SDS > 2): (38%). Ten patients with prolactinoma were treated with dopamine agonist alone, 3 also required surgery and 2 patients, cabergoline, surgery plus radiotherapy. Five patients had Cushing's disease (20.8%, age: 14.0, 4.0-15.7 years; 2 female), including one macroadenoma (24 mm). Patients presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure (09.00 cortisol < 50 nmol/L). Two patients relapsed 3- and 6 years following surgery, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six patients had nonfunctioning pituitary adenoma (25.0%, age: 15.8, 12.5-16.0 years; 2 female), including two macroadenomas (20.0-53.0 mm). Patients presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections; two recurred following surgery and required radiotherapy. On latest follow-up; 13 (54.1%) patients were obese (BMI 3.09 SDS; range: 2.05-3.73 SDS). CONCLUSION: Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment. Adenomas were larger, more resistant to treatment, and more likely to recur than in adult populations.

Reduction of cadmium toxicity in wheat through plasma technology.

Cadmium (Cd) contamination in plant-derived food is a big concern. This study examines whether and how Ar/O2 and Ar/Air plasma techniques lead to Cd detoxification in wheat. Treatment with Ar/O2 and Ar/Air changed the seed surface and decreased the pH of seeds as well as the cultivation media. Generally, plants subjected to Cd treatment from seeds treated with Ar/O2and Ar/Air plasma showed considerable progress in morphology and total chlorophyll synthesis compared to Cd-treated wheat, suggesting that plasma technology is effective for Cd detoxification. Furthermore, Ar/O2 and Ar/Air plasma treated plants showed a significant decrease in root and shoot Cd concentration, which is consistent with the reduced expression of Cd transporters in the root (TaLCT1 and TaHMA2) compared with the plants not treated with plasma in response to Cd stress. This Cd inhibition is possibly accomplished by the decrease of pH reducing the bioavailability of Cd in the rhizosphere. These observations are in line with maintenance of total soluble protein along with reduced electrolyte leakage and cell death (%) in root and shoot due to Ar/O2 and Ar/Air treatments. Further, Cd-induced elevated H2O2 or oxidative damage in tissues was mainly diminished through the upregulation of antioxidant enzymes (SOD and CAT) and their corresponding genes (TaSOD and TaCAT) induced by Ar/O2 and Ar/Air plasma. Grafting results suggest that root originating nitric oxide signal possibly drives the mechanisms of Cd detoxification due to plasma treatment in wheat. These findings provide a novel and eco-friendly use of plasma technology for the mitigation of Cd toxicity in wheat plants.