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The fisheries sector plays a vital role in the food, nutritional and livelihood security of people, especially in the rural regions of India. Reservoirs, the man made impoundments built on rivers/streams obstructing the surface flow, form an important resource for the fish production besides holding up economic growth through various cultural and ecological services. India has enormous reservoir resources to the tune of 3.42 million ha (19,386 numbers). The distribution of reservoirs is quite uneven and most of the reservoirs are located in the southern and central Indian states. In the last few decades, India has made tremendous progress in reservoir fisheries and overall management strategies have been considerably innovated. The average annual fish productivity realized from reservoirs was very low (small: 49.9, medium: 12.3 and large: 11.4 kg ha−1yr−1) against the annual potential yield of 100, 75, and 50 kg ha−1yr−1. The fish yield from Indian reservoirs has enhanced through fingerling stocking and adoption of improved management practices and the average productivity increased to 33, 94, and 174 kg ha−1yr−1 from large, medium, and small reservoirs respectively. The production potential has been re-casted to a level of 100, 200, and 500 kg ha−1yr−1 from large, medium and small reservoirs, respectively. The increase in fish productivity is about one third of the present production potential and there exists scope for developing effective and sustainable strategies for further enhancing the fish yield. The present review synthesizes the updated information available on Indian reservoirs and the developments during the last decade with reference to fisheries, biodiversity, potential, threats, and recommends strategies for sustainable management of the reservoir fisheries in India. [ABSTRACT FROM AUTHOR]

Receptor for advanced glycation end products (RAGE) has been implicated in the pathophysiology of Alzheimer’s disease (AD) due to its ability to interact with amyloid beta and to elicit an inflammatory response. sRAGE, one of the splice variants of RAGE, has been reported to be a decoy receptor for amyloid beta peptides. The present study addresses the occurrence of G82S RAGE polymorphism in AD, and its association with the expression of sRAGE and amyloid beta load (Aβ peptide). The results indicated that the heterozygous genotype (GS) was distributed more than the wild genotype (GG) in patients with AD. Moreover, in patients with AD, there was decreased expression of sRAGE and increased expression of tRAGE and TNF-α. The data show that G82S RAGE polymorphism is highly associated with the development of AD, with decreased expression of sRAGE and increased expression of tRAGE and TNF-α.

Discovery of evolutionarily conserved, nonprotein-coding, endogenous microRNAs has induced a paradigm shift in the overall understanding of gene regulation. Now, microRNAs are considered and classified as master regulators of gene expression as they regulate a wide range of processes – gene regulation, splicing, translation and posttranscriptional modifications. Besides, dysregulated microRNAs have been related to many diseases, including Parkinson's and related disorders. Several studies proposed that differentially expressed microRNAs as a potential biomarker. So far, there is no accepted clinical diagnostic test for Parkinson's disease based on biochemical analysis of biological fluids. However, circulating microRNAs possess many vital features typical of reliable biomarkers and discriminates Parkinson's patients from healthy control with much higher sensitivity and specificity. Though they show tremendous promise as a putative biomarker, translating these research findings to clinical application is often met with many obstacles. Most of the candidate microRNAs reported as a diagnostic biomarker is not organ-specific, and their overlap is low between studies. Therefore this review aimed to highlight the challenges in the application of microRNA in guiding disease discrimination decisions and its future prospects as a diagnostic biomarker in Parkinson's Disease.

An elephant, being a mega herbivore, consumes large amounts of food. Due to the lack of availability of fodder inside the forest, the elephants move out of their habitat areas and also find agricultural crops attractive, which further results in man–animal conflict. To improve the elephant habitat area, the current study was conducted to assess the availability of native fodder grasses inside the Coimbatore Elephant Reserve, Western Ghats, from April 2021–April 2022. The area falls between 10°37′and 11°31′ North latitudes and 76°39′and 77°5′ East longitudes. It was approached in a systematic random sampling method. A total of 128 sample plots of 1 sq.m size were randomly placed, and the density of grass species was recorded in percentage (%). The collected samples were shade dried for one week, ground to pass through a 1 mm sieve, and stored in polythene bags. Furthermore, the samples were chemically analyzed to determine their nutritional values. The dry matter (DM) content of various grass fodder varied from 28.18% to 59.75%. The crude protein (CP) content differed between 5.94% and 11.94%. The highest CP was recorded in Cynodon dactylon (11.94%) and the least in Aristida setacea (5.94%). Ether extract content was found in the ranges of 1.00% to 5.00%. The acid detergent fibre (ADF) content of Aristida setacea (45.74%) was observed as the highest, whereas the lowest was observed in Oplismenus burmannii (26.78%), followed by Themeda triandra (26.85%), Heteropogon contortus (30.12%) and Enteropogon monostachyos (30.31%). The average neutral detergent fibre content of grass fodder was 52.27%, with a range of 37.89% (Oplismenus burmannii) to 67.87% (Cymbopogon martinii). The average total digestible nutrient (TDN) content of grass was 77.45%; relative forage quality (RFQ) exhibited wider variations among the grasses and ranged between 107.51 and 198.83. This study is a pioneer in evaluating the nutritional values of native grass fodder species for elephants in the Western Ghats. The study gives strategies for the selection of high nutritive fodder grass for the habitat improvement of elephants, and it also provides scientific and baseline information for the conservation of native grass fodder species in the Western Ghats.

Progressive supranuclear palsy (PSP) is the second most common Parkinsonian disorder with complex etiology. The underlying molecular mechanism of PSP pathogenesis remains unclear. The present study aims to find the feasibility of using plasma miRNAs as novel biomarkers. Plasma-focused qPCR panels were used for microRNA profiling and identified differentially expressed microRNAs in PSP compared to controls. The DIANA-miRPath v3.0 was used to perform KEGG pathway analysis. We then confirmed the expression of selected candidates by RT-qPCR and their clinical utility was assessed by ROC analysis. Profiling data revealed 28 differentially expressed microRNAs in PSP. Five overexpressed miRNAs were selected for further analysis. The KEGG pathway analysis revealed 48 high-risk pathways. The study revealed that as a single marker—miR-19b-3p, miR-33a-5p, miR-130b-3p, miR-136-3p, and miR-210-3p had a specificity of 64.71%, 82.35%, 68.75%, 82.35%, and 70.59% at sensitivity 77.78%, 77.78%, 66.67%, 73.33%, and 66.67%, respectively. The result suggests that circulating plasma miRNAs were altered in PSP compared to control. The findings of this study may provide potential biomarkers and pathways associated with PSP. Further large-scale validation studies are required to confirm the same.

Performance appraisal is a formal, structured system of measuring and evaluating an employee's job related behaviours and outcomes as well as to discover how and why the employee is presently performing on the job and how the employee can perform more effectively in the future. Performance appraisal system is important to any organizational work performance; it determines the organization's success or failure. This paper summarizes the conceptual framework of performance appraisal system and its relationship between Job Satisfaction, Organization Commitment, Organization Citizenship Behavior, Employee Engagement and thus with Productivity. [ABSTRACT FROM AUTHOR]

- One hundred and eighty-seven patients with urethral strictures have been treated over a period of 24 years. In nearly 50%, strictures were confined to the penile urethra, involving the meatus, the fossa navicularis or varying lengths of the urethra up to the bulb. Of these, 95.3% were inflammatory in nature. Overall, 85.5% were managed with a single surgical procedure. The single-stage technique using a skin inversion pedicled flap was done in 15 cases and was found to be useful, with less morbidity than the staged procedure. [ABSTRACT FROM AUTHOR]

Many factors are involved in Alzheimer’s disease (AD) pathology including tau phosphorylation, amyloid β protein (Aβ) accumulation, lipid dysregulation, oxidative stress, and inflammation. The markers of these pathological processes in cerebral spinal fluid are used currently for AD diagnosis. However, peripheral biomarkers are the need of the hour for large population screening for AD. The main objective of the present study is to evaluate the peripheral levels of redox markers, lipid peroxidation (LPO) indicators, and pathological markers in AD patients. Blood was collected from AD patients (n = 45), controls (n = 45), and analyzed for pathological markers of AD including Aβ42 and tau, LPO, and redox indicators. Plasma Aβ42 was significantly (P

A 22-year-old male with obstructive uropathy and renal failure was given pre-operative haemodialysis. He collapsed five hours later. Autopsy revealed massive intrarenal haemorrhage and rupture of a dilated superior calyx intraperitoneally. Anticoagulation employed during haemodialysis was probably responsible for this spontaneous renal haemorrhage and subsequent calyceal rupture. [ABSTRACT FROM PUBLISHER]

- Of 250 men with urethral strictures seen over a period of 40 months 50 had complications such as periurethral abscesses, inflammatory masses, urethral fistulas, sinuses and urinary extravasation. The strictures were multiple and showed diffuse involvement of the urethra; 90% were of inflammatory origin. [ABSTRACT FROM AUTHOR]

Strategies to enhance rice productivity in response to global demand have been the paramount focus of breeders worldwide. Multiple factors, including agronomical traits such as plant architecture and grain formation and physiological traits such as photosynthetic efficiency and NUE (nitrogen use efficiency), as well as factors such as phytohormone perception and homeostasis and transcriptional regulation, indirectly influence rice grain yield. Advances in genetic analysis methodologies and functional genomics, numerous genes, QTLs (Quantitative Trait Loci), and SNPs (Single-Nucleotide Polymorphisms), linked to yield traits, have been identified and analyzed in rice. Genome editing allows for the targeted modification of identified genes to create novel mutations in rice, avoiding the unintended mutations often caused by random mutagenesis. Genome editing technologies, notably the CRISPR/Cas9 system, present a promising tool to generate precise and rapid modifications in the plant genome. Advancements in CRISPR have further enabled researchers to modify a larger number of genes with higher efficiency. This paper reviews recent research on genome editing of yield-related genes in rice, discusses available gene editing tools, and highlights their potential to expedite rice breeding programs.

A major global source of disability as well as mortality is respiratory illness. Though visual evaluation of computed tomography (CT) images and chest radiographs are a primary diagnostic for respiratory illnesses, it is limited in its ability to assess severity and predict patient outcomes due to low specificity and fundamental infectious organisms. In order to address these problems, world cup optimization-based Bi-LSTM classification and lung disease prediction on CT images using REINF-net were employed. To enhance the image quality, the gathered lung CT images are pre-processed using Lucy Richardson and CLAHE algorithms. For the purpose of lung infection segmentation, the pre-processed images are segmented using the REInf-net. The GLRLM method is used to extract features from the segmented images. In order to predict lung disease in CT images, the extracted features are trained using the Bi-LSTM based on world cup optimization. Accuracy, Precision, recall, Error and Specificity for the proposed model are 97.8%, 96.7%, 96.7%, 2.2% and 98.3%. These evaluated values are contrasted with the results of existing methods like WCO-BiLSTM, MLP, CNN and LSTM. Finally, the Lung disease prediction based on CT images using REINF-Net and world cup optimization based BI-LSTM classification performs better than the existing model.

Carotenoids are potential antioxidants offering extensive human health benefits including protection against chronic diseases. Augmenting the supply of health-benefiting compounds/metabolites through dietary supplements is the most sustainable way for a healthy life. Our study compares the traditional rice cultivar Kavuni and the white rice variety ASD 16. RNA-Seq analysis was carried out in the maturing panicles of Kavuni, which are enriched with antioxidants such as the therapeutic carotenoid lutein, polyphenols, and anthocyanins, along with "ASD 16", a popularly eaten white rice variety, to elucidate the molecular networks regulating accumulation of health benefiting compounds. Systematic analysis of transcriptome data identified preferential up-regulation of carotenoid precursors ( OsDXS , OsGGPS ) and key carotenoid biosynthetic genes ( OsPSY1 , OsZ-ISO ) in the maturing grains of Kavuni. Our study also identified enhanced expression of OsLYC-E , OsCYP97A, and OsCYP97C transcripts involved in the alpha-carotenoid biosynthetic pathway and thereby leading to elevated lutein content in the grains of Kavuni. Kavuni grains showed preferential down-regulation of negative regulators of carotenoid metabolism viz., AP2 and HY5 and preferential up-regulation of positive modulators of carotenoid metabolism viz., Orange , OsDjB7, and OsSET29 , thus creating a favorable molecular framework for carotenoid accumulation. Our study has unearthed valuable gene control points for precise manipulation of carotenoid profiles through CRISPR-based gene editing in rice grains. Perturbation of carotenoid biosynthesis holds unprecedented potential for the rapid development of the next generation of 'Golden rice'., Competing Interests: All the authors have declared no conflict of interest. Funding The study was supported by the financial grant from Department of Biotechnology, Government of India, New Delhi (Grant # BT/PR42156)., (© 2024 The Authors.)

Introduction: Rice, one of the major staple food crops is frequently affected by various biotic/abiotic stresses including drought, salinity, submergence, heat, Bacterial leaf blight, Brown plant hopper, Gall midge, Stem borer, Leaf folder etc. Sustained increase of yield growth is highly necessary to meet the projected demand in rice production during the year 2050. Hence, development of high yielding and multiple stress tolerant rice varieties adapted to wider environments will serve the need., Methods: A systematic MAB approach was followed to pyramid eight major QTLs/genes controlling tolerance to major abiotic/biotic stresses viz., drought ( qDTY1.1 and qDTY2.1 ), salinity ( Saltol ), submergence ( Sub1 ), bacterial leaf blight ( xa13 and Xa21 ), blast ( Pi9 ) and gall midge ( Gm4 ) in the genetic background of an elite rice culture CBMAS 14065 possessing high yield and desirable grain quality traits. Two advanced backcross derivatives of CBMAS 14065 possessing different combinations of target QTLs namely #27-1-39 ( qDTY1.1 + qDTY2.1 + Sub1 + xa13 + Xa21 + Gm4+Pi9 ) and #29-2-2 ( qDTY1.1 + qDTY2.1 + Saltol + Xa21 + Gm4+Pi9 ) were inter-mated., Results: Inter-mated F 1 progenies harboring all the eight target QTLs/genes were identified through foreground selection. Genotyping of the inter-mated F 4 population identified 14 progenies possessing all eight target QTLs/genes under homozygous conditions. All the fourteen progenies were forwarded up to F 8 generation and evaluated for their yield and tolerance to dehydration, salinity, submergence, blast and bacterial leaf blight. All the 14 progenies exhibited enhanced tolerance to dehydration and salinity stresses by registering lesser reduction in their chlorophyll content, relative water content, root length, root biomass etc., against their recurrent parent Improved White Ponni/CBMAS 14065. All the 14 progenies harboring Sub1 loci from FR13A exhibited enhanced survival (90 - 95%) under 2 weeks of submergence /flooding when compared to their recurrent parent CBMAS 14065 which showed 100% susceptibility The inter-mated population showed a enhanced level of resistance to bacterial leaf blight (Score = 0 to 2) against blast (Score - 0) whereas the susceptible check CO 39 and the recurrent parent CBMAS 14065 recorded high level of susceptibility (Score = 7 to 9)., Conclusion or Discussion: Our study demonstrated the accelerated development of multiple stress tolerant rice genotypes through marker assisted pyramiding of target QTLs/genes using tightly linked markers. These multiple stress tolerant rice lines will serve as excellent genetic stocks for field testing/variety release and also as parental lines in future breeding programs for developing climate resilient super rice varieties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mohanavel, Muthu, Kambale, Palaniswamy, Seeli, Ayyenar, Rajagopalan, Manickam, Rajasekaran, Rahman, Nallathambi, Swaminathan, Chellappan, Vellingiri and Muthurajan.)

The precise anatomical degree of brain X chromosome inactivation (XCI) that is sufficient to alter X-linked disorders in females is unclear. Here, we quantify whole-brain XCI at single-cell resolution to discover a prevalent activation ratio of maternal to paternal X at 60:40 across all divisions of the adult brain. This modest, non-random XCI influences X-linked disease penetrance: maternal transmission of the fragile X mental retardation 1 (Fmr1)-knockout (KO) allele confers 55% of total brain cells with mutant X-active, which is sufficient for behavioral penetrance, while 40% produced from paternal transmission is tolerated. Local XCI mosaicism within affected maternal Fmr1-KO mice further specifies sensorimotor versus social anxiety phenotypes depending on which distinct brain circuitry is most affected, with only a 50%-55% mutant X-active threshold determining penetrance. Thus, our results define a model of X-linked disease penetrance in females whereby distributed XCI among single cells populating brain circuitries can regulate the behavioral penetrance of an X-linked mutation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Developing rice varieties with enhanced levels of functional bioactives is an important intervention for achieving food and nutritional security in Asia where rice is the staple food and Type II diabetes incidences are higher. The present study was aimed at dissecting out the molecular events underlying the accumulation of bio active compounds in pigmented traditional rice Kavuni. Comparative transcriptome profiling in the developing grains of Kavuni and a white rice variety ASD 16 generated 37.7 and 29.8 million reads respectively. Statistical analysis identified a total of 9177 exhibiting significant differential expression (DEGs) between the grains of Kavuni and ASD 16. Pathway mapping of DEGs revealed the preferential up-regulation of genes involved in the biosynthesis of amylose and dietary fibres in Kavuni accounting for its low glycemic index (GI). Transcripts involved in the biosynthesis of carotenoids, flavonoids, anthocyanins, phenolic acids and phenylpropanoids were also found to be up-regulated in the grains of Kavuni. This study identified up-regulation of key transcripts involved in the accumulation of phenolic acids having potential for inhibiting major hydrolytic enzymes α-amylase and α-glucosidase and thus accounting for the slow digestibility leading to low GI. Overall, this study has identified molecular targets for the genetic manipulation of anti-diabetic and anti-oxidant traits in rice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Endosulfan remains as a lipophilic insecticide that causes serious medical problems because of biological stability and toxicity also found in air, water, soil sediments, and foodstuffs. Henceforward, the present study reveals a novel bacterial species isolated from pesticide-contaminated soil for enhanced endosulfan degradation. Next, isolated bacterial species was characterized with biochemical assays and 16S rRNA sequencing technique. Subsequently, the optimal conditions for endosulfan biodegradation such as pH, concentration of endosulfan, and bacterial growth were estimated with non-sulfur medium (NSM). Sequentially, the amount of endosulfan and compound degradation were analyzed through thin-layer chromatography and gas chromatography/mass spectrometry. Overall, the obtained results revealed the endosulfan acting as primary carbon source for bacterial growth. From the GC-MS analysis, the metabolic products released during endosulfan degradation by Pseudomonas sp. MSCAS BT01 were compared with standard GC-MS spectra. The highest (98%) endosulfan degradation was obtained at pH 7.0. The complete endosulfan degradation was achieved at 14th day of incubation and the less toxic endosulfan diol produced was observed via GC-MS. To conclude, the pesticide-contaminated isolate Pseudomonas sp. MSCAS BT01 emerged as a promising bioremediation tool and effectively employed to degrade endosulfan from contaminated soils, sediments, and wastewaters in the days yet to come., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted 1 . Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture., (© 2021. The Author(s).)

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex 1,2 , yet all derive from neural progenitors of the embryonic dorsal telencephalon 3,4 . Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels., (© 2021. The Author(s).)

The striosome compartment within the dorsal striatum has been implicated in reinforcement learning and regulation of motivation, but how striosomal neurons contribute to these functions remains elusive. Here, we show that a genetically identified striosomal population, which expresses the Teashirt family zinc finger 1 (Tshz1) and belongs to the direct pathway, drives negative reinforcement and is essential for aversive learning in mice. Contrasting a "conventional" striosomal direct pathway, the Tshz1 neurons cause aversion, movement suppression, and negative reinforcement once activated, and they receive a distinct set of synaptic inputs. These neurons are predominantly excited by punishment rather than reward and represent the anticipation of punishment or the motivation for avoidance. Furthermore, inhibiting these neurons impairs punishment-based learning without affecting reward learning or movement. These results establish a major role of striosomal neurons in behaviors reinforced by punishment and moreover uncover functions of the direct pathway unaccounted for in classic models., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fragrance in rice grains is a key quality trait determining its acceptability and marketability. Intensive research on rice aroma identified mutations in betaine aldehyde dehydrogenase (OsBADH2) leading to production of aroma in rice. Gene editing technologies like CRISPR/Cas9 system has opened new avenues for accelerated improvement of rice grain quality through targeted mutagenesis. In this study, we have employed CRISPR/Cas9 tool to create novel alleles of OsBADH2 leading to introduction of aroma into an elite non-aromatic rice variety ASD16. PCR analysis of putative transformants using primers targeting the flanking regions of sgRNA in the 7th exon of OsBADH2 identified 37.5% potential multi-allelic mutations in T0 generation. Sensory evaluation test in the leaves of T0 lines identified thirteen lines belonging to five independent events producing aroma. Sequence analysis of these aromatic T0 lines identified 22 different types of mutations located within -17 bp to +15bp of sgRNA region. The -1/-2 bp deletion in the line # 8-19 and -8/-5 bp deletion in the line # 2-16 produced strong aroma and the phenotype was stably inherited in the T1 generation. Comparative volatile profiling detected novel aromatic compounds viz., pyrrolidine, pyridine, pyrazine, pyradazine and pyrozole in the grains of T1 progenies of line # 8-19. This study has demonstrated the use of CRISPR/Cas9 in creating novel alleles of OsBADH2 to introduce aroma into any non-aromatic rice varieties., Competing Interests: The authors have no competing interests

This research proposes a multimodal multifeature biometric system for human recognition using two traits, that is, palmprint and iris. The purpose of this research is to analyse integration of multimodal and multifeature biometric system using feature level fusion to achieve better performance. The main aim of the proposed system is to increase the recognition accuracy using feature level fusion. The features at the feature level fusion are raw biometric data which contains rich information when compared to decision and matching score level fusion. Hence information fused at the feature level is expected to obtain improved recognition accuracy. However, information fused at feature level has the problem of curse in dimensionality; here PCA (principal component analysis) is used to diminish the dimensionality of the feature sets as they are high dimensional. The proposed multimodal results were compared with other multimodal and monomodal approaches. Out of these comparisons, the multimodal multifeature palmprint iris fusion offers significant improvements in the accuracy of the suggested multimodal biometric system. The proposed algorithm is tested using created virtual multimodal database using UPOL iris database and PolyU palmprint database.

The Hedgehog (HH) signaling pathway has important roles in tumorigenesis and in embryonal patterning. The Glioma-associated oncogene 1 (GLI1) is a key molecule in HH signaling, acting as a transcriptional effector and, moreover, is considered to be a potential therapeutic target for several types of cancer. To extend our previous focus on the implications of alternative splicing for HH signal transduction, we now report on an additional post-transcriptional mechanism with an impact on GLI1 activity, namely RNA editing. The GLI1 mRNA is highly edited at nucleotide 2179 by adenosine deamination in normal cerebellum, but the extent of this modification is reduced in cell lines from the cerebellar tumor medulloblastoma. Additionally, basal cell carcinoma tumor samples exhibit decreased GLI1 editing compared with normal skin. Interestingly, knocking down of either ADAR1 or ADAR2 reduces RNA editing of GLI1. This adenosine to inosine substitution leads to a change from Arginine to Glycine at position 701 that influences not only GLI1 transcriptional activity, but also GLI1-dependent cellular proliferation. Specifically, the edited GLI1, GLI1-701G, has a higher capacity to activate most of the transcriptional targets tested and is less susceptible to inhibition by the negative regulator of HH signaling suppressor of fused. However, the Dyrk1a kinase, implicated in cellular proliferation, is more effective in increasing the transcriptional activity of the non-edited GLI1. Finally, introduction of GLI1-701G into medulloblastoma cells confers a smaller increase in cellular growth relative to GLI1. In conclusion, our findings indicate that RNA editing of GLI1 is a regulatory mechanism that modulates the output of the HH signaling pathway.

Antioxidants are an essential defense mechanism to protect our body against free radical damage. They balance the production of free radicals and detoxify them when in excess. The objective of the study is to determine the free radical scavenging potential of the candidate plant leaves when subjected to a battery of free radical scavenging assays. The different leaf extracts used were aqueous, methanol and chloroform. The results suggest that Majorana hortensis (L.) H. Karst leaves could serve as a potential source of antioxidant and can be used in any preparation for combating free radical mediated damage to the body.

Background: Alternative splicing is one of the key mechanisms that generate biological diversity. Even though alternative splicing also occurs in the 5' and 3' untranslated regions (UTRs) of mRNAs, the understanding of the significance and the regulation of these variations is rather limited., Results: We investigated 5' UTR mRNA variants of the mouse Gli1 oncogene, which is the terminal transcriptional effector of the Hedgehog (HH) signaling pathway. In addition to identifying novel transcription start sites, we demonstrated that the expression ratio of the Gli1 splice variants in the 5' UTR is regulated by the genotype of the mouse strain analyzed. The GT allele, which contains the consensus intronic dinucleotides at the 5' splice site of intron 1B, favors exon 1B inclusion, while the GC allele, having a weaker 5' splice site sequence, promotes exon 1B skipping. Moreover, the alternative Gli1 5' UTRs had an impact on translational capacity, with the shorter and the exon 1B-skipped mRNA variants being most effective., Conclusions: Our findings implicate novel, genome-based mechanisms as regulators of the terminal events in the mouse HH signaling cascade.

Hedgehog (HH) signaling is one of the key pathways with major significance for embryogenesis, tumorigenesis, and stem cell maintenance. Glioma-associated oncogene 1 (GLI1) is a transcription factor that acts as the terminal signaling effector but also represents a pathway target gene. Here we report the identification and functional properties of novel GLI1 splice variants generated by skipping exons 2 and 3 and encoding an N-terminal truncated GLI1 protein (GLI1DeltaN). Analysis of the GLI1DeltaN mRNAs in adult human tissues revealed comparable expression levels to the full-length GLI1 (GLI1FL), whereas in tumor cell lines a generally lower and more variable expression pattern was observed. Furthermore, GLI1DeltaN is up-regulated by HH signaling to the same extent as GLI1FL but has a weaker capacity to activate transcription. However, in specific cellular contexts GLI1DeltaN may be more potent than GLI1FL in activating endogenous gene expression. Moreover, the dual-specificity tyrosine phosphorylation-regulated kinase 1 (Dyrk1) potentiates the transcriptional activity of GLI1FL but not GLI1DeltaN. Interestingly, GLI1FL, in contrast to GLI1DeltaN, is localized solely at the nucleus, in line with its increased transcriptional capacity. The negative regulator of the pathway, Suppressor of Fused (SUFU), elicits a cytoplasmic retention of the GLI1 isoforms, which is more pronounced for GLI1FL, as this contains an N-terminal SUFU binding domain. Collectively, our findings reveal that the activation mechanism of the terminal transducer of the pathway, GLI1, is mediated not only by GLI1FL but also by the GLI1DeltaN variant.

Males attending the urology clinic with strictures of the terminal urethra were studied. Evident frank balanoposthitis, subpreputial calculi and infected urine in the preputial sac were seen in a sizable number, 35% of them were suffering from a second urethral stricture also, either in continuity over the whole length of the penile urethra or in the bulbomembranous area. Balanitis xerotica obliterans was responsible for those terminal urethral strictures in nearly 20%. All patients required terminal urethroplasty in addition to appropriate surgical procedures for other stigmata. Knowledge and sense of hygiene of the genitalia were lacking in most of the patients.