Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep / Mutações no gene da proteína morfogenética óssea 15 causadoras de defeitos na secreção proteica em ovelhas inférteis Cholistani

Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Mutações de ocorrência natural na proteína morfogenética 15 (BMP15) estão associadas à diminuição da taxa de ovulação (TO), tamanho da ninhada (TN) e esterilidade. Estudar a BMP15 na raça Cholistani para elevar o status socioeconômico e o conhecimento da criação de ovinos Cholistani no sul de Punjab, Paquistão. Em nosso estudo, 50 ovelhas Cholistani inférteis sem parentesco sanguíneo foram rastreadas para mutações BMP15. Para tanto, um DNA de alta qualidade foi extraído do sangue dessas ovelhas, seguido de concepção do primer, amplificação da reação em cadeia da polimerase (PCR), sequenciamento de DNA e análises in silico. Do total de 50 amostras, 9, incluindo caso 1 (T3), caso 2 (T8), caso 3 (T17), caso 4 (T22), caso 5 (T25), caso 6 (T33), caso 7 (T40), caso 8 (T44) e caso 9 (T47), foram consideradas positivas para uma variedade de mutações BMP15 novas e já relatadas. Mais análises in silico das mutações observadas mostraram o impacto funcional dessas mutações em diferentes características (peso molecular, PI teórico, meia-vida estimada, índice de instabilidade, localização subcelular e confirmação 3D) das proteínas codificadas, possivelmente alterando a funcionalidade normal. Nossos achados confirmaram o possível papel essencial das mutações BMP15 na infertilidade de ovelhas Cholistani.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep

Abstract Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Resumo Mutações de ocorrência natural na proteína morfogenética 15 (BMP15) estão associadas à diminuição da taxa de ovulação (TO), tamanho da ninhada (TN) e esterilidade. Estudar a BMP15 na raça Cholistani para elevar o status socioeconômico e o conhecimento da criação de ovinos Cholistani no sul de Punjab, Paquistão. Em nosso estudo, 50 ovelhas Cholistani inférteis sem parentesco sanguíneo foram rastreadas para mutações BMP15. Para tanto, um DNA de alta qualidade foi extraído do sangue dessas ovelhas, seguido de concepção do primer, amplificação da reação em cadeia da polimerase (PCR), sequenciamento de DNA e análises in silico. Do total de 50 amostras, 9, incluindo caso 1 (T3), caso 2 (T8), caso 3 (T17), caso 4 (T22), caso 5 (T25), caso 6 (T33), caso 7 (T40), caso 8 (T44) e caso 9 (T47), foram consideradas positivas para uma variedade de mutações BMP15 novas e já relatadas. Mais análises in silico das mutações observadas mostraram o impacto funcional dessas mutações em diferentes características (peso molecular, PI teórico, meia-vida estimada, índice de instabilidade, localização subcelular e confirmação 3D) das proteínas codificadas, possivelmente alterando a funcionalidade normal. Nossos achados confirmaram o possível papel essencial das mutações BMP15 na infertilidade de ovelhas Cholistani.

Tracing probiotic producing bacterial species from gut of buffalo (Bubalus bubalis), South-East-Asia

Abstract Due to extensive application of antibiotics as growth promoters in animal feed, antimicrobial resistance has been increased. To overcome this challenge, rumen microbiologists search for new probiotics to improve the rate of livestock production. The present study was aimed to isolate and evaluate breed-specific lactic acid bacteria (LAB) as potential animal probiotics. The current study was conducted during 10 months from July 2020 to April 2021, in which a total of n=12 strains were isolated from different samples including milk, rumen, and feces of Nilli Ravi Buffaloes. These isolates were evaluated for their antimicrobial potential against common animal pathogens (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). All the isolates were identified using 16S rRNA gene sequencing and the phylogenetic analyses inferred that these strains showed close relations to the species of various genera; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis, and Lactococcus lactis. NMCC-Ru2 has exhibited the enormous potential of antimicrobial activity, 28 mm, for Salmonella typhimurium;23 mm for Listeria monocytogenes 21 mm for E.coil. Highest resistance was seen in NMCC-Ru2 agasint test antbiotic, like 25.5 mm for Tetracycline. Overall results revesl that the probiotic profile of isolates was achieved using standard criteria, particularly with animal probiotic properties

Resumo Devido à extensa aplicação de antibióticos como promotores de crescimento na alimentação animal, a resistência aos antimicrobianos aumentou. Para superar esse desafio, os microbiologistas do rúmen buscam novos probióticos para melhorar a produtividade do gado. O presente estudo teve como objetivo isolar e avaliar bactérias lácticas específicas de raças (BAL) como potenciais probióticos animais. 12 cepas foram isoladas de diferentes amostras, incluindo leite, rúmen e fezes de búfalos Nilli Ravi. Esses isolados foram avaliados quanto ao seu potencial antimicrobiano contra patógenos animais comuns (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). Todos os isolados foram identificados por meio do sequenciamento do gene 16S rRNA e as análises filogenéticas inferiram que essas cepas apresentaram estreita relação com as espécies de vários gêneros; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis, Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis e Lactococcus lactis. O perfil probiótico dos isolados foi obtido usando critérios padrão, particularmente com propriedades probióticas animais.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer / A regulação positiva de GINS1 destacou um bom potencial diagnóstico e prognóstico de sobrevivência em três subtipos diferentes de câncer humano

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.

Tracing probiotic producing bacterial species from gut of buffalo (Bubalus bubalis), South-East-Asia / Rastreando espécies bacterianas produtoras de probióticos de intestino de búfalo (Bubalus bubalis), sudeste da Ásia

Due to extensive application of antibiotics as growth promoters in animal feed, antimicrobial resistance has been increased. To overcome this challenge, rumen microbiologists search for new probiotics to improve the rate of livestock production. The present study was aimed to isolate and evaluate breed-specific lactic acid bacteria (LAB) as potential animal probiotics. The current study was conducted during 10 months from July 2020 to April 2021, in which a total of n=12 strains were isolated from different samples including milk, rumen, and feces of Nilli Ravi Buffaloes. These isolates were evaluated for their antimicrobial potential against common animal pathogens (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). All the isolates were identified using 16S rRNA gene sequencing and the phylogenetic analyses inferred that these strains showed close relations to the species of various genera; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis, and Lactococcus lactis. NMCC-Ru2 has exhibited the enormous potential of antimicrobial activity, 28 mm, for Salmonella typhimurium;23 mm for Listeria monocytogenes 21 mm for E.coil. Highest resistance was seen in NMCC-Ru2 agasint test antbiotic, like 25.5 mm for Tetracycline. Overall results revesl that the probiotic profile of isolates was achieved using standard criteria, particularly with animal probiotic properties

Devido à extensa aplicação de antibióticos como promotores de crescimento na alimentação animal, a resistência aos antimicrobianos aumentou. Para superar esse desafio, os microbiologistas do rúmen buscam novos probióticos para melhorar a produtividade do gado. O presente estudo teve como objetivo isolar e avaliar bactérias lácticas específicas de raças (BAL) como potenciais probióticos animais. 12 cepas foram isoladas de diferentes amostras, incluindo leite, rúmen e fezes de búfalos Nilli Ravi. Esses isolados foram avaliados quanto ao seu potencial antimicrobiano contra patógenos animais comuns (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). Todos os isolados foram identificados por meio do sequenciamento do gene 16S rRNA e as análises filogenéticas inferiram que essas cepas apresentaram estreita relação com as espécies de vários gêneros; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis, Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis e Lactococcus lactis. O perfil probiótico dos isolados foi obtido usando critérios padrão, particularmente com propriedades probióticas animais.

A detailed multi-omics analysis of GNB2 gene in human cancers.

The Guanine-nucleotide binding protein 2 (GNB2) encodes for ß2 subunit (Gß2) of the G-protein complex. Keeping in view the increased demand of reliable biomarkers in cancer, the current study was planned to extensively explored GNB2 expression variation and its roles in different cancers using online available databases and diverse methodology. In view of our results, the GNB2 was notably up-regulated relative to corresponding controls in twenty three cancer types. As well, the elevated expression of GNB2 was found to be associated with the reduced overall survival (OS) of the Liver Hepatocellular Carcinoma (LIHC) and Rectum Adenocarcinoma (READ) only out of all analyzed cancer types. This implies GNB2 plays vital role in the tumorigenesis of LIHC and READ. Several additional analysis also explored six critical pathways and few important correlations related to GNB2 expression and different other parameters such as promoter methylation, tumor purity, CD8+ T immune cells infiltration, and genetic alteration, and chemotherapeutic drugs. In conclusion, GNB2 gene has been identified in this study as a shared potential biomarker (diagnostic and prognostic) of LIHC and READ.

Anti-bacterial activity of essential oils against multidrug-resistant foodborne pathogens isolated from raw milk.

The presence of pathogenic bacteria in food is considered as a primary cause of food-borne illness and food quality deterioration worldwide. The present study aimed to determine the effectiveness of five essential oils (EOs) against multidrug-resistant foodborne pathogens. In the current study Gram-negative bacteria (Escherichia, Enterobacter, Citrobacter, Proteus, Pseudomonas, and Klebsiella) and the Gram-positive bacteria Staphylococcus were isolated from raw milk and biochemically characterized. The anti-bacterial effect of different antibiotics and EOs (thyme, oregano, lemongrass, mint, and rosemary) was determined using the standard disc diffusion method. The antibiogram study revealed that Gram-negative bacteria were highly resistant to penicillin while Staphylococcus was resistant to streptomycin, amoxicillin, and lincomycin. Moderate resistance was observed to doxycycline, amikacin, enrofloxacin, kanamycin and cefixime. Isolates were found less resistant to gentamycin, chloramphenicol, and ciprofloxacin. EOs showed a broad range of antimicrobial activity against all bacteria except P. aeruginosa. Of these, thyme was more effective against most of the multi-drug resistant bacterial strains and formed the largest zone of inhibition (26 mm) against Escherichia followed by oregano oil (18 mm) against Staphylococcus (p<0.05). Klebsiella spp and Citrobacter spp showed resistance to mint and lemongrass oil respectively. The EOs such as lemongrass, mint and rosemary were less active against all the bacteria. The findings of the recent study suggest the use of EOs as natural antibacterial agents for food preservation.

Tracing probiotic producing bacterial species from gut of buffalo (Bubalus bubalis), South-East-Asia.

Due to extensive application of antibiotics as growth promoters in animal feed, antimicrobial resistance has been increased. To overcome this challenge, rumen microbiologists search for new probiotics to improve the rate of livestock production. The present study was aimed to isolate and evaluate breed-specific lactic acid bacteria (LAB) as potential animal probiotics. The current study was conducted during 10 months from July 2020 to April 2021, in which a total of n=12 strains were isolated from different samples including milk, rumen, and feces of Nilli Ravi Buffaloes. These isolates were evaluated for their antimicrobial potential against common animal pathogens (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). All the isolates were identified using 16S rRNA gene sequencing and the phylogenetic analyses inferred that these strains showed close relations to the species of various genera; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis, and Lactococcus lactis. NMCC-Ru2 has exhibited the enormous potential of antimicrobial activity, 28 mm, for Salmonella typhimurium;23 mm for Listeria monocytogenes 21 mm for E.coil. Highest resistance was seen in NMCC-Ru2 agasint test antbiotic, like 25.5 mm for Tetracycline. Overall results revesl that the probiotic profile of isolates was achieved using standard criteria, particularly with animal probiotic properties.

Mutations in the bone morphogenetic protein 15 gene causing defective protein secretion in Cholistani infertile sheep.

Naturally occurring mutations in morphogenetic protein 15 (BMP15) are associated with decreased ovulation rate (OR), litter size (LS), and sterility. It is of a great interest to elucidate BMP15 gene in Cholistani sheep breed to uplift socio-economic status and the knowledge of Cholistani sheep breeding in Southern Punjab, Pakistan. In our study, a total of 50 infertile Cholistani sheep aged between 2-6 years and having no blood relation were screened for BMP15 mutations. For this purpose, a high-quality DNA was extracted from the blood of sheep followed by primer designing, Polymerase Chain Reaction (PCR) amplification, DNA sequencing, and in silico analyses. Out of total 50 samples, 9 samples including case 1 (T3), case 2 (T8), case 3 (T17), case 4 (T22), case 5 (T25), case 6 (T33), case 7 (T40), case 8 (T44), and case 9 (T47) were found positive for a variety of already reported and novel BMP15 mutations. Further in silico analyses of the observed mutations have shown the functional impact of these mutations on different characteristics (molecular weight, theoretical PI, estimated half-life, instability index, sub-cellular localization, and 3D confirmation) of the encoded proteins, possibly altering the normal functionality. In a nutshell, findings of this study have confirmed the possible essential role of the BMP15 mutations in the infertility of the Cholistani sheep.

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer.

Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Assessing the effects of manual dexterity and playing computer games on catheter-wire manipulation for inexperienced operators.

AIM: To investigate the effect of playing computer games and manual dexterity on catheter-wire manipulation in a mechanical aortic model. MATERIAL AND METHODS: Medical student volunteers filled in a preprocedure questionnaire assessing their exposure to computer games. Their manual dexterity was measured using a smartphone game. They were then shown a video clip demonstrating renal artery cannulation and were asked to reproduce this. All attempts were timed. Two-tailed Student's t-test was used to compare continuous data, while Fisher's exact test was used for categorical data. RESULTS: Fifty students aged 18-22 years took part in the study. Forty-six completed the task at an average of 168 seconds (range 103-301 seconds). There was no significant difference in the dexterity score or time to cannulate the renal artery between male and female students. Students who played computer games for >10 hours per week had better dexterity scores than those who did not play computer games: 9.1 versus 10.2 seconds (p=0.0237). Four of 19 students who did not play computer games failed to complete the task, while all of those who played computer games regularly completed the task (p=0.0168). CONCLUSION: Playing computer games is associated with better manual dexterity and ability to complete a basic interventional radiology task for novices.

Waiting time variation in Early Intervention Psychosis services: longitudinal evidence from the SEPEA naturalistic cohort study.

PURPOSE: Early Intervention Psychosis [EIP] services have gained traction internationally, but are currently undergoing various forms of reconfiguration. In England, such services are now mandated to ensure 50% of accepted referrals commence care within 14 days, but no empirical evidence exists. We sought to estimate waiting times to EIP services in a large, representative epidemiological cohort in England, and investigate possible reasons for any variation. METHODS: We estimated median waiting time from referral to acceptance by EIP services and investigated whether this varied by clinical, demographic or neighbourhood-level factors, amongst 798 participants, 16-35 years old, presenting to six EIP services over 3.5 years in a defined catchment area serving 2.5 million people. We used parametric survival analysis to inspect variation in waiting times (in days). RESULTS: Median waiting time was 15 days (interquartile range 7-30), although this varied across services (p < 0.01). Waiting times increased over the case ascertainment period by an average of 4.3 days (95% CI 1.3, 6.2; p < 0.01). Longer waiting times were associated with greater diagnostic uncertainty, indexed by an organic presentation (+ 9.1 days; 95% CI 1.9, 16.6; p < 0.01), polysubstance abuse (+ 2.6; 0.6, 3.9; p < 0.01), absence of psychotic disorder (+1.8; -0.1, 3.0; p = 0.05) and insidious onset (+1.8; -0.1, 3.0; p = 0.06). Waiting times did not vary by most demographic or neighbourhood-level characteristics. CONCLUSIONS: EIP services operate close to new waiting time standards in England, with little systematic variation by sociodemographic position. However, waiting times increased over the study period, coinciding with substantial service reorganisation. Longer waiting times associated with greater diagnostic uncertainty highlight opportunities to reduce delays in certain clinical groups at initial referral.