High potential for biomass-degrading CAZymes revealed by pine forest soil metagenomics.

The undisturbed environment in Netarhat, with its high levels of accumulated lignocellulosic biomass, presents an opportunity to identify microbes for biomass digestion. This study focuses on the bioprospecting of native soil microbes from the Netarhat forest in Jharkhand, India, with the potential for lignocellulosic substrate digestion. These biocatalysts could help overcome the bottleneck of biomass saccharification and reduce the overall cost of biofuel production, replacing harmful fossil fuels. The study used metagenomic analysis of pine forest soil via whole genome shotgun sequencing, revealing that most of the reads matched with the bacterial species, very low percentage of reads (0.1%) belongs to fungal species, with 13% of unclassified reads. Actinobacteria were found to be predominant among the bacterial species. MetaErg annotation identified 11,830 protein family genes and 2 metabolic marker genes in the soil samples. Based on the Carbohydrate Active EnZyme (CAZy) database, 3,996 carbohydrate enzyme families were identified, with family Glycosyl hydrolase (GH) dominating with 1,704 genes. Most observed GH families in the study were GH0, 3, 5, 6. 9, 12. 13, 15, 16, 39, 43, 57, and 97. Modelling analysis of a representative GH 43 gene suggested a strong affinity for cellulose than xylan. This study highlights the lignocellulosic digestion potential of the native microfauna of the lesser-known pine forest of Netarhat.Communicated by Ramaswamy H. Sarma.

Toward α-1,3/4 fucosyltransferases targeted drug discovery: In silico uncovering of promising natural inhibitors of fucosyltransferase 6.

Sialyl Lewis X (sLex ) antigen is a fucosylated cell-surface glycan that is normally involved in cell-cell interactions. The enhanced expression of sLex on cell surface glycans, which is attributed to the upregulation of fucosyltransferase 6 (FUT6), has been implicated in facilitating metastasis in human colorectal, lung, prostate, and oral cancers. The role that the upregulated FUT6 plays in the progression of tumor to malignancy, with reduced survival rates, makes it a potential target for anticancer drugs. Unfortunately, the lack of experimental structures for FUT6 has hampered the design and development of its inhibitors. In this study, we used in silico techniques to identify potential FUT6 inhibitors. We first modeled the three-dimensional structure of human FUT6 using AlphaFold. Then, we screened the natural compound libraries from the COCONUT database to sort out potential natural products (NPs) with best affinity toward the FUT6 model. As a result of these simulations, we identified three NPs for which we predicted binding affinities and interaction patterns quite similar to those we calculated for two experimentally tested FUT6 inhibitors, that is, fucose mimetic-1 and a GDP-triazole derived compound. We also performed molecular dynamics (MD) simulations for the FUT6 complexes with identified NPs, to investigate their stability. Analysis of the MD simulations showed that the identified NPs establish stable contacts with FUT6 under dynamics conditions. On these grounds, the three screened compounds appear as promising natural alternatives to experimentally tested FUT6 synthetic inhibitors, with expected comparable binding affinity. This envisages good prospects for future experimental validation toward FUT6 inhibition.

Secreted Aspartyl Proteinases Targeted Multi-Epitope Vaccine Design for Candida dubliniensis Using Immunoinformatics.

Candida dubliniensis is an opportunistic pathogen associated with oral and invasive fungal infections in immune-compromised individuals. Furthermore, the emergence of C. dubliniensis antifungal drug resistance could exacerbate its treatment. Hence, in this study a multi-epitope vaccine candidate has been designed using an immunoinformatics approach by targeting C. dubliniensis secreted aspartyl proteinases (SAP) proteins. In silico tools have been utilized to predict epitopes and determine their allergic potential, antigenic potential, toxicity, and potential to elicit interleukin-2 (IL2), interleukin-4 (IL4), and IFN-γ. Using the computational tools, eight epitopes have been predicted that were then linked with adjuvants for final vaccine candidate development. Computational immune simulation has depicted that the immunogen designed emerges as a strong immunogenic candidate for a vaccine. Further, molecular docking and molecular dynamics simulation analyses revealed stable interactions between the vaccine candidate and the human toll-like receptor 5 (TLR5). Finally, immune simulations corroborated the promising candidature of the designed vaccine, thus calling for further in vivo investigation.

Total rhinectomy with prosthesis placement as a treatment for moderately differentiated squamous cell carcinoma of the nose.

Squamous cell carcinoma is one of the most common head and neck types of skin cancer. This main objective of this paper is to present a case of a patient who had a moderately differentiated squamous cell carcinoma of the nose and whose tumor had an aggressive growth.

Designing a multi-epitope candidate vaccine by employing immunoinformatics approaches to control African swine fever spread.

The African swine fever virus has been circulating for decades and is highly infectious, often fatal to farmed and wild pigs. There is currently no approved vaccine or treatment for the disease, making prevention even more difficult. Therefore, vaccine development is necessary and urgent to limit the consequences of ASF and ensure the food chain and sustainability of the swine industry. This research study was conducted to design a multi-epitope vaccine for controlling veterinary diseases caused by the African swine fever virus. We employed the immunoinformatics approaches to reveal 37 epitopes from different viral proteins of ASFV. These epitopes were linked to adjuvants and linkers to form a full-fledged immunogenic vaccine construct. The tertiary structure of the final vaccine was predicted using a deep-learning approach. The molecular docking and molecular dynamics predicted stable interactions between the vaccine and immune receptor TLR5 of Sus scrofa (Pig). The MD simulation studies reflect that the calculated parameters like RMSD, RMSF, number of hydrogen bonds, and finally, the buried interface surface area for the complex remained stable throughout the simulation time. This analysis suggests the stability of interface interactions between the TLR5 and the multi-epitope vaccine construct. Further, the physiochemical analysis demonstrated that our designed vaccine construct was expected to have high stability and prolonged half-life time in mammalian cells. Traditional vaccine design experiments require significant time and financial input from the development stage to the final product. Studies like this can assist in accelerating vaccine development while minimizing the cost.Communicated by Ramaswamy H. Sarma.

Immunoinformatics-aided rational design of a multi-epitope vaccine targeting feline infectious peritonitis virus.

Feline infectious peritonitis (FIP) is a grave and frequently lethal ailment instigated by feline coronavirus (FCoV) in wild and domestic feline species. The spike (S) protein of FCoV assumes a critical function in viral ingress and infection, thereby presenting a promising avenue for the development of a vaccine. In this investigation, an immunoinformatics approach was employed to ascertain immunogenic epitopes within the S-protein of FIP and formulate an innovative vaccine candidate. By subjecting the amino acid sequence of the FIP S-protein to computational scrutiny, MHC-I binding T-cell epitopes were predicted, which were subsequently evaluated for their antigenicity, toxicity, and allergenicity through in silico tools. Our analyses yielded the identification of 11 potential epitopes capable of provoking a robust immune response against FIPV. Additionally, molecular docking analysis demonstrated the ability of these epitopes to bind with feline MHC class I molecules. Through the utilization of suitable linkers, these epitopes, along with adjuvants, were integrated to design a multi-epitope vaccine candidate. Furthermore, the stability of the interaction between the vaccine candidate and feline Toll-like receptor 4 (TLR4) was established via molecular docking and molecular dynamics simulation analyses. This suggests good prospects for future experimental validation to ascertain the efficacy of our vaccine candidate in inducing a protective immune response against FIP.

Carcinoma neuroendocrino moderadamente diferenciado (carcinoide atípico) de cavidad nasal: Reporte de un caso y revisión del tema / Moderately differentiated neuroendocrine carcinoma of the nasal cavity, a case report and literature review

Resumen Los carcinomas neuroendocrinos son tumores poco frecuentes en nariz y senos paranasales. Se consideran tumores primitivos y son los menos diferenciados del sistema neuroendocrino difuso. Se discute el caso de una paciente femenina de 49 años quien acude al servicio de otorrinolaringología en el Hospital Central Militar refiriendo masa en cavidad nasal izquierda de crecimiento progresivo en un periodo de 9 meses, así como epistaxis y obstrucción nasal izquierda. Mediante resonancia magnética y tomografía computada se observó tumoración de la cavidad nasal izquierda en su totalidad hasta nasofaringe, con captación heterogénea del medio de contraste. Se decide resección de tumoración mediante abordaje endoscópico (sinusotomía maxilar tipo III, etmoidectomía anterior y posterior izquierda, Draf esfenoidal tipo II izquierdo, Draf IIa del seno frontal izquierdo, así como septectomía posterior). El estudio histopatológico reportó un carcinoma neuroendocrino moderadamente diferenciado, por lo que se trató de forma conjunta con servicio de oncología médica. Este tipo de tumores son un reto diagnostico por la complejidad para diferenciarlos en un estudio histopatológico. La diferenciación efectiva de los mismos puede tener un impacto clínico, por lo que los avances en la intervención terapéutica podrían prolongar la supervivencia del paciente, mejorar la calidad de vida e incluso la cura.

Abstract Neuroendocrine carcinomas are rare tumors of the nose and sinuses. They are considered primitive tumors and are the least differentiated from the diffuse neuroendocrine system. We report a 49-year-old female patient who attends the otolaryngology service at the Central Military Hospital referring mass in the left nasal cavity with a progressive growth over a period of 9 months, including epistaxis, as well as left nasal obstruction. Magnetic Resonance Imaging and Computed Tomography imaging studies showed a tumor occupying the entirety of the left nasal cavity to the nasopharynx, with heterogeneous uptake of the contrast medium. Tumor resection is decided by endoscopic approach (maxillary sinusotomy type III, left anterior and posterior ethmoidectomy, left sphenoid Draf type II, left frontal Draf IIa as well as posterior septectomy). The pathology service reported a moderately differentiated neuroendocrine carcinoma. The treatment was decided joint session with the medical oncology service. These types of tumors are a diagnostic challenge because of the complexity to differentiate them in a histopathological study. Their effective differentiation can have a clinical impact, that's why the advances in therapeutic intervention could prolong patient survival, improve quality of life and even find a cure.

Juvenile nasopharyngeal angiofibroma in a male of 16 years old. A case report.

We present a multisystemic approach involving diverse specialists of a rare disease. Bringing into the perspective the importance of multidisciplinary work and complete patient knowledge in order to an adequate clinical practice and patient outcome.

Longitudinal relationships between job satisfaction and creative performance: a three-wave cross-lagged panel design / Relações longitudinais entre satisfação no trabalho e desempenho criativo: um projeto de painel com três ondas cruzadas / Relaciones longitudinales entre la satisfacción laboral y el desempeño creativo: diseño de panel de correlaciones cruzadas, con tres momentos temporales

Despite the assumption about the positive relationship between wellbeing and performance within the happy and productive worker thesis (HPWT), the matter is still under discussion due to inconclusive results. To better understand the link between wellbeing and performance and delineate their possible causal relationships, it is necessary to conduct longitudinal studies with data collection at different moments, as well as broaden the focus by considering different types of wellbeing and performance. To achieve this, the authors of this study analyzed the relationship between intrinsic (IJS) and extrinsic job satisfaction (EJS) with creative performance. The design consisted of a three-time cross-lagged panel design since it permits analyzation of the reciprocal and longitudinal relationship between two or more variables. Our sample was composed of 209 employees from nine different organizations in Spain. The results demonstrated that only IJS predicted creative performance at one of the time intervals. The conclusions were: 1) the relationship between IJS and creative performance might be spurious, 2) it is important to consider IJS and EJS separately because they yield differential results, 3) the relationship between IJS and creative performance is not reciprocal, and 4) it is necessary to increase longitudinal studies in the field.

Apesar do pressuposto sobre a relação positiva entre bem-estar e desempenho dentro da Tese do Trabalhador Feliz e Produtivo (happy and productive worker thesis - HPWT), o assunto ainda está em discussão devido aos resultados inconclusivos. Para melhor compreender a relação entre bem-estar e desempenho e delinear suas possíveis relações causais, é necessário realizar estudos longitudinais com coleta de dados em diferentes momentos, bem como ampliar o foco considerando diferentes tipos de bem-estar e desempenho. Para alcançar este objetivo, os autores deste estudo analisaram a relação entre satisfação intrínseca (intrinsic job satisfaction - IJS) e extrínseca no trabalho (extrinsic job satisfaction - EJS) com o desempenho criativo. O desenho consistiu em um projeto de painel com retardo cruzado de três ondas, uma vez que permite a análise da relação recíproca e longitudinal entre duas ou mais variáveis. Nossa amostra foi composta por 209 funcionários de nove organizações diferentes na Espanha. Os resultados demonstraram que apenas IJS previu desempenho criativo em um dos intervalos de tempo. As conclusões foram: 1) a relação entre IJS e desempenho criativo pode ser espuria, 2) é importante considerar IJS e EJS separadamente porque eles produzem resultados diferenciais, 3) a relação entre IJS e desempenho criativo não é recíproca e 4) é necessário aumentar os estudos longitudinais na área.

A pesar de la suposición sobre la relación positiva entre el bienestar y el desempeño dentro de la tesis del trabajador feliz y productivo (happy and productive worker thesis - HPWT), el tema aún está en discusión debido a resultados no concluyentes. Para comprender mejor el vínculo entre bienestar y desempeño y delinear sus posibles relaciones causales, es necesario realizar estudios longitudinales con recolección de datos en diferentes momentos, así como ampliar el enfoque considerando diferentes tipos de bienestar y desempeño. Para lograrlo, los autores de este estudio analizaron la relación entre la satisfacción laboral intrínseca (intrinsic job satisfaction - IJS) y extrínseca (extrinsic job satisfaction - EJS) con el desempeño creativo. Se utilizó un diseño de panel de correlaciones cruzadas, con tres momentos temporales, ya que permite el análisis de la relación recíproca y longitudinal entre dos o más variables. Nuestra muestra estuvo compuesta por 209 empleados de nueve organizaciones diferentes en España. Los resultados demostraron que solo IJS predijo el rendimiento creativo en uno de los intervalos de tiempo. Las conclusiones fueron: 1) la relación entre IJS y el desempeño creativo podría ser espuria, 2) es importante considerar IJS y EJS por separado porque producen resultados diferenciales, 3) la relación entre IJS y el desempeño creativo no es recíproca, y 4) es necesario incrementar los estudios longitudinales en el campo.