Successful Embolization of a Direct Carotid Cavernous Fistula under Gadolinium-Based Angiography.

Endovascular neurointervention is typically performed with iodinated contrast medium (ICM) under fluoroscopy. However, some patients may be contraindicated to such procedures based on their sensitivity to ICM. In this report, we describe a case of successful coil embolization of a direct carotid cavernous fistula using angiography with gadolinium-based contrast agents in a patient with severe allergic reaction to ICM. The clinical decision-making for this patient was further complicated by comorbidities of renal impairment, drug allergies, and previously severe gastrointestinal bleeding.

Unravelling a novel CTNND1-RAB6A fusion transcript: Implications in colon cancer cell migration.

The interchange of DNA sequences between genes may occur because of chromosomal rearrangements leading to the formation of chimeric genes. These chimeric genes have been linked to various cancers, accumulated significant interest in recent times. We used paired-end RNA-seq. data of four CRC and one normal sample generated from our previous study. The STAR-Fusion pipeline was utilized to identify the fusion genes unique to CRC. The in-silico identified fusion gene(s) were explored for their diagnostic, prognostic and therapeutic biomarker potential using TCGA-datasets, then validated through PCR and DNA sequencing. Further, cell line-based studies were performed to gain functional insights of the novel fusion transcript CTNND1-RAB6A, which was amplified in one sample. Sequencing revealed that there was a total loss of the CTNND1 gene, whereas RAB6A retained its coding sequence. Further, RAB6A was functionally characterized for its oncogenic potential in HCT116 cell line. RAB6A under-expression was found to be significantly associated with increased cell migration and is proposed to be regulated via the RAB6A-ECR1-Liprin-α axis. We conclude that RAB6A gene may play significant role in CRC oncogenesis, and could be used as a potential biomarker and therapeutic target in future for better management of a subset of CRCs harbouring this fusion.

Integrated Analysis Identifies Novel Fusion Transcripts in Laterally Spreading Tumors Suggestive of Distinct Etiology Than Colorectal Cancers.

BACKGROUND: Laterally spreading tumors (LSTs) of the colon and rectum are a class of abnormality which spreads laterally and appears ulcerated. They are a subclass of colorectal cancer (CRCs) with higher invasive potential than CRCs. Moreover, the etiology of LST still remains obscure. METHODS: This study aimed to identify unique fusion transcript(s) in LSTs and evaluate their role in LST development and progression. RNA-Seq data for LST samples from the EMBL-EBI database were used to identify fusion transcripts. An integrated approach using Gene Ontology, pathway analysis, hub gene, and co-expression network analysis functionally characterized fusion transcripts to shed light upon the etiology of LSTs. RESULT: We identified 48 unique fusion genes in LSTs. GO terms were enriched in mRNA metabolic (p ≤ 2.06E-06), mRNA stabilization (p ≤ 1.60E-05), in cytosol (1.20E-05), RBP (p ≤ 2.30E-04), and RNA binding activity (p ≤ 3.51E-08) processes. Pathway analysis revealed an inflammatory phenotype of LSTs suggesting a distinct etiology than CRCs as pathways were enriched in salmonella infection (p ≤ 4.41 e-03), proteoglycans in cancer (p ≤ 1.18 e-02), and insulin signaling (p ≤ 2.13 e-02). Our exclusion and inclusion criteria and hub gene analysis finally identified 9 hub genes. Co-expression analysis of hub genes identified the most significant transcription factors (NELFE, MYC, TAF1, MAX) and kinases (MAPK14, CSNK2A1, CDK1, MAPK1) which were implicated in various cancer pathways. Furthermore, an overall survival analysis of hub genes was performed. Our predefined criterion resulted in the enrichment of NPM1-PTMA (NPM1: p ≤ 0.005) and HIST1H2BO-YBX1 (YBX1: p ≤ 0.02) fusion transcripts, significantly associated with the patient's overall survival. CONCLUSION: Our systematic analysis resulted in novel fusion genes in LSTs suggesting a different etiology than CRCs. Fusion transcripts were observed more frequently in non-granular LSTs suggestive of genetically more unstable than granular LST. We hypothesize that NPM1-PTMA and HIST1H2BO-YBX1 could be implicated in LST development and progression and may also serve as a prognostic or diagnostic biomarker in future for better management of LSTs.

Eco-evolutionary impact of ultraviolet radiation (UVR) exposure on microorganisms, with a special focus on our skin microbiome.

Sunlight is pivotal for our survival, and daily UV exposure has impacted the evolutionary course of all forms of life, from microorganisms to humans. Deciphering the role of UVR in regulating the microbial dynamics of environmental and host-associated microbes is crucial. UVR may be responsible for affecting skin pathology by influencing the skin microbiome, both qualitatively and quantitatively, as evident in low-dose narrow-band UVB phototherapy. Some findings have suggested that the skin microbiome has immunomodulatory roles when exposed to UVR; however, its involvement in UV screening or protection has yet to be fully explored. Furthermore, numerous skin disorders are associated not only with an altered skin microbiome but also with an altered gut microbiome. Hence, the skin-gut axis needs to be in physiological homeostasis and immunological harmony. The purpose of this review is to examine the impact of natural UVR on human immunomodulatory mechanisms and the associated cutaneous microbiome, with an emphasis on interactions among UVR, skin homeostasis, vitamin D, and the related skin-gut axis. With the 'nature as an inspiration' approach, ongoing research is trying to decipher photoprotective secrets in several microbial-based natural compounds to be used as sunscreens or other topical formulations. In addition, various probiotics have also been shown to have significant antioxidant, antiwrinkle, and antiaging effects that ameliorate UV-induced cellular and molecular damage, as highlighted in the review. These cosmetics, nutricosmetics, and probiotaceuticals will undoubtedly be next-generation solutions against photoaging and maintaining skin health.

Activation of CO2 and CH4 on MgO surfaces: mechanistic insights from first-principles theory.

One of the most challenging topics in heterogeneous catalysis is conversion of CH4 to higher hydrocarbons. Direct conversion of CH4 to ethylene can be achieved via the oxidative coupling of methane (OCM) reaction. Despite studies which have shown MgO to activate CH4 and initiate the OCM reaction, its large-scale applications face a significant impediment due to formation of a byproduct, CO2, and poisoning of the catalyst due to carbonate formation. In the present work, we address two aspects of the OCM reaction on MgO surfaces: carbonate formation on the surface of the catalyst, and (dissociative) adsorption of CH4. We use first-principles density functional theoretical calculations to determine the energetics and underlying mechanisms of interaction of CO2 and CH4 with various surfaces of MgO: (100), (110), and (111) (both Mg- and O-terminations), and the seldom studied, hydroxylated (111) MgO surface with O-termination. We find that the strength of the interaction of CO2 with MgO surfaces depends on several factors: their surface energies, coordination number of surface O atoms, and ability to donate electrons. However, the O-terminated (111) surface of MgO bucks all aforementioned factors, with only oxygen richness affecting its reactivity towards CO2. The interaction of CH4 with MgO surfaces depends primarily on the coordination number of the surface O atoms and the orientation of the CH4 molecule with respect to the surface. Finally, we provide insights into (a) formation of surface carbonates, which is relevant to CO2 capture and conversion, and (b) C-H bond activation on MgO surfaces, which is crucial for direct conversion of CH4 to value-added chemicals.

Bacteriophage therapeutics to confront multidrug-resistant Acinetobacter baumannii - a global health menace.

We have already entered the post-antibiotic era as the outbreaks of numerous multidrug-resistant strains in the community as well as hospital-acquired infections are ringing alarm bells in the health sector. Acinetobacter baumannii is one such pathogen that has been considered a worldwide threat as it acquires multidrug resistance. It is one of the most challenging hospital-acquired pathogens as World Health Organization has listed carbapenem-resistant A. baumannii as a critical priority pathogen with limited therapeutic options. There is an urgent need to develop novel strategies against such pathogens to tackle the global crisis. Bacteriophages (phages), especially the lytic ones have re-emerged as a potential therapeutic approach. This review encompasses vast majority of phages against A. baumannii strains with special references related to single phage or monophage therapy, use of phage cocktails, combination therapy with antibiotics, use of phage-derived enzymes like endolysins and depolymerases to combat the pathogen and explore their therapeutic aspects. The concurrent ecological as well as evolutionary interplay between the phages and host bacteria demands in depth-research and knowledge, so as to utilize the maximum potential of the bacteriophage therapy.

Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients.

Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure. This study is aimed towards the identification of genes and pathways implicated in the EOCRC. In the present study, we performed high throughput RNA sequencing of colorectal tumor tissues for four EOCRC (median age 43.5 years) samples with adjacent mucosa and performed subsequent bioinformatics analysis to identify novel deregulated pathways and genes. Our integrated analysis identifies 17 hub genes (INSR, TNS1, IL1RAP, CD22, FCRLA, CXCL3, HGF, MS4A1, CD79B, CXCR2, IL1A, PTPN11, IRS1, IL1B, MET, TCL1A, and IL1R1). Pathway analysis of identified genes revealed that they were involved in the MAPK signaling pathway, hematopoietic cell lineage, cytokine-cytokine receptor pathway and PI3K-Akt signaling pathway. Survival and stage plot analysis identified four genes CXCL3, IL1B, MET and TNS1 genes (p = 0.015, 0.038, 0.049 and 0.011 respectively), significantly associated with overall survival. Further, differential expression of TNS1 and MET were confirmed on the validation cohort of the 5 EOCRCs (median age < 50 years and sporadic origin). This is the first approach to find early age onset biomarkers in Indian CRC patients. Among these TNS1 and MET are novel for EOCRC and may serve as potential biomarkers and novel therapeutic targets in future.

Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) results from a series of genetic alteration in squamous cells. This particular type of cancer considers one of the most aggressive malignancies to control because of its frequent local invasions to the regional lymph node. Although several biomarkers have been reported, the key marker used to predict the behavior of the disease is largely unknown. Here we report Long INterpersed Element-1 (LINE1 or L1) retrotransposon activity in post-operative oral cancer samples. L1 is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. Several studies report that the L1 retrotransposon is highly active in many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lower expression and unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. METHODS: Immunohistochemistry and Western blotting were performed on the post-operative oral cancer samples and murine tissues. RESULTS: Using in house novel antibodies against both the L1 proteins (L1ORF1p and L1ORF2p), we found L1 retrotransposon is extremely active in post-operative oral cancer tissues. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in human oral squamous cell carcinoma (OSCC) samples and murine germ tissues. CONCLUSIONS: We report exceptionally high L1ORF1p and L1ORF2p expression in post-operative oral cancer samples. The novel L1ORF2p antibody reported in this study will serve as a useful tool to understand why L1 activity is deregulated in OSCC and how it contributes to the progression of this particular cancer. Cross-species reactivity of L1ORF2p antibody due to the conserved epitope will be useful to study the retrotransposon biology in mice and rat germ tissues.

Molecular subtypes of colorectal cancer: An emerging therapeutic opportunity for personalized medicine.

Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings. Current treatment strategies in colorectal cancer are largely 'one drug fit all' model for patients that display same pathological conditions. However, CRC is a very heterogenous set of malignancy that does not support for above criteria. Each subtype displays different pathological and genetic signatures. Based on these features, therapeutic stratification for individual patients may be designed, which may ultimately lead to improved therapeutic outcomes. In this comprehensive review, we have attempted to briefly outline major CRC pathways. A detailed overview of molecular subtypes and their clinical significance has been discussed. Present and future methods, governing CRC subtyping in the era of personalized therapy with a special emphasis on CMS subtypes of CRC has been reviewed. Together, discovery and validation of new CRC patient stratification methods, screening for novel therapeutic targets, and enhanced diagnosis of CRC may improve the treatment outcome.

Microbial, environmental and anthropogenic factors influencing the indoor microbiome of the built environment.

A built environment is a human-made environment providing surroundings for human occupancy, activities, and settlement. It is supposed to safeguard humans from all undesirable and harmful pollutants; however, indoor concentrations of some pollutants are much greater than that of the outdoors. Bioaerosols infiltrate from the outdoors in addition to many indoor sources of bioaerosols including the use of various chemicals as well as activities like cooking, smoking, cleaning, or even normal movement. They are also associated with a number of serious health concerns. Various ecological factors associated with the generation, the persistence as well as the dispersal of these microbial components of indoor bioaerosols, are discussed in this review, that have not been considered all together till now. The factors like microbial taxa, environmental factors, and anthropogenic activities (human occupancy, activities, and impact of urbanization) are addressed in the review. Effects of both indoor environmental factors like architectural design, lighting, ventilation, temperature, humidity, indoor/outdoor ratio, particulate matter, indoor chemistry as well as outdoor environmental factors like geography, seasons, and meteorology on the microbial concentrations have been discussed. Efforts are underway to design selective pressures for microbes to create a healthy symbiotic built microbiome as the "right" indoor microbiome is a "healthy" indoor microbiome.

Timberline structure and woody taxa regeneration towards treeline along latitudinal gradients in Khangchendzonga National Park, Eastern Himalaya.

With main purpose of developing a coherent baseline information of timberline forests of Sikkim, Eastern Himalaya, we investigated, (i) forest structure and composition, (ii) regeneration status of dominant timberline tree species between timberline and treeline, (iii) influence of environmental variables in species composition, and (iv) relationship between environmental variables and ecological attributes. The study was conducted along the timberline stretch of Dzongri landscape nested within the Khangchendzonga National Park (UNESCO's World Heritage Site, 2016), a core zone of Khangchendzonga Biosphere Reserve (in UNESCO WNBRs, 2018), Sikkim, India. We employed quadrat method to sample 9 contiguous sites to capture all possible variations in timberline composition. Transect method was used to study the regeneration of woody taxa between timberline to treeline. In total, 20 woody species belonging to 10 genera and 6 families were recorded. Among these, Abies densa, Rhododendron lanatum and Sorbus microphylla exhibited higher dominance, comprising of 50% of the total importance value index (IVI) weightage. Betula utilis the common treeline species in much of the western and central parts of Himalaya was absent here. Tree density in studied timberline was significantly higher than its western Himalayan counterparts of Indian Himalayan region. Environmental variables viz., elevation, slope, and humus were observed determinants of species composition across the study area. The species dominance correlated negatively (p<0.01; n = 9) with species diversity and richness. We observed an irregular spatial pattern of timberline across the 9 study sites, and the extent of timberline elements (seedling; sapling; live tree or dead tree) ranged between 5.3m to 187.7m higher than the current timberline at different sites. The present trends suggest that upslope advancement is unlikely to occur in near future, while treeline densification is anticipated. Further investigations are suggested to develop a holistic understating of these timberline patterns across the Indian Himalayan region.

Genetic and epigenetic markers in colorectal cancer screening: recent advances.

INTRODUCTION: Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFß, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.

Nucleobases tagged to gold nanoclusters cause a mechanistic crossover in the oxidation of CO.

DNA is considered as a programmable building block for the assembly of nanomaterials that play a significant role in modern day nanotechnology and catalysis. In this work, density functional theory (DFT) is used to explore the possible application of complexes of DNA bases (adenine (A), thymine (T), guanine (G), and cytosine (C)) and their size expanded (x) counterparts with Au3 gold clusters as a model catalyst system for oxidation of CO to CO2. We investigate how the catalytic potential of the Au3 cluster is modulated on being tagged with the nuclebases. The CO oxidation can take place via the ER or the LH mechanism. On a pristine cluster, the LH pathway is thermodynamically favored. However, the CO oxidation reaction on the nucleobase tagged gold cluster is found to be more facile following the ER mechanism, with a significant reduction in the barrier height. The reduction in barrier height is attributed to the formation of additional hydrogen bonds between O2 and the polar sites of the attached base in the transition state. This indicates an interesting implication of tagging the cluster to a nucleobase resulting in a mechanistic crossover which is responsible for making nucleobase tagged gold clusters a better catalyst in comparison to pristine Au3 clusters. Our results indicate that nucleobase-gold cluster complexes open new avenues as efficient catalytic models having a wider range of technological applications.

Dynamics of soil diazotrophic community structure, diversity, and functioning during the cropping period of cotton (Gossypium hirsutum).

The soil sampled at different growth stages along the cropping period of cotton were analyzed using various molecular tools: restriction fragment length polymorphism (RFLP), terminal restriction length polymorphism (T-RFLP), and cloning-sequencing. The cluster analysis of the diazotrophic community structure of early sampled soil (0, 15, and 30 days) was found to be more closely related to each other than the later sampled one. Phylogenetic and diversity analysis of sequences obtained from the first (0 Day; C0) and last soil sample (180 day; C180) confirmed the data. The phylogenetic analysis revealed that C0 was having more unique sequences than C180 (presence of γ-Proteobacteria exclusively in C0). A relatively higher richness of diazotrophic community sequences was observed in C0 (S(ACE) : 30.76; S(Chao1) : 20.94) than C180 (S(ACE) : 18.00; S(Chao1) : 18.00) while the evenness component of Shannon diversity index increased from C0 (0.97) to C180 (1.15). The impact of routine agricultural activities was more evident based on diazotrophic activity (measured by acetylene reduction assay) than its structure and diversity. The nitrogenase activity of C0 (1264.85 ± 35.7 ηmol of ethylene production g(-1) dry soil h(-1) ) was statistically higher when compared to all other values (p < 0.05). There was no correlation found between diazotrophic community structure/diversity and N2 fixation rates. Thus, considerable functional redundancy of nifH was concluded to be existing at the experimental site.

Electronic structure theory based study of proline interacting with gold nano clusters.

Interaction between metal nanoparticles and biomolecules is important from the view point of developing and designing biosensors. Studies on proline tagged with gold nanoclusters are reported here using density functional theory (DFT) calculations for its structural, electronic and bonding properties. Geometries of the complexes are optimized using the PBE1PBE functional and mixed basis set, i. e., 6-311++G for the amino acid and SDD for the gold clusters. Equilibrium configurations are analyzed in terms of interaction energies, molecular orbitals and charge density. The complexes associated with cluster composed of an odd number of Au atoms show higher stability. Marked decrease in the HOMO-LUMO gaps is observed on complexation. Major components of interaction between the two moieties are: the anchoring N-Au and O-Au bond; and the non covalent interactions between Au and N-H or O-H bonds. The electron affinities and vertical ionization potentials for all complexes are calculated. They show an increased value of electron affinity and ionization potential on complexation. Natural bond orbital (NBO) analysis reveals a charge transfer between the donor (proline) and acceptor (gold cluster). The results indicate that the nature of interaction between the two moieties is partially covalent. Our results will be useful for further experimental studies and may be important for future applications.