Biology subjects

Sen, D.

Publications and source records attributed to Sen, D..

15 recordsLinked to original sources

bioRxiv2026

Elucidating the effect of a rationally designed nanostructured form-switching ASO (NaFASO) for targeting long non-coding RNA to alleviate Japanese encephalitis virus infection

RNA therapeutic modalities such as antisense oligonucleotides (ASOs) have emerged as promising tools to target previously "undruggable" targets. Despite their great promise as precision therapeutic agents, their clinical adoption remains limited due to production costs, sequence-length restrictions, limited structural heterogeneity, and the generation of environmentally hazardous waste during synthesis. Biocatalytic synthesis strategies provide a sustainable alternative; however, their reliance on specialized enzymes and precursors often limits sequence diversity and scalability. To address these limitations, we report the design and biocatalytic synthesis of a novel circular ASO: Nanostructured Form-switching Antisense Oligonucleotide (NaFASO) for targeting Japanese Encephalitis Virus (JEV) infection-associated host long non-coding RNA (lncRNA) JINR1 (JEV-induced non-coding RNA1) in SH-SY5Y cells. The novel modular architecture in NaFASO has been designed to have a metastable stem that separates the functional antisense domain from the splint-padlock circularizing region, ensuring both structural integrity and efficient target engagement. The serum- and nuclease-stable NaFASOs achieved knockdown of the lncRNA JINR1 during JEV infection, resulting in a reduction in JEV replication and neuronal cell death. NaFASO-mediated JINR1 depletion also resulted in downregulation of the JEV replication-associated gene GRP78. Together, these findings establish NaFASO as a first-of-its-kind structure-switching circular ASO platform for combating JEV infection, combining stability, efficacy, and environmental sustainability. Beyond the JEV, the generalizability of this design suggests broad applicability for targeting diverse RNA species implicated in genetic disorders, viral infections, and cancer, thus highlighting a promising paradigm for developing next-generation transformational nucleic acid therapeutics.

biochemistry↗

bioRxiv2026

Targeting lncRNA JINR1 with programmable Circular Active Nano DNAzyme (CANDe) suppresses Japanese Encephalitis Virus infection

Oligonucleotide therapeutics such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) enable sequence-specific gene silencing but rely on endogenous cellular machinery and often require extensive chemical modification for stability and efficacy. DNAzymes offer a mechanistically distinct alternative through intrinsic catalytic RNA cleavage; however, their therapeutic translation has been limited by nuclease susceptibility, structural constraints, and synthetic challenges. Here, we report the development of Circular Active Nano DNAzyme (CANDe), an enzymatically synthesized circular DNAzyme platform designed to enhance stability without backbone modification. The therapeutic potential of CANDe constructs was investigated against Japanese Encephalitis Virus (JEV) infection associated host long-noncoding RNA JINR1 (LINC01518). CANDe constructs were generated via splint-assisted ligation and incorporate modular elements, including catalytic cores (8-17 or 10-23), target-binding arms, and structural stems. Circularization conferred marked resistance to exonuclease-mediated degradation compared to linear DNA, maintaining structural integrity under nuclease-rich conditions.,CANDe targeting the lncRNA JINR1 achieved effective JINR1 knockdown in SHSY-5Y with and without JEV infection. This was accompanied by reduced expression JEV RNA and titers. In line with this, CANDe constructs attenuated of virus-induced cytotoxicity and apoptosis. Among the constructs, 10-23-based CANDe targeting the JINR1-1 site exhibited the strongest overall activity. These findings establish CANDe as a modular, modification-free DNAzyme platform that combines catalytic efficiency with enhanced stability, enabling effective host-directed antiviral intervention. This approach highlights topological engineering as a viable alternative to chemical modification for advancing DNAzyme-based therapeutics.

biochemistry↗

bioRxiv2025

Relationship between SARC-F score and Peripheral Blood Lymphocytes in Juvenile Idiopathic Arthritis: An Observational Pilot Study

BackgroundGiven the relatively high prevalence of sarcopenia and immune profile abnormalities in inflammatory arthritis such as rheumatoid arthritis (RA), we investigated the relationship between exercise habits, SARC-F score and peripheral blood lymphocyte profiles in patients with Juvenile idiopathic arthritis (JIA). MethodsAll participants with JIA completed the SARC-F survey and self-reported exercise habits through online questionnaires. We defined two groups based on SARC-F scores as musculoskeletal function impaired (SARC-Fhi+) and musculoskeletal function not impaired (SARC-Fhi-). We used flow cytometry of peripheral blood mononuclear cells to define immune cell subpopulations. Statistical analyses were performed using GraphPad Prism software version10. ResultsOf the 18 participants with a median age of 24 years - five belonged to the SARC-Fhi+ group and 13 to the SARC-Fhi-group, of whom 80% and 38% were female, respectively. The SARC-Fhi + group had fewer CD45RA+CD27+ naive CD4+ T cells (26.60% vs. 45.30%, p=0.0264) and greater CD45RA-CD27-effector memory CD4+ T cells (11.90% vs. 7.00%, p=0.0350). The SARC-Fhi+ group also had fewer CD56-CD16+ NK cells compared to the SARC-Fhi-group (2.60% v. 4.28%, p = 0.0194). The moderate exercise group (n = 13) had increased numbers of total CD4+ T cells (54.06% vs. 37.30%, p=0.0140) and 3-fold fewer CD45RA+CD27-EMRA CD8+ T cells (3.17% vs. 10.40%, p=0.0350). There were no other significant differences for other immune cells / subpopulations including B cells. ConclusionsOur study findings suggest notable differences in immune profile relative to SARC-F score. Furthermore, the 3-fold lower frequency of CD8+ TEMRA subpopulation of T cells, reflective of immunosenescence, suggest a potential inverse relationship between moderate exercise and peripheral immune cell profile in JIA. Key messagesO_LISARC-F score was used as a clinically relevant tool to identify musculoskeletal function in JIA C_LIO_LISARC-Fhi+ group had fewer naive CD4+ T cells and greater effector memory CD4+ T cells C_LIO_LIModerate exercise group had 3-fold lower frequency of CD8+ TEMRA T cells C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=54 SRC="FIGDIR/small/681879v1_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1eb9d4org.highwire.dtl.DTLVardef@13a18a4org.highwire.dtl.DTLVardef@127d55corg.highwire.dtl.DTLVardef@28bddf_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

A Human Angelman Syndrome Class II Pluripotent Stem Cell line with Fluorescent Paternal UBE3A Reporter

IntroductionAngelman Syndrome (AS) is characterized in large part by the loss of functional UBE3A protein in mature neurons. A majority of AS etiologies is linked to deletion of the maternal copy of the UBE3A gene and epigenetic silencing of the paternal copy. A common therapeutic strategy is to unsilence the intact paternal copy thereby restoring UBE3A levels. Identifying novel therapies has been aided by a UBE3A-YFP reporter mouse model. This study presents an analogous fluorescent UBE3A reporter system in human cells. MethodsPreviously derived induced Pluripotent Stem Cells (iPSCs) with a Class II large deletion at the UBE3A locus are used in this study. mGL and eGFP are integrated downstream of the endogenous UBE3A using CRISPR/Cas9. These reporter iPSCs are differentiated into 2D and 3D neural cultures to monitor long-term neuronal maturation. Green fluorescence dynamics are analyzed by immunostaining and flow cytometry. ResultsThe reporter is successfully integrated into the genome and reports paternal UBE3A expression. Fluorescence expression gradually reduces with UBE3A silencing in neurons as they mature. Expression patterns also reflect expected responses to molecules known to reactivate paternal UBE3A. DiscussionThis human-cell-based model can be used to screen novel therapeutic candidates, facilitate tracking of UBE3A expression in time and space, and study human-specific responses. However, its ability to restore UBE3A function cannot be studied using this model. Further research in human cells is needed to engineer systems with functional UBE3A to fully capture the therapeutic capabilities of novel candidates.

cell biology↗

bioRxiv2025

Associations between floor material and E. coli contamination in rural Bangladeshi households

Soil floors are common in low-income countries and can harbor contamination from unsafely managed human and animal fecal waste. Soil/dust ingestion directly from floors or indirectly via hands, drinking water and food can significantly contribute to childrens ingestion of fecal organisms. We assessed if finished (e.g., concrete) floors are associated with lower E. coli contamination in the domestic environment in rural Bangladesh. We collected samples from 1864 households over 3.5 years, including stored drinking water, child and caregiver hand rinses, courtyard soil, food, and flies (n=24,118 samples), and enumerated E. coli using IDEXX Quanti-Tray/2000. Controlling for potential confounders (socio-demographics, water/sanitation status, animal ownership), households with finished floors had slightly lower log10-transformed E. coli counts ({Delta}log10= -0.10 (-0.20, 0.00)) and prevalence (prevalence ratio=0.90 (0.83, 0.98)) on child hands than households with soil floors; floor material was not associated with contamination levels in other sample types. Finished floors were associated with lower E. coli contamination of child hands, food and stored drinking water following periods of higher rainfall and temperature, and lower E. coli contamination of child hands in households with more domestic animals. Measures to control enteric infections in low-income countries should test flooring improvements to reduce exposure to fecal contamination.

microbiology↗

bioRxiv2024

In vivo CRISPR screens identify key modifiers of CAR T cell function in myeloma

Chimeric antigen receptor (CAR) T cells are highly effective in hematologic malignancies. However, loss of CAR T cells can contribute to relapse in a significant number of patients. These limitations could potentially be overcome by targeted gene editing to increase CAR T cell persistence. Here, we performed in vivo loss-of-function CRISPR screens in BCMA-targeting CAR T cells to investigate genes that influence CAR T cell persistence, function and efficacy in a human multiple myeloma model. We tracked the expansion and persistence of CRISPR-library edited T cells in vitro and then at early and late timepoints in vivo to track the performance of gene modified CAR T cells from manufacturing to survival in tumors. The screens revealed several context-specific regulators of CAR T cell expansion and persistence. Ablation of RASA2 and SOCS1 enhanced T cell expansion in vitro, while loss of PTPN2, ZC3H12A, and RC3H1 conferred early selective growth advantages to CAR T cells in vivo. Strikingly, we identified cyclin-dependent kinase inhibitor 1B (CDKN1B), a cell cycle regulator, as the most important factor limiting CAR T cell fitness at late timepoints in vivo. CDKN1B ablation increased BCMA CAR T cell proliferation and effector function in response to antigen, significantly enhancing tumor clearance and overall survival. Thus, our findings reveal differing effects of gene-perturbation on CAR T cells over time and in different selective environments, highlight CDKN1B as a promising target to generate highly effective CAR T cells for multiple myeloma, and underscore the importance of in vivo screening as a tool for identifying genes to enhance CAR T cell function and efficacy.

immunology↗

bioRxiv2024

Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids

Angelman syndrome is a neurodevelopmental disorder caused by (epi)genetic lesions of maternal UBE3A. Research has focused largely on the role of UBE3A in neurons due to its imprinting in that cell type. Yet, evidence suggests there may be broader neurodevelopmental impacts of UBE3A dysregulation. Human cerebral organoids might reveal these understudied aspects of UBE3A as they recapitulate diverse cell types of the developing human brain. We performed scRNAseq on organoids to reveal the effects of UBE3A disruption on cell type-specific compositions and transcriptomic alterations. In the absence of UBE3A, progenitor proliferation and structures were disrupted while organoid composition shifted away from proliferative cell types. We observed impacts on non-neuronal cells, including choroid plexus enrichment. Furthermore, EMX1+ cortical progenitors were negatively impacted, disrupting corticogenesis, and potentially delaying excitatory neuron maturation. This work reveals novel impacts of UBE3A on understudied cell types and related neurodevelopmental processes and elucidates potential new therapeutic targets. TeaserHuman cerebral organoids exhibit compositional and transcriptomic alterations in both neuronal and non-neuronal cells in the absence of UBE3A.

developmental biology↗

bioRxiv2023

Genomic, effector protein and culture-based analysis of Cyclaneusma minus in New Zealand provides evidence for multiple morphotypes

Cyclaneusma needle cast, caused by Cyclaneusma minus, affects Pinus species around the world. Previous studies suggested the presence of two distinct morphotypes in New Zealand, verum and simile. Traditional mycological analyses revealed a third morphotype with clear differences in colony morphology and cardinal growth rates at varying temperatures. Genome sequencing of eight C. minus isolates provided further evidence of the existence of a third morphotype, named novus in this study. To further analyse these morphotypes, we predicted candidate effector proteins for all eight isolates, and also characterized a cell-death eliciting effector family, Ecp32, which is present in other pine phytopathogens. In concordance with their distinct classification into three different morphotypes, the number of Ecp32 family members differed, with patterns of pseudogenization and some family members being found exclusively in some morphotypes. We also showed that proteins belonging to the Ecp32 family trigger cell death responses in non-host Nicotiana species, and, as previously demonstrated for other plant pathogens, the C. minus proteins belonging to the Ecp32 family adopt a {beta}-trefoil fold. Understanding the geographical range and variations in virulence and pathogenicity of these morphotypes will provide a better understanding of pine needle diseases as well as enable the development of more durable methods to control this disease.

molecular biology↗

bioRxiv2023

Left or right: Handedness in free-ranging Hanuman langurs (Semnopithecus entellus) residing in an urban ecosystem.

Examining manual lateralization (handedness) in nonhuman primates might be an interesting approach to gaining insight into the evolution of asymmetry in humans. Moreover, handedness could also reflect the effect of environmental alterations on the free-ranging animals who are forced to live with anthropogenic interferences. Despite addressing the handedness among monkeys and apes, only a few studies have focused on these free-ranging urban-adapted nonhuman primates, which could challenge our perception of habitat loss and deforestation. Here, we conducted 193 field-based experimental trials with two experimental tasks, one unimanual (simple reaching) and one bimanual (tube task) to explore manual lateralization in a highly human-provisioned group of free-ranging Hanuman langur (Semnopithecus entellus). Experimental outcomes revealed an asymmetrical hand-use distribution, with a bias toward the left hand. As bimanual tasks evoked a higher degree of lateralization, these tasks seem to be more suited to study manual laterality, and our results also highlight the significance of experimental tasks in establishing hand preference in langurs. Furthermore, this study also reveals that such lateralization developed with age as adults distinctly displayed their preference toward left-hand usage in contrast to juveniles and subadults who used both hands comparably. Mostly considered to be arboreal, the langurs of our study group spend a considerable amount of time with humans on the ground, thereby portraying a terrestrial tendency. Postural Origin Theory states that terrestrial animals tend to use their right hand and arboreal their left. Therefore, here the presence of group-level left-hand biasness in the adult langurs of Dakshineswar creates a dilemma in the Postural Origin Theory.

animal behavior and cognition↗

bioRxiv2022

Strategic in vitro bioaugmentation of indigenous Actinobacteria isolated from east Kolkata wetlands (Ramsar site) to degrade highly toxic waste engine oil in free and emulsified state

The present study investigates the bioremediation of waste engine oil at both dissolved or being suspended in oily wastewater using an actinobacterium, Gordonia terrae DSM 43249 strain isolated from East Kolkata wetlands. The isolated strain was found capable of sustaining in highly toxic oil contaminated wastewater and simultaneously can efficiently biodegrade the pollutants in both simulated fresh and marine water system at optimized environmental conditions. Moreover, in order to understand the effect of physical presence of oil in oily wastewater on the bioremediation process, three types of simulated oil-water forms were studied: water with free waste engine oil, oil-water mixture in the form of coarse emulsion and microemulsion. It was observed that the percentage degradation became maximum with the microemulsion form (72.73%) followed by the coarse one (65.45%). The minimum percentage degradation of 39.74% was seen with the free oil. Statistical interpretation also revalidates the experimental observations, showing that the oil percentage degradation is much sensitive to the oil and water composition in an oily-water system (F=772.64> Fcritical =5.143). Hence, it is presumed from the present study that such a high percentage degradation of oil especially, when oil is thoroughly mixed with water, can be considered as one of the potential applications for oil treatment such as during oil spillage using G.terrae DSM 43249. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/503898v3_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@154b649org.highwire.dtl.DTLVardef@8b86cborg.highwire.dtl.DTLVardef@3e8f3forg.highwire.dtl.DTLVardef@12e88d1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2021

Effects of early geometric confinement on the transcriptomic profile of human cerebral organoids

BackgroundBiophysical factors such as shape and mechanical forces are known to play crucial roles in stem cell differentiation, embryogenesis and neurodevelopment. However, the complexity and experimental challenges capturing such early stages of development, and ethical concerns associated with human embryo and fetal research, limit our understanding of how these factors affect human brain organogenesis. Human cerebral organoids (hCO) are attractive models due to their ability to model important brain regions and transcriptomics of early in vivo brain development. Furthermore, they provide three-dimensional environments that better mimic the in vivo environment. To date, they have been used to understand the effects of genetics and soluble factors on neurodevelopment. Establishing links between spatial factors and hCO development will require the development of new approaches. ResultsHere, we investigated the effects of early geometric confinements on transcriptomic changes during hCO differentiation. Using a custom and tunable agarose microwell platform we generated embryoid bodies (EB) of diverse shapes and then further differentiated those EBs to whole brain hCOs. Our results showed that the microwells did not have negative gross impacts on the ability of the hCOs to differentiate generally towards neural fates, and there were clear shape dependent effects on neural lineage specification. In particular, we observed that non-spherical shapes showed signs of altered neurodevelopmental kinetics and favored the development of medial ganglionic eminence-associated brain regions and cell types over cortical regions. ConclusionsThe findings presented here suggest a role for spatial factors in brain region specification during hCO development. Understanding these spatial patterning factors will not only improve understanding of in vivo development and differentiation, but also provide important handles with which to advance and improve control over human model systems for in vitro applications.

bioengineering↗

bioRxiv2020

Effect of sanitation improvements on soil-transmitted helminth eggs in courtyard soil from rural Bangladesh: Evidence from a cluster-randomized controlled trial

Improved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and abundance of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the sanitation intervention (n=419) and control (n=914) groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura, and hookworm eggs by microscopy. We estimated prevalence ratios (PR) and relative egg count reductions (ECR) to compare the prevalence of any STH eggs and arithmetic and geometric mean egg counts for any STH per gram of soil between the sanitation and control arms. Among intervention households, latrines achieved high and sustained user uptake by adults while child open defecation remained common and most households did not dispose of child feces hygienically. In courtyard soil from control households, the prevalence of any STH eggs was 75.7% and the prevalence of any larvated STH eggs was 67.3%. A. lumbricoides was detected in 63.0% of control samples and T. trichiura in 55.7% of control samples; hookworm was not detected in any sample. The arithmetic mean egg count for any STH was 3.96 eggs/dry gram, while the geometric mean was 1.58 eggs/dry gram. There was no difference between the intervention and control groups in the prevalence of any STH eggs (PR=0.98 (95% CI: 0.91-1.05)) or mean egg counts (ECR=0.08 (95% CI: -0.10, 0.26) for geometric mean and 0.07 (95% CI: -0.22, 0.37) for arithmetic mean). Adjusted models gave similar results. A compound-level sanitation intervention that provided improved latrines and tools for disposal of child and animal feces did not have an impact on environmental reservoirs of STH eggs. In order to effectively reduce the prevalence and abundance of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces. Author summaryImproved sanitation has been hypothesized to reduce soil-transmitted helminth (STH) infections by reducing the prevalence and abundance of STH eggs/larvae in soil. We evaluated the effect of a randomized sanitation program (providing households with an improved dual-pit latrine, tools for child/animal feces management, and behavioral messaging) on reducing STH eggs in soil from household courtyards. We collected soil samples from 1405 households enrolled in the control and sanitation groups of a cluster-randomized controlled trial (WASH Benefits) in rural Bangladesh approximately 2 years after the initiation of the interventions. We analyzed samples for Ascaris lumbricoides, Trichuris trichiura and hookworm eggs by microscopy. We found no effect of the sanitation intervention on STH eggs in soil. In order to effectively reduce the prevalence and abundance of STH eggs in the environment, sustained, widespread use of sanitation strategies to isolate and hygienically dispose of child and animal feces may need to complement traditional strategies for containment of adult human feces.

ecology↗

bioRxiv2019

Human cerebral organoids capture the spatiotemporal complexity and disease dynamics of UBE3A

Human neurodevelopment and its associated diseases are complex and challenging to study. This has driven recent excitement for human cerebral organoids (hCOs) as research and screening tools. These models are steadily proving their utility; however, it remains unclear what limits they will face in recapitulating the complexities of neurodevelopment and disease. Here we show that their utility extends to key (epi)genetic and disease processes that are complex in space and time. Specifically, hCOs capture UBE3As dynamically imprinted expression and subcellular localization patterns. Furthermore, given UBE3As direct links to Angelman Syndrome and Autism Spectrum Disorder, we show that hCOs respond to candidate small molecule therapeutics. This work demonstrates that hCOs can provide important insights to focus the scope of mechanistic and therapeutic strategies including revealing difficult to access prenatal developmental time windows and cell types key to disease etiology.

bioengineering↗

bioRxiv2017

Genome-wide discovery of somatic coding and regulatory variants in Diffuse Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Many known driver mutations are over-represented in one of its two molecular subgroups, knowledge of which has aided in the development of therapeutics that target these features. The heterogeneity of DLBCL determined through prior genomic analysis suggests an incomplete understanding of its molecular aetiology, with a limited diversity of genetic events having thus far been attributed to the activated B-cell (ABC) subgroup. Through an integrative genomic analysis we uncovered genes and non-coding loci that are commonly mutated in DLBCL including putative regulatory sequences. We implicate recurrent mutations in the 3UTR of NFKBIZ as a novel mechanism of oncogene deregulation and found small amplifications associated with over-expression of FC-{gamma} receptor genes. These results inform on mechanisms of NF-{kappa}B pathway activation in ABC DLBCL and may reveal a high-risk population of patients that might not benefit from standard therapeutics.

genomics↗

bioRxiv2016

EuMicrobedbLite: A lightweight genomic resource and analytic platform for draft oomycete genomes

We have developed EuMicrobedbLite - A light weight comprehensive genome resource and sequence analysis platform for oomycete organisms. EuMicrobedbLite is a successor of the VBI Microbial Database (VMD) that was built using the Genome Unified Schema (GUS). In this version, the GUS schema has been greatly simplified with removal of many obsolete modules and redesign of others to incorporate contemporary data. Several dependencies such as perl object layers used for data loading in VMD have been replaced with independent light weight scripts. EumicrobedbLite now runs on a powerful annotation engine developed at our lab called \"Genome Annotator Lite\". Currently this database has 26 publicly available genomes and 10 EST datasets of oomycete organisms. The browser page has dynamic tracks presenting comparative genomics analyses, coding and non-coding data, tRNA genes, repeats and EST alignments. In addition, we have defined 44,777 core conserved proteins from twelve oomycete organisms that form 2974 clusters. Synteny viewing is enabled by incorporation of the Genome Synteny Viewer (GSV) tool. The user interface has undergone major changes for ease of browsing. Queryable comparative genomics information, conserved orthologous genes and pathways are among the new key features updated in this database. The browser has been upgraded to enable user upload of GFF files for quick view of genome annotation comparisons. The toolkit page integrates the EMBOSS package and has a gene prediction tool. Annotations for the organisms are updated once every six months to ensure quality. The database resource is available at www.eumicrobedb.org.

bioinformatics↗