Study of transcription factor druggabilty for prostate cancer using structure information, gene regulatory networks and protein moonlighting.

Prostate cancer is the second leading cause of cancer-related death in men. Metastasis shows poor survival even though the recovery rate is high. In spite of numerous studies regarding prostate carcinoma, multiple questions are still unanswered. In this regards, gene regulatory network can uncover the mechanisms behind cancer progression, and metastasis. Under a feed forward loop, transcription factors (TFs) can be a good druggable candidate. We have proposed a computational model to study the uncertainty of TFs and suggest the appropriate cellular conditions for drug targeting. We have selected feed-forward loops depending on the shared list of the functional annotations among TFs, genes and miRNAs. From the potential feed forward loop cores, six TFs were identified as druggable targets, which include AR, CEBPB, CREB1, ETS1, NFKB1 and RELA. However, TFs are known for their Protein Moonlighting properties, which provide unrelated multi-functionalities within the same or different subcellular localizations. Following that, we have identified such functions that are suitable for drug targeting. On the other hand, we have tried to identify membraneless organelles for providing more specificity to the proposed time and space theory. The study has provided certain possibilities on TF-based therapeutics. The controlled dynamic nature of the TF may have enhanced the chances where TFs can be considered as one of the prime drug targets. Finally, the combination of membranless phase separation and protein moonlighting has provided possible druggable period within the biological clock.

Unveiling COVID-19-associated organ-specific cell types and cell-specific pathway cascade.

The novel coronavirus or COVID-19 has first been found in Wuhan, China, and became pandemic. Angiotensin-converting enzyme 2 (ACE2) plays a key role in the host cells as a receptor of Spike-I Glycoprotein of COVID-19 which causes final infection. ACE2 is highly expressed in the bladder, ileum, kidney and liver, comparing with ACE2 expression in the lung-specific pulmonary alveolar type II cells. In this study, the single-cell RNAseq data of the five tissues from different humans are curated and cell types with high expressions of ACE2 are identified. Subsequently, the protein-protein interaction networks have been established. From the network, potential biomarkers which can form functional hubs, are selected based on k-means network clustering. It is observed that angiotensin PPAR family proteins show important roles in the functional hubs. To understand the functions of the potential markers, corresponding pathways have been researched thoroughly through the pathway semantic networks. Subsequently, the pathways have been ranked according to their influence and dependency in the network using PageRank algorithm. The outcomes show some important facts in terms of infection. Firstly, renin-angiotensin system and PPAR signaling pathway can play a vital role for enhancing the infection after its intrusion through ACE2. Next, pathway networks consist of few basic metabolic and influential pathways, e.g. insulin resistance. This information corroborate the fact that diabetic patients are more vulnerable to COVID-19 infection. Interestingly, the key regulators of the aforementioned pathways are angiontensin and PPAR family proteins. Hence, angiotensin and PPAR family proteins can be considered as possible therapeutic targets. Contact: sagnik.sen2008@gmail.com, umaulik@cse.jdvu.ac.in Supplementary information: Supplementary data are available online.

Understanding structural malleability of the SARS-CoV-2 proteins and relation to the comorbidities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (COVID-19), is a part of the $\beta $-Coronaviridae family. The virus contains five major protein classes viz., four structural proteins [nucleocapsid (N), membrane (M), envelop (E) and spike glycoprotein (S)] and replicase polyproteins (R), synthesized as two polyproteins (ORF1a and ORF1ab). Due to the severity of the pandemic, most of the SARS-CoV-2-related research are focused on finding therapeutic solutions. However, studies on the sequences and structure space throughout the evolutionary time frame of viral proteins are limited. Besides, the structural malleability of viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins. This dysfunctionality may lead to comorbidities during the infection and may continue at the post-infection stage. In this regard, we conduct the evolutionary sequence-structure analysis of the viral proteins to evaluate their malleability. Subsequently, intrinsic disorder propensities of these viral proteins have been studied to confirm that the short intrinsically disordered regions play an important role in enhancing the likelihood of the host proteins interacting with the viral proteins. These interactions may result in molecular dysfunctionality, finally leading to different diseases. Based on the host cell proteins, the diseases are divided in two distinct classes: (i) proteins, directly associated with the set of diseases while showing similar activities, and (ii) cytokine storm-mediated pro-inflammation (e.g. acute respiratory distress syndrome, malignancies) and neuroinflammation (e.g. neurodegenerative and neuropsychiatric diseases). Finally, the study unveils that males and postmenopausal females can be more vulnerable to SARS-CoV-2 infection due to the androgen-mediated protein transmembrane serine protease 2.

Artificial intelligence in retinal disease: clinical application, challenges, and future directions.

Retinal diseases are a leading cause of blindness in developed countries, accounting for the largest share of visually impaired children, working-age adults (inherited retinal disease), and elderly individuals (age-related macular degeneration). These conditions need specialised clinicians to interpret multimodal retinal imaging, with diagnosis and intervention potentially delayed. With an increasing and ageing population, this is becoming a global health priority. One solution is the development of artificial intelligence (AI) software to facilitate rapid data processing. Herein, we review research offering decision support for the diagnosis, classification, monitoring, and treatment of retinal disease using AI. We have prioritised diabetic retinopathy, age-related macular degeneration, inherited retinal disease, and retinopathy of prematurity. There is cautious optimism that these algorithms will be integrated into routine clinical practice to facilitate access to vision-saving treatments, improve efficiency of healthcare systems, and assist clinicians in processing the ever-increasing volume of multimodal data, thereby also liberating time for doctor-patient interaction and co-development of personalised management plans.

Retinopathy secondary to flare-up of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) can have widespread ocular manifestations, and posterior segment involvement may be associated with poor visual outcome. We report a clinical flare-up of SLE presenting as combined vascular occlusion in one eye and drusen-like deposits, which is a newly described entity in both eyes. As an ophthalmologist, a knowledge of such presentations helps us identify and possibly help the rheumatologist titrate treatment accordingly, to prevent severe life-threatening systemic complications.

Anatomical and functional features of photic retinopathy: a spectral domain optical coherence tomography-based longitudinal study.

BACKGROUND: Photic retinopathy may lead to permanent foveal structural injury, leading to irreversible visual acuity loss. METHOD: This prospective observational study evaluated 51 eyes of 30 patients with photic retinopathy. Optical coherence tomography (OCT) imaging was performed for all the eyes at baseline and final follow-up. All the eyes showed a focal outer retinal defect on spectral-domain OCT (SD-OCT) at the junction of the inner and outer photoreceptor segments. SD-OCT was used to measure central macular thickness, maximum horizontal dimension of the defect, maximum defect thickness, and the photic retinopathy index (PRI) through the foveal raster scan. RESULTS: Although PRI improved significantly at the final follow-up from baseline with a 17% improvement in PRI after a period of 6 months in photic retinopathy eyes, visual acuity declined for 14% of the patients and was stable for 84%. There was mild correlation of visual acuity with baseline PRI. Baseline PRI was significantly higher in eyes with poorer presenting visual acuity (VA). In total, 33.3% of the eyes showed partial ellipsoid zone recovery at 6 months. The area under curve of the receiver operator characteristic curve for partial ellipsoid zone recovery with the mean baseline PRI as the independent variable was poor at 0.612. CONCLUSION: OCT-based ultrastructural features in photic retinopathy seem to have poor correlation with presenting or final visual acuity. To the best of our knowledge, this is the largest study on longitudinal OCT evaluation of photic retinopathy eyes in literature.

Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review.

INTRODUCTION: The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes a system-wide thromboembolic state, leading to serious cardiovascular, cerebrovascular and peripheral vascular manifestations. However, our knowledge regarding retinal manifestations due to systemic COVID-19 is minimal. This systematic review has comprehensively summarized all retinal manifestations secondary to COVID-19 disease recorded till date since the beginning of the pandemic. METHODS: All studies published till November 27, 2020, which have reported retinal manifestations in COVID-19 patients were systematically reviewed using the PRISMA statement. RESULTS: We included 15 articles: 11 case reports and four cross-sectional case series. The most commonly reported manifestations which did not affect visual acuity were retinal hemorrhages and cotton wool spots. The most common vision threatening manifestation was retinal vein occlusion with associated macular edema. Rarely, patients may also present with retinal arterial occlusions and ocular inflammation. These manifestations may occur from as soon as within a week after the onset of COVID-19 symptoms to more than 6 weeks after. CONCLUSION: Mostly causing milder disease, COVID-19 may however lead to severe life-threatening thromboembolic complications, and systemic antithrombotic therapy has been suggested as a prophylactic and therapeutic management strategy for patients affected with serious systemic disease. However, both sick and apparently healthy patients may suffer from various retinal complications which may lead to loss of vision as well. No consensus regarding management of retinal complications with anticoagulants or anti-inflammatory medications have been proposed; however, they may be tackled on individual basis.

Real-world outcomes of intravitreal anti-vascular endothelial growth factor monotherapy in proliferative type 2 macular telangiectasia.

BACKGROUND: To study the effect of anti-VEGFs in proliferative MacTel 2 METHODS: Sixty-four eyes of 51 patients of MacTel 2 with subretinal neovascular membrane (SRNVM) undergoing intravitreal anti-VEGF monotherapy at our institution between January 2015 and December 2018 were evaluated for visual acuity, central macular thickness (CMT) and total macular volume (TMV) using optical coherence tomography (OCT). Repeat investigations were performed at the final follow-up. RESULTS: Location of SRNVM was foveal (F) in 65.6% eyes and extrafoveal (EF) in 34.4% eyes. Both CMT and TMV were lower significantly at baseline in EF-SRNVM. Fifty-six eyes received intravitreal bevacizumab and 8 eyes received ranibizumab. Average 2.14 ± 1.21 injections (range, 1-6) were administered. After a mean follow-up duration of 16.01 ± 12.96 months, the final visual acuity (VA) improved in 35.9% eyes, reduced in 28.1% and remained unchanged in 35.9% eyes. Significant improvement of VA was seen in F-SRNVM; however, overall, there was no significant improvement in visual acuity. Significant reduction in CMT was seen in F-SRNVM from 391.73 ± 152.45 µm to 293.33 ± 114.77 µm (p < 0.05) while EF-SRNVM did not show significant reduction. Total macular volume overall changed significantly from 8.79 ± 1.69 to 8.05 ± 1.27 (p < 0.05) and individually in F- and EF-SRNVM (p < 0.05). Intravitreal bevacizumab and ranibizumab monotherapy both had similar efficacy. CONCLUSIONS: Anti-VEGF agents can be successfully used to treat proliferative MacTels. Macular volume measurement on OCT may be a useful parameter for evaluating EF-SRNVM and as a prognostic marker of management outcomes.

Clinico-demographic profile and outcomes of 25-gauge vitrectomy in advanced stage 5 retinopathy of prematurity.

BACKGROUND: Stage 5 retinopathy of prematurity is a difficult condition to treat despite technological advances in vitreous surgery. METHODS: A retrospective chart review of all consecutive cases of stage 5 ROP was performed between December 2016 and December 2018, and 21 babies were included for assessment of surgical outcomes using a modified vitrectomy technique. Data extracted from documents included demography, ROP screening status, preoperative prophylactic therapy, clinical presentation, surgery performed, and postsurgical outcomes. RESULTS: Out of the 21 babies, ophthalmologist screening was done in 42.9%. Mean birth weight was 1185 ± 222.4 g with a mean gestational age of 29.86 ± 2.0 weeks and mean post-menstrual age of 44.55 ± 9.82 weeks. Lesser than stage 5 disease was seen in 16.7% of eyes and they were managed accordingly. Seventy percent of babies had bilateral disease. 21 eyes underwent 25-gauge pars plicata vitrectomy using a modified technique. After an average follow-up duration of 6.33 ± 2.18 months, the final macular attachment rate was 19%. Anteriorly closed-posteriorly closed type configuration of retinal detachments had a poorer outcome. Fix and follow visual acuity was achieved in 23.8% of eyes, while 57.1% of eyes had a perception of light. CONCLUSIONS: Management of stage 5 ROP is mostly surgical; however, the risk of ending up with a poor vision or vision loss is high, irrespective of whether surgery is performed. The modified surgical technique with a spacer described in this study may help in better manipulation of instruments inside the vitreous cavity.

A comparison of using digitally assisted vitreoretinal surgery during repair of rhegmatogenous retinal detachments to the conventional analog microscope: A prospective interventional study.

BACKGROUND: To compare outcomes and complications of pars plana vitrectomy (PPV) using a three-dimensional heads-up visualisation system (digitally assisted vitreoretinal system, DAVS) versus conventional analog microscope (CAM) in primary rhegmatogenous retinal detachment (RRD). METHODS: This prospective interventional institutional study evaluated 60 eyes of 60 subjects with primary RRD undergoing PPV between September 2017 and February 2018. Subjects were randomly put into DAVS and CAM group and pre-operative ocular characteristics and final outcomes recorded at each visit. All subjects were followed up for a duration of 6 months. Main outcome measures recorded were post-operative retinal status, visual acuity (VA), intraocular pressure (IOP) and surgical complications. RESULTS: Overall final retinal attachment at 6 months was 91.7% (90% in DAVS eyes and 93.3% in CAM eyes; p = 0.999). Final VA improved significantly from baseline in both groups (p < 0.001). Overall, VA improved to > = 20/40 in 18.3% eyes (6 DAVS, 5 CAM). Median duration of silicone oil endotamponade was 3.5 months (3.5 months in DAVS, 3 months in CAM). Redetachment rate in the series was 25% (20% in DAVS, 30% in CAM). Post-operative proliferative vitreoretinopathy grade C and more was present in 15% of eyes (10% in DAVS, 20% in CAM). Average duration of surgery was 37 ± 6.2 min in DAVS group and 39.8 ± 6.6 min in CAM group (p = 0.09). All steps of vitrectomy could be performed with relative ease and comfort with the DAVS platform. CONCLUSION: Anatomical and functional outcomes of RRD were favourable with DAVS and comparable to that with conventional microscope surgery.

Retrospective analysis of visual outcomes in retropupillary iris-suture-fixated rigid intraocular lens in a tertiary eye center in southern India.

PURPOSE: To report clinical outcomes of retropupillary iris-suture-fixated rigid intraocular lens (IFIOL) SETTING: Tertiary care ophthalmic hospital DESIGN: Retrospective study METHODS: This study included all eyes undergoing IFIOL with a minimum follow-up of 6 months between April 2017 and January 2019. Patients with preexisting anterior or posterior segment pathologies causing defective vision, uveitis or history of previous intraocular surgeries with exception of cataract surgery were excluded from the study. Data were retrieved from electronic medical records, and we documented demographics, history, position of cataractous lens or IOL, primary/secondary surgery and its complications. Postoperative visual acuity, pupillary response, diplopia, centration of IOL, inflammation were also recorded at the baseline visit and at 1 month, 3 months and 6 months postoperatively. RESULTS: One hundred and ten eyes of 110 patients that underwent IFIOL were evaluated. Twenty-two patients (20%) underwent primary IFIOL, whereas 67 (60.9%) patients had secondary IFIOL. In 18 patients (16.36%), IFIOL was done to reposition decentered/dislocated IOLs. At the final follow-up, there was a significant improvement in corrected distance visual acuity (CDVA) with 87 patients (79.09%) achieving CDVA of 6/12 or better. IFIOL was stable and centered in 101 eyes (91.81%). Two patients (1.81%) had intraoperative complications. Postoperative iritis was seen in 7 patients (6.36%), and 4 patients (3.63%) had rise in IOP. CONCLUSION: This is a safe, reliable, reproducible technique for aphakia rehabilitation and decentered IOL stabilization with good clinical outcome, especially in a limited resource setting.

Two-staged surgery as an alternative to buckle-vitrectomy for rhegmatogenous retinal detachment complicated by choroidal detachment.

AIM: To evaluate the outcome and safety profile of short-term perfluorocarbon liquids (PFCL) tamponade in comparison with buckle-vitrectomy in case of rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS: Records of patients who underwent surgery for RRD/CD from January 2016 to July 2019 were reviewed retrospectively. The patients were allocated into two groups-group 1 patients underwent buckle-vitrectomy, while those in group 2 underwent a two-staged vitrectomy with short-term (5 days) PFCL tamponade. RESULTS: The study included 33 eyes (33 patients) with mean age of 50.3 ± 17.2 years. Group 1 included 15 patients, while group 2 included 18. The pre-operative characteristics were similar in both the groups. The mean pre-operative intraocular pressure in group 1 and 2 was 9.1 ± 4.0 and 8.6 ± 5.2 mmHg, respectively (p = 0.755). Retinal re-attachment after single surgery was achieved in 10 (66.7%) and 14 eyes (77.8%), respectively. All the eyes achieved retinal re-attachment after repeat surgery in both the groups (1.40 vs 1.39 surgeries, p = 0.963). Post-surgery visual improvement was seen in 13 (86.7%) and 17 eyes (94.4%), respectively (p = 0.579). Final visual acuity of ≥ 6/60 was obtained in 7 (46.7%) and 9 eyes (50.0%), respectively (p > 0.999). None of the patients needed retinectomy during repeat surgery. None of the patients experienced exaggerated inflammation or intractable raised IOP spike which could not be controlled with medications. CONCLUSION: Surgical outcomes were similar in both the groups. No clinically apparent toxicity was seen with post-operative short-term PFCL tamponade. Two-staged surgery is a good alternative to buckle-vitrectomy for eyes with RRD associated with CD.

Ten-year trends in the incidence, clinical profile and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and sutureless, glueless and flapless scleral fixation of intraocular lenses.

PURPOSE: To evaluate the frequency and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and scleral fixation of intraocular lens. METHODS: We evaluated patients undergoing a sutureless, glueless, flapless technique of scleral fixation of intraocular lenses (SFIOL) implantation for various causes of aphakia and documented the clinico-demographic data, microbiological profile and final outcome after acute endophthalmitis in this cohort of eyes. RESULTS: The frequency of suspected acute endophthalmitis diagnosed post-surgery was 0.112% (4/3541 eyes), with culture-positive endophthalmitis frequency being 0.028% (1 eye), showing growth of Pseudomonas aeruginosa. Mean age of patients with endophthalmitis was 51.75 ± 9.28 years, and mean interval between surgery and acute endophthalmitis presentation was 10.25 ± 9.6 days. Patients were managed with intravitreal antibiotics with or without core vitrectomy. Visual acuity of patients increased from baseline 1.43 ± 0.32 logMAR (Snellen equivalent = 6/150) to 0.79 ± 0.16 logMAR (Snellen equivalent = 6/36) after an average follow-up of 11 ± 2 weeks. CONCLUSION: Endophthalmitis is a rare complication following SFIOL surgery, and all ophthalmic surgeons must be aware of this inadvertent possibility, since SFIOLs are gaining wider acceptability recently. Moreover, these cases of endophthalmitis may show a different pattern of microorganisms than post-cataract surgery endophthalmitis; however, with prompt diagnosis and effective timely management, favorable outcomes can be achieved.

Ophthalmic genetics practice and research in India: Vision in 2020.

Ophthalmic genetics is a much needed and growing area in India. Ethnic diversity, with a high degree of consanguinity, has led to a high prevalence of genetic disorders in the country. As the second most populous country in the world, this naturally results in a significant number of affected people overall. Practice involves coherent association between ophthalmologists, genetic counselor and pediatricians. Eye genetics in India in recent times has witnessed advanced research using cutting edge diagnostics, next generation sequencing (NGS) approaches, stem cell therapies, gene therapy and genomic editing. This article will highlight the studies reporting genetic variations in the country, challenges in practice, and the latest advances in ophthalmic genetic research in India.

Network mapping of the conformational heterogeneity of SOD1 by deploying statistical cluster analysis of FTIR spectra.

A crucial contribution to the heterogeneity of the conformational landscape of a protein comes from the way an intermediate relates to another intermediate state in its journey from the unfolded to folded or misfolded form. Unfortunately, it is extremely hard to decode this relatedness in a quantifiable manner. Here, we developed an application of statistical cluster analyses to explore the conformational heterogeneity of a metalloenzyme, human cytosolic copper-zinc superoxide dismutase (SOD1), using the inputs from infrared spectroscopy. This study provides a quantifiable picture of how conformational information at one particular site (for example, the copper-binding pocket) is related to the information at the second site (for example, the zinc-binding pocket), and how this relatedness is transferred to the global conformational information of the protein. The distance outputs were used to quantitatively generate a network capturing the folding sub-stages of SOD1.

Clinical presentation and prognostic factors affecting surgical outcomes of secondary macular holes after retinal vein occlusions.

PURPOSE: To describe clinical presentation, morphological features and surgical outcomes of macular hole (MH) secondary to retinal vein occlusion (RVO). METHOD: This prospective interventional study evaluated eight eyes with atypical MH (secondary to RVO) and data regarding medical management, pars plana vitrectomy, postoperative anatomical hole closure, visual acuity improvement, morphological features of hole were noted till the last follow-up. RESULTS: Eight eyes with full-thickness MH in an RVO eye were followed-up for a minimum period of 3 months postoperatively. Five subjects had a RVO episode which occurred more than 6 months before the onset of the recent symptoms (Group 1; 4 branch RVO and 1 central RVO), and 3 subjects had a recent onset branch RVO within 6 months (Group 2). All FTMH cases except one showed closure at the last follow-up. Visual acuity of all eyes improved from 0.91 ± 0.57 logMAR to 0.5 ± 0.3 logMAR (p = 0.093). At baseline, visual acuities of the two groups had no significant difference. Postoperatively, group 1 holes had better visual prognosis, than Group 2 holes, further substantiated by persistence of subretinal fluid in Group 2 eyes till last follow-up. Minimum hole diameter was higher in the recent RVO group, although anatomical closure was obtained in all of these eyes. Most holes had favorable morphological hole features like raised configuration with rounded edges. CONCLUSION: In the presence of favorable morphological features, secondary macular holes associated with retinal vein occlusion may show optimal outcomes after surgery. It is not clear whether acutely created holes in recent onset RVO should be operated early. Older holes may have better prognosis.

Understanding the evolutionary trend of intrinsically structural disorders in cancer relevant proteins as probed by Shannon entropy scoring and structure network analysis.

BACKGROUND: Malignant diseases have become a threat for health care system. A panoply of biological processes is involved as the cause of these diseases. In order to unveil the mechanistic details of these diseased states, we analyzed protein families relevant to these diseases. RESULTS: Our present study pivots around four apparently unrelated cancer types among which two are commonly occurring viz. Prostate Cancer, Breast Cancer and two relatively less frequent viz. Acute Lymphoblastic Leukemia and Lymphoma. Eight protein families were found to have implications for these cancer types. Our results strikingly reveal that some of the proteins with implications in the cancerous cellular states were showing the structural organization disparate from the signature of the family it constitutes. The sequences were further mapped onto respective structures and compared with the entropic profile. The structures reveal that entropic scores were able to reveal the inherent structural bias of these proteins with quantitative precision, otherwise unseen from other analysis. Subsequently, the betweenness centrality scoring of each residue from the structure network models was resorted to explore the changes in dependencies on residue owing to structural disorder. CONCLUSION: These observations help to obtain the mechanistic changes resulting from the structural orchestration of protein structures. Finally, the hydropathy indexes were obtained to validate the sequence space observations using Shannon entropy and in-turn establishing the compatibility.

Multifocal electroretinogram in eyes with intravitreal silicone oil and changes following silicone oil removal.

PURPOSE: To determine the effect of intravitreal silicone oil (SO) on multifocal electroretinogram (mfERG) and the changes in mfERG following SO removal. METHODS: Twelve eyes of 12 patients with SO in vitreous cavity with corrected distance visual acuity (CDVA) > 20/200 were prospectively enrolled as cases over a period from July 2016 to June 2018. The fellow normal eyes served as control. The eyes were evaluated with P1 and N1 wave amplitude and implicit time on mfERG at baseline, 1 and 4 weeks after SO removal. RESULTS: The mean age was 44.9 ± 18.9 (range 18-74) years. The indication for SO injection was retinal detachment (n = 9, three macula-on eyes, six macula-off eyes) and endophthalmitis (n = 3). The median (range) LogMAR CDVA at baseline was 0.54 (0.18-0.78) in cases and did not change post-SO removal (p = 0.29). There was a significant decrease in average P1 and N1 wave amplitude (p = 0.0001 and 0.0001, respectively) and delay in average P1 and N1 wave implicit time (p = 0.0002 and 0.021, respectively) in cases as compared to controls. The macular status and duration of SO tamponade did not have a significant correlation with mfERG parameters. There was a significant increase in average P1 and N1 wave amplitude (p = 0.009 and 0.003, respectively) at 1 week following SO removal but no change in average P1 and N1 wave implicit time (p = 0.41 and 0.37, respectively). CONCLUSION: mfERG may be reliably performed for the assessment of macular function in SO-filled eyes. Intravitreal SO exerts an insulating effect on the density of the electric potentials.

Detecting TF-miRNA-gene network based modules for 5hmC and 5mC brain samples: a intra- and inter-species case-study between human and rhesus.

BACKGROUND: Study of epigenetics is currently a high-impact research topic. Multi stage methylation is also an area of high-dimensional prospect. In this article, we provide a new study (intra and inter-species study) on brain tissue between human and rhesus on two methylation cytosine variants based data-profiles (viz., 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) samples) through TF-miRNA-gene network based module detection. RESULTS: First of all, we determine differentially 5hmC methylated genes for human as well as rhesus for intra-species analysis, and differentially multi-stage methylated genes for inter-species analysis. Thereafter, we utilize weighted topological overlap matrix (TOM) measure and average linkage clustering consecutively on these genesets for intra- and inter-species study.We identify co-methylated and multi-stage co-methylated gene modules by using dynamic tree cut, for intra-and inter-species cases, respectively. Each module is represented by individual color in the dendrogram. Gene Ontology and KEGG pathway based analysis are then performed to identify biological functionalities of the identified modules. Finally, top ten regulator TFs and targeter miRNAs that are associated with the maximum number of gene modules, are determined for both intra-and inter-species analysis. CONCLUSIONS: The novel TFs and miRNAs obtained from the analysis are: MYST3 and ZNF771 as TFs (for human intra-species analysis), BAZ2B, RCOR3 and ATF1 as TFs (for rhesus intra-species analysis), and mml-miR-768-3p and mml-miR-561 as miRs (for rhesus intra-species analysis); and MYST3 and ZNF771 as miRs(for inter-species study). Furthermore, the genes/TFs/miRNAs that are already found to be liable for several brain-related dreadful diseases as well as rare neglected diseases (e.g., wolf Hirschhorn syndrome, Joubarts Syndrome, Huntington's disease, Simian Immunodeficiency Virus(SIV) mediated enchaphilits, Parkinsons Disease, Bipolar disorder and Schizophenia etc.) are mentioned.