المؤلفون: Faye M. Walker, Lays Martin Sobral, Etienne Danis, Bridget Sanford, Sahiti Donthula, Ilango Balakrishnan, Dong Wang, Angela Pierce, Sana D. Karam, Soudabeh Kargar, Natalie J. Serkova, Nicholas K. Foreman, Sujatha Venkataraman, Robin Dowell, Rajeev Vibhakar, Nathan A. Dahl

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-21 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract Dynamic regulation of gene expression is fundamental for cellular adaptation to exogenous stressors. P-TEFb-mediated pause-release of RNA polymerase II (Pol II) is a conserved regulatory mechanism for synchronous transcriptional induction in response to heat shock, but this pro-survival role has not been examined in the applied context of cancer therapy. Using model systems of pediatric high-grade glioma, we show that rapid genome-wide reorganization of active chromatin facilitates P-TEFb-mediated nascent transcriptional induction within hours of exposure to therapeutic ionizing radiation. Concurrent inhibition of P-TEFb disrupts this chromatin reorganization and blunts transcriptional induction, abrogating key adaptive programs such as DNA damage repair and cell cycle regulation. This combination demonstrates a potent, synergistic therapeutic potential agnostic of glioma subtype, leading to a marked induction of tumor cell apoptosis and prolongation of xenograft survival. These studies reveal a central role for P-TEFb underpinning the early adaptive response to radiotherapy, opening avenues for combinatorial treatment in these lethal malignancies.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/d56159185f7f4564adf980120f3ab2ba

المؤلفون: Selina Fecht, Patricia Paracuellos, Sujatha Subramoni, Casandra Ai Zhu Tan, Aravindan Ilangovan, Tiago R. D. Costa, Alain Filloux

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract The genome of Pseudomonas aeruginosa encodes three type VI secretion systems, each comprising a dozen distinct proteins, which deliver toxins upon T6SS sheath contraction. The least conserved T6SS component, TssA, has variations in size which influence domain organisation and structure. Here we show that the TssA Nt1 domain interacts directly with the sheath in a specific manner, while the C-terminus is essential for oligomerisation. We built chimeric TssA proteins by swapping C-termini and showed that these can be functional even when made of domains from different TssA sub-groups. Functional specificity requires the Nt1 domain, while the origin of the C-terminal domain is more permissive for T6SS function. We identify two regions in short TssA proteins, loop and hairpin, that contribute to sheath binding. We propose a docking mechanism of TssA proteins with the sheath, and a model for how sheath assembly is coordinated by TssA proteins from this position.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2041-1723

URL الوصول: https://doaj.org/article/3abfa31a14b442cfb7b894626719e8d1

المؤلفون: Harsh Sheth, Aadhira Nair, Riddhi Bhavsar, Mahesh Kamate, Vykuntaraju K. Gowda, Ashish Bavdekar, Sandeep Kadam, Sheela Nampoothiri, Inusha Panigrahi, Anupriya Kaur, Siddharth Shah, Sanjeev Mehta, Sujatha Jagadeesan, Indrani Suresh, Seema Kapoor, Shruti Bajaj, Radha Rama Devi, Ashka Prajapati, Koumudi Godbole, Harsh Patel, Zulfiqar Luhar, Raju C. Shah, Anand Iyer, Sunita Bijarnia, Ratna Puri, Mamta Muranjan, Ami Shah, Suvarna Magar, Neerja Gupta, Naresh Tayade, Ajit Gandhi, Ajit Sowani, Shrutikaa Kale, Anil Jalan, Dhaval Solanki, Ashwin Dalal, Shrikant Mane, C. Ratna Prabha, Frenny Sheth, Chaitanya G. Joshi, Madhvi Joshi, Jayesh Sheth

المصدر: Human Genomics, Vol 18, Iss 1, Pp 1-20 (2024)

مصطلحات موضوعية: Lysosomal storage disorders, smMIP probes, Dried blood spot, Diagnostic yield, Cost effective, Medicine, Genetics, QH426-470

الوصف: Abstract Background Current clinical diagnosis pathway for lysosomal storage disorders (LSDs) involves sequential biochemical enzymatic tests followed by DNA sequencing, which is iterative, has low diagnostic yield and is costly due to overlapping clinical presentations. Here, we describe a novel low-cost and high-throughput sequencing assay using single-molecule molecular inversion probes (smMIPs) to screen for causative single nucleotide variants (SNVs) and copy number variants (CNVs) in genes associated with 29 common LSDs in India. Results 903 smMIPs were designed to target exon and exon–intron boundaries of targeted genes (n = 23; 53.7 kb of the human genome) and were equimolarly pooled to create a sequencing library. After extensive validation in a cohort of 50 patients, we screened 300 patients with either biochemical diagnosis (n = 187) or clinical suspicion (n = 113) of LSDs. A diagnostic yield of 83.4% was observed in patients with prior biochemical diagnosis of LSD. Furthermore, diagnostic yield of 73.9% (n = 54/73) was observed in patients with high clinical suspicion of LSD in contrast with 2.4% (n = 1/40) in patients with low clinical suspicion of LSD. In addition to detecting SNVs, the assay could detect single and multi-exon copy number variants with high confidence. Critically, Niemann-Pick disease type C and neuronal ceroid lipofuscinosis-6 diseases for which biochemical testing is unavailable, could be diagnosed using our assay. Lastly, we observed a non-inferior performance of the assay in DNA extracted from dried blood spots in comparison with whole blood. Conclusion We developed a flexible and scalable assay to reliably detect genetic causes of 29 common LSDs in India. The assay consolidates the detection of multiple variant types in multiple sample types while having improved diagnostic yield at same or lower cost compared to current clinical paradigm.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/1479-7364

URL الوصول: https://doaj.org/article/8292fe789fb04f60a6890327d1f87871

المؤلفون: Leena HN, Savitha B Raghavan, Yogesh HR, Sujatha Sowmyanarayan, Amberkar Mohanbabu Vittalrao, Abhineetha Hosthota

المصدر: Perspectives In Medical Research, Vol 12, Iss 1, Pp 45-48 (2024)

مصطلحات موضوعية: facial angiofibroma, topical sirolimus, tuberous sclerosis complex, Medicine

الوصف: Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder. Facial angiofibromas are the most common cutaneous findings of TSC. Treatment modalities such as laser, surgery, and/or cryotherapy are employed. Topical therapy with Sirolimus, an mTOR inhibitor, showed beneficial effects. Objective: To study the effects of topical sirolimus (0.1%) on Facial Angiofibromas in patients of TSC. Methodology: Four patients with facial angiofibromas were included. They applied Sirolimus preparation twice daily, for 3 months. The Facial Angiofibroma Severity Index (FASI) was recorded pre-intervention, at 3 months and after 6 months. Results: All the patients showed a reduction in the FASI score at the end of three months of therapy. In three patients, on discontinuing therapy, there was no change in the FASI score at the end of six months, i.e., FASI 3 and FASI 6 were the same. Conclusion: Topical sirolimus is an effective treatment for facial angiofibroma in patients with TSC.

وصف الملف: electronic resource

Relation: https://www.pimr.org.in/2024-vol12-issue-1/originalarticle9_v1.pdf; https://doaj.org/toc/2348-1447; https://doaj.org/toc/2348-229X

URL الوصول: https://doaj.org/article/d7a1be79927b46179aaae0fac526c216

المؤلفون: Akhilash Mohanan Pillai, Sumol V. Gopinadh, Peddinti V. R. L. Phanendra, Patteth S. Salini, Bibin John, Sujatha SarojiniAmma, Mercy Thelakkattu Devassy

المصدر: Discover Nano, Vol 19, Iss 1, Pp 1-14 (2024)

مصطلحات موضوعية: Lithium-ion batteries, Green-synthesis, TiO2-NPs, Water-based binder, Electrochemical performance, Materials of engineering and construction. Mechanics of materials, TA401-492

الوصف: Abstract Titanium dioxide nanoparticles (TiO2-NPs) are a promising anode material for Lithium-ion batteries (LIBs) due to their good rate capability, low cost, non-toxicity, excellent structural stability, extended cycle life, and low volumetric change (∼4%) during the Li+ insertion/de-insertion process. In the present paper, anatase TiO2-NPs with an average particle size of ~ 12 nm were synthesized via a green synthesis route using Beta vulgaris (Beetroot) extract, and the synthesized TiO2-NPs were evaluated as anode material in LIBs. Furthermore, we employed an aqueous binder (1:1 mixture of carboxy methyl cellulose and styrene butadiene) for electrode processing, making the process cost-effective and environmentally friendly. The results revealed that the Li/TiO2 half-cells delivered an initial discharge capacity of 209.7 mAh g−1 and exhibited superior rate capability (149 mAh g−1 at 20 C) and cycling performances. Even at the 5C rate, the material retained a capacity of 82.2% at the end of 100 cycles. The synthesis route of TiO2-NPs and the aqueous binder-based electrode processing described in the present work are facile, green, and low-cost and are thus practically beneficial for producing low-cost and high-performance anodes for advanced LIBs.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2731-9229

URL الوصول: https://doaj.org/article/a155585615e44deb9d38c8939d8ad2ab

المؤلفون: Louis Robert W. Belem, Sylvester Agha Ibemgbo, Michel Kiréopori Gomgnimbou, Dileep Kumar Verma, Antoinette Kaboré, Ankit Kumar, Ibrahim Sangaré, Sujatha Sunil

المصدر: Current Issues in Molecular Biology, Vol 46, Iss 3, Pp 2093-2104 (2024)

مصطلحات موضوعية: multiplex, molecular, detection, dengue virus, chikungunya virus, arbovirus, Biology (General), QH301-705.5

الوصف: The major arboviruses mainly belong to the Bunyaviridae, Togaviridae, and Flaviviridae families, among which the chikungunya virus and dengue virus have emerged as global public health problems. The main objective of this study was to develop specific, sensitive, and cost-effective molecular multiplex RT-PCR and RT-qPCR assays for the rapid and simultaneous detection of CHIKV and the four serotypes of DENV for arbovirus surveillance. Specific primers for all viruses were designed, and one-step multiplex RT-PCR (mRT-PCR) and RT-qPCR (mRT-qPCR) were developed using reference strains of the CHIKV and DENV serotypes. The specificity of the test for all the viruses was confirmed through sequencing. The standard curves showed a high correlation coefficient, R2 = 0.99, for DENV-2 and DENV-3; R2 = 0.98, for DENV-4; and CHIKV; R2 = 0.93, for DENV-1. The limits of detection were calculated to be 4.1 × 10−1 copies/reaction for DENV-1, DENV-3, and CHIKV and 4.1 × 101 for DENV-2 and DENV-4. The specificity and sensitivity of the newly developed mRT-PCR and mRT-qPCR were validated using positive serum samples collected from India and Burkina Faso. The sensitivity of mRT-PCR and mRT-qPCR are 91%, and 100%, respectively. The specificity of both assays was 100%. mRT-PCR and mRT-qPCR assays are low-cost, and a combination of both will be a useful tool for arbovirus surveillance.

وصف الملف: electronic resource

Relation: https://www.mdpi.com/1467-3045/46/3/134; https://doaj.org/toc/1467-3037; https://doaj.org/toc/1467-3045

URL الوصول: https://doaj.org/article/3c11c3ab55724249912494436d16bafb

المؤلفون: Sravani Kamatham, Manoharan Seeralan, Uma Sekar, Sujatha Kuppusamy

المصدر: ACS Omega, Vol 9, Iss 11, Pp 12801-12809 (2024)

مصطلحات موضوعية: Chemistry, QD1-999

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2470-1343

URL الوصول: https://doaj.org/article/70384bce1cf448819564d2f73b0c5502

المؤلفون: Naveed Akhtar, Rajvir Singh, Saadat Kamran, Sujatha Joseph, Deborah Morgan, Ryan Ty Uy, Sarah Treit, Ashfaq Shuaib

المصدر: BMC Neurology, Vol 24, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: Ischemic stroke, Triglyceride, Small vessel disease, Outcome, Major adverse cardiovascular events, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Background and objectives Hypertriglyceridemia (HT) may increase the risk of stroke. Limited studies have shown that stroke severity and infarction size are smaller in patients with HT. We explored the relationship between triglyceride levels and stroke risk factors, severity and outcome in a large prospective database. Design Prospective Cross-sectional study. Setting We retrospectively interrogated the Qatar Stroke Database in all patients admitted between 2014-2022 with acute ischemic stroke and evaluated the relationship between triglyceride, diabetes, stroke severity (measured on NIHSS), stroke type (TOAST classification) and the short- (mRS at 90 days) and long-term outcomes (MACE at 1 year) in patients with HT. Participants Six thousand five hundred fifty-eight patients ≥20 years were included in this study Results Six thousand five hundred fifty-eight patients with ischemic stroke [mean age 54.6 ± 12. 9; male 82.1%) were included. Triglyceride levels upon admission were low-normal (≤1.1 mmol/L) in 2019 patients, high-normal (1.2-1.7 mmol/L) in 2142 patients, borderline-high (1.8-2.2 mmol/L) in 1072 patients and high (≥2.3 mmol/L) in 1325 patients. Higher triglyceride levels were associated with stroke and increased likelihood of having diabetes, obesity, active smoking, and small vessel/lacunar stroke type. An inverse relationship was noted whereby higher triglyceride levels were associated with lower stroke severity and reduced likelihood of poorer outcome (mRS 3-6) at discharge and 90 days. Long-term MACE events were less frequent in patients with higher triglyceride levels. After adjusting age, gender, diabetes, prior stroke, CAD, and obesity, multivariate analysis showed that hypertension and triglyceride levels were higher in mild ischemic strokes patients. Conclusions Increasing triglycerides are associated with higher risk of small vessel disease and requires further prospective cohort studies for confirmation.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/1471-2377

URL الوصول: https://doaj.org/article/e242090c34c649c3b6a59ed92e2727bc

المؤلفون: Stalin Ramprakash, C.P. Raghuram, Anoop P, Veerabhadra Gupta, Sujatha Thyagarajan

المصدر: Pediatric Hematology Oncology Journal, Vol 9, Iss 1, Pp 24-27 (2024)

مصطلحات موضوعية: Immune-mediated thrombotic thrombocytopenic purpura (iTTP), COVID-19, Children, Pediatrics, RJ1-570

الوصف: Acute COVID-19 infection typically results in mild disease in children, but can lead to several immune manifestations. One such severe manifestation is immune-mediated thrombotic thrombocytopenia (iTTP). It is exceedingly rare in children, and only a few cases have been reported worldwide. We report a case of severe iTTP in a 17-year-old girl. She was positive for COVID-19 infection by reverse-transcription polymerase chain reaction at presentation and had received a Covaxin injection two weeks earlier. She responded to therapeutic plasma exchange, corticosteroids, and rituximab. Early recognition of this complication and prompt initiation of therapeutic plasma exchange and corticosteroids is paramount to achieving a good outcome in this rare, life-threatening complication.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S2468124524000032; https://doaj.org/toc/2468-1245

URL الوصول: https://doaj.org/article/f4ed8b7a470145bf91088e6f9073474f

المؤلفون: Subitcha Jayasankar, Sujatha Narayanan Unni

المصدر: Results in Optics, Vol 16, Iss , Pp 100707- (2024)

مصطلحات موضوعية: Endogenous fluorescence spectroscopy, FAD and NADH, Redox ratio, Time-varying analysis, Machine learning, Optics. Light, QC350-467

الوصف: Body fluids carry several biomarkers and genetic material that enable the detection of carcinogenesis and tumor metastasis. Owing to this, liquid biopsy is gaining importance and entering clinical practice as an adjunct modality to the current standard of practice in cancer detection. Liquid biopsy involving specimens such as urine is non-invasive and has biomarkers reflecting the tumor microenvironment. We investigate the normal and altered levels of cellular metabolic by-products in liquid phantoms and demonstrate their photon-induced excited-state interaction behaviour for potential diagnostic applications. Short-span temporal analysis of metabolic by-products FAD and NADH in liquid phantoms with fiber optic fluorescence spectroscopy is carried out. The mixed liquid phantom of FAD and NADH, showed excited state interactions that manifested as simultaneous inverse variation in the fluorescence emission from FAD and NADH in varying pH environments. Linear discriminant analysis of the time-varying integrated fluorescence intensity resulted in a 100% accuracy in classifying liquid samples between high and low metabolite concentrations. An extension of application of the experiment model for analysis of body fluids such as urine is also discussed.

وصف الملف: electronic resource

Relation: http://www.sciencedirect.com/science/article/pii/S2666950124001044; https://doaj.org/toc/2666-9501

URL الوصول: https://doaj.org/article/adfb01a2652e4c1fa4e820a387301214