Publications by authors named "Pankaj Sharma"

468 Publications

The two non-visual arrestins engage ERK2 differently.

J Mol Biol 2022 Jan 22:167465. Epub 2022 Jan 22.

Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-0146; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232-0146; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232-0146; Vanderbilt Institute for Chemical Biology, Vanderbilt University, Nashville, TN 37232-0146. Electronic address:

Arrestin binding to active phosphorylated G protein-coupled receptors terminates G protein coupling and initiates another wave of signaling. Among the effectors that bind directly to receptor-associated arrestins are extracellular signal-regulated kinases 1/2 (ERK1/2), which promote cellular proliferation and survival. Arrestins may also engage ERK1/2 in isolation in a pre- or post-signaling complex that is likely in equilibrium with the full signal initiation complex. Molecular details of these binary complexes remain unknown. Here, we investigate the molecular mechanisms whereby arrestin-2 and arrestin-3 (a.k.a. β-arrestin1 and β-arrestin2, respectively) engage ERK1/2 in pairwise interactions. We find that purified arrestin-3 binds ERK2 more avidly than arrestin-2. A combination of biophysical techniques and peptide array analysis demonstrates that the molecular basis in this difference of binding strength is that the two non-visual arrestins bind ERK2 via different parts of the molecule. We propose a structural model of the ERK2-arrestin-3 complex in solution using size-exclusion chromatography coupled to small angle X-ray scattering (SEC-SAXS). This binary complex exhibits conformational heterogeneity. We speculate that this drives the equilibrium either toward the full signaling complex with receptor-bound arrestin at the membrane or toward full dissociation in the cytoplasm. As ERK1/2 regulates cell migration, proliferation, and survival, understanding complexes that relate to its activation could be exploited to control cell fate.
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http://dx.doi.org/10.1016/j.jmb.2022.167465DOI Listing
January 2022

Experience of quantity and quality of DNA and RNA extraction from limited pediatric blood samples: A comparative analysis of automated and manual kit-based method.

Indian J Pathol Microbiol 2022 Jan-Mar;65(1):105-110

Pediatric Hematology-Oncology Laboratory, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: Optimal DNA and RNA quantity and purity is essential for downstream molecular biology experimentation and to avoid re-processing of sample. Despite availability of different kits and automated systems for nucleic acid isolation there is limited data on their performance evaluation, more so with pediatric blood samples, that are usually compromised in quantity. Hence, we evaluated the performance of automated QIAcube platform using pediatric blood samples in parallel with manual Qiagen extraction kits.

Materials And Methods: : A total of 500 samples were analyzed based on groups of PBMC and direct blood input. The isolated DNA and RNA were surveyed for quantity and quality tests by spectrophotometric and downstream analysis.

Results: : There was no significant difference in the DNA quantity (ng/ul) between manual and automated method based on similar sample input but quality (260/280) was significantly better with the QIAcube platform when direct blood and or PBMCs were used for extraction respectively (1.82 ± 004 Vs. 1.84.002; P-0.000008 and 1.859 ± 005 Vs. 1.843 ± 0.003; P-0.02). Moreover, the standard error mean was low for both quantity and quality in the QIAcube method suggesting uniformity. Comparison of quality assessment by spectrophotometer and qubit fluorimeter showed that QIAcube sheared DNA less (P- 0.038) as compared to manual method (P-0.013). Also, time taken to process the samples in QIAcube was 23% less than the kit-based method.

Conclusion: Overall analysis of QIAcube platform suggests that it yields more better, uniform, and less-sheared quality of nucleic acid in a relatively less time as compared to manual extraction kits.
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http://dx.doi.org/10.4103/IJPM.IJPM_946_20DOI Listing
January 2022

Endovascular Management of Hemorrhagic Stroke.

Biomedicines 2022 Jan 4;10(1). Epub 2022 Jan 4.

Department of Neurosurgery and Neurointerventional Radiology, Louisiana State University, Shreveport, LA 70803, USA.

Significant advances in endovascular neurosurgery tools, devices, and techniques are changing the approach to the management of acute hemorrhagic stroke. The endovascular treatment of intracranial aneurysms emerged in the early 1990s with Guglielmi detachable coils, and since then, it gained rapid popularity that surpassed open surgery. Stent-assisted coiling and balloon remodeling techniques have made the treatment of wide-necked aneurysms more durable. With the introduction of flow diverters and flow disrupters, many aneurysms with complex geometrics can now be reliably managed. Arteriovenous malformations and fistulae can also benefit from endovascular therapy by embolization using n-butyl cyanoacrylate (NBCA), Onyx, polyvinyl alcohol (PVA), and coils. In this article, we describe the role of endovascular treatment for the most common causes of intracerebral and subarachnoid hemorrhages, particularly ruptured aneurysms and vascular malformations.
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http://dx.doi.org/10.3390/biomedicines10010100DOI Listing
January 2022

Antiplatelet therapy in cardiovascular disease: current status and future directions.

Br J Clin Pharmacol 2022 Jan 9. Epub 2022 Jan 9.

School of Cardiovascular Medicine and Sciences, British Heart Foundation Centre of Research Excellence, King's College London, London, UK.

Antiplatelet medications remain a cornerstone of therapy for atherosclerotic cardiovascular and cerebrovascular diseases. In primary prevention (patients with cardiovascular risk factors but no documented events, symptoms or angiographic disease), there is little evidence of benefit of any antiplatelet therapy, and such therapy carries the risk of excess bleeding. Where there is documented disease (secondary prevention), stable patients benefit from long-term antiplatelet monotherapy, aspirin being first choice in those with coronary heart disease and clopidogrel in those with cerebrovascular disease; moreover, recent evidence shows that low-dose rivaroxaban in combination with aspirin confers added benefit, in patients with stable cardiovascular and peripheral arterial disease. In patients with acute cerebrovascular disease, aspirin combined with clopidogrel reduces subsequent risk, while in acute coronary syndrome, dual antiplatelet therapy comprising aspirin and a P2Y inhibitor (clopidogrel, prasugrel or ticagrelor) confers greater protection than aspirin monotherapy, with prasugrel and ticagrelor offering greater antiplatelet efficacy with faster onset of action than clopidogrel. Although greater antiplatelet efficacy is advantageous in preventing thrombotic events, this must be tempered by increased risk of bleeding which may be a particular issue in certain patient groups, as will be discussed. We will also discuss possible future approaches to personalisation of antiplatelet therapy.
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http://dx.doi.org/10.1111/bcp.15221DOI Listing
January 2022

Monosomy 1p36: Report of a cohort of 13 Asian Indian patients.

Am J Med Genet A 2022 Jan 6. Epub 2022 Jan 6.

Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Monosomy 1p36 is one of the common microdeletion syndromes with a recognizable facial phenotype. Failure to thrive, developmental delay, congenital heart disease, and other abnormalities are common in these patients. This is the first study on Asian Indian patients with monosomy 1p36, documenting the phenotypic characteristics of 13 patients, indicating phenotypic similarities in a diverse population and broadening the clinical spectrum.
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http://dx.doi.org/10.1002/ajmg.a.62630DOI Listing
January 2022

Alkali-Metal-Mediated Reversible Chemical Hydrogen Storage Using Seawater.

JACS Au 2021 Dec 3;1(12):2339-2348. Epub 2021 Nov 3.

School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-gil, Ulsan 44919, Republic of Korea.

The economic viability and systemic sustainability of a green hydrogen economy are primarily dependent on its storage. However, none of the current hydrogen storage methods meet all the targets set by the US Department of Energy (DoE) for mobile hydrogen storage. One of the most promising routes is through the chemical reaction of alkali metals with water; however, this method has not received much attention owing to its irreversible nature. Herein, we present a reconditioned seawater battery-assisted hydrogen storage system that can provide a solution to the irreversible nature of alkali-metal-based hydrogen storage. We show that this system can also be applied to relatively lighter alkali metals such as lithium as well as sodium, which increases the possibility of fulfilling the DoE target. Furthermore, we found that small (1.75 cm) and scaled-up (70 cm) systems showed high Faradaic efficiencies of over 94%, even in the presence of oxygen, which enhances their viability.
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http://dx.doi.org/10.1021/jacsau.1c00444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715542PMC
December 2021

Synthesis of SAPO-34 Nanoplates with High Si/Al Ratio and Improved Acid Site Density.

Nanomaterials (Basel) 2021 Nov 25;11(12). Epub 2021 Nov 25.

Reaction and Separation Nanomaterials Laboratory, Graduate School of Energy Science and Technology, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.

Two-dimensional SAPO-34 molecular sieves were synthesized by microwave hydrothermal process. The concentrations of structure directing agent (SDA), phosphoric acid, and silicon in the gel solution were varied and their effect on phase, shape, and composition of synthesized particles was studied. The synthesized particles were characterized by various techniques using SEM, XRD, BET, EDX, and NH-TPD. Various morphologies of particles including isotropic, hyper rectangle, and nanoplates were obtained. It was found that the Si/Al ratio of the SAPO-34 particles was in a direct relationship with the density of acid sites. Moreover, the gel composition and preparation affected the chemistry of the synthesized particles. The slow addition of phosphoric acid improved the homogeneity of synthesis gel and resulted in SAPO-34 nanoplates with high density of acid sites, 3.482 mmol/g. The SAPO-34 nanoplates are expected to serve as a high performance catalyst due to the low mass transfer resistance and the high density of active sites.
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http://dx.doi.org/10.3390/nano11123198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703864PMC
November 2021

Disproportionate Mitral Regurgitation Determines Survival in Acute Heart Failure.

Front Cardiovasc Med 2021 2;8:742224. Epub 2021 Dec 2.

Department of Cardiology, St. Peter's Hospital, Surrey, United Kingdom.

To assess the prevalence and impact of mitral regurgitation (MR) on survival in patients presenting to hospital in acute heart failure (AHF) using traditional echocardiographic assessment alongside more novel indices of proportionality. It remains unclear if the severity of MR plays a significant role in determining outcomes in AHF. There is also uncertainty as to the clinical relevance of indexing MR to left ventricular volumes. This concept of disproportionality has not been assessed in AHF. A total of 418 consecutive patients presenting in AHF over 12 months were recruited and followed up for 2 years. MR was quantitatively assessed within 24 h of recruitment. Standard proximal isovelocity surface area (PISA) and a novel proportionality index of effective regurgitant orifice/left ventricular end-diastolic volume (ERO/LVEDV) >0.14 mm/ml were used to identify severe and disproportionate MR. Every patient had MR. About 331/418 (78.9%) patients were quantifiable by PISA. About 165/418 (39.5%) patients displayed significant MR. A larger cohort displayed disproportionate MR defined by either a proportionality index using ERO/LVEDV > 0.14 mm/ml or regurgitant volumes/LVEDV > 0.2 [217/331 (65.6%) and 222/345 (64.3%), respectively]. The LVEDV was enlarged in significant MR-129.5 ± 58.95 vs. 100.0 ± 49.91 ml in mild, [ < 0.0001], but remained within the normal range. Significant MR was associated with a greater mortality at 2 years {44.2 vs. 34.8% in mild MR [hazard ratio (HR) 1.39; 95% CI: 1.01-1.92, = 0.04]}, which persisted with adjustment for comorbid conditions (HR; 1.43; 95% CI: 1.04-1.97, = 0.03). Disproportionate MR defined by ERO/LVEDV >0.14 mm/ml was also associated with worse outcome [42.4 vs. 28.3% (HR 1.62; 95% CI 1.12-2.34, = 0.01)]. MR was a universal feature in AHF and determines outcome in significant cases. Furthermore, disproportionate MR, defined either by effective regurgitant orifice (ERO) or volumetrically, is associated with a worse prognosis despite the absence of adverse left ventricular (LV) remodeling. These findings outline the importance of adjusting acute volume overload to LV volumes and call for a review of the current standards of MR assessment. https://clinicaltrials.gov/ct2/show/NCT02728739, identifier NCT02728739.
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http://dx.doi.org/10.3389/fcvm.2021.742224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675886PMC
December 2021

"Does Mandibular Condylar Morphology After Fracture Healing Predict Functional Outcomes in Patients Treated With Closed Reduction?"

J Oral Maxillofac Surg 2021 Nov 13. Epub 2021 Nov 13.

Senior Resident, Department of Oral and maxillofacial surgery, Maulana Azad institute of Dental Sciences, New Delhi, India.

Purpose: The purpose of the study is to assess the healing temporomandibular joint morphology and function after closed treatment of unilateral mandibular condylar fracture.

Materials And Methods: A prospective interventional cohort study was designed in patients recruited from the outpatient department who underwent closed reduction for unilateral condylar fractures, and mean mouth opening, mean maximum protrusion, laterotrusion, and radiological pattern of healing were noted.

Results: Forty patients in the age group of 18-50 years (mean 24.5 years) were included. The difference between the pretreatment mean mouth opening (26.94 mm), mean maximum protrusion (1.22 mm), and laterotrusion (3.82 mm and 1.45 mm) values and the 6-month post-treatment values (46.3 mm, 4.45 mm, and 11.82 mm and 9.82 mm, respectively) was found to be statistically significant (P < .001). Deranged pretreatment occlusion seen in 20 cases was improved in 18 patients (85%) at the 6-month post-treatment visit, with persisting malocclusion in 2 patients (5%). Clinically, cases that had healed with the anatomical pattern (M1) were found to have significantly better clinical outcomes (P value < .05) than that achieved with cases healed with spherical pattern (M2), L-shaped pattern (M3), or detached pattern (M4). On radiographs, the greatest improvement (21.16 mm) in mean mouth opening values was seen in the M1 group (anatomical pattern), followed by similar improvement in groups M2 and M3 (18.39 and 18.66 mm, respectively). Least improvement (7.06 mm) was seen in the single case of the M4 group (detached pattern), although the 6-month post-treatment value was still an acceptable one (34 mm).

Conclusions: Favorable functional outcomes can be achieved after closed treatment, including adequate mouth opening, pain-free jaw excursions, and stable occlusion, with the anatomical healing pattern showing the most superior results and the detached pattern being associated with relatively poorer outcomes compared with other healing patterns.
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http://dx.doi.org/10.1016/j.joms.2021.11.008DOI Listing
November 2021

Microstructural Evaluation of Phase Instability in Large Bandgap Metal Halide Perovskites.

ACS Nano 2021 Dec 30;15(12):20391-20402. Epub 2021 Nov 30.

Australian Centre for Advanced Photovoltaics (ACAP), School of Photovoltaic and Renewable and Engineering, University of New South Wales, Sydney, New South Wales 2052, Australia.

The optoelectronic performance of organic-inorganic halide perovskite (OIHP)-based devices has been improved in recent years. Particularly, solar cells fabricated using mixed-cations and mixed-halides have outperformed their single-cation and single-halide counterparts. Yet, a systematic evaluation of the microstructural behavior of mixed perovskites is missing despite their known composition-dependent photoinstability. Here, we explore microstructural inhomogeneity in (FAPbI)(MAPbBr) using advanced scanning probe microscopy techniques. Contact potential difference (CPD) maps measured by Kelvin probe force microscopy show an increased fraction of grains exhibiting a low CPD with flat topography as MAPbBr concentration is increased. The higher portion of low CPD contributes to asymmetric CPD distribution curves. Chemical analysis reveals these grains being rich in MA, Pb, and I. The composition-dependent phase segregation upon illumination, reflected on the emergence of a low-energy peak emission in the original photoluminescence spectra, arises from the formation of such grains with flat topology. Bias-dependent piezo-response force microscopy measurements, in these grains, further confirm vigorous ion migration and cause a hysteretic piezo-response. Our results, therefore, provide insights into the microstructural evaluation of phase segregation and ion migration in OIHPs pointing toward process optimization as a mean to further enhance their optoelectronic performance.
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http://dx.doi.org/10.1021/acsnano.1c08726DOI Listing
December 2021

Comparative evaluation and analysis of outcomes in non-idiopathic and idiopathic clubfeet with Ponseti method at a tertiary care centre of a developing country.

Foot (Edinb) 2021 Dec 12;49:101841. Epub 2021 Jun 12.

Department of Orthopaedics, Pt B.D. Sharma, Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India. Electronic address:

Background: Idiopathic clubfoot (congenital talipes equinovarus, CTEV) is being managed worldwide by Ponseti method with high success rates, while for non-idiopathic clubfoot surgical interventions is being widely used with variable results. This study evaluated the effectiveness of Ponseti method in non-idiopathic clubfoot and compared the results with idiopathic clubfoot.

Methods: The paper evaluated the epidemiological incidence and demographic profile of non-idiopathic clubfoot in a tertiary centre of developing country. A total of 108 subjects with 85 having idiopathic (group I;125 feet) and 23 having non-idiopathic variety (group II;34 feet) were managed with Ponseti method and were followed for a mean duration of 38.33 (12-62) and 36.27 months (12-58) in group I and II respectively. The most common associations were meningomyelocele (MMC/spina bifida,5), arthrogryposis multiplex congenita (AMC,4), developmental dysplasia of hip (DDH,3) and Down's syndrome and amniotic band syndrome (2 each).

Results: Primary correction was achieved in both the groups in 98% and 87% in group I and II respectively, while recurrences of at least one deformity was observed in 11 (9%) and 12 (40%) feet in group I and II respectively. Favourable outcomes were noticed in 22 (65%) feet in non-idiopathic group and 12 feet (35%) underwent extensive soft tissue release as compared to 3 feet (2.4%) in idiopathic variety.

Conclusion: Deformities improved significantly in non-idiopathic clubfeet with Ponseti methods although complete correction was not possible. Extensive surgical interventions were reduced in up to 35% feet in non-idiopathic variety and hence, it is recommended as primary treatment for all variety of clubfeet, irrespective of their etiology.
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http://dx.doi.org/10.1016/j.foot.2021.101841DOI Listing
December 2021

Diffuse Meningiomatosis without Neurofibromatosis: A Rare Diagnosis with Atypical Presentation.

Indian J Radiol Imaging 2021 Jul 13;31(3):768-771. Epub 2021 Nov 13.

Department of Radiodiagnosis and Imaging, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

Meningiomas are amongst the most common neoplasms of the central nervous system; however, "multiple meningiomas" or "meningiomatosis" account for < 10% of cases. The association with neurofibromatosis 2 is seen in ∼50% of cases. We report a case of 35-year-old female patient who presented with left eye proptosis, left forehead swelling, and multiple cranial nerve palsies predominantly on the left side. Imaging evaluation revealed innumerable en plaque meningiomas forming a sheet-like nodular thickening along the dura, causing marked hyperostosis and extending into the orbits, cavernous sinuses, sellar-suprasellar regions, various skull foramina, basal cisterns and into the cervical spinal canal causing mass effect on vital structures of the brain and cervical spinal cord. Similar lesions were found scattered in rest of the spine. We intend to highlight the role of imaging in accurately establishing the diagnosis and evaluating the extent and burden of disease in such rare cases.
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http://dx.doi.org/10.1055/s-0041-1736394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590543PMC
July 2021

Chemoprophylaxis under sporozoites-lumefantrine (CPS-LMF) immunization induce protective immune responses against sporozoites infection in mice.

3 Biotech 2021 Nov 19;11(11):465. Epub 2021 Oct 19.

Department of Biology, College of Science, University of Ha'il, PO Box 2440, Ha'il, Saudi Arabia.

Malaria represents one of the major life-threatening diseases that poses a huge socio-economic impact, worldwide. Chemoprophylaxis vaccination using a relatively low number of wild-type infectious sporozoites represents an attractive and effective vaccine strategy against malaria. However, the role of immune responses to pre-erythrocytic versus blood-stage parasites in protection against different antimalarial drugs remains unclear. Here, in the present study, we explored the immune responses against the repetitive inoculation of live () sporozoites in an experimental Swiss mouse model under antimalarial drug lumefantrine chemoprophylaxis (CPS-LMF). We monitored the liver stage parasitic load, pro/anti-inflammatory cytokines expression, and erythrocytic stage patency, following repetitive cycles of sporozoites inoculations. It was found that repetitive sporozoites inoculation under CPS-LMF results in delayed blood-stage infection during the fourth sporozoites challenge, while sterile protection was produced in mice following the fifth cycle of sporozoites challenge. Intriguingly, we observed a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α and IL-12) and iNOS response and down-regulation of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) in the liver HMNC (hepatic mononuclear cells) and spleen cells after 4th and 5th cycle of sporozoites challenge in the CPS-LMF mice. Meanwhile, we also noticed that the liver stage parasites load under CPS-LMF immunization has gradually reduced after 2nd, 3rd, 4th and 5th sporozoites challenge. Overall, our study suggests that chemoprophylaxis vaccination under LMF drug cover develops strong immune responses and confer superior long-lasting protection against sporozoites. Furthermore, this vaccination strategy can be used to study the protective and stage-specific immunity against new protective antigens.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-021-03022-0.
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http://dx.doi.org/10.1007/s13205-021-03022-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526652PMC
November 2021

Clinico-Hematological Profile and Copy Number Abnormalities in a Cohort of and Positive Pediatric T-Cell Acute Lymphoblastic Leukemia.

Indian J Hematol Blood Transfus 2021 Oct 25;37(4):555-562. Epub 2021 Jan 25.

Pediatric Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

T cell acute lymphoblastic leukaemia (T-ALL) is a genetically heterogeneous and aggressive form of malignancy. Although a number of recurrent fusion genes are reported in T-ALL, their involvement in disease stratification and therapeutic intervention is still controversial. Considering the prognostic value of fusion and tyrosine kinase inhibitor (TKI) based therapeutic potential of , the present study aimed to investigate their frequency and clinical correlation in pediatric T-ALL cases. Our cohort consisted of 48 T-ALL pediatric cases (age ≤ 12 years) with a median age of 6 years and male to female ratio of 20.5:1. The median TLC of the study group was noted to be 220,000/ cu mm with a range from 26,810/cu mm to 785,430/cu mm. By MLPA and RT-PCR analysis we observed that 11/48 cases (23%) showed fusion and 4/48 cases (8.3%) had fusion gene. Both of the fusion genes did not show any significant correlation with any of the clinico-hematological or treatment outcome parameters. However, upon analysis of copy number variations (CNVs) with other clinically relevant genes, we found significant correlation between ( = 0.024) and ( = 0.049) gene deletions with fusion in T-ALL patients. fusion gene did not reveal any association with either CNVs or with survival. Although limited with the small cohort size and follow up, our study supports the similar frequency of these fusions as compared to other Asian and Western studies and also highlights utility of MLPA technique as a good diagnostic modality to screen for both and fusions in a single assay with additional data on secondary copy number changes.
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http://dx.doi.org/10.1007/s12288-020-01394-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523619PMC
October 2021

Nanotechnology for Sustainable Agriculture: An Emerging Perspective.

J Nanosci Nanotechnol 2021 06;21(6):3453-3465

Department of Chemistry.

The realm of agriculture has to confront an expansive gamut of challenges including climatic change, stagnant crop yield and the increasing resistance against pesticides. The explicit usage of agrochemicals along with the introduction of high yielding varieties and genetically modified seeds has already directed the agricultural systems towards a state of saturation in production. Therefore, the increasing need of sustainability demands the involvement of advanced nanotechnological approaches for enhancing crop productivity. Enhanced solubility, absorption and target specificity of nannofertilizers prepared using materials like silver, copper, gold and oxides of zinc and iron could address some of nutritional challenges. Nanopesticides such as chitosan loaded with spino sad, silica encapsulating fipronil and sodium alginate enclosing imidacloprid find applications in pest control while fluorescence nanosensor, carbon and graphene nanodots are exploited in herbicide and heavy metal detection. Nanofilteration involving grapheme, cellulose and cyclodextrin for removal of salt, heavy metals and organic pollutants, respectively, could significantly improve quality of hard and waste water making it suitable for irrigation.
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http://dx.doi.org/10.1166/jnn.2021.19012DOI Listing
June 2021

Adenosine: a partially discovered medicinal agent.

Futur J Pharm Sci 2021 21;7(1):214. Epub 2021 Oct 21.

Department of Pharmaceutics, ShriRam College Pharmacy, Banmore, Morena, M.P 476444 India.

Background: A plethora of chemicals exists in human body which can alter physiology in one way or other. Scientists have always been astounded by such abilities of chemicals but as the technology advances, even the chemical which was once expected to be well known changes its status to not really well known. Adenosine is one of the chemicals which is in consonance with the aforementioned statements, although previous articles have covered vast information on role of adenosine in cardiovascular physiology, bacterial pathophysiology and inflammatory diseases. In this review we have discussed adenosine and its congeners as potential promising agents in the treatment of Huntington's disease, post-traumatic stress disorder, erectile dysfunction, viral infections (SARS-CoV) and anxiety.

Main Text: Adenosine is a unique metabolite of ATP; which serves in signalling as well. It is made up of adenine (a nitrogenous base) and ribo-furanose (pentose) sugar linked by β-N9-glycosidic bond. Adenosine on two successive phosphorylation forms ATP (Adenosine Triphosphate) which is involved in several active processes of cell. It is also one of the building blocks (nucleotides) involved in DNA (Deoxy-ribonucleic Acid) and RNA (Ribonucleic Acid) synthesis. It is also a component of an enzyme called S-adenosyl-L-methionine (SAM) and cyano-cobalamin (vitamin B-12). Adenosine acts by binding to G protein-coupled receptor (GPCR: A1, A2A, A2B and A3) carries out various responses some of which are anti-platelet function, hyperaemic response, bone remodelling, involvement in penile erection and suppression of inflammation. On the other hand, certain microorganisms belonging to genus utilize adenosine in order to escape host immune response (phagocytic clearance). These microbes evade host immune response by synthesizing and releasing adenosine (with the help of an enzyme: adenosine synthase-A), at the site of infection.

Conclusion: With the recent advancement in attribution of adenosine in physiology and pathological states, adenosine and its congeners are being looked forward to bringing a revolution in treatment of inflammation, viral infections, psychiatric and neurodegenerative disorders.
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http://dx.doi.org/10.1186/s43094-021-00353-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529566PMC
October 2021

Predicting Stroke Complications in Hospital and Functional Status at Discharge by Clustering of Cardiovascular Diseases a Multi-Centre Registry-Based Study of Acute Stroke.

J Stroke Cerebrovasc Dis 2022 Jan 22;31(1):106162. Epub 2021 Oct 22.

Institute of Cardiovascular Research, Royal Holloway University of London, Egham, TW20 0EX, UK; Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London W6 8RF, UK. Electronic address:

Objective: Indicators for outcomes following acute stroke are lacking. We have developed novel evidence-based criteria for identifying outcomes of acute stroke using the presence of clusters of coexisting cardiovascular disease (CVD).

Materials And Methods: Analysis of prospectively collected data from the Sentinel Stroke National Audit Programme (SSNAP). A total of 1656 men (mean age ±SD=73.1yrs±13.2) and 1653 women (79.3yrs±13.0) were admitted with acute stroke (83.3% ischaemic, 15.7% intracranial haemorrhagic), 1.0% unspecified) in four major UK hyperacute stroke units (HASU) between 2014 and 2016. Four categories from cardiovascular disease Congestive heart failure, Atrial fibrillation, pre-existing Stroke and Hypertension (CASH).were constructed: CASH-0 (no coexisting CVD); CASH-1 (any one coexisting CVD); CASH-2 (any two coexisting CVD); CASH-3 (any three or all four coexisting CVD). These were tested against outcomes, adjusted for age and sex.

Results: Compared to CASH-0, individuals with CASH-3 had greatest risks of in-hospital mortality (11.1% vs 24.5%, OR=1.8, 95%CI=1.3-2.7) and disability (modified Rankin Scale score ≥4) at discharge (24.2% vs 46.2%, OR=1.9, 95%CI=1.4-2.7), urinary tract infection (3.8% vs 14.6%, OR= 3.3, 95%CI= 1.9-5.5), and pneumonia (7.1% vs 20.6%, OR= 2.6, 95%CI= 1.7-4.0); length of stay on HASU >14 days (29.8% vs 39.3%, OR=1.8, 95%CI=1.3-2.6); and joint-care planning (20.9% vs 29.8%, OR=1.4, 95%CI=1.0-2.0).

Conclusions: We present a simple tool for estimating the risk of adverse outcomes of acute stroke including death, disability at discharge, nosocomial infections, prolonged length of stay, as well as any joint care planning. CASH-0 indicates a low level and CASH-3 indicates a high level of risk of such complications after stroke.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106162DOI Listing
January 2022

Molecular Docking and Dynamics Simulation Revealed Ivermectin as Potential Drug against -Associated Bladder Cancer Targeting Protein Signaling: Computational Drug Repositioning Approach.

Medicina (Kaunas) 2021 Oct 3;57(10). Epub 2021 Oct 3.

Department of Biology, College of Science, University of Hail, Hail 2440, Saudi Arabia.

Urogenital schistosomiasis is caused by  () infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the -associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.
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http://dx.doi.org/10.3390/medicina57101058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539496PMC
October 2021

Association of risk of malnutrition with adverse outcomes and early support on discharge in acute stroke patients without prestroke disability: A multicenter, registry-based cohort study.

Nutr Clin Pract 2021 Oct 19. Epub 2021 Oct 19.

Institute of Cardiovascular Research, Royal Holloway University of London, Egham, UK.

Background: Malnutrition in hospitals remains highly prevalent. As part of quality improvement initiatives, the Royal College of Physicians recommends nutrition screening for all patients admitted with acute stroke. We aimed to examine the associations of patients at risk of malnutrition with poststroke outcomes.

Methods: We analyzed prospectively collected data from four hyperacute stroke units (HASUs) (2014-2016). Nutrition status was screened in 2962 acute stroke patients without prestroke disability (1515 men, [mean ± SD] 73.5 years ± 13.1; 1447 women, 79.2 ± 13.0 years). The risk of malnutrition was tested against stroke outcomes and adjusted for age, sex, and comorbidities.

Results: Risk of malnutrition was identified in 25.8% of patients). Compared with well-nourished patients, those at risk of malnutrition had, within 7 days of admission, increased risk of stay on the HASU of >14 days (odds ratio [OR]: 9.9 [7.3-11.5]), disability on discharge (OR: 8.1 [6.6-10.0]), worst level of consciousness in the first 7 days (score ≥ 1) (OR: 7.5 [6.1-9.3]), mortality (OR: 5.2 [4.0-6.6], pneumonia (OR: 5.1 [3.9-6.7]), and urinary tract infection (OR: 1.5 [1.1-2.0]). They also required palliative care (OR: 12.3 [8.5-17.8]), discharge to new care home (OR: 3.07 [2.18-4.3]), activities of daily living support (OR: 1.8 [1.5-2.3]), planned joint care (OR: 1.5 [1.2-1.8]), and weekly visits (OR: 1.4 [1.1-1.8]).

Conclusion: Patients at risk of malnutrition more commonly have multiple adverse outcomes after acute stroke and greater need for early support on discharge.
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http://dx.doi.org/10.1002/ncp.10790DOI Listing
October 2021

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia.

JAMA Neurol 2021 11;78(11):1314-1323

Department of Neurology, Saudi German Hospital, Jeddah, Saudi Arabia.

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).

Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.

Design, Setting, And Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.

Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.

Main Outcomes And Measures: Clinical characteristics and mortality rate.

Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.

Conclusions And Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.
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http://dx.doi.org/10.1001/jamaneurol.2021.3619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479648PMC
November 2021

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke.

Front Neurol 2021 10;12:700616. Epub 2021 Sep 10.

Centogene AG, Rostock, Germany.

To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), < 0.01, respectively]. The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.
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http://dx.doi.org/10.3389/fneur.2021.700616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461233PMC
September 2021

Oral Fluconazole Therapy in Patients With Active Ulcerative Colitis Who Have Detectable Candida in the Stool: A Double-Blind Randomized Placebo-controlled Trial.

J Clin Gastroenterol 2021 Sep 9. Epub 2021 Sep 9.

Departments of Gastroenterology Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: There is an emerging role of fungal dysbiosis in the pathogenesis of inflammatory bowel disease. Prevalence of Candida in patients with active ulcerative colitis (UC) and the effect of fluconazole therapy in reducing disease activity of UC are not known.

Patients And Methods: All consecutive consenting patients with active UC defined as Mayo score ≥3 were evaluated for presence of Candida by stool culture and predictors for presence of Candida were identified. Those who had evidence of Candida in the stool were randomized to receive oral fluconazole 200 mg daily or placebo for 3 weeks along with standard medical therapy. Patients were assessed by clinical, sigmoidoscopy, and laboratory parameters at baseline and at 4 weeks. The primary outcome was clinical and endoscopic response at 4 weeks defined by a 3-point reduction in Mayo score. Secondary outcomes were reduction in fecal calprotectin, histologic response, and adverse events.

Results: Of the 242 patients with active UC, 68 (28%) patients had Candida in stool culture. Independent predictors for presence of Candida in patients with active UC were partial Mayo score of ≥3 and steroid exposure. Among those with Candida on stool culture (n=68), 61 patients fulfilled eligibility criteria and were randomized to receive fluconazole (n=31) or placebo (n=30). Three-point reduction in Mayo score though was numerically higher in the fluconazole group than the placebo group but was not statistically significant [5 (16.1%) vs. 1 (3.33%); P=0.19]. Postintervention median Mayo score was lower in fluconazole than placebo group [4 (3, 5) vs. 5 (4, 6); P=0.034]. Patients in fluconazole group had more often reduction in fecal calprotectin [26 (83.9%) vs. 11 (36.7%); P=0.001] and histologic scores [23 (74.1%) vs. 10 (33.3%); P=0.001] compared with placebo. All patients were compliant and did not report any serious adverse event.

Conclusion: Candida colonization is found in 28% of patients with UC. Steroid exposure and active disease were independent predictors for the presence of Candida. There was no statistically significant difference in the number of patients who achieved 3-point reduction in Mayo score between 2 groups. However, clinical, histologic, and calprotectin levels showed significant improvement in fluconazole group.
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http://dx.doi.org/10.1097/MCG.0000000000001609DOI Listing
September 2021

Intraosseous Lipoma of the Calcaneum.

Cureus 2021 Aug 6;13(8):e16929. Epub 2021 Aug 6.

Anaesthesiology, All India Institute of Medical Sciences, Bathinda, IND.

Lipomas are benign lesions of adipose tissue, which commonly affect the soft tissues but are rarely found in the musculoskeletal system. Intraosseous lipomas are rare benign tumors and even rarer in calcaneum, only to be found incidentally in the majority of cases. We report a case of a 45-year-old male patient who presented to the outpatient department with complaints of bilateral heel pain, which was initially treated conservatively as the presentation was similar to plantar fasciitis. On further follow-up, a plain radiograph of the ankles was taken, which showed a lytic lesion of the calcaneum with mild sclerotic margins on the right side with normal left foot radiographs. On magnetic resonance imaging, the lytic lesion demonstrated hyperintense signals on T1-weighted sagittal images, characteristic of fatty tissue, which helped us in arriving at the diagnosis of an intraosseous lipoma. The patient was treated by conservative means with physiotherapy, which relieved the pain, and on serial follow-ups, the lesion was found non-progressive on successive radiological evaluation. The differential diagnosis of such an entity includes plantar fasciitis, tumors such as an aneurysmal bone cyst, bone infarct, etc. With the increasing use of magnetic resonance imaging and computed tomography scans, physicians should be aware of the possibility of an intraosseous lipoma of the calcaneum, which should be ruled out during evaluation. Although possible, malignant pathology or aggressive transformation of such lesions is very rare; however, the lesion should be evaluated adequately and managed by surgical means in cases non-responsive to various conservative modalities.
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http://dx.doi.org/10.7759/cureus.16929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412882PMC
August 2021

A hydrogel-based implantable multidrug antitubercular formulation outperforms oral delivery.

Nanoscale 2021 Aug 30;13(31):13225-13230. Epub 2021 Jul 30.

Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, Haryana, India.

We present a non-immunogenic, injectable, low molecular weight, amphiphilic hydrogel-based drug delivery system (TB-Gel) that can entrap a cocktail of four front-line antitubercular drugs, isoniazid, rifampicin, pyrazinamide, and ethambutol. We showed that TB-Gel is more effective than oral delivery of the combination of four drugs in reducing the mycobacterial infection in mice. Results show that half the dose of chemotherapeutic drugs is sufficient to achieve a comparable therapeutic effect to that of oral delivery.
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http://dx.doi.org/10.1039/d0nr08806dDOI Listing
August 2021

A Review on Biosensors and Nanosensors Application in Agroecosystems.

Nanoscale Res Lett 2021 Aug 30;16(1):136. Epub 2021 Aug 30.

Wolaita Sodo University, P.O. Box: 138, Wolaita, Ethiopia.

Previous decades have witnessed a lot of challenges that have provoked a dire need of ensuring global food security. The process of augmenting food production has made the agricultural ecosystems to face a lot of challenges like the persistence of residual particles of different pesticides, accretion of heavy metals, and contamination with toxic elemental particles which have negatively influenced the agricultural environment. The entry of such toxic elements into the human body via agricultural products engenders numerous health effects such as nerve and bone marrow disorders, metabolic disorders, infertility, disruption of biological functions at the cellular level, and respiratory and immunological diseases. The exigency for monitoring the agroecosystems can be appreciated by contemplating the reported 220,000 annual deaths due to toxic effects of residual pesticidal particles. The present practices employed for monitoring agroecosystems rely on techniques like gas chromatography, high-performance liquid chromatography, mass spectroscopy, etc. which have multiple constraints, being expensive, tedious with cumbersome protocol, demanding sophisticated appliances along with skilled personnel. The past couple of decades have witnessed a great expansion of the science of nanotechnology and this development has largely facilitated the development of modest, quick, and economically viable bio and nanosensors for detecting different entities contaminating the natural agroecosystems with an advantage of being innocuous to human health. The growth of nanotechnology has offered rapid development of bio and nanosensors for the detection of several composites which range from several metal ions, proteins, pesticides, to the detection of complete microorganisms. Therefore, the present review focuses on different bio and nanosensors employed for monitoring agricultural ecosystems and also trying to highlight the factor affecting their implementation from proof-of-concept to the commercialization stage.
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http://dx.doi.org/10.1186/s11671-021-03593-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405745PMC
August 2021

Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.

Ann Neurol 2021 11 29;90(5):777-788. Epub 2021 Sep 29.

Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, Brescia, Italy.

Objective: Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood.

Methods: A genome-wide association study was performed to identify genetic variants influencing susceptibility to CVT. A 2-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1,205 ethnicity-matched control subjects divided into discovery and independent replication datasets.

Results: In the overall case-control cohort, we identified highly significant associations with 37 single nucleotide polymorphisms (SNPs) within the 9q34.2 region. The strongest association was with rs8176645 (combined p = 9.15 × 10 ; odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.76-2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR = 2.65 (95% CI = 2.21-3.20, p = 2.00 × 10 ). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. The ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B, or AB, were at 2.85 times (95% CI = 2.32-3.52, p = 2.00 × 10 ) increased risk of CVT compared with individuals with blood group O.

Interpretation: We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT. ANN NEUROL 2021;90:777-788.
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http://dx.doi.org/10.1002/ana.26205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666091PMC
November 2021

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use.

Pathogens 2021 Jul 23;10(8). Epub 2021 Jul 23.

Serum Institute of India Pvt. Ltd., Hadapsar, Pune 411028, India.

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine's critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide -acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.
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http://dx.doi.org/10.3390/pathogens10080928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400332PMC
July 2021

New strategy for liquefying corn stover pellets.

Bioresour Technol 2021 Dec 15;341:125773. Epub 2021 Aug 15.

Laboratory of Renewable Resources Engineering (LORRE), Purdue University, West Lafayette, IN 47907 United States; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907 United States; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907 United States. Electronic address:

The movement of solid material into and between unit operations within a biorefinery is a bottleneck in reaching design capacity, with formation of biomass slurries needed to introduce feedstock. Corn stover slurries have been achieved from dilute acid, pretreated materials resulting in slurry concentrations of up to about 150 g/L, above which flowability is compromised. We report a new strategy to liquefy corn stover at higher solids concentration (300 g/L) by initially cooking it with the enzyme mimetic maleic acid at 40 mM and 150 °C. This is followed by 6 h of enzymatic modification at 1 FPU (2.2 mg protein)/g solids, resulting in a yield stress of 171 Pa after 6 h and 58 Pa in 48 h compared to 6806 Pa for untreated stover. Mimetic treatment of corn stover pellets minimizes the inhibitory effect of xylo-oligomers on hydrolytic enzymes. This strategy allows for the delivery of solid lignocellulosic slurry into a pretreatment reactor by pumping, improving operability of a biorefinery.
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http://dx.doi.org/10.1016/j.biortech.2021.125773DOI Listing
December 2021

Molecular docking analysis of pyruvate kinase M2 with a potential inhibitor from the ZINC database.

Bioinformation 2021 31;17(1):139-146. Epub 2021 Jan 31.

School of Life Sciences, IIMT University Meerut,India.

The pyruvate kinase M2 isoform (PKM2) is linked with cancer. Therefore, it is of interest to document the molecular docking analysis of Pyruvate Kinase M2 (PDB ID: 4G1N) with potential activators from the ZINC database. Thus, we document the optimal molecular docking features of a compound having ID ZINC000034285235 with PKM2 for further consideration.
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http://dx.doi.org/10.6026/97320630017139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340708PMC
January 2021

Pathogenicity Determinants of Sclerotinia sclerotiorum and Their Association to Its Aggressiveness on Brassica juncea.

Plant Pathol J 2021 Aug 1;37(4):365-374. Epub 2021 Aug 1.

DBT Centre of Excellence on Brassicas, Department of Plant Breeding and Genetics, Punjab Agricultural University, Ludhiana 141004, Punjab, India.

White rot or stem rot caused by Sclerotinia sclerotiorum is one of the most destructive fungal diseases that have become a serious threat to the successful cultivation of oilseed Brassicas. The study was designed with an aim to investigate the association between the pathogenic aggressiveness and pathogenicity determinants of this pathogen specifically in Brassica for the first time. For this, a total of 58 isolates of S. sclerotiorum from different geographical regions were collected and purified. These isolates were inoculated on a Brassica juncea cv. RL-1359 and they exhibited high level of variation in their disease progression. The isolates were grouped and then 24 isolates were selected for the biochemical analysis of pathogenicity determinants. The isolates varied significantly with respect to their total organic acids, oxalic acid production and pectin methyl esterase and polygalacturonase activity. The oxalic acid production corresponded to the disease progression of the isolates; the isolates with higher oxalic acid production were the more aggressive ones and vice-versa. This is, in our knowledge, the first study to establish a correlation between oxalic acid production and pathogenic aggressiveness of S. sclerotiorum on B. juncea. However, the pectinases' enzyme activity did not follow the trend as of disease progression. These suggest an indispensable role of oxalic acid in pathogenicity of the fungus and the potential to be used as biochemical marker for preliminary assessment of pathogenic aggressiveness of various isolates before incorporating them in a breeding program.
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http://dx.doi.org/10.5423/PPJ.OA.03.2021.0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357566PMC
August 2021
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