Publications by authors named "I T Baldwin"

567 Publications

Cytotoxic furanosesquiterpenoids and steroids from sponges.

Pharm Biol 2021 Dec;59(1):575-583

Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Context: Wilson (Irciniidae) is a sponge with antimicrobial and cytotoxic constituents.

Objective: Our objective was to characterise the cytotoxic constituents of two seasonal collections of .

Materials And Methods: The sponges were extracted in methanol-dichloromethane and their constituents were purified and characterised using column chromatography, GC-MS, 1 D and 2 D NMR. Anti-proliferative activities of the compounds, were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (0.25-100 μg/mL, 72 h) against leukaemia (MOLT-4), breast (MCF-7) and colon cancer (HT-29) human cells.

Results: Three furanosesquiterpoids; furodysin (), -furodysinin () and furoircin () and ten sterols were characterised in , for the first time. Cholesterol (), cholesta-5, 7-dien-3β-ol () and ergosterol () were determined in the sponge from the winter collections, while cholesta-5, 22-dien-3β-ol (), 24-methyldesmosterol (), campesterol (), stigmasterol (), γ-ergostenol (), chondrillasterol () and γ-sitosterol () were detected in the summer samples. The steroids from the winter collection exhibited cytotoxic activity with IC values of 13.0 ± 0.9, 11.1 ± 1.7 and 1.1 ± 0.4 µg/mL, against the mentioned cancer cell lines, respectively, while those from the summer sample, showed greater activity, IC = 1.1 ± 0.2 μg/mL against MOLT-4. The purified steroids showed potent MOLT-4 cytotoxic activity, IC values = 2.3-7.8 µg/mL.

Discussion And Conclusion: The present study suggests that is a rich source of cytotoxic steroids, and introduces as new natural product. Considering the high cytotoxic activity of the steroids, these structures could be candidates for anticancer drug development in future research.
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http://dx.doi.org/10.1080/13880209.2021.1920620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168774PMC
December 2021

Vascular access, membranes and circuit for CRRT.

Semin Dial 2021 May 3. Epub 2021 May 3.

Department of Intensive Care, Austin Hospital, Melbourne, Vic., Australia.

The advances in the technology for providing continuous renal replacement therapy (CRRT) have led to an increase in its utilization throughout the world. However, circuit life continues to be a major problem. It leads not only to decreased delivery of dialysis but also causes blood loss, waste of disposables, alters dose delivery of medications and nutrition, and increases nurse workload, all of which increases healthcare cost. Premature circuit failure can be caused by numerous factors that can be difficult to dissect out. The first component is the vascular access; without a well-placed, functioning access, delivery of CRRT becomes very difficult. This is usually accomplished by placing a short-term dialysis catheter into either the right internal jugular or femoral vein. The tips should be located at the caval atrial junction or inferior vena cava. In addition to establishing suitable vascular access, a comprehensive understanding of the circuit facilitates the development of a methodical approach in providing efficient CRRT characterized by optimal circuit life. Moreover, it aids in determining the cause of circuit failure in patients experiencing recurrent episodes. This review therefore summarizes the essential points that guide providers in establishing optimal vascular access. We then provide an overview of the main components of the CRRT circuit including the blood and fluid pumps, the hemofilter, and pressure sensors, which will assist in identifying the key mechanisms contributing to premature failure of the CRRT circuit.
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http://dx.doi.org/10.1111/sdi.12977DOI Listing
May 2021

Natural variation in linalool metabolites: One genetic locus, many functions?

J Integr Plant Biol 2021 Apr 30. Epub 2021 Apr 30.

Department of Molecular Ecology, Max Planck Institute for Chemical Ecology, 07745, Jena, Germany.

The ubiquitous volatile linalool is metabolized in plants to non-volatile derivatives. We studied Nicotiana attenuata plants which naturally vary in (S)-(+)-linalool contents, and lines engineered to produce either (R)-(-)- or (S)-(+)-linalool. Only (S)-(+)-linalool production was associated with slower growth of a generalist herbivore, and a large fraction was present as non-volatile derivatives. We found that variation in volatile linalool and its nonvolatile glycosides mapped to the same genetic locus which harbored the biosynthetic gene, NaLIS, but that free linalool varied more in environmental responses. This study reveals how (S)-(+)-linalool and conjugates differ in their regulation and possible functions in resistance. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jipb.13104DOI Listing
April 2021

Genomic, Clinical, and Behavioral Characterization of 15q11.2 BP1-BP2 Deletion (Burnside-Butler) Syndrome in Five Families.

Int J Mol Sci 2021 Feb 7;22(4). Epub 2021 Feb 7.

Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, 3901 Rainbow Blvd. MS 4015, Kansas City, KS 66160, USA.

The 15q11.2 BP1-BP2 deletion (Burnside-Butler) syndrome is emerging as the most common cytogenetic finding in patients with neurodevelopmental or autism spectrum disorders (ASD) presenting for microarray genetic testing. Clinical findings in Burnside-Butler syndrome include developmental and motor delays, congenital abnormalities, learning and behavioral problems, and abnormal brain findings. To better define symptom presentation, we performed comprehensive cognitive and behavioral testing, collected medical and family histories, and conducted clinical genetic evaluations. The 15q11.2 BP1-BP2 region includes the , , , and genes. To determine if additional genomic variation outside of the 15q11.2 region influences expression of symptoms in Burnside-Butler syndrome, whole-exome sequencing was performed on the parents and affected children for the first time in five families with at least one parent and child with the 15q1l.2 BP1-BP2 deletion. In total, there were 453 genes with possibly damaging variants identified across all of the affected children. Of these, 99 genes had exclusively de novo variants and 107 had variants inherited exclusively from the parent without the deletion. There were three genes (, , and ) with de novo variants that encode proteins evidenced to interact with CYFIP1. In addition, one other gene of interest () had variants inherited from the parent without the deletion and encoded a protein interacting with CYFIP1. The affected individuals commonly displayed a neurodevelopmental phenotype including ASD, speech delay, abnormal reflexes, and coordination issues along with craniofacial findings and orthopedic-related connective tissue problems. Of the 453 genes with variants, 35 were associated with ASD. On average, each affected child had variants in 6 distinct ASD-associated genes (x¯ = 6.33, sd = 3.01). In addition, 32 genes with variants were included on clinical testing panels from Clinical Laboratory Improvement Amendments (CLIA) approved and accredited commercial laboratories reflecting other observed phenotypes. Notably, the dataset analyzed in this study was small and reported results will require validation in larger samples as well as functional follow-up. Regardless, we anticipate that results from our study will inform future research into the genetic factors influencing diverse symptoms in patients with Burnside-Butler syndrome, an emerging disorder with a neurodevelopmental behavioral phenotype.
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http://dx.doi.org/10.3390/ijms22041660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914695PMC
February 2021

Specific decorations of 17-hydroxygeranyllinalool diterpene glycosides solve the autotoxicity problem of chemical defense in Nicotiana attenuata.

Plant Cell 2021 Feb 9. Epub 2021 Feb 9.

Max Planck Institute for Chemical Ecology, Department of Molecular Ecology, Hans Knöll Straße 8, 07745 Jena, Germany.

The native diploid tobacco Nicotiana attenuata produces abundant, potent anti-herbivore defense metabolites known as 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) whose glycosylation and malonylation biosynthetic steps are regulated by jasmonate signaling. To characterize the biosynthetic pathway of HGL-DTGs, we conducted a genome-wide analysis of uridine diphosphate glycosyltransferases (UGTs) and identified 107 family-1 UGT members. The transcript levels of three UGTs were highly correlated with the transcript levels two key HGL-DTG biosynthetic genes: geranylgeranyl diphosphate synthase (NaGGPPS) and geranyllinalool synthase (NaGLS). NaGLS's role in HGL-DTG biosynthesis was confirmed by virus-induced gene silencing. Silencing the UDP-rhamnosyltransferase gene UGT91T1 demonstrated its role in the rhamnosylation of HGL-DTGs. In vitro enzyme assays revealed that UGT74P3 and UGT74P4 use UDP-glucose for the glucosylation of 17-hydroxygeranyllinalool (17-HGL) to lyciumoside I. Plants with stable silencing of UGT74P3 and UGT74P5 were severely developmentally deformed, pointing to a phytotoxic effect of the aglycone. The application of synthetic 17-HGL and silencing of the UGTs in HGL-DTG-free plants confirmed this phytotoxic effect. Feeding assays with tobacco hornworm (Manduca sexta) larvae revealed the defensive functions of the glucosylation and rhamnosylation steps in HGL-DTG biosynthesis. Glucosylation of 17-HGL is therefore a critical step that contributes to the resulting metabolites' defensive function and solves the autotoxicity problem of this potent chemical defense.
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http://dx.doi.org/10.1093/plcell/koab048DOI Listing
February 2021