Glycosaminoglycan-based biomaterials for growth factor and cytokine delivery: Making the right choices

Hachim, Daniel,Whittaker, Thomas E.,Kim, Hyemin,Stevens, Molly M. Elsevier 2019 Journal of controlled release Vol.313 No.-

<P><B>Abstract</B></P> <P>Controlled, localized drug delivery is a long-standing goal of medical research, realization of which could reduce the harmful side-effects of drugs and allow more effective treatment of wounds, cancers, organ damage and other diseases. This is particularly the case for protein “drugs” and other therapeutic biological cargoes, which can be challenging to deliver effectively by conventional systemic administration. However, developing biocompatible materials that can sequester large quantities of protein and release them in a sustained and controlled manner has proven challenging. Glycosaminoglycans (GAGs) represent a promising class of bio-derived materials that possess these key properties and can additionally potentially enhance the biological effects of the delivered protein. They are a diverse group of linear polysaccharides with varied functionalities and suitabilities for different cargoes. However, most investigations so far have focused on a relatively small subset of GAGs – particularly heparin, a readily available, promiscuously-binding GAG. There is emerging evidence that for many applications other GAGs are in fact more suitable for regulated and sustained delivery. In this review, we aim to illuminate the beneficial properties of various GAGs with reference to specific protein cargoes, and to provide guidelines for informed choice of GAGs for therapeutic applications.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Evaluating the effects of finishing diet and feeding location on sheep performance, carcass characteristics, and internal parasites

( Devon L Ragen ),( Molly R Butler ),( Jane A Boles ),( William A Layton ),( Thomas M Craig ),( Patrick G Hatfield ) 한국축산학회(구 한국동물자원과학회) 2021 한국축산학회지 Vol.63 No.3

A 3 yr experiment was conducted to evaluate the influence of diet and feeding location on animal performance, carcass characteristics, whole blood counts, and internal parasite burden of lambs assigned to 1 of 4 treatments: 1) confinement fed 71% alfalfa, 18% barley pellet, 5% molasses, 0.013% Bovatec, 6.1% vitamin/mineral package diet (CALF), 2) confinement fed 60% barley, 26% alfalfa pellet, 4% molasses, 2.5% soybean-hi pro, 0.016% Bovatec, 7.4% vitamin/mineral package diet (CBAR), 3) field fed 71% alfalfa, 18% barley pellet, 5% molasses, 0.013% Bovatec, 6.1% vitamin/mineral package diet (FALF), and 4) field fed 60% barley, 26% alfalfa pellet, 4% molasses, 2.5% soybean-hi pro, 0.016% Bovatec, 7.4% vitamin/mineral package diet (FBAR). A year × location interaction was detected for ending body weight (BW), average daily gain (ADG), and dry matter intake (DMI); therefore results are presented by year. In all years, cost of gain and DMI were greater for CALF and FALF than for CBAR and FBAR feed treatments (p ≤ 0.03). In yr 2 and 3 field treatments had greater ending BW and ADG than confinement treatments. For all years, diet did not affect ending BW or ADG. In yr 1 dressing percent and rib eye area were greater for field finished lambs than confinement finished (p ≤ 0.02) and Warner-Bratzler shear force was greater for CALF and FALF (p = 0.03). In yr 2 lambs in FALF and FBAR treatments had greater leg scores and conformation than CALF and CBAR (p = 0.09). In yr 1, FALF had a greater small intestine total worm count than all other treatments. In yr 1, ending Trichostrongyle type egg counts were greater for FALF (p = 0.05). In yr 2, ending Nematodirus spp. egg counts were greater for FALF and lowest for CBAR (p < 0.01). Abomasum Teladorsagia circumcinta worm burden was greater in CALF than all other treatments (p = 0.07) in yr 2. While field finishing lambs with a grain- or forage-based diet we conclude that it is possible to produce a quality lamb product without adverse effects to animal performance, carcass quality or increasing parasite burdens.

Identification and Validation of Cold Responsive MicroRNAs of Hevea brasiliensis Using High Throughput Sequencing

Linu Kuruvilla,MB Mohamed Sathik,Molly Thomas,Lisha P Luke,Sumesh KV 한국작물학회 2017 Journal of crop science and biotechnology Vol.20 No.5

Cold stress is one of the major abiotic factors that influence the productivity and geographical distribution of many agriculturally important crops like Hevea brasiliensis. Cultivation of H. brasiliensis in India is being extended to northeastern regions, where low temperature during winter adversely affects its survival, growth, and productivity. Developing cold-tolerant genotypes is a primary requisite to maximize the productivity under such challenging environmental conditions. However, lack of methods for early evaluation of cold tolerance in the newly developed clones and the extensive time required for assessing their tolerance in the field are major constraints for clonal selection. The present study was initiated with an objective to identify and characterize cold stress responsive miRNAs from H. brasiliensis that show stronger association with cold tolerance. Next generation sequencing using Illumina HiSeq method revealed the expression of 21 and 29 conserved miRNA (from clone RRIM 600) families in cold-stressed and control samples, respectively. Forty-two novel miRNAs were identified from this study. Upon differential expression analysis, eight conserved miRNAs were found commonly expressed in both the samples. When expression analyses were performed subsequently with six selected miRNAs in two Hevea clones (viz. RRII 105 and RRIM 600), miR169 showed a strong association with cold tolerance. miRNAs such as miR482 and miR159 also exhibited association with cold tolerance. This study suggests the possibility of employing these miRNAs as markers for cold tolerance after validation in more number of genotypes with varying levels of cold tolerance.

Expression of NAC transcription factor is altered under intermittent drought stress and re-watered conditions in Hevea brasiliensis

Luke, Lisha P.,Sathik, M.B. Mohamed,Thomas, Molly,Kuruvilla, Linu,Sumesh, K.V. The Korean Society of Plant Biotechnology 2017 식물생명공학회지 Vol.26 No.4

Drought stress is one of the important factors that restrict the expansion of Hevea brasiliensis cultivation to non-traditional regions experiencing extreme weather conditions. Plants respond to drought stress by triggering expression of several drought responsive genes including transcription factors which in turn trigger expression of various downstream signalling pathways and adaptive networks. Expression of such drought responsive genes may revert back to their original level upon re-watering. However, no reports are available on such phenomenon in Hevea and hence, this study was initiated. For this purpose, NAC transcription factor (NAC tf) was chosen as candidate gene. Its expression levels were monitored under intermittent drought as well as irrigated conditions in two clones (RRII 105 and RRIM 600) of H. brasiliensis with contrasting tolerance level. Copy number of NAC tf was found similar in both the clones. Expression of NAC tf was found highly up-regulated in RRIM 600 (a relatively drought tolerant clone) than in RRII 105 (a relatively drought susceptible clone) throughout the drought incidences which upon re-watering, reached back to its original levels in both the clones. The study indicated the existence of an association between expression of NAC tf and drought tolerance trait exhibited by the tolerant clone RRIM 600. The study also proves the influence of drought and re-watering on the leaf photosynthesis and expression of NAC tf in H. brasiliensis.

Expression of NAC transcription factor is altered under intermittent drought stress and re-watered conditions in Hevea brasiliensis

Lisha P. Luke,M. B. Mohamed Sathik,Molly Thomas,Linu Kuruvilla,K.V. Sumesh 한국식물생명공학회 2017 JOURNAL OF PLANT BIOTECHNOLOGY Vol.44 No.2

Drought stress is one of the important factors that restrict the expansion of Hevea brasiliensis cultivation to nontraditional regions experiencing extreme weather conditions. Plants respond to drought stress by triggering expression of several drought responsive genes including transcription factors which in turn trigger expression of various downstream signalling pathways and adaptive networks. Expression of such drought responsive genes may revert back to their original level upon re-watering. However, no reports are available on such phenomenon in Hevea and hence, this study was initiated. For this purpose, NAC transcription factor (NAC tf) was chosen as candidate gene. Its expression levels were monitored under intermittent drought as well as irrigated conditions in two clones (RRII 105 and RRIM 600) of H. brasiliensis with contrasting tolerance level. Copy number of NAC tf was found similar in both the clones. Expression of NAC tf was found highly up-regulated in RRIM 600 (a relatively drought tolerant clone) than in RRII 105 (a relatively drought susceptible clone) throughout the drought incidences which upon re-watering, reached back to its original levels in both the clones. The study indicated the existence of an association between expression of NAC tf and drought tolerance trait exhibited by the tolerant clone RRIM 600. The study also proves the influence of drought and re-watering on the leaf photosynthesis and expression of NAC tf in H. brasiliensis.

Duplex-Specific Nuclease-Amplified Detection of MicroRNA Using Compact Quantum Dot-DNA Conjugates

Wang, Ye,Howes, Philip D.,Kim, Eunjung,Spicer, Christopher D.,Thomas, Michael R.,Lin, Yiyang,Crowder, Spencer W.,Pence, Isaac J.,Stevens, Molly M. American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.34

<P>Advances in nanotechnology have provided new opportunities for the design of next-generation nucleic acid biosensors and diagnostics. Indeed, combining advances in functional nanoparticles, DNA nanotechnology, and nuclease-enzyme-based amplification can give rise to new assays with advantageous properties. In this work, we developed a microRNA (miRNA) assay using bright fluorescent quantum dots (QDs), simple DNA probes, and the enzyme duplex-specific nuclease. We employed an isothermal target-recycling mechanism, where a single miRNA target triggers the cleavage of many DNA signal probes. The incorporation of DNA-functionalized QDs enabled a quantitative fluorescent readout, mediated by Förster resonance energy transfer (FRET)-based interaction with the DNA signal probes. Our approach splits the reaction in two, performing the enzyme-mediated amplification and QD-based detection steps separately such that each reaction could be optimized for performance of the active components. Target recycling gave ca. 3 orders of magnitude amplification, yielding highly sensitive detection with a limit of 42 fM (or 1.2 amol) of miR-148, with excellent selectivity versus mismatched sequences and other miRNAs. Furthermore, we used an alternative target (miR-21) and FRET pair for direct and absolute quantification of miR-21 in RNA extracts from human cancer and normal cell lines.</P> [FIG OMISSION]</BR>

Dose-volume histogram parameters and patient-reported EPIC-Bowel domain in prostate cancer proton therapy

Gabriella F. Bulman,Ronik S. Bhangoo,Todd A. DeWees,Molly M. Petersen,Cameron S. Thorpe,William W. Wong,Jean Claude M. Rwigema,Thomas B. Daniels,Sameer R. Keole,Steven E. Schild,Carlos E. Vargas 대한방사선종양학회 2021 Radiation Oncology Journal Vol.39 No.2

Purpose: To analyze rectal dose and changes in quality of life (QOL) measured with the Expanded Prostate and Cancer Index Composite (EPIC) bowel domain in patients being treated for prostate cancer with curative-intent proton beam therapy (PBT) within a large single-institution prospective registry. Materials and Methods: Data was collected from 243 patients with localized prostate cancer treated with PBT from 2016 to 2018. The EPIC survey was administered at baseline, end-of-treatment, 3, 6, and 12 months, then annually. Dose-volume histogram (DVH) parameters for the rectum were computed, and rectal dose was analyzed using BED (α/β = 3), EQD2Gy, and total dose. Repeated measures mixed models were implemented to determine the effect of patient, clinical, and treatment factors (including DVH) on patient-reported bowel symptom burden (EPIC-Bowel). Results: Treatment overall resulted in changes in EPIC-Bowel scores (baseline score = 93.7), most notably at end-of-treatment (90.6) and 12 months (89.7). However, they returned to baseline at 36 months (92.9). On multivariate modeling, rectal BED D25 (Gy) ≥23% was significantly associated with decline in QOL scores measuring bother (p < 0.01; 4.06 points different). Conclusion: Rectal doses, specifically BED D25 (Gy) ≥23%, are significantly associated with decline in bowel bother-related QOL in patients undergoing definitive radiotherapy for localized prostate cancer. This study demonstrates BED as an independent predictor of bowel QOL across dose fractionations of PBT.

Automated brainstem segmentation detects differential involvement in atypical parkinsonian syndromes

Martina Bocchetta,Juan Eugenio Iglesias,Viorica Chelban,Edwin Jabbari,Ruth Lamb,Lucy L. Russell,Caroline V. Greaves,Mollie Neason,David M. Cash,David L. Thomas,Jason D. Warren,John Woodside,Henry Houl 대한파킨슨병및이상운동질환학회 2020 Journal Of Movement Disorders Vol.13 No.1

Brainstem segmentation has been useful in identifying potential imaging biomarkers for diagnosis and progression in atypical parkinsonian syndromes (APS). However, the majority of work has been performed using manual segmentation, which is time consuming for large cohorts.