scholarly journals Transferrin-Conjugated SNALPs Encapsulating 2′-O-Methylated miR-34a for the Treatment of Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Immacolata Scognamiglio ◽  
Maria Teresa Di Martino ◽  
Virginia Campani ◽  
Antonella Virgilio ◽  
Aldo Galeone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Zeta Potential ◽  
Lipid Vesicles ◽  
Significant Inhibition ◽  
The Other ◽  
Transferrin Receptors ◽  
Proof Of Concept ◽  
Wild Type ◽  
Chemical Conjugation ◽  
Mean Size

Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2′-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept for the use of SNALPs encapsulating miR-34a for the treatment of MM.

scholarly journals Chromatin Manipulation and Editing: Challenges, New Technologies and Their Use in Plants

2021 ◽  
Vol 22 (2) ◽  
pp. 512
Author(s):  
Kateryna Fal ◽  
Denisa Tomkova ◽  
Gilles Vachon ◽  
Marie-Edith Chabouté ◽  
Alexandre Berr ◽  
...  
Keyword(s):  
Cell Fate ◽  
Dna Sequence ◽  
Zinc Finger ◽  
Chromatin Structure ◽  
New Technologies ◽  
Dna Interaction ◽  
The Other ◽  
Proof Of Concept ◽  
Epigenetic Marks ◽  
Molecular Events

An ongoing challenge in functional epigenomics is to develop tools for precise manipulation of epigenetic marks. These tools would allow moving from correlation-based to causal-based findings, a necessary step to reach conclusions on mechanistic principles. In this review, we describe and discuss the advantages and limits of tools and technologies developed to impact epigenetic marks, and which could be employed to study their direct effect on nuclear and chromatin structure, on transcription, and their further genuine role in plant cell fate and development. On one hand, epigenome-wide approaches include drug inhibitors for chromatin modifiers or readers, nanobodies against histone marks or lines expressing modified histones or mutant chromatin effectors. On the other hand, locus-specific approaches consist in targeting precise regions on the chromatin, with engineered proteins able to modify epigenetic marks. Early systems use effectors in fusion with protein domains that recognize a specific DNA sequence (Zinc Finger or TALEs), while the more recent dCas9 approach operates through RNA-DNA interaction, thereby providing more flexibility and modularity for tool designs. Current developments of “second generation”, chimeric dCas9 systems, aiming at better targeting efficiency and modifier capacity have recently been tested in plants and provided promising results. Finally, recent proof-of-concept studies forecast even finer tools, such as inducible/switchable systems, that will allow temporal analyses of the molecular events that follow a change in a specific chromatin mark.

Normal Synaptonemal Complex and Abnormal Recombination Nodules in Two Alleles of the Drosophila Meiotic Mutant mei-W68

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1337-1356 ◽  
Author(s):  
Adelaide T C Carpenter
Keyword(s):  
Electron Microscopy ◽  
Synaptonemal Complex ◽  
High Frequency ◽  
Serial Section ◽  
The Other ◽  
Wild Type ◽  
Recombination Nodules ◽  
Section Electron ◽  
Serial Section Electron Microscopy ◽  
Section Electron Microscopy

Abstract The meiotic phenotypes of two mutant alleles of the mei-W68 gene, 1 and L1, were studied by genetics and by serial-section electron microscopy. Despite no or reduced exchange, both mutant alleles have normal synaptonemal complex. However, neither has any early recombination nodules; instead, both exhibit high numbers of very long (up to 2 μm) structures here named “noodles.” These are hypothesized to be formed by the unchecked extension of identical but much shorter structures ephemerally seen in wild type, which may be precursors of early recombination nodules. Although the mei-W68L1 allele is identical to the mei-W681 allele in both the absence of early recombination nodules and a high frequency of noodles (i.e., it is amorphic for the noodle phene), it is hypomorphic in its effects on exchange and late recombination nodules. The differential effects of this allele on early and late recombination nodules are consistent with the hypothesis that Drosophila females have two separate recombination pathways—one for simple gene conversion, the other for exchange.

scholarly journals A Screen for Genes That Function in Abscisic Acid Signaling in Arabidopsis thaliana

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1247-1255 ◽  
Author(s):  
Eiji Nambara ◽  
Masaharu Suzuki ◽  
Suzanne Abrams ◽  
Donald R McCarty ◽  
Yuji Kamiya ◽  
...  
Keyword(s):  
Abscisic Acid ◽  
Growth And Development ◽  
Plant Hormone ◽  
The Other ◽  
Aba Signaling ◽  
Wild Type ◽  
Plant Growth And Development ◽  
Diverse Range ◽  
Abscisic Acid Signaling ◽  
Aba Insensitive

Abstract The plant hormone abscisic acid (ABA) controls many aspects of plant growth and development under a diverse range of environmental conditions. To identify genes functioning in ABA signaling, we have carried out a screen for mutants that takes advantage of the ability of wild-type Arabidopsis seeds to respond to (−)-(R)-ABA, an enantiomer of the natural (+)-(S)-ABA. The premise of the screen was to identify mutations that preferentially alter their germination response in the presence of one stereoisomer vs. the other. Twenty-six mutants were identified and genetic analysis on 23 lines defines two new loci, designated CHOTTO1 and CHOTTO2, and a collection of new mutant alleles of the ABA-insensitive genes, ABI3, ABI4, and ABI5. The abi5 alleles are less sensitive to (+)-ABA than to (−)-ABA. In contrast, the abi3 alleles exhibit a variety of differences in response to the ABA isomers. Genetic and molecular analysis of these alleles suggests that the ABI3 transcription factor may perceive multiple ABA signals.

scholarly journals Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms

2014 ◽  
Vol 307 (9) ◽  
pp. G941-G949 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Rubina Kapadia ◽  
Arundhati Biswas ◽  
Hamid M. Said
Keyword(s):  
Transgenic Mice ◽  
Chronic Exposure ◽  
Methylation Status ◽  
Acinar Cells ◽  
Alcohol Exposure ◽  
Significant Inhibition ◽  
Pancreatic Acinar Cells ◽  
Chronic Alcohol ◽  
Wild Type ◽  
Chronic Alcohol Exposure

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

scholarly journals act Operon Control of Developmental Gene Expression in Myxococcus xanthus

2002 ◽  
Vol 184 (4) ◽  
pp. 1172-1179 ◽  
Author(s):  
Thomas M. A. Gronewold ◽  
Dale Kaiser
Keyword(s):  
Fruiting Body ◽  
Myxococcus Xanthus ◽  
The Other ◽  
Loss Of Function ◽  
Wild Type ◽  
Developmental Gene ◽  
Developmental Gene Expression ◽  
Mutant Strains ◽  
Genes Encoding ◽  
Signal Production

ABSTRACT Cell-bound C-signal guides the building of a fruiting body and triggers the differentiation of myxospores. Earlier work has shown that transcription of the csgA gene, which encodes the C-signal, is directed by four genes of the act operon. To see how expression of the genes encoding components of the aggregation and sporulation processes depends on C-signaling, mutants with loss-of-function mutations in each of the act genes were investigated. These mutations were found to have no effect on genes that are normally expressed up to 3 h into development and are C-signal independent. Neither the time of first expression nor the rate of expression increase was changed in actA, actB, actC, or actD mutant strains. Also, there was no effect on A-signal production, which normally starts before 3 h. By contrast, the null act mutants have striking defects in C-signal production. These mutations changed the expression of four gene reporters that are related to aggregation and sporulation and are expressed at 6 h or later in development. The actA and actB null mutations substantially decreased the expression of all these reporters. The other act null mutations caused either premature expression to wild-type levels (actC) or delayed expression (actD), which ultimately rose to wild-type levels. The pattern of effects on these reporters shows how the C-signal differentially regulates the steps that together build a fruiting body and differentiate spores within it.

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

128 Differences in PRRSV Resilience for Reproductive Performance Between Landrace and Duroc Sows

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 18-19
Author(s):  
Felipe Hickmann ◽  
José Braccini Neto ◽  
Luke M Kramer ◽  
Kent A Gray ◽  
Yijian Huang ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Mixed Model ◽  
Performance Data ◽  
The Other ◽  
Wild Type ◽  
Prrs Virus ◽  
The Difference ◽  
The Impact

Abstract Studies on differences in resilience to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) between breeds are scarce in the literature. Thus, the objective of this work was to assess PRRSV resilience in PRRSV wild-type infected sows from two breeds. Farrowing data included 2546 and 2522 litters from 894 Duroc and 813 Landrace sows, respectively, which were housed together and experienced the same PRRSV outbreak. Traits used for this study were number of piglets born alive (NBA), number born dead (NBD), total number born (TNB), and number weaned (NW). The impact of PRRSV infection was evaluated by comparing the reproductive performance of breeds between PRRS phases (pre-PRRS, PRRS, and post-PRRS). PRRS phases were defined based on the reproductive performance data. NBA, NBD, and NW were analyzed as a proportion of TNB using a Poisson mixed model. Pre-defined contrasts were used to evaluate the effect of breed on PRRSV resilience and on return to PRRSV-free performance, representing the differences between breeds for the difference between pre-PRRS and PRRS phases, and pre-PRRS and post-PRRS phases, respectively. There was a significant (P ≤ 0.003) interaction between PRRS phase and breed for all traits, as shown in Table 1. In general, reproductive performance reduced from pre-PRRS to PRRS, and then increased from PRRS to post-PRRS, as expected. The resilience contrast was significant for all traits (P ≤ 0.003). In all cases, the drop in percent reproductive performance from pre-PRRS to PRRS was lower for Duroc than for Landrace, indicating that Duroc sows have greater PRRSV resilience than Landrace sows. The return to PRRSV-free performance contrast had a trending effect for NBD (P = 0.055), and it was not significant for the other traits (P ≥ 0.515). These results indicate that Duroc sows have overall greater phenotypic PRRSV resilience for reproductive performance than Landrace sows.

Practicality Assessment of a Frugal Nanoparticle Generator: Opening doors to Nano Pharmaceuticals for the researchers and students of underprivileged academic institutions.

2021 ◽  
Vol 17 ◽  
Author(s):  
Swayamprakash Patel ◽  
Ashish Patel ◽  
Mruduka Patel ◽  
Umang Shah ◽  
Mehul Patel ◽  
...  
Keyword(s):  
Zeta Potential ◽  
Organic Solvent ◽  
Ultrasonic Vibration ◽  
High Speed ◽  
Patent Application ◽  
Entrapment Efficiency ◽  
Proof Of Concept ◽  
Research Institutions ◽  
Novel Approach ◽  
Sophisticated Equipment

Background: Probe sonication and High-speed homogenizer are comparatively costly equipment to fabricate the nanoparticles. Many academic and research institutions cannot afford the procurement and maintenance of such sophisticated equipment. In the present work, a newer idea is conceptualized, which can be adopted by the underprivileged research institutions to fabricate solid lipid nanoparticles (SLN) in the absence of sophisticated equipment. The current work describes the pilot-level trials of this novel approach. This study represents the preliminary proof-of-concept trials for which the Indian patent application (3508/MUM/2015) is filed. Method: A frugal piece of equipment was made using a 50 ml centrifuge tube with conical bottom and a piezoelectric mist maker or humidifier. SLNs were prepared by combining the quasi-emulsion solvent evaporation approach and ultrasonic vibration approach. A quasi-emulsion was composed by the dropwise mixing of the organic solvent containing drug & lipid with an aqueous solution containing surfactant under continuous ultrasonic vibration in the piezoelectric chamber. The size of the droplets was significantly reduced due to piezoelectric ultrasonic vibration. Under the provision of mild vacuum and heat generated by vibration, the organic solvent was evaporated, which leaves behind a suspension of SLN. In the present work, albendazole was selected as a model drug. Various trials with Compritol 888 ATO® and Precirol ATO 5® as a lipid carrier and Tween 80 and Poloxamer 188 as a surfactant were performed. Zeta potential of SLNs was improved by the addition of polyelectrolytes like K2SO4 and Na4P2O7. Result and Conclusion: The ratio of drug to lipid was optimized to 1:4 for the most favorable results. SLN with a minimum Z-average diameter of 98.59 nm, -21 mV zeta potential, and 34.064 % (SD 10.78, n=9) entrapment efficiency were developed using the Precirol ATO 5 ® as a lipid carrier. The proof of concept for this novel approach is established through the development of Albendazole SLNs. This approach must also be evaluated for the development of polymeric nanoparticles and vesicular formulations. The further sophistication of the frugal equipment may allow more control over the quality of SLN. This approach will enable underprivileged researchers to prepare Nanopharmaceuticals. Researchers and students of such institutions can focus on the application of SLN by resolving the constraint of sophisticated equipment with this novel approach. This novel approach should also be tried for polymeric and vesicular nanopharmaceuticals.

Étude du polymorphisme intraclonal chez le Verticillium albo-atrum, forme à microsclérotes. IV. L'aptitude à varier chez les variants morphologiques

1983 ◽  
Vol 61 (12) ◽  
pp. 3536-3542
Author(s):  
Claude Boisson ◽  
Houria Lahlou
Keyword(s):  
Mixed Type ◽  
The Other ◽  
Wild Type ◽  
Irreversible Loss ◽  
Verticillium Albo Atrum

The capacity for variation was studied using 10- to 18-month-old cultures of the main variants of two Moroccan isolates of Verticillium albo-atrum R. et B. (microsclerotial form). The hyaline variants were very stable and never returned to the wild type. The other variants gave rise to new variants which differed even more from the wild type but never reverted. A "mixed" type of variant, hyaline but with patches or sectors resembling the wild type, gave rise to wild or hyaline cultures when subcultured, depending on the conditions of transfer. All other variation tended toward a stronger alteration of sclerogenesis without reversing and an irreversible loss of ability to produce microsclerotia (hyaline cultures).

scholarly journals Observations on the Fat Globules in Milk

1913 ◽  
Vol 5 (3) ◽  
pp. 331-356 ◽  
Author(s):  
W. F Cooper ◽  
W. H Nuttall ◽  
G. A Freak
Keyword(s):  
Annual Report ◽  
The Other ◽  
Optimum Temperature ◽  
Fat Globules ◽  
Chief Factors ◽  
Mean Size ◽  
The Subject ◽  
The Mean ◽  
Definite Result

Results of our previous work were published in the Journ. of Agric. Sri., IV, 1911. There, also, a brief summary of the chief papers published on the subject of the fat globules was given, to which it is unnecessary to refer in detail here.When the work was first commenced in 1909, the problem before us was the consideration of the variation in the size of the fat globules, with relation to churning, as regards the different breeds of cattle. The breed was considered because it was usually supposed that this was one of the chief factors which influenced churning. The most definite result of our work was that it was shown that consideration must be given to the character of the milk, irrespective of the breed. This conclusion is quite contrary to that of other workers, but an examination of their figures shows, undoubtedly, that this is actually the case: the results given by Woll (Digestion Expts., Seventh Annual Report, Agric. Expt. Stat, Wisconsin, 1890, 238; also Agric. Sci., 1892, vi, 445) emphasise this point particularly. It is also shown by this year's work, as may be seen from Tables V–XI.The comparative size of the globules has been worked out very thoroughly by Gutzeit, who measured the mean volume of the globule. Other workers give their results as “relative sizes.” In our work we attempted to ascertain the distribution of the fat in the globules, and to this end the number of globules of each size was determined, and curves were drawn. The result of this, however, was negative. At that time we were considering the breeds of the cows from which the milks were obtained; had we considered them solely as milks of a certain mean size of globule, much more might have been achieved.An apparatus was devised to give an absolute figure for the churnability of any cream, but, until the effect of the other factors has been determined, it is impossible to interpret the results. Some experiments to ascertain the optimum temperature were described also.

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