scholarly journals Premature MicroRNA-Based Therapeutic: A “One-Two Punch” against Cancers

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3831
Author(s):  
Luyue Chen ◽  
Kai Huang ◽  
Kaikai Yi ◽  
Yanlin Huang ◽  
Xinhua Tian ◽  
...  

Up-to-date knowledge regarding the biogenesis and functioning of microRNAs (miRNAs) has provided a much more comprehensive and concrete view of miRNA biology than anyone ever expected. Diverse genetic origins and biogenesis pathways leading to functional miRNAs converge on the synthesis of ≈21-nucleotide RNA duplex, almost all of which are processed from long premature sequences in a DICER- and/or DROSHA-dependent manner. Formerly, it was assumed that one mature strand of the duplex is preferentially selected for entry into the silencing complex, and the paired passenger strands (miRNA*) are subjected to degradation. However, given the consolidated evidence of substantial regulatory activity of miRNA* species, currently, this preconception has been overturned. Here, we see the caveat and opportunity toward exogenously manipulating the expression of premature miRNA, leading to simultaneous upregulation or downregulation of dual regulatory strands due to altered expressions. The caveat is the overlooked miRNA* interference while manipulating the expression of a target miRNA at the premature stage, wherein lies the opportunity. If the dual strands of a pre-miRNA function synergistically, the overlooked miRNA* interference may inversely optimize the therapeutic performance. Insightfully, targeting the premature miRNAs may serve as the “one-two punch” against diseases, especially cancers, and this has been discussed in detail in this review.

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Dong Huang ◽  
Yan-Qing Liu ◽  
Li-Shuang Liang ◽  
Xue-Wu Lin ◽  
Tao Song ◽  
...  

At present, there are many constantly updated guidelines and consensuses on the diagnosis and treatment of osteoarthritis both at home and abroad. The recommendations established using methods of evidence-based medicine has experienced strict research on controlling bias and promoting reproduction rate. As a result, the previous evidence was reevaluated, and a lot of changes were provoked in the diagnosis and treatment concept of osteoarthritis. However, several methods not recommended by foreign guidelines are still in use in the current clinical practice in China. On the one hand, Chinese experts have not reached extensive consensus on whether it is necessary to make changes according to foreign guidelines. On the other hand, almost all the current relevant guidelines are on osteoarthritis, but the lesions around knee joints which, as a whole, bear the largest weight in human body, cannot be ignored. For this purpose, Chinese Association for the Study of Pain (CASP) organized some leading experts to formulate this Chinese Pain Specialist Consensus on the diagnosis and treatment of degenerative knee osteoarthritis (DKOA) in combination with the guidelines in foreign countries and the expert experience of clinical practice in China. The consensus, which includes the definition, pathophysiology, epidemiology, clinical manifestation, diagnostic criteria, and treatments of DKOA, is intended to be used by first-line doctors, including pain physicians to manage patients with DKOA.


Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 835
Author(s):  
Jose Alvarez ◽  
Elvira Martinez ◽  
Belén Diezma

Hyperspectral imaging is an appropriate method to thoroughly investigate the microscopic structure of internally heterogeneous agro-food products. By using hyperspectral technology, identifying stress symptoms associated with salinity, before a human observer, is possible, and has obvious benefits. The objective of this paper was to prove the suitability of this technique for the analysis of Triticale seeds subjected to both magneto-priming and drought and salt stress conditions, in terms of image differences obtained among treatments. It is known that, on the one hand, drought and salt stress treatments have negative effects on seeds of almost all species, and on the other hand, magneto-priming enhances seed germination parameters. Thus, this study aimed to relate hyperspectral imaging values—neither positive nor negative in themselves—to the effects mentioned above. Two main conclusions were reached: Firstly, the hyperspectral application is a feasible method for exploring the Triticale structure and for making distinctions under different drought and salt stress treatments, in line with the data variability obtained. Secondly, the lower spectral reflectance in some treatments—in the 400–1000 nm segment—is the result of a great number of chemical compounds in the seed that could be related to magneto-priming.


1997 ◽  
Vol 17 (12) ◽  
pp. 7268-7282 ◽  
Author(s):  
R Verona ◽  
K Moberg ◽  
S Estes ◽  
M Starz ◽  
J P Vernon ◽  
...  

E2F directs the cell cycle-dependent expression of genes that induce or regulate the cell division process. In mammalian cells, this transcriptional activity arises from the combined properties of multiple E2F-DP heterodimers. In this study, we show that the transcriptional potential of individual E2F species is dependent upon their nuclear localization. This is a constitutive property of E2F-1, -2, and -3, whereas the nuclear localization of E2F-4 is dependent upon its association with other nuclear factors. We previously showed that E2F-4 accounts for the majority of endogenous E2F species. We now show that the subcellular localization of E2F-4 is regulated in a cell cycle-dependent manner that results in the differential compartmentalization of the various E2F complexes. Consequently, in cycling cells, the majority of the p107-E2F, p130-E2F, and free E2F complexes remain in the cytoplasm. In contrast, almost all of the nuclear E2F activity is generated by pRB-E2F. This complex is present at high levels during G1 but disappears once the cells have passed the restriction point. Surprisingly, dissociation of this complex causes little increase in the levels of nuclear free E2F activity. This observation suggests that the repressive properties of the pRB-E2F complex play a critical role in establishing the temporal regulation of E2F-responsive genes. How the differential subcellular localization of pRB, p107, and p130 contributes to their different biological properties is also discussed.


1967 ◽  
Vol 71 (677) ◽  
pp. 342-343
Author(s):  
F. H. East

The Aviation Group of the Ministry of Technology (formerly the Ministry of Aviation) is responsible for spending a large part of the country's defence budget, both in research and development on the one hand and production or procurement on the other. In addition, it has responsibilities in many non-defence fields, mainly, but not exclusively, in aerospace.Few developments have been carried out entirely within the Ministry's own Establishments; almost all have required continuous co-operation between the Ministry and Industry. In the past the methods of management and collaboration and the relative responsibilities of the Ministry and Industry have varied with time, with the type of equipment to be developed, with the size of the development project and so on. But over the past ten years there has been a growing awareness of the need to put some system into the complex business of translating a requirement into a specification and a specification into a product within reasonable bounds of time and cost.


Author(s):  
Akira Yamada ◽  
Fuminori Niikura ◽  
Koji Ikuta

Biodegradable polymers are employed in medicine and its further application is expected with eagerness. But the lack of an appropriate processing method retards the progress. To overcome this problem, we have developped a novel three-dimensional microfabrication system. The system design allows us the processing of the free three-dimensional micro-level forms by stacking up melted polymers from the nozzle. Different from the conventional method, we adopted a batch process to supply materials in order to eliminate the prior process that required toxic solvents. In addition, it is possible to handle almost all biodegradable thermoplastic resins by adopting this system. A single layer from the piled-up layers of extruded lines was observed to evaluate the resolution. The lateral and depth resolutions attained are 40 μm and 45 μm, respectively. Biodegradable polymers enable three-dimensional microstructures such as micro-pipes, micro-bends, and micro-coil springs to be manufactured in less than 15 min. The biocompatibility of the newly fabricated structure was evaluated using a cell line (PC12). For this purpose, a small vessel, with a transparent base, was fabricated using PLA and cells were cultivated in it. The results were then compared with the results obtained using the standard method. The mechanical strength of our microstructures was evaluated using a tensile strength test. The tensile strength of the microstructure was lower than the one obtained from the conventional method, but has enough strength for fabrication of medical devices. Our system renders it possible to produce toxic-free, as well as transparent and leakage-free devices. Our system is expected to have potential applications in optimum design and fabrication of implantable devices, especially in tissue engineering.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ljubica Milosavljević ◽  
Bogdan Dražeta

Multiple processes in modern Serbia occurred at the end of the twentieth and the beginning of the twenty first century. Almost all of them regard political, economic, and social changes. Influences caused by these changes can be seen in the social template across the spectrum of plans, encompassing various spheres of life of individuals from business to private, all the way to the point where this division, for many, is gradually disappearing. In that sense, this paper will follow the most anthropologically interesting example of research, the one that follows the influences of the undertaken reform processes and observed changes. This is the example that regards the experience and evaluation of time among employed inhabitants of Belgrade, the capital of Serbia. The aim of this paper was to refer to the results of anthropological fieldwork conducted in 2005, which focused on the experiences, strategies and expectations of employed Belgraders in terms of their working hours and certain temporal boundaries that characterize it. Due to the increasingly intensive business contacts with foreign partners and colleagues since 2000, the working hours of employees were analyzed in a narrower context, as they were on the long list of adjustments, mostly to Western influences. These contacts were not only more frequent after the period of the 1990s, which, among other things, is characterized by a sudden break in cooperation with foreigners, but were often dictated by the EU integration process, the increase of the private sector in which operated companies were oriented towards profit, and the acceleration of time. The last aspect was examined in 2005 through a sample comprising 30 interlocutors of various business backgrounds. The ethnographic material was categorized and analyzed with regard to the differentiation of respondents by age. Fifteen respondents were chosen to represent the older generation (born in the 1940s and 1950s) and as many the younger generation (born in the 1960s and 1980s). The blurring of the boundaries between the employees’ business and private life in Belgrade became more marked at the turn of the century, and it could be clearly stated through the example of working time. Differences between the period of socialism and the period of reforms since the 1990s relate also to a sense of insecurity and fear of losing one's job or having inadequate work, and the simultaneous development of the private sector, which is characterized by stricter rules for employees. More intensive was the influence of business on the private domain of life, but also the intrusion of the private into business life. This has become a necessity and a pledge of individual functioning on both levels, which show combined characteristics of acceleration through the increase of obligations.


2021 ◽  
Author(s):  
◽  
Krunoslav Puškar

This thesis deals with the analysis and description of the historical and contemporary anthroponymy of the Kalnik area of the Prigorje region on the basis of both archival and field research carried out throughout a longer period of time. Since there has not been any extensive onomastic reasearch in the very area to date, our goal was to determine the influence of linguistic and extralinguistic changes in the reaserched onomastic categories. The introduction of this thesis provides the geographical, sociohistorical, demographical and linguistic context of the researched area, whereas the subsequent chapters provide a list and analysis of confirmed first names, personal and family nicknames, as well as family names of the reaserched area. First names were researched during nine time periods with a duration of five years, beginning from 1802 and ending in 2014. Because of a wide researched area, we limited our research on the anthroponymic repertoire of the city of Križevci, in which 3020 first names (1579 male and 1441 female names) were confirmed. In the 19th century, during five analysed time periods, 1519 first names were confirmed, out of which 814 male and 705 female names, which were mostly simple based on their structure (91.64%). Concerning the provenance of the first names, we established that almost all names were either Christian names or translated Christian names and that national names occur very rarely and sporadically, only in the second half of the 19th century. By comparison, in the 20th and 21st century, during the last four time periods, 1501 first names have been confirmed, out of which 765 were male and 736 female names. Concerning their structure, they turned out to be mostly compound first names in the 1946- 1950 time period (55.69%), whereas in the 2010-2014 time period they turned out to be predominantly single (97.02%). Concerning their provenance, in the 1946-1950 time period 48.39% of male and 57.58% of female national names were confirmed, whereas in the last time period male national names amount to 4.05%, and female national names to only 1.27%. Personal nicknames are a special anthroponymic category which has not been researched in the Kalnik area. Having limited our field research on 13 places throughout the area, we confirmed 288 real personal nicknames, 245 male and 43 female nicknames, of mostly simple structure (95.14%), which are still mostly used in oral and informal communication. The motivation behind the nicknames has faithfully shown us the extralinguistic reality of the researched area. The most frequent motivational group of nicknames is the one of unknown motivation (23.96%), while the other confirmed groups are nicknames motivated by a first name (12,15%), a physical characteristic of the owner (12.15%), another characteristic of the owner (11,81%), a specific word used by the owner (8.33%), an animal (6.94%), a family name (6.60%), an occupation (6.25%), an ethnonym or toponym (4.51%), a family or social role (2.78%), a professional designation (1.38%), food (1.04%), a name for a plant (1.04%), a subject (0.69%), and another nickname (0.35%). The high frequency of nicknames of unknown motivation shows us the importance of future research of this anthroponymic category because, due to the passage of time, it is difficult to determine the real motivation of every nickname. We came to the same conclusion during our research of family nicknames, another specific anthroponymic category, still quite present in the Kalnik area. Having limited our field research on 12 places throughout the wide researched area, we managed to confirm 173 real family nicknames, whose designated motivational groups provided us with important sociolinguistic pieces of information. Concerning their structure, the majority of family nicknames turned out to be simple (N = 129), whereas concerning their motivation, the majority of family nicknames were of unknown motivation (N = 33). Other motivational groups were the following: a first name (N = 27), an occupation (N = 27), a family name (N = 25), a personal nickname (N = 22), a certain characteristic (N = 13), an ethnonym (N = 10), a toponym (N = 6), a certain subject (N = 6), and an animal (N = 4). All these mentioned different anthroponymic categories (first names, personal and family nicknames) can be confirmed profusely in the last anthroponymic category researched and analysed in this thesis – family names. Having employed the criterion of their minimum continuity of 100 years in the researched area, we have managed to confirm 1360 family names with centuries old continuity, since the 14th century to this very day. With this criterion we also managed to reduce a significant number of over 3000 family names with mostly no continuity, as well as to confirm those last names which had left their trace in the researched area. Of course, not all family names confirmed by this criterion are necessarily connected to the researched area, but are only detected in it. Out of 1360 confirmed family names, we succeeded in determining 189 family names which occur exclusively or mostly in the researched area, 100 family names which do not occur in contemporary anthroponymy of the area, and 97 family names which could also become extinguished in near future. Concerning their structure, the majority of all family names occur without a suffix (N = 681). All the confirmed family names were analysed according to their structure and motivation and listed in our Lexicon of family names at the end of this very thesis.


Author(s):  
Stephen Fowl

The use of material images of various gods (idols) in religious worship has a long history and a central place in the polytheistic religions of the ancient world. The worship of these gods is strictly prohibited in Judaism, Christianity and Islam. This practice is generally referred to as idolatry. In addition, the making of images of the one God along with the use of such images in worship is also considered idolatry within these three monotheistic faiths. In the ancient societies within which Judaism, Christianity and, later, Islam emerged, almost all aspects of life were touched by the presence of idols. For a Jew (particularly in the diaspora) or a Christian to faithfully negotiate one’s way through the activities of daily life in such a world required sustained attentiveness and resolve. Over time, idolatry became more generally and metaphorically associated with ideas, motivations, beliefs and commitments that draw believers’ attention away from God. In some instances in Christianity, idolatry simply becomes a synonym for sin. Although it is not common today for Jews, Christians or Muslims to worship fabricated images of their own or other gods, some of the ongoing philosophical and theological issues concern how God’s creation can manifest the invisible God. In what ways, if any, can the created world mediate God truthfully to humans? Can such things as icons be instrumental in the worship of the one God without that worship being idolatrous? In recent French phenomenological writing, some of these issues receive attention. Although these concerns may seem distant from those of the Bible and Quran, they share a common recognition that idolatry stems from a failure of attentiveness, an inability or unwillingness to focus one’s attention and desire upon God in the face of myriad distractions.


2019 ◽  
pp. 289-318
Author(s):  
Lawrence M. Friedman

This chapter discusses the bar, covering its organization, legal education, and the legal literature of the law. The bar was open to almost all men in a technical sense. But class and background did make a difference. Jacksonian ideology should not be taken at face value. The bar was, for one thing, somewhat stratified, even in the nineteenth century. At the beginning of the twenty-first century, there is a tremendous social distance between a Wall Street partner on the one hand, and on the other hand, lawyers who scrambled for a living at the bottom of the heap. Lawyers from wealthy or professional backgrounds were far more likely to reach the heights than lawyers from working-class homes. In 1800 and 1850, there were no large law firms, and hardly any firms at all.


Author(s):  
Joachim König ◽  
François Legrand

We provide evidence for this conclusion: given a finite Galois cover $f:X\rightarrow \mathbb{P}_{\mathbb{Q}}^{1}$ of group $G$ , almost all (in a density sense) realizations of $G$ over $\mathbb{Q}$ do not occur as specializations of $f$ . We show that this holds if the number of branch points of $f$ is sufficiently large, under the abc-conjecture and, possibly, the lower bound predicted by the Malle conjecture for the number of Galois extensions of $\mathbb{Q}$ of given group and bounded discriminant. This widely extends a result of Granville on the lack of $\mathbb{Q}$ -rational points on quadratic twists of hyperelliptic curves over $\mathbb{Q}$ with large genus, under the abc-conjecture (a diophantine reformulation of the case $G=\mathbb{Z}/2\mathbb{Z}$ of our result). As a further evidence, we exhibit a few finite groups $G$ for which the above conclusion holds unconditionally for almost all covers of $\mathbb{P}_{\mathbb{Q}}^{1}$ of group $G$ . We also introduce a local–global principle for specializations of Galois covers $f:X\rightarrow \mathbb{P}_{\mathbb{Q}}^{1}$ and show that it often fails if $f$ has abelian Galois group and sufficiently many branch points, under the abc-conjecture. On the one hand, such a local–global conclusion underscores the ‘smallness’ of the specialization set of a Galois cover of $\mathbb{P}_{\mathbb{Q}}^{1}$ . On the other hand, it allows to generate conditionally ‘many’ curves over $\mathbb{Q}$ failing the Hasse principle, thus generalizing a recent result of Clark and Watson devoted to the hyperelliptic case.


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