RNA therapeutics refers to the use of oligonucleotides to target primarily ribonucleic acids (RNA) for therapeutic efforts or in research studies to elucidate functions of genes. Oligonucleotides are distinct from other pharmacological modalities, such as small molecules and antibodies that target mainly proteins, due to their mechanisms of action and chemical properties. Nucleic acids come in two forms: deoxyribonucleic acids (DNA) and ribonucleic acids (RNA). Although DNA is more stable, RNA offers more structural variety ranging from messenger RNA (mRNA) that codes for protein to non-coding RNAs, microRNA (miRNA), transfer RNA (tRNA), short interfering RNAs (siRNAs), ribosomal RNA (rRNA), and long-noncoding RNAs (lncRNAs). As our understanding of the wide variety of RNAs deepens, researchers have sought to target RNA since >80% of the genome is estimated to be transcribed. These transcripts include non-coding RNAs such as miRNAs and siRNAs that function in gene regulation by playing key roles in the transfer of genetic information from DNA to protein, the final product of the central dogma in biology. Currently there are.....
As described in this issue’s review about scientific teaching (pp 5-15), an evidence-based approach to pedagogy is gradually gaining momentum across a wide range of academic disciplines, most notably the STEM fields. A number of challenges still remain on the road ahead but substantial progress has been made. One topic to emerge as a particularly active research area is the identification of misconceptions in learning or teaching processes. Misconceptions of this type can be harbored by either the student or instructor (and sometimes both). In recent years, an array of diverse research has been conducted to identify misconceptions across a number of academic disciplines, offering startling insights into the relationship between student or instructor perception and outcomes in different learning processes. In many respects, the results from this area have yielded some of the biggest surprises in evidence-based pedagogy.
Research investigating the relationship between teaching quality and student outcomes has found that teachers with higher knowledge for content and pedagogy are more likely to spend more time using effective practices while teaching than teachers with less knowledge. This is important, especially for teachers of students with specific learning disabilities, whose teachers require specialized knowledge and skill to support them in making gains. This qualitative study investigates three teachers’ knowledge and skill of effective fluency instruction for teaching students with specific learning disabilities. Using three different approaches to assessing teacher knowledge, researchers examined the misconceptions, consistencies, and contradictions revealed in teachers’ understandings across data sources. The researchers encourage researchers, teacher educators, and those involved in teacher evaluation to examine teacher understanding from multiple perspectives.
In the recent years, novel regulatory functions of non-coding RNAs have been discovered. Non-coding RNAs (ncRNAs) are diverse classes of RNA molecules not translated into proteins that possess intricate regulatory and structural functions. The human genome sequencing performed by the International Human Genome Sequencing Consortium revealed that only 20–25,000 genes are protein coding, corresponding to less than 2% of the human genome (2004). Although the common belief that the remaining and larger portion of the human genome was not functional and considered as “junk DNA”, recent studies based on tiling arrays and RNA deep sequencing show thousands of RNA transcripts not derived from known genes and not encoding proteins (KAPRANOV et al. 2007 ; CARNINCI et al. 2005). These molecules......
The treatment of pedagogy as a scientific subject, a process known as scientific teaching, has been ongoing for over a decade now, particularly in higher education STEM fields. The Howard Hughes Medical Institute (HHMI) has been at the forefront of this effort, investing over $100 million in a wide variety of educational initiatives targeted across a diverse array of students, primarily at the university level. Although the range of progress has been substantial, much work remains to be done. This review, though not exhaustive, will attempt to summarize some of the important advancements made thus far while also offering commentary on current and future challenges.
Gene expression can be regulated in many ways at the level of transcription or translation. The quickest way is to modify the gene product or protein. Post-translational modifications (PTMs) of proteins can alter their activity, interaction partners, complex affiliation, subcellular localization, or stability in response to changes in the cellular environment. There is a well-established and diverse range of PTMs. Phosphorylation is best characterized due to its essential role in a wide range of cellular processes such as the DNA damage response (DDR).
Recent studies have shown the presence of functional brown adipose tissue (BAT) in adult humans in glucose and energy metabolism. This short study by Chondronikola et al published in Cell Metabolism 1 shows that during prolonged non-shivering cold exposure in obese/overweight individuals, brown adipose tissue is activated. This is associated with increased lipolysis, increased free fatty acid (FFA) oxidation and cycling. These changes in the BAT also affect insulin sensitivity in the white adipose tissue. This study provides insight into an unexplored role of function of BAT in lipid metabolism during prolonged cold exposure.
Wnt5a is one of the most extensively studied proteins of the Wnt family and is known to play an important role in cellular motility and proliferation. Wnt5a is a ligand of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), an onco-embryonic protein expressed on chronic lymphocytic leukemia (CLL) B cells, and on a variety of solid tumors, but not on normal adult tissues. This mini-review summarizes recent results regarding the inhibition of effects of Wnt5a signaling by targeting ROR1.
Almost 20 incurable neurodegenerative disorders are caused by trinucleotide repeat (TNR) expansion beyond a certain threshold, with disease time of onset and severity positively correlating with repeat length. Typically, long TNRs display a bias toward further expansion and repeats continue to expand not only during germline transmissions from parents to offspring, but also remain highly unstable in somatic tissues of patients. Hence, understanding TNR instability mechanisms sheds light on underlying disease pathology. Recently, we showed that activated ATR (ataxia-telangiectasia mutated ï›ATMï and Rad3 related) is the major signal for convergent-transcription-induced cell death at CAG repeats and is regulated by the mismatch repair (MMR) pathway. Additionally, components of other DNA repair pathways such as transcription-coupled nucleotide excision repair (TC-NER) and R-loop resolution by RNaseH (ribonuclease H) reduce cell death. Because activated ATR signals ....
Tumor associated carbohydrate antigens (TACAs) are a class of glycans with important structural and signaling functions playing a major role in cell proliferation, differentiation, and apoptosis relevant to oncology. Tumor cells expressing TACAs influence prognosis and survival of cancer patients. Careful consideration must be given to structural aspects during rational design of small molecule therapeutics that mimic the molecular topology of different classes of TACAs even though they are chemically dissimilar but functionally equivalent molecular structures.