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.
Synthetic biology is an interdisciplinary science, combining engineering and biological principles to design and construct new biological entities. Not only is synthetic biology useful for understanding life’s complex circuitries, this discipline has many practical applications such as modifying biological pathways to produce nanoparticles, proteins and other molecules for specific uses. As a rapidly evolving field, particularly due to recent advances in DNA sequencing and synthesis, synthetic biology holds great potential for transforming the future of biological research.
Pyranones play an important role towards the synthesis of carbohydrate containing natural products and are the key building blocks for most of the natural/unnatural oligosaccharides. Boc-Pyranones synthesis is a De Novo approach (i.e, achiral starting material, 2-acetyl furan (1) converted to chiral products) via Noyori asymmetric hydrogenation, Achmatowicz oxidative rearrangement, Upjohn dihydroxylation. Particularly, Boc-protected pyranones have established broad applications towards the synthesis of natural/unnatural products containing carbohydrate motifs (e.g., total synthesis of mezzettiasides, a class of partially acetylated anti-cancer natural products via Pd-/B-dual catalysis and synthesis of cleistriosides/cleistetrosides, a series of rhamno-oligosaccharides).
Cytokinesis is the final stage of mitosis that leads to the physical separation of two daughter cells and comprises a sequence of events such as actomyosin ring contraction, ingression and remodeling of the extracellular matrix. All these processes are tightly regulated in space and time through a network of proteins. Defects in cytokinesis may increase the risk of tumor formation. Using a combination of cell biology and molecular techniques, along with biochemical experiments, Foltman et al.  have dissected how the “ingression protein complexes” (IPCs) localize and coordinate to ensure proper cytokinesis. Interestingly, a particular glycosyltransferase, named Chs2, is the hub protein that assures a successful cytokinesis in budding yeast.
A recent advance in corrosion-resistance technology overcomes the problem of steel corrosion in CO2-enriched environments. At an inhibitor concentration of 10−3 M, the inhibition efficiency exceeded 98% where the steel corrosion rate is decreased by a factor of at least 100.
In this research article, a novel way to observe the micro-scale plastic deformation coupling atomic force microscopy and finite element calculation is introduced. The proposed methodology was also applied to study plastic strain localization quantitatively at the grain scale due to hydrogen embrittlement in the article.
The Ruth L. Kirschstein National Research Service Award program was created by Congress in 1974, and has successfully funded thousands of postdocs. The program includes a requirement for postdocs who receive funding from the program to sign a payback agreement. This obligates postdocs to continue performing health-related research or teaching for up to a year after receiving funds, or else pay back the stipend money they received. Economic and other concerns lead me to conclude that the payback requirement should be abandoned. Until that happens, the NIH, the NRSA Payback Service Center, training program directors, and university professors can take measures in administering NRSAs to ensure the fair treatment of postdocs.
The impact of technology in modern science is unequivocal. As scientific thought and design moves from traditional reductionism towards holism, advances in technology have altered the landscape of modern science. The modern systems biology approach models the dynamics and structure of biological systems. Implementing systems biology models in conjunction with imaging provides a way to refine understanding of biological systems.
Imaging mass spectrometry (IMS) has emerged as a powerful analytical tool enabling the direct molecular mapping of many types of tissue. Specifically, matrix-assisted laser desorption/ ionization (MALDI) represents one of the most broadly applicable IMS technologies. In recent years, advances in solid state laser technology, mass spectrometry instrumentation, computer technology, and experimental methodology have produced IMS systems capable of unprecedented data acquisition speeds (>50 pixels/second). In applications of this technology, throughput is an important consideration when designing an IMS experiment. As IMS becomes more widely adopted, continual improvements in experimental setups will be important to address biologically and clinically relevant time scales.