37 research outputs found
In vitro synthesis of uniform poly(dG)–poly(dC) by Klenow exo(−) fragment of polymerase I
In this paper, we describe a production procedure of the one-to-one double helical complex of poly(dG)–poly(dC), characterized by a well-defined length (up to 10 kb) and narrow size distribution of molecules. Direct evidence of strands slippage during poly(dG)–poly(dC) synthesis by Klenow exo(−) fragment of polymerase I is obtained by fluorescence resonance energy transfer (FRET). We show that the polymer extension results in an increase in the separation distance between fluorescent dyes attached to 5′ ends of the strands in time and, as a result, losing communication between the dyes via FRET. Analysis of the products of the early steps of the synthesis by high-performance liquid chromatography and mass spectroscopy suggest that only one nucleotide is added to each of the strand composing poly(dG)–poly(dC) in the elementary step of the polymer extension. We show that proper pairing of a base at the 3′ end of the primer strand with a base in sequence of the template strand is required for initiation of the synthesis. If the 3′ end nucleotide in either poly(dG) or poly(dC) strand is substituted for A, the polymer does not grow. Introduction of the T-nucleotide into the complementary strand to permit pairing with A-nucleotide results in the restoration of the synthesis. The data reported here correspond with a slippage model of replication, which includes the formation of loops on the 3′ ends of both strands composing poly(dG)–poly(dC) and their migration over long-molecular distances (μm) to 5′ ends of the strands
Photon momentum enabled light absorption in bulk silicon
Photons do not carry sufficient momentum to induce indirect optical
transitions in semiconducting materials such as silicon, necessitating the
assistance of lattice phonons to conserve momentum. Compared to direct bandgap
semiconductors, this renders silicon a less attractive material for a wide
variety of optoelectronic applications. In this work, we introduce an
alternative strategy to fulfill the momentum-matching requirement in indirect
optical transitions. We demonstrate that when confined to scales below ~3 nm,
photons acquire sufficient momentum to allow electronic transitions at the band
edge of Si without the assistance of a phonon. Confined photons allow
simultaneous energy and momentum conservation in two-body photon-electron
scattering; in effect, converting silicon into a direct bandgap semiconductor.
We show that this less-explored concept of light-matter interaction leads to a
marked increase in the absorptivity of Si from the UV to the near-IR. The
strategy provides opportunities for more efficient use of indirect
semiconductors in photovoltaics, energy conversion, light detection and
emission
Drugst.One -- A plug-and-play solution for online systems medicine and network-based drug repurposing
In recent decades, the development of new drugs has become increasingly
expensive and inefficient, and the molecular mechanisms of most pharmaceuticals
remain poorly understood. In response, computational systems and network
medicine tools have emerged to identify potential drug repurposing candidates.
However, these tools often require complex installation and lack intuitive
visual network mining capabilities. To tackle these challenges, we introduce
Drugst.One, a platform that assists specialized computational medicine tools in
becoming user-friendly, web-based utilities for drug repurposing. With just
three lines of code, Drugst.One turns any systems biology software into an
interactive web tool for modeling and analyzing complex protein-drug-disease
networks. Demonstrating its broad adaptability, Drugst.One has been
successfully integrated with 21 computational systems medicine tools. Available
at https://drugst.one, Drugst.One has significant potential for streamlining
the drug discovery process, allowing researchers to focus on essential aspects
of pharmaceutical treatment research.Comment: 45 pages, 6 figures, 7 table
Women with PCOS who undergo IVF: a comprehensive review of therapeutic strategies for successful outcomes
Abstract Polycystic ovarian syndrome (PCOS) is a widespread syndrome that poses unique challenges and constraints to the field of assisted reproductive technology. This condition is the most common cause of anovulation among infertile couples. Debate exists over the best therapeutic course of action when patients with PCOS proceed to IVF. In this review, we evaluate the best-performing and safest methods of IVF preparation, ovarian stimulation, trigger method for maturation of stimulated egg growth, and planning for embryo transfer. Pre-IVF considerations include being aware of individual AMH and vitamin D levels as well as BMI prior to selecting an ovarian stimulation protocol. Numerous supplements such as myo-inositol complement the benefits of lifestyle change and may enhance IVF performance including oocyte yield and pregnancy rate. Concerning stimulation protocols, antagonist cycles with the judicious use of GnRH agonist trigger, pre-treatment with metformin and vitamin D repletion may help mitigate the accompanied risk of ovarian hyperstimulation syndrome (OHSS). Following ovarian stimulation, PCOS patients typically undergo programmed frozen embryo transfer (FET) cycles which are more conducive for women with irregular cycles, but likely carry a higher risk of hypertensive disorders of pregnancy. However, newer stimulated FET protocols using Letrozole may offer improved outcomes. Overall, patients with PCOS require careful individual tailoring of their IVF cycle to achieve optimal results
The puzzle of contrast inversion in DNA STM imaging (issue cover)
DNA has been at the center of an imaging effort since the invention of the scanning tunneling microscope (STM). In some of the STM imaging reports the molecules appeared with negative contrast, i.e., ``submerged'' under the metal background and darker. We demonstrate the phenomenon of contrast inversion in DNA STM imaging by controlled and spontaneous contrast inversions and by the dependence of the DNA apparent height with respect to the surface on the imaging bias voltage. Using these characterizations, we formulate a model explaining the above phenomenon by resonant tunneling through virtual states in the vacuum between the STM tip and the DNA molecule
Disparities in ART Live Birth and Cumulative Live Birth Outcomes for Hispanic and Asian Women Compared to White Non-Hispanic Women
BACKGROUND: Conflicting disparities have been seen in assisted reproductive technology (ART) outcomes for Hispanic and Asian women compared to white, non-Hispanic (WNH) women. We, therefore, sought to clarify these disparities and calculated cumulative live birth rates (CLBR) for these racial or ethnic groups using the SARTCORS database. METHODS: We performed an analysis of the 2014–2016 SARTCORS database for member clinics doing at least 50 cycles of ART each year. RESULTS: In comparison to cycles in WNH women, cycles in Hispanic and Asian patients were in older (p < 0.001), more nulliparous women, that were less likely to have a history of endometriosis compared WNH women regardless of prior ART status. ART cycles in Hispanic and Asian women, exhibited lower rates of live birth (LB) per cycle start (p < 0.001) compared to cycles in WNH women. Multivariate logistic regression demonstrated that cycles from Hispanic and Asian women were less likely to have a LB and CLBR than white women (OR 0.86; p = 0.004, OR 0.69; p < 0.001, respectively) independent of age, parity, BMI, etiology of infertility, use of ICSI or number of embryos transferred. CONCLUSIONS: Race or ethnicity continues to be an independent prognostic factor for LB and CLBR for ART. Additional analysis of trends among Hispanic and Asian women is warranted to enable addressing disparities in outcomes in ART treatment
Effect of oxygen on activation state of complex I and lack of oxaloacetate inhibition of complex II in Langendorff perfused rat heart
AbstractTwo main entry points for electrons into the mitochondrial respiratory chain are NADH:ubiquinone oxidoreductase (complex I) and succinate:ubiquinone oxidoreductase (complex II). Metabolic regulation of these two respiratory complexes is not understood in detail. It has been suggested that the Krebs cycle metabolic intermediate oxaloacetate (OAA) inhibits complex II in vivo, whereas complex I undergoes a reversible active/de-active transition. In normoxic and anoxic hearts it has been shown that the proportion of complex I in the active and de-active states is different suggesting a possible mode of regulation of the enzyme by oxygen concentration. In the current studies rapid isolation of mitochondrial membranes in a state that preserves the activity of both complex I and complex II has been achieved using Langendorff perfused rat hearts. The findings indicate that the state of activation of complex I is controlled by the oxygen saturation in the perfusate. In addition, these studies show that complex II is fully active in the mitochondrion and not inhibited by OAA regardless of the oxygen concentration