22 research outputs found
Evaluating Children’s Advocacy Centers’ Response to Child Sexual Abuse
Children’s Advocacy Centers (CACs) play an increasingly significant role in the response to child sexual abuse and other child maltreatment in the United States. First developed in the 1980s, CACs were designed to reduce the stress on child abuse victims and families created by traditional child abuse investigation and prosecution procedures and to improve the effectiveness of the response. According to several experts (Fontana, 1984; Pence and Wilson, 1992; Whitcomb, 1992), child victims were subjected to multiple, redundant interviews about their abuse by different agencies, and were questioned by professionals who had no knowledge of children’s developmental limitations or experience working with children. Child interviews would take place in settings like police stations that would further stress already frightened children. Moreover, the response was hampered because the multiple agencies involved did not coordinate their investigations, and children’s need for services could be neglected
RNA-Catalyzed Cross-Chiral Polymerization of RNA
Biology relies almost exclusively on homochiral building blocks to drive the processes
of life. Yet cross-chiral interactions can occur between macromolecules of the opposite
handedness, including a previously described polymerase ribozyme that catalyzes the template-directed synthesis of enantio-RNA. The present study sought to optimize and generalize this
activity, employing in vitro evolution to select cross-chiral polymerases that use either mono- or
trinucleotide substrates that are activated as the 5´-triphosphate. There was only modest
improvement of the former activity, but dramatic improvement of the latter, which enables the
trinucleotide polymerase to react 10^2–10^3-fold faster than its ancestor and to accept substrates
with all possible sequence combinations. The evolved ribozyme can assemble long RNAs from a
mixture of trinucleotide building blocks, including a two-fragment form of the ancestral
polymerase ribozyme. Further improvement of this activity could enable the generalized cross-chiral
replication of RNA, which would establish a new paradigm for the chemical basis of
Darwinian evolution
Specific Inhibition of MicroRNA Processing Using l‑RNA Aptamers
<i>In vitro</i> selection was used to obtain l-RNA aptamers that bind the
distal stem-loop of various precursor
microRNAs (pre-miRs). These l-aptamers, termed “aptamiRs”,
bind their corresponding pre-miR target through highly specific tertiary
interactions rather than Watson–Crick pairing. Formation of
a pre-miR–aptamiR complex inhibits Dicer-mediated processing
of the pre-miR, which is required to form the mature functional microRNA.
One of the aptamiRs, which was selected to bind oncogenic pre-miR-155,
inhibits Dicer processing under simulated physiological conditions,
with an IC<sub>50</sub> of 87 nM. Given that l-RNAs are intrinsically
resistant to nuclease degradation, these results suggest that aptamiRs
might be pursued as a new class of miR inhibitors
RNA-Catalyzed Cross-Chiral Polymerization of RNA
Biology relies almost exclusively on homochiral building blocks to drive the processes
of life. Yet cross-chiral interactions can occur between macromolecules of the opposite
handedness, including a previously described polymerase ribozyme that catalyzes the template-directed synthesis of enantio-RNA. The present study sought to optimize and generalize this
activity, employing in vitro evolution to select cross-chiral polymerases that use either mono- or
trinucleotide substrates that are activated as the 5´-triphosphate. There was only modest
improvement of the former activity, but dramatic improvement of the latter, which enables the
trinucleotide polymerase to react 10^2–10^3-fold faster than its ancestor and to accept substrates
with all possible sequence combinations. The evolved ribozyme can assemble long RNAs from a
mixture of trinucleotide building blocks, including a two-fragment form of the ancestral
polymerase ribozyme. Further improvement of this activity could enable the generalized cross-chiral
replication of RNA, which would establish a new paradigm for the chemical basis of
Darwinian evolution
Catalysing mirror life
Origin of life: Although current life is homochiral (with D nucleic acids), little is known about how homochirality emerged or even if it was a necessary step. The isolation of cross-chiral nucleic acid ligases demonstrate that an early heterochiral life could have been possible