2,164 research outputs found
Massively parallel single-molecule manipulation using centrifugal force
Precise manipulation of single molecules has already led to remarkable
insights in physics, chemistry, biology and medicine. However, widespread
adoption of single-molecule techniques has been impeded by equipment cost and
the laborious nature of making measurements one molecule at a time. We have
solved these issues with a new approach: massively parallel single-molecule
force measurements using centrifugal force. This approach is realized in a
novel instrument that we call the Centrifuge Force Microscope (CFM), in which
objects in an orbiting sample are subjected to a calibration-free,
macroscopically uniform force-field while their micro-to-nanoscopic motions are
observed. We demonstrate high-throughput single-molecule force spectroscopy
with this technique by performing thousands of rupture experiments in parallel,
characterizing force-dependent unbinding kinetics of an antibody-antigen pair
in minutes rather than days. Additionally, we verify the force accuracy of the
instrument by measuring the well-established DNA overstretching transition at
66 3 pN. With significant benefits in efficiency, cost, simplicity, and
versatility, "single-molecule centrifugation" has the potential to
revolutionize single-molecule experimentation, and open access to a wider range
of researchers and experimental systems.Comment: 5 pages, 3 figure
Association between furosemide in premature infants and sensorineural hearing loss and nephrocalcinosis: a systematic review
Abstract
Furosemide is a potent loop diuretic commonly and variably used by neonatologists to improve oxygenation and lung compliance in premature infants. There are several safety concerns with use of furosemide in premature infants, specifically the risk of sensorineural hearing loss (SNHL), and nephrocalcinosis/nephrolithiasis (NC/NL). We conducted a systematic review of all trials and observational studies examining the association between these outcomes with exposure to furosemide in premature infants.
We searched MEDLINE, EMBASE, CINAHL, and
clinicaltrials.gov
. We included studies reporting either SNHL or NC/NL in premature infants (<β37Β weeks completed gestational age) who received at least one dose of enteral or intravenous furosemide. Thirty-two studies met full inclusion criteria for the review, including 12 studies examining SNHL and 20 studies examining NC/NL. Only one randomized controlled trial was identified in this review. We found no evidence that furosemide exposure increases the risk of SNHL or NC/NL in premature infants, with varying quality of studies and found the strength of evidence for both outcomes to be low. The most common limitation in these studies was the lack of control for confounding factors.
The evidence for the risk of SNHL and NC/NL in premature infants exposed to furosemide is low. Further randomized controlled trials of furosemide in premature infants are urgently needed to adequately assess the risk of SNHL and NC/NL, provide evidence for improved FDA labeling, and promote safer prescribing practices.https://deepblue.lib.umich.edu/bitstream/2027.42/146523/1/40748_2018_Article_92.pd
Association between furosemide in premature infants and sensorineural hearing loss and nephrocalcinosis: a systematic review
Abstract
Furosemide is a potent loop diuretic commonly and variably used by neonatologists to improve oxygenation and lung compliance in premature infants. There are several safety concerns with use of furosemide in premature infants, specifically the risk of sensorineural hearing loss (SNHL), and nephrocalcinosis/nephrolithiasis (NC/NL). We conducted a systematic review of all trials and observational studies examining the association between these outcomes with exposure to furosemide in premature infants.
We searched MEDLINE, EMBASE, CINAHL, and
clinicaltrials.gov
. We included studies reporting either SNHL or NC/NL in premature infants (<β37Β weeks completed gestational age) who received at least one dose of enteral or intravenous furosemide. Thirty-two studies met full inclusion criteria for the review, including 12 studies examining SNHL and 20 studies examining NC/NL. Only one randomized controlled trial was identified in this review. We found no evidence that furosemide exposure increases the risk of SNHL or NC/NL in premature infants, with varying quality of studies and found the strength of evidence for both outcomes to be low. The most common limitation in these studies was the lack of control for confounding factors.
The evidence for the risk of SNHL and NC/NL in premature infants exposed to furosemide is low. Further randomized controlled trials of furosemide in premature infants are urgently needed to adequately assess the risk of SNHL and NC/NL, provide evidence for improved FDA labeling, and promote safer prescribing practices
Critical Structural and Functional Roles for the N-Terminal Insertion Sequence in Surfactant Protein B Analogs
Surfactant protein B (SP-B; 79 residues) belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78), confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7) attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity.FTIR spectra of Mini-B and Super Mini-B in either lipids or lipid-mimics indicated that these peptides share similar conformations, with primary alpha-helix and secondary beta-sheet and loop-turns. Gel electrophoresis demonstrated that Super Mini-B was dimeric in SDS detergent-polyacrylamide, while Mini-B was monomeric. Surface plasmon resonance (SPR), predictive aggregation algorithms, and molecular dynamics (MD) and docking simulations further suggested a preliminary model for dimeric Super Mini-B, in which monomers self-associate to form a dimer peptide with a "saposin-like" fold. Similar to native SP-B, both Mini-B and Super Mini-B exhibit in vitro activity with spread films showing near-zero minimum surface tension during cycling using captive bubble surfactometry. In vivo, Super Mini-B demonstrates oxygenation and dynamic compliance that are greater than Mini-B and compare favorably to full-length SP-B.Super Mini-B shows enhanced surfactant activity, probably due to the self-assembly of monomer peptide into dimer Super Mini-B that mimics the functions and putative structure of native SP-B
Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).
We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome
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