8/4/01. Two brief notes on the translation: Jetztzeit was translated as "here-and-now", in order to distinguish it from its polar opposite, the empty and homogenous time of positivism. Stillstellung was rendered as "zero-hour", rather than the misleading "standstill"; the verb "stillstehen" means to come to a stop or standstill, but Stillstellung is Benjamin's own unique invention, which connotes an objective interruption of a mechanical process, rather like the dramatic pause at the end of an action-adventure movie, when the audience is waiting to find out if the timebomb/missile/terrorist device was defused or not).
The morphogenetic transition between yeast and filamentous forms of the human
fungal pathogen Candida albicans is regulated by a variety of
signaling pathways. How these pathways interact to orchestrate morphogenesis,
however, has not been as well characterized. To address this question and to
identify genes that interact with the Regulation of Ace2 and Morphogenesis (RAM)
pathway during filamentation, we report the first large-scale genetic
interaction screen in C. albicans. Our strategy for this screen
was based on the concept of complex haploinsufficiency (CHI). A heterozygous
mutant of CBK1
(cbk1Δ/CBK1), a key RAM pathway
protein kinase, was subjected to transposon-mediated, insertional mutagenesis.
The resulting double heterozygous mutants (6,528 independent strains) were
screened for decreased filamentation on Spider Medium (SM). From the 441 mutants
showing altered filamentation, 139 transposon insertion sites were sequenced,
yielding 41 unique CBK1-interacting genes. This gene set was
enriched in transcriptional targets of Ace2 and, strikingly, the cAMP-dependent
protein kinase A (PKA) pathway, suggesting an interaction between these two
pathways. Further analysis indicates that the RAM and PKA pathways co-regulate a
common set of genes during morphogenesis and that hyper-activation of the PKA
pathway may compensate for loss of RAM pathway function. Our data also indicate
that the PKA–regulated transcription factor Efg1 primarily localizes to
yeast phase cells while the RAM–pathway regulated transcription factor
Ace2 localizes to daughter nuclei of filamentous cells, suggesting that Efg1 and
Ace2 regulate a common set of genes at separate stages of morphogenesis. Taken
together, our observations indicate that CHI–based screening is a useful
approach to genetic interaction analysis in C. albicans and
support a model in which these two pathways regulate a common set of genes at
different stages of filamentation.
Early warning scores are predictive of severe adverse events in postoperative patients. eCART is significantly more accurate in this patient population than both NEWS and MEWS.
The term big data has been popularized over the past decade and is often used to refer to data sets that are too large or complex to be analyzed by traditional means. Although the term has been utilized for some time in business and engineering, the concept of big data is relatively new to medicine. The reception from the medical community has been mixed; however, the widespread utilization of electronic health records in the United States, the creation of large clinical data sets and national registries that capture information on numerous vectors affecting healthcare delivery and patient outcomes, and the sequencing of the human genome are all opportunities to leverage big data. This review was inspired by a lively panel discussion on big data that took place at the 75th Central Surgical Association Annual Meeting. The authors' aim was to describe big data, the methodologies used to analyze big data, and their practical clinical application.
Disparities in pediatric firearm-related injury are associated with the Social Vulnerability Index (SVI). SVI can identify social factors, structural elements, & at-risk communities to assist in designing targeted prevention efforts. #SocialVulnerability #Pediatric #FirearmInjury
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