Midtropospheric frontogenesis associated with antecedent indirect precipitation ahead of tropical cyclones over the Korean Peninsula

On the Korean Peninsula (KP), heavy rainfall often precedes the landfall of a tropical cyclone (TC). This rainfall is called antecedent indirect precipitation (AIP), because it occurs well beyond the effective radius of the TC. The present study examines the statistical characteristics and physical mechanism of the AIP produced by TCs that influenced the KP during the period 1993-2004. Composite analyses demonstrate that the AIP events were accompanied by midtropospheric frontogenesis due to the TC-mid-latitude environment interaction. When an approaching TC encountered an approaching mid-latitude upper-level trough, this encounter resulted in confluent and deformed flows at the mid-level by the combination of westerlies from the trough and southerlies from the TC. The delicate balance of horizontal winds related to the two systems at the mid-level led to the midtropospheric frontogenesis to the north of the KP. The frontogenetic feature related to the AIP was in marked contrast to those of the remote rainfall event over the KP and the predecessor rainfall event over the United States suggested by previous studies. Quasi-geostrophic analysis demonstrates that the midtropospheric front induced thermally direct circulation, which led to ascending motion over the KP. Consequently, the midtropospheric front helped to intensify the AIP, together with the convective instability that was amplified by the transport of warm and moist air along the conduit between the TC and subtropical high.open110Ysciescopu

Crystal Structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates

The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during DNA repair after interstrand cross-links, replication fork collapse, or double-strand breaks. To explain the molecular basis of 3 ' flap substrate recognition and cleavage mechanism by Mus81-Eme1, we determined crystal structures of human Mus81-Eme1 bound to various flap DNA substrates. Mus81-Eme1 undergoes gross substrate-induced conformational changes that reveal two key features: (i) a hydrophobic wedge of Mus81 that separates pre- and post-nick duplex DNA and (ii) a 5 ' end binding pocket that hosts the 5 ' nicked end of post-nick DNA. These features are crucial for comprehensive protein-DNA interaction, sharp bending of the 3 ' flap DNA substrate, and incision strand placement at the active site. While Mus81-Eme1 unexpectedly shares several common features with members of the 5 ' flap nuclease family, the combined structural, biochemical, and biophysical analyses explain why Mus81-Eme1 preferentially cleaves 3 ' flap DNA substrates with 5 ' nicked ends.X11119Ysciescopu

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

How to avoid complications of distraction osteogenesis for first brachymetatarsia

Background and purpose Distraction osteogenesis may be used for the treatment of brachymetatarsia. However, few reports have been published on first metatarsal lengthening by this method. We evaluated the complications of distraction osteogenesis for first brachymetatarsia and here we provide a solution

Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils

Wnt5a is a ligand that activates the noncanonical Wnt signaling pathways (??-catenin-independent pathways). Human neutrophils expressed several Wnt5a receptors, such as Frizzled 2, 5 and 8. Stimulation of human neutrophils with Wnt5a caused chemotactic migration and the production of two important chemokines, CXCL8 and CCL2. CCL2 production by Wnt5a was mediated by a pertussis toxin-sensitive G-protein-dependent pathway. Wnt5a also stimulated the phosphorylation of three mitogen-activated protein kinases (MAPKs: ERK, p38 MAPK and JNK) and Akt. Inhibition of ERK, p38 MAPK or JNK by specific inhibitors induced a dramatic reduction in Wnt5a-induced CCL2 production. Supernatant collected from lipopolysaccharide-stimulated macrophages induced neutrophil chemotaxis, which was significantly inhibited by anti-Wnt5a antibody. Our results suggested that Wnt5a may contribute to neutrophil recruitment, mediating the inflammation response.open4

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

The JCMT Transient Survey: Four-year Summary of Monitoring the Submillimeter Variability of Protostars

We present the four-year survey results of monthly submillimeter monitoring of eight nearby (<500 pc) star-forming regions by the JCMT Transient Survey. We apply the Lomb–Scargle Periodogram technique to search for and characterize variability on 295 submillimeter peaks brighter than 0.14 Jy beam−1, including 22 disk sources (Class II), 83 protostars (Class 0/I), and 190 starless sources. We uncover 18 secular variables, all of them protostars. No single-epoch burst or drop events and no inherently stochastic sources are observed. We classify the secular variables by their timescales into three groups: Periodic, Curved, and Linear. For the Curved and Periodic cases, the detectable fractional amplitude, with respect to mean peak brightness, is ∼4% for sources brighter than ∼0.5 Jy beam−1. Limiting our sample to only these bright sources, the observed variable fraction is 37% (16 out of 43). Considering source evolution, we find a similar fraction of bright variables for both Class 0 and Class I. Using an empirically motivated conversion from submillimeter variability to variation in mass accretion rate, six sources (7% of our full sample) are predicted to have years-long accretion events during which the excess mass accreted reaches more than 40% above the total quiescently accreted mass: two previously known eruptive Class I sources, V1647 Ori and EC 53 (V371 Ser), and four Class 0 sources, HOPS 356, HOPS 373, HOPS 383, and West 40. Considering the full protostellar ensemble, the importance of episodic accretion on few years timescale is negligible—only a few percent of the assembled mass. However, given that this accretion is dominated by events on the order of the observing time window, it remains uncertain as to whether the importance of episodic events will continue to rise with decades-long monitoring

E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis

Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. In contrast, UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS-81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling. Our findings establish a central role of UFD-2 in the coordination between the DNA-repair process and the apoptotic response

Targeting of SUMO substrates to a Cdc48-Ufd1-Npl4 segregase and STUbL pathway in fission yeast

In eukaryotes, the conjugation of proteins to the small ubiquitin-like modifier (SUMO) regulates numerous cellular functions. A proportion of SUMO conjugates are targeted for degradation by SUMO-targeted ubiquitin ligases (STUbLs) and it has been proposed that the ubiquitin-selective chaperone Cdc48/p97-Ufd1-Npl4 facilitates this process. However, the extent to which the two pathways overlap, and how substrates are selected, remains unknown. Here we address these questions in fission yeast through proteome-wide analyses of SUMO modification sites. We identify over a thousand sumoylated lysines in a total of 468 proteins and quantify changes occurring in the SUMO modification status when the STUbL or Ufd1 pathways are compromised by mutations. The data suggest the coordinated processing of several classes of SUMO conjugates, many dynamically associated with centromeres or telomeres. They provide new insights into subnuclear organization and chromosome biology, and, altogether, constitute an extensive resource for the molecular characterization of SUMO function and dynamics