The fast-growing travel tech startup is moving into payments after securing $500 million in debt financing from Silicon Valley Bank, Goldman Sachs and Comerica Bank

Yifei Zhu
Trans. Amer. Math. Soc. 373 (2020), 3733-3764.
Abstract, references and article information

Jungang Li, Guozhen Lu and Qiaohua Yang
Trans. Amer. Math. Soc. 373 (2020), 3483-3513.
Abstract, references and article information

S. S. Lohvinenko and K. V. Ralchenko
Theor. Probability and Math. Statist. 99 (2020), 149-168.
Abstract, references and article information

N. N. Leonenko, I. Papić, A. Sikorskii and N. Šuvak
Theor. Probability and Math. Statist. 99 (2020), 137-147.
Abstract, references and article information

Curtis Triplitt
Oct 1, 2006; 19:202-211
Pharmacy Update

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.

Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals.

VOLUME 292 (2017) PAGES 3531–3540This article has been withdrawn by Shuofeng Hu, Xiaomin Ying, Xiangming Zhang, and Ya Wang. Baocheng Hu, Xiang Wang, Ping Wang, Jian Wang, and Hongyan Wang could not be reached. In Fig. 1C, the DAPI and merged images for the no IR control were switched. The DNA-PKcs and actin immunoblots on the left appear to have been spliced. In Fig. 4C, the DNA-PKcs immunoblot appears to have been spliced. In Fig. 4D, lanes 1 and 5; lanes 2, 6, and 8; and lanes 3 and 7 of the DNA-PKcs immunoblot are the same. In the p-DNA-PKcs immunoblot, lanes 1 and 8, lanes 2 and 6, and lanes 3 and 7 are the same. In the CRY2 immunoblot, lanes 5 and 7 are the same. In the CDC25A immunoblot, lanes 3 and 8 are the same. In the GSK3B immunoblot, lanes 1 and 5 and lanes 3 and 7 are the same. Also in the GSK3B immunoblot, the upper GSK3B bands in lanes 6 and 8 are the same. Lanes 4 and 8 of the cyclin D1 immunoblot are the same. In Fig. 5A, the CDC25A immunoblot appears to have been spliced. Also in Fig. 5A, lanes 2–4 and lanes 6–8 of the CDC25A immunoblot are the same. Lanes 4–6 and 7–9 of the actin immunoblot are the same. In Fig. 5C, lane 1 of the CDC25A immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. In the...

VOLUME 289 (2014) PAGES 30635–30644This article has been withdrawn by Guangnan Chen, Dongkyoo Park, Francis A. Cucinotta, David S. Yu, Xingming Deng, William S. Dynan, Paul W. Doetsch, and Ya Wang. Hongyan Wang, Xiang Wang, Xiangming Zhang, and Xiaobing Tang could not be reached. The last two lanes of the actin immunoblot in Fig. 1A were reused in the last two lanes of the actin immunoblot in Fig. 1C. In Fig. 2A, the γ-H2AX and the merge with DAPI images for no IR treatment do not match. In Fig. 3A, lanes 3 and 4 of the γ-H2AX immunoblot were reused in lanes 7 and 8, and lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3B, lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3C, lanes 5 and 6 of the γ-H2AX immunoblot were reused in lanes 7 and 8. Additionally, lanes 1 and 2 of the H2A immunoblot were reused in lanes 3 and 4. In Fig. 3D, lanes 1 and 2 of the Mre11 immunoblot from lysates were reused in lanes 4 and 5. In the γ-H2AX immunoblot, lane 3 was reused in lane 7, and lane 4 was reused in lanes 6 and 8. Also in the H2A immunoblot, lanes 1 and 2 were reused in lanes 3 and 4. In Fig. 4B, lanes 2 and 6 of the Mre11 immunoblot from Ogg1−/− cells are the same. In the Ape1...

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.

Araceli Bonifant and John Milnor
Bull. Amer. Math. Soc. 57 (2020), 171-267.
Abstract, references and article information

Do you know which main gases are contained in the composition of air? Under climate change and global warming, carbon dioxide ...

(University of Chicago Press Journals) A recent study confirms that Mesoamerican priests ripped the hearts out of their still-living victims in three different ways. New forensic evidence, historic witness accounts and native representations now show that the most common form of native heart extraction was from beneath the rib cage, second was forceful chest penetration between two ribs and at mid-chest level between the nipples, and thirdly, a mid-chest opening of one single blow, extracting the heart from the front.

(Bentham Science Publishers) This comprehensive review presented by researchers from K.S. Rangasamy College of Arts and Science, Tiruchengode, Tamil-Nadu, India, gives readers a brief overview of phytoconstituents, nutritional values and medicinal properties of the plant.

(University of Portsmouth) The first major UK study into victims of computer misuse crime has exposed the serious harm some victim's experience, as well as barriers to reporting such offences, receiving support, achieving justice and the precarious resources dedicated by the police to cybercrime.

(University of Sydney) Data centres and digital information processors are reaching their capacity limits and producing heat. Foundational work here on optical-acoustic microchips opens door to low-heat, low-energy, fast internet.

(University of Tsukuba) Researchers from the University of Tsukuba discovered that fish schools showed a significant change in behavior with varying school sizes. Using integrated information theory, they showed that a significant change in the interaction between the fish and the overall collective behavior occurred between three- and four-fish schools, including the emergence of leadership within the group. These findings help understand the dynamics of collective behavior.

Curtis Triplitt
Oct 1, 2006; 19:202-211
Pharmacy Update

β-Glucocerebrosidase (GBA) hydrolyzes glucosylceramide (GlcCer) to generate ceramide. Previously, we demonstrated that lysosomal GBA1 and nonlysosomal GBA2 possess not only GlcCer hydrolase activity, but also transglucosylation activity to transfer the glucose residue from GlcCer to cholesterol to form β-cholesterylglucoside (β-GlcChol) in vitro. β-GlcChol is a member of sterylglycosides present in diverse species. How GBA1 and GBA2 mediate β-GlcChol metabolism in the brain is unknown. Here, we purified and characterized sterylglycosides from rodent and fish brains. Although glucose is thought to be the sole carbohydrate component of sterylglycosides in vertebrates, structural analysis of rat brain sterylglycosides revealed the presence of galactosylated cholesterol (β-GalChol), in addition to β-GlcChol. Analyses of brain tissues from GBA2-deficient mice and GBA1- and/or GBA2-deficient Japanese rice fish (Oryzias latipes) revealed that GBA1 and GBA2 are responsible for β-GlcChol degradation and formation, respectively, and that both GBA1 and GBA2 are responsible for β-GalChol formation. Liquid chromatography–tandem MS revealed that β-GlcChol and β-GalChol are present throughout development from embryo to adult in the mouse brain. We found that β-GalChol expression depends on galactosylceramide (GalCer), and developmental onset of β-GalChol biosynthesis appeared to be during myelination. We also found that β-GlcChol and β-GalChol are secreted from neurons and glial cells in association with exosomes. In vitro enzyme assays confirmed that GBA1 and GBA2 have transgalactosylation activity to transfer the galactose residue from GalCer to cholesterol to form β-GalChol. This is the first report of the existence of β-GalChol in vertebrates and how β-GlcChol and β-GalChol are formed in the brain.

Katrina Meyer
Apr 28, 2020; 0:R120.002034v1-mcp.R120.002034
Review

Andreas Linden
Apr 24, 2020; 0:RA120.002028v1-mcp.RA120.002028
Research