Proceedings of the National Academy of Sciences of the United States of America

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• Mfn2-dependent fusion pathway of PE- enriched micron- sized vesicles AI翻译
  作者：Penalva, Daniel A.; Monnappa, Ajay K.; Natale, Paolo; Lopez-Montero, Ivan
  作者单位：National University of the South; Instituto de Investigaciones en Ingenieria Electrica (IIIE); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); National University of the South; Instituto de Investigaciones en Ingenieria Electrica (IIIE); Complutense University of Madrid; Complutense University of Madrid
  摘要：Mitofusins (Mfn1 and Mfn2) are the mitochondrial outer- membrane fusion proteins in mammals and belong to the dynamin superfamily of multidomain GTPases. Recent structural studies of truncated variants lacking alpha helical transmembrane domains suggested that Mfns dimerize to promote the approximation and the fusion of the mitochondrial outer membranes upon the hydrolysis of guanine 5 '- triphosphate disodium salt (GTP). However, next to the presence of GTP, the fusion activity seems to requi...
• Life stage-specific poly(A) site selection regulated by Trypanosoma brucei DRBD18 AI翻译
  作者：Bard, Jonathan E.; Tylec, Brianna L.; Dubey, Ashutosh P.; Lamb, Natalie A.; Yergeau, Donald A.; Read, Laurie K.
  作者单位：State University of New York (SUNY) System; University at Buffalo, SUNY; State University of New York (SUNY) System; University at Buffalo, SUNY; State University of New York (SUNY) System; University at Buffalo, SUNY; United States Department of Energy (DOE); National Renewable Energy Laboratory - USA
  摘要：The kinetoplastid parasite, Trypanosoma brucei, , undergoes a complex life cycle entailing slender and stumpy bloodstream forms in mammals and procyclic and metacyclic forms (MFs) in tsetse fly hosts. The numerous gene regulatory events that underlie T. brucei differentiation between hosts, as well as between active and quiescent stages within each host, take place in the near absence of transcriptional control. Rather, differentiation is controlled by RNA-- binding proteins (RBPs) that associ...
• Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer AI翻译
  作者：Li, Jiayun; Moresco, Philip; Fearon, Douglas T.
  作者单位：Cold Spring Harbor Laboratory; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University; Stony Brook University Hospital; Cornell University; Weill Cornell Medicine
  摘要：Pancreatic ductal adenocarcinoma (PDA) is a potentially lethal disease lacking effective treatments. Its immunosuppressive tumor microenvironment (TME) allows it to evade host immunosurveillance and limits response to immunotherapy. Here, using the mouse KRT19-- deficient (sgKRT19-- edited) PDA model, we find that intratumoral accumulation of natural killer T (NKT) cells is required to establish an immunologically active TME. Mechanistically, intratumoral NKT cells facilitate type I interferon...
• A new phylogeny for Aves is compromised by pervasive misalignment and homology problems AI翻译
  作者：Springer, Mark S.; Gatesy, John
  作者单位：University of California System; University of California Riverside; American Museum of Natural History (AMNH)
• Attenuating midline thalamus bursting to mitigate absence epilepsy AI翻译
  作者：Dong, Ping; Bakhurin, Konstantin; Li, Yuhui; Mikati, Mohamad A.; Cui, Jianmin; Grill, Warren M.; Yin, Henry H.; Yang, Huanghe
  作者单位：Duke University; Duke University; Duke University; Duke University; Duke University; Duke University
  摘要：Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain- of- function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK- D434G MLT neurons promotes synchronized...
• A distal enhancer of GATA3 regulates Th2 differentiation and allergic inflammation AI翻译
  作者：Kumagai, Takashi; Iwata, Arifumi; Furuya, Hiroki; Kato, Kodai; Okabe, Atsushi; Toda, Yosuke; Kanai, Mizuki; Fujimura, Lisa; Sakamoto, Akemi; Kageyama, Takahiro; Tanaka, Shigeru; Suto, Akira; Hatano, Masahiko; Kaneda, Atsushi; Nakajima, Hiroshi
  作者单位：Chiba University; Chiba University; Chiba University; Chiba University; Chiba University; Chiba University
  摘要：Asthma is a widespread airway disorder where GATA3- dependent Type- 2 helper T (Th2) cells and group 2 innate lymphoid cells (ILC2s) play vital roles. Asthma- associated single nucleotide polymorphisms (SNPs) are enriched in a region located 926- 970 kb downstream from GATA3 in the 10p14 (hG900). However, it is unknown how hG900 affects the pathogenesis of allergic airway inflammation. To investigate the roles of the asthma- associated GATA3 enhancer region in experimental allergic airway infl...
• Altered circadian rhythm, sleep, and rhodopsin 7 -dependent shade preference during diapause in Drosophila melanogaster AI翻译
  作者：Meyerhof, Geoff T.; Easwaran, Sreesankar; Bontempo, Angela E.; Montell, Craig; Montell, Denise J.
  作者单位：University of California System; University of California Santa Barbara
  摘要：To survive adverse environments, many animals enter a dormant state such as hibernation, dauer, or diapause. Various Drosophila species undergo adult reproductive diapause in response to cool temperatures and/or short day - length. While flies are less active during diapause, it is unclear how adverse environmental conditions affect circadian rhythms and sleep. Here we show that in diapause - inducing cool temperatures, Drosophila melanogaster exhibit altered circadian activity profiles, inclu...
• Post- immunotherapy CTLA-4 Ig treatment improves antitumor efficacy AI翻译
  作者：Mok, Stephen; Cobanoglu, Didem Agac; Liu, Huey; Mancuso, James J.; Allison, James P.
  作者单位：University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center
  摘要：Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune - related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyteassociated antigen 4 immunoglobulin fusion protein (CTLA - 4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA - 4 Ig 1) concomitantly with ICT or 2) aft...
• The DNA damage response of Escherichia coli, revisited: Differential gene expression after replication inhibition AI翻译
  作者：Sass, Thalia H.; Lovett, Susan T.
  作者单位：Brandeis University; Brandeis University
  摘要：In 1967, in this journal, Evelyn Witkin proposed the existence of a coordinated DNA damage response in Escherichia coli , which later came to be called the SOS response. We revisited this response using the replication inhibitor azidothymidine (AZT) and RNA - Seq analysis and identified several features. We confirm the induction of classic Save our ship (SOS) loci and identify several genes, including many of the pyrimidine pathway, that have not been previously demonstrated to be DNA damage -...
• Structural insights into the regulation of RyR1 by S100A1 AI翻译
  作者：Weninger, Gunnar; Miotto, Marco C.; Tchagou, Carl; Reiken, Steven; Dridi, Haikel; Brandenburg, Soeren; Riedemann, Gabriel C.; Yuan, Qi; Liu, Yang; Chang, Alexander; Wronska, Anetta; Lehnart, Stephan E.; Marks, Andrew R.
  作者单位：Columbia University; University of Gottingen; UNIVERSITY GOTTINGEN HOSPITAL; University of Gottingen
  摘要：S100A1, a small homodimeric EF - hand Ca 2+ - binding protein ( - 21 kDa), plays an important regulatory role in Ca 2+ signaling pathways involved in various biological functions including Ca 2+ cycling and contractile performance in skeletal and cardiac myocytes. One key target of the S100A1 interactome is the ryanodine receptor (RyR), a huge homotetrameric Ca 2+ release channel ( - 2.3 MDa) of the sarcoplasmic reticulum. Here, we report cryoelectron microscopy structures of S100A1 bound to R...