Evolutionarily conserved inhibitory uORFs sensitize Hox mRNA translation to start codon selection stringency [Biochemistry]
Translation start site selection in eukaryotes is influenced by context nucleotides flanking the AUG codon and by levels of the eukaryotic translation initiation factors eIF1 and eIF5. In a search of mammalian genes, we identified five homeobox (Hox) gene paralogs initiated by AUG codons in conserved suboptimal context as well... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Ivaylo P. Ivanov, James A. Saba, Chen-Ming Fan, Ji Wang, Andrew E. Firth, Chune Cao, Rachel Green, Thomas E. Dever Tags: Biochemistry Biological Sciences Source Type: research

Axioms for the category of Hilbert spaces [Mathematics]
We provide axioms that guarantee a category is equivalent to that of continuous linear functions between Hilbert spaces. The axioms are purely categorical and do not presuppose any analytical structure. This addresses a question about the mathematical foundations of quantum theory raised in reconstruction programs such as those of von... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Chris Heunen, Andre Kornell Tags: Mathematics Physical Sciences Source Type: research

Automorphic Bloch theorems for hyperbolic lattices [Physics]
Hyperbolic lattices are a new form of synthetic quantum matter in which particles effectively hop on a discrete tessellation of two-dimensional (2D) hyperbolic space, a non-Euclidean space of uniform negative curvature. To describe the single-particle eigenstates and eigenenergies for hopping on such a lattice, a hyperbolic generalization of band theory... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Joseph Maciejko, Steven Rayan Tags: Physics Physical Sciences Source Type: research

Heritable changes in division speed accompany the diversification of single T cell fate [Biophysics and Computational Biology]
Rapid clonal expansion of antigen-specific T cells is a fundamental feature of adaptive immune responses. It enables the outgrowth of an individual T cell into thousands of clonal descendants that diversify into short-lived effectors and long-lived memory cells. Clonal expansion is thought to be programmed upon priming of a single... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Marten Plambeck, Atefeh Kazeroonian, Dirk Loeffler, Lorenz Kretschmer, Ciro Salinno, Timm Schroeder, Dirk H. Busch, Michael Flossdorf, Veit R. Buchholz Tags: Immunology and Inflammation Biological Sciences Source Type: research

Drosophila carrying epilepsy-associated variants in the vitamin B6 metabolism gene PNPO display allele- and diet-dependent phenotypes [Genetics]
Pyridox(am)ine 5′-phosphate oxidase (PNPO) catalyzes the rate-limiting step in the synthesis of pyridoxal 5′-phosphate (PLP), the active form of vitamin B6 required for the synthesis of neurotransmitters gamma-aminobutyric acid (GABA) and the monoamines. Pathogenic variants in PNPO have been increasingly identified in patients with neonatal epileptic encephalopathy and early-onset epilepsy.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Wanhao Chi, Atulya S. R. Iyengar, Wenqin Fu, Wei Liu, Abigayle E. Berg, Chun-Fang Wu, Xiaoxi Zhuang Tags: Genetics Biological Sciences Source Type: research

Molecular mechanisms underlying metamorphosis in the most-ancestral winged insect [Evolution]
Insects comprise over half of the described species, and the acquisition of metamorphosis must have contributed to their diversity and prosperity. The order Odonata (dragonflies and damselflies) is among the most-ancestral insects with drastic morphological changes upon metamorphosis, in which understanding of the molecular mechanisms will provide insight into the... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Genta Okude, Minoru Moriyama, Ryouka Kawahara-Miki, Shunsuke Yajima, Takema Fukatsu, Ryo Futahashi Tags: Evolution Biological Sciences Source Type: research

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization [Medical Sciences]
Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here,... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Valeria Governa, Hugo Talbot, Kelin Goncalves de Oliveira, Myriam Cerezo–Magana, Anna Bang–Rudenstam, Maria C. Johansson, Ann–Sofie Mansson, Karin Forsberg–Nilsson, Gyorgy Marko–Varga, Julio Enriquez Perez, Anna Darabi, Johan Tags: Medical Sciences Biological Sciences Source Type: research

PRDM9 losses in vertebrates are coupled to those of paralogs ZCWPW1 and ZCWPW2 [Evolution]
In most mammals and likely throughout vertebrates, the gene PRDM9 specifies the locations of meiotic double strand breaks; in mice and humans at least, it also aids in their repair. For both roles, many of the molecular partners remain unknown. Here, we take a phylogenetic approach to identify genes that... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Maria Izabel A. Cavassim, Zachary Baker, Carla Hoge, Mikkel H. Schierup, Molly Schumer, Molly Przeworski Tags: Evolution Biological Sciences Source Type: research

Nanobodies as allosteric modulators of Parkinson’s disease-associated LRRK2 [Biochemistry]
Mutations in the gene coding for leucine-rich repeat kinase 2 (LRRK2) are a leading cause of the inherited form of Parkinson’s disease (PD), while LRRK2 overactivation is also associated with the more common idiopathic form of PD. LRRK2 is a large multidomain protein, including a GTPase as well as a... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Ranȷan K. Singh, Ahmed Soliman, Giambattista Guaitoli, Eliza Stormer, Felix von Zweydorf, Thomas Dal Maso, Asmaa Oun, Laura Van Rillaer, Sven H. Schmidt, Deep Chatterȷee, Joshua A. David, Els Pardon, Thomas U. Schwartz, Stefan Knapp, Eileen Tags: Biochemistry Biological Sciences Source Type: research

BIN1 modulation in vivo rescues dynamin-related myopathy [Medical Sciences]
The mechanoenzyme dynamin 2 (DNM2) is crucial for intracellular organization and trafficking. DNM2 is mutated in dominant centronuclear myopathy (DNM2-CNM), a muscle disease characterized by defects in organelle positioning in myofibers. It remains unclear how the in vivo functions of DNM2 are regulated in muscle. Moreover, there is no therapy... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Valentina Maria Lionello, Christine Kretz, Evelina Edelweiss, Corinne Crucifix, Raquel Gomez–Oca, Nadia Messaddeq, Suzie Buono, Pascale Koebel, Xenia Massana Munoz, Nadege Diedhiou, Belinda S. Cowling, Marc Bitoun, Jocelyn Laporte Tags: Medical Sciences Biological Sciences Source Type: research

BEND3 safeguards pluripotency by repressing differentiation-associated genes [Genetics]
BEN domain–containing proteins are emerging rapidly as an important class of factors involved in modulating gene expression, yet the molecular basis of how they regulate chromatin function and transcription remains to be established. BEND3 is a quadruple BEN domain–containing protein that associates with heterochromatin and functions as a transcriptional repressor.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Fredy Kurniawan, Neha Chetlangia, Mohammad Kamran, Christophe E. Redon, Lorinc Pongor, Qinyu Sun, Yo-Chuen Lin, Vijay Mohan, Oways Shaqildi, Darya Asoudegi, Qinyu Hao, Abid Khan, Mirit I. Aladjem, Kannanganattu V. Prasanth, Supriya G. Prasanth Tags: Genetics Biological Sciences Source Type: research

Modeling suggests gene editing combined with vaccination could eliminate a persistent disease in livestock [Genetics]
Recent breakthroughs in gene-editing technologies that can render individual animals fully resistant to infections may offer unprecedented opportunities for controlling future epidemics in farm animals. Yet, their potential for reducing disease spread is poorly understood as the necessary theoretical framework for estimating epidemiological effects arising from gene-editing applications is currently... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Gertje Eta Leony Petersen, Jaap B. Buntjer, Fiona S. Hely, Timothy John Byrne, Andrea Doeschl-Wilson Tags: Genetics Biological Sciences Source Type: research

Scaling laws in enzyme function reveal a new kind of biochemical universality [Biophysics and Computational Biology]
All life on Earth is unified by its use of a shared set of component chemical compounds and reactions, providing a detailed model for universal biochemistry. However, this notion of universality is specific to known biochemistry and does not allow quantitative predictions about examples not yet observed. Here, we introduce... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Dylan C. Gagler, Bradley Karas, Christopher P. Kempes, John Malloy, Veronica Mierzejewski, Aaron D. Goldman, Hyunju Kim, Sara I. Walker Tags: Biophysics and Computational Biology Biological Sciences Source Type: research

An in-frame deletion mutation in the degron tail of auxin coreceptor IAA2 confers resistance to the herbicide 2,4-D in Sisymbrium orientale [Agricultural Sciences]
The natural auxin indole-3-acetic acid (IAA) is a key regulator of many aspects of plant growth and development. Synthetic auxin herbicides such as 2,4-D mimic the effects of IAA by inducing strong auxinic-signaling responses in plants. To determine the mechanism of 2,4-D resistance in a Sisymbrium orientale (Indian hedge mustard)... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Marcelo R. A. de Figueiredo, Anita Kupper, Jenna M. Malone, Tiȷana Petrovic, Ana Beatriz T. B. de Figueiredo, Grace Campagnola, Olve B. Peersen, Kasavaȷhala V. S. K. Prasad, Eric L. Patterson, Anireddy S. N. Reddy, Martin F. Kubeš, Ri Tags: Agricultural Sciences Biological Sciences Source Type: research

Precision targeting tumor cells using cancer-specific InDel mutations with CRISPR-Cas9 [Medical Sciences]
In this study, we have developed a therapeutic strategy... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 25, 2022 Category: Science Authors: Taejoon Kwon, Jae Sun Ra, Soyoung Lee, In-Joon Baek, Keon Woo Khim, Eun A Lee, Eun Kyung Song, Daniyar Otarbayev, Woojae Jung, Yong Hwan Park, Minwoo Wie, Juyoung Bae, Himchan Cheng, Jun Hong Park, Namwoo Kim, Yuri Seo, Seongmin Yun, Ha Eun Kim, Hyo Eun M Tags: Medical Sciences Biological Sciences Source Type: research