How the discovery of microbial opsins led to the development of optogenetics.

This year's Lasker Award recognizes Dieter Oesterhelt, Peter Hegemann, and Karl Deisseroth for their discovery of microbial opsins as light-activated ion conductors and the development of optogenetics using these proteins to regulate neural activity in awake, behaving animals. Optogenetics has revolutionized neuroscience and transformed our understanding of brain function.

Identification of rare, transient post-mitotic cell states that are induced by injury and required for whole-body regeneration in Schmidtea mediterranea.

Regeneration requires the coordination of stem cells, their progeny and distant differentiated tissues. Here, we present a comprehensive atlas of whole-body regeneration in Schmidtea mediterranea and identify wound-induced cell states. An analysis of 299,998 single-cell transcriptomes captured from regeneration-competent and regeneration-incompetent fragments identified transient regeneration-activated cell states (TRACS) in the muscle, epidermis and intestine.

[Internationalized background of developing modern acupuncture and moxibustion-on the reform of teaching material of ].

This paper analyzes the severe challenges posed by the localization process in the internationalization of Chinese acupuncture and moxibustion to Chinese traditional acupuncture and moxibustion, and the ways to deal with the challenges. It is believed that the lack of deep understanding of the challenges in the process of internationalization of acupuncture and moxibustion is mainly due to the lack of knowledge structure of acupuncture and moxibustion, and the innovation of acupuncture and moxibustion teaching materials is the basis of effectively adjusting the knowledge structure. The direction of the reform of acupuncture and moxibustion teaching materials should separate the modern version of acupuncture and moxibustion that conforms to the nature of science and teach it in parallel with the traditional version of acupuncture and moxibustion.

Safety and outcome of gastrostomy tube placement in patients with Loeys-Dietz syndrome.

Background: Loeys-Dietz syndrome (LDS) is a systemic connective tissue disease (CTD) associated with a predisposition for intestinal inflammation, food allergy, and failure to thrive, often necessitating nutritional supplementation via gastrostomy tube. Poor wound healing has also been observed in in some patients with CTD, potentially increasing the risk of surgical interventions. We undertook to determine the safety and efficacy of gastrostomy tube placement in this population.

Wnt and TGFβ coordinate growth and patterning to regulate size-dependent behaviour.

Differential coordination of growth and patterning across metazoans gives rise to a diversity of sizes and shapes at tissue, organ and organismal levels. Although tissue size and tissue function can be interdependent, mechanisms that coordinate size and function remain poorly understood. Planarians are regenerative flatworms that bidirectionally scale their adult body size and reproduce asexually, via transverse fission, in a size-dependent manner.

Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance.

Individuals with robust natural killer (NK) cell function incur lower rates of malignancies. To expand our understanding of genetic factors contributing to this phenomenon, we analyzed NK cells from cancer resistant and susceptible strains of mice. We identified a correlation between NK levels of the X-chromosome-located adaptor protein SLy1 and immunologic susceptibility to cancer.

Loeys-Dietz syndrome: a primer for diagnosis and management.

Loeys-Dietz syndrome is a connective tissue disorder predisposing individuals to aortic and arterial aneurysms. Presenting with a wide spectrum of multisystem involvement, medical management for some individuals is complex. This review of literature and expert opinion aims to provide medical guidelines for care of individuals with Loeys-Dietz syndrome.

Antigenic conservation and immunogenicity of the HIV coreceptor binding site.

Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4).

Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance.

The immune system generally avoids horror autotoxicus or autoimmunity, an attack against the body's own constituents. This avoidance requires that self-reactive T cells be actively silenced or tolerized. We propose that dendritic cells (DCs) play a critical role in establishing tolerance, especially in the periphery, after functioning T cells have been produced in the thymus.

Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family.

To simplify the analysis of asthma susceptibility genes located at human chromosome 5q23-35, we examined congenic mice that differed at the homologous chromosomal segment. We identified a Mendelian trait encoded by T cell and Airway Phenotype Regulator (Tapr). Tapr is genetically distinct from known cytokine genes and controls the development of airway hyperreactivity and T cell production of interleukin 4 (IL-4) and IL-13.

A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube.

Cell pattern in the ventral neural tube is organized by Sonic hedgehog (Shh) secreted by floor plate cells. To assay the range of direct Shh action, we developed a general method for blocking transduction of Hedgehog (Hh) signals through ectopic expression of a deleted form of the Hh receptor Patched (Ptc), termed Ptc(Deltaloop2). We validated this method in Drosophila and used mouse Ptc1(Deltaloop2) (mPtc1(Deltaloop2)) to block Shh transduction in the chick neural tube.

Proximity and orientation underlie signaling by the non-receptor tyrosine kinase ZAP70.

Signaling by the antigen receptor of T lymphocytes initiates different developmental transitions, each of which require the tyrosine kinase ZAP70. Previous studies with agonist and antagonist peptides have indicated that ZAP70 might respond differently to different structures of the TCR-CD3 complex induced by bound peptides. The roles of membrane proximity and orientation in activation of ZAP70 signaling were explored using synthetic ligands and their binding proteins designed to produce different architectures of membrane-bound complexes composed of ZAP70 fusion proteins.

WNTs modulate cell fate and behavior during vertebrate development.

Wnt genes encode a family of secreted glycoproteins that modulate cell fate and behavior in embryos through activation of receptor-mediated signaling pathways. Wnt sequences, patterns of expression and activities are highly conserved in evolution, so it has been possible to gain insights into the functions, and mechanisms of action, of the Wnt genes through a synthesis of genetic and cell biological approaches in different organisms. These studies suggest that there are functionally distinct WNT proteins as assayed by the ability to transform cells and by differences in embryonic responses to ectopic WNT signals.

Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y.

Neuropeptide Y (NPY), a 36-amino-acid transmitter distributed throughout the nervous system, is thought to function as a central stimulator of feeding behaviour. NPY has also been implicated in the modulation of mood, cerebrocortical excitability, hypothalamic-pituitary signalling, cardiovascular physiology and sympathetic function. However, the biological significance of NPY has been difficult to establish owing to a lack of pharmacological antagonists.