"For Me, 'Normality' is Not Normal": Rethinking Medical and Cultural Ideals of Midlife ADHD Diagnosis.

According to psychiatry, Attention-Deficit/Hyperactivity Disorder (ADHD) is a chronic condition beginning in early life. Psychiatry advocates for early diagnosis to prevent comorbidities that may emerge in untreated cases. "Late"-diagnosis is associated with various hazards that might harm patients' lives and society.

T Cells Expressing a Modified FcγRI Exert Antibody-Dependent Cytotoxicity and Overcome the Limitations of CAR T-cell Therapy against Solid Tumors.

The pioneering design of chimeric antigen receptor (CAR) T-cell therapy demonstrated the potential of reprogramming the immune system. Nonetheless, T-cell exhaustion, toxicity, and suppressive microenvironments limit their efficacy in solid tumors. We previously characterized a subset of tumor-infiltrating CD4+ T cells expressing the FcγRI receptor.

A conformational switch in the SCF-D3/MAX2 ubiquitin ligase facilitates strigolactone signalling.

Strigolactones (SLs) are a class of plant hormones that regulate numerous processes of growth and development. SL perception and signal activation involves interaction between F-box E3 ubiquitin ligase D3/MAX2 and DWARF14 (D14) α/β-hydrolase in a SL-dependent manner and targeting of D53/SMXL6/7/8 transcriptional repressors (SMXLs) for proteasome-mediated degradation. D3/MAX2 has been shown to exist in multiple conformational states in which the C-terminal helix (CTH) undergoes a closed-to-open dynamics and regulates D14 binding and SL perception.

Dissection of floral transition by single-meristem transcriptomes at high temporal resolution.

The vegetative-to-floral transition is a dramatic developmental change of the shoot apical meristem, promoted by the systemic florigen signal. However, poor molecular temporal resolution of this dynamic process has precluded characterization of how meristems respond to florigen induction. Here, we develop a technology that allows sensitive transcriptional profiling of individual shoot apical meristems.

Conserved pleiotropy of an ancient plant homeobox gene uncovered by cis-regulatory dissection.

Divergence of gene function is a hallmark of evolution, but assessing functional divergence over deep time is not trivial. The few alleles available for cross-species studies often fail to expose the entire functional spectrum of genes, potentially obscuring deeply conserved pleiotropic roles. Here, we explore the functional divergence of WUSCHEL HOMEOBOX9 (WOX9), suggested to have species-specific roles in embryo and inflorescence development.

Structural insights into photoactivation of plant Cryptochrome-2.

Cryptochromes (CRYs) are evolutionarily conserved photoreceptors that mediate various light-induced responses in bacteria, plants, and animals. Plant cryptochromes govern a variety of critical growth and developmental processes including seed germination, flowering time and entrainment of the circadian clock. CRY's photocycle involves reduction of their flavin adenine dinucleotide (FAD)-bound chromophore, which is completely oxidized in the dark and semi to fully reduced in the light signaling-active state.

Characterization of the cytokinin sensor TCSv2 in arabidopsis and tomato.

Background: Hormones are crucial to plant life and development. Being able to follow the plants hormonal response to various stimuli and throughout developmental processes is an important and increasingly widespread tool. The phytohormone cytokinin (CK) has crucial roles in the regulation of plant growth and development.

Melanoma-Secreted Lysosomes Trigger Monocyte-Derived Dendritic Cell Apoptosis and Limit Cancer Immunotherapy.

The recent success of checkpoint blockade therapies has established immunotherapy as one of the most promising treatments for melanoma. Nonetheless, a complete curative response following immunotherapy is observed only in a fraction of patients. To identify what factors limit the efficacy of immunotherapies, we established mouse models that cease to respond to immunotherapies once their tumors exceed a certain stage.

Structural Aspects of Plant Hormone Signal Perception and Regulation by Ubiquitin Ligases.

Hormonal cues regulate many aspects of plant growth and development, facilitating the plant's ability to systemically respond to environmental changes. Elucidating the molecular mechanisms governing these signaling pathways is crucial to understanding how plants function. Structural and functional biology methods have been essential in decoding plant genetic findings and revealing precise molecular actions at the protein level.

A distinct subset of FcγRI-expressing Th1 cells exert antibody-mediated cytotoxic activity.

While a high frequency of Th1 cells in tumors is associated with improved cancer prognosis, this benefit has been attributed mainly to support of cytotoxic activity of CD8+ T cells. By attempting to potentiate antibody-driven immunity, we found a remarkable synergy between CD4+ T cells and tumor-binding antibodies. This surprising synergy was mediated by a small subset of tumor-infiltrating CD4+ T cells that express the high-affinity Fcγ receptor for IgG (FcγRI) in both mouse and human patients.

Coordination of Meristem Doming and the Floral Transition by Late Termination, a Kelch Repeat Protein.

Enlargement and doming of the shoot apical meristem (SAM) is a hallmark of the transition from vegetative growth to flowering. While this change is widespread, its role in the flowering process is unknown. The () tomato () mutant shows severely delayed flowering and precocious doming of the vegetative SAM encodes a kelch domain-containing protein, with no link to known meristem maintenance or flowering time pathways.

The Putative O-Linked N-Acetylglucosamine Transferase SPINDLY Inhibits Class I TCP Proteolysis to Promote Sensitivity to Cytokinin.

Arabidopsis (Arabidopsis thaliana) SPINDLY (SPY) is a putative serine and threonine O-linked N-acetylglucosamine transferase (OGT). While SPY has been shown to suppress gibberellin signaling and to promote cytokinin (CK) responses, its catalytic OGT activity was never demonstrated and its effect on protein fate is not known. We previously showed that SPY interacts physically and functionally with TCP14 and TCP15 to promote CK responses.

GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway.

Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules produced by solanaceous species. They contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. Here we show that GLYCOALKALOID METABOLISM 9 (GAME9), an APETALA2/Ethylene Response Factor, related to regulators of alkaloid production in tobacco and Catharanthus roseus, controls SGA biosynthesis.

Optimization of crop productivity in tomato using induced mutations in the florigen pathway.

Naturally occurring genetic variation in the universal florigen flowering pathway has produced major advancements in crop domestication. However, variants that can maximize crop yields may not exist in natural populations. Here we show that tomato productivity can be fine-tuned and optimized by exploiting combinations of selected mutations in multiple florigen pathway components.

Wheat hybridization and polyploidization results in deregulation of small RNAs.

Speciation via interspecific or intergeneric hybridization and polyploidization triggers genomic responses involving genetic and epigenetic alterations. Such modifications may be induced by small RNAs, which affect key cellular processes, including gene expression, chromatin structure, cytosine methylation and transposable element (TE) activity. To date, the role of small RNAs in the context of wide hybridization and polyploidization has received little attention.