PIN-FORMED is required for shoot phototropism/gravitropism and facilitates meristem formation in Marchantia polymorpha.

PIN-FORMED auxin efflux transporters, a subclass of which is plasma membrane-localised, mediate a variety of land-plant developmental processes via their polar localisation and subsequent directional auxin transport. We provide the first characterisation of PIN proteins in liverworts using Marchantia polymorpha as a model system. Marchantia polymorpha possesses a single PIN-FORMED gene, whose protein product is predicted to be plasma membrane-localised, MpPIN1.

Solanum lycopersicum CLASS-II KNOX genes regulate fruit anatomy via gibberellin-dependent and independent pathways.

The pericarp is the predominant tissue determining the structural characteristics of most fruits. However, the molecular and genetic mechanisms controlling pericarp development remain only partially understood. Previous studies have identified that CLASS-II KNOX genes regulate fruit size, shape, and maturation in Arabidopsis thaliana and Solanum lycopersicum.

CLASS-II KNOX genes coordinate spatial and temporal ripening in tomato.

Fruits can be divided into dry and fleshy types. Dry fruits mature through senescence and fleshy fruits through ripening. Previous studies have indicated that partially common molecular networks could govern fruit maturation in these different fruit types.

Arousal elevation drives the development of oscillatory vocal output.

Adult behaviors, such as vocal production, often exhibit temporal regularity. In contrast, their immature forms are more irregular. We ask whether the coupling of motor behaviors with arousal changes gives rise to temporal regularity: Do they drive the transition from variable to regular motor output over the course of development? We used marmoset monkey vocal production to explore this putative influence of arousal on the nonlinear changes in their developing vocal output patterns.

KANADI promotes thallus differentiation and FR-induced gametangiophore formation in the liverwort Marchantia.

In angiosperms, KANADI transcription factors have roles in the sporophyte generation regulating tissue polarity, organogenesis and shade avoidance responses, but are not required during the gametophyte generation. Whether these roles are conserved in the gametophyte-dominant bryophyte lineages is unknown, which we examined by characterising the sole KANADI ortholog, MpKAN, in the liverwort Marchantia polymorpha. In contrast to angiosperm orthologs, MpKAN functions in the gametophyte generation in Marchantia, where it regulates apical branching and tissue differentiation, but does not influence tissue polarity in either generation.

Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation.

We analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter's transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5%] vs.

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study.

Background: Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases.

Methods: We did a two-part, open-label, phase 1/2a study at 21 hospitals in Australia, Israel, Poland, Spain, Turkey, and the USA.

Capgras syndrome in substance-induced psychosis.

Capgras Syndrome is a subcategory of delusional disorder. People affected by this syndrome believe that a close associate such as a friend or family member has been replaced by an identical imposter. This case report describes a 23-year-old woman with no prior psychiatric history, whom developed Capgras syndrome, via , in the setting of poly-substance use.

The Tomato and Regulate Leaf Axil Patterning Along the Proximal-Distal Axes.

Leaf axil patterning occurs concomitantly with leaf development and takes place at the boundary zone which demarcates the initiating leaf primordium from the shoot apical meristem. Subsequent growth and differentiation result in establishment of the axillary meristem and abscission zone (AZ) along the proximal-distal axis of the leaf axil, yet the molecular mechanisms that regulate these events are poorly understood. We studied the role of the tomato () boundary gene family on the development of the leaf axil using -silenced plants as well as -mutated lines.

The KNOXI Transcription Factor SHOOT MERISTEMLESS Regulates Floral Fate in Arabidopsis.

Plants have evolved a unique and conserved developmental program that enables the conversion of leaves into floral organs. Elegant genetic and molecular work has identified key regulators of flower meristem identity. However, further understanding of flower meristem specification has been hampered by redundancy and by pleiotropic effects.

Integrative analysis reveals CD38 as a therapeutic target for plasma cell-rich pre-disease and established rheumatoid arthritis and systemic lupus erythematosus.

Background: Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE.

Methods: RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target.

Elderly dendritic cells respond to LPS/IFN-γ and CD40L stimulation despite incomplete maturation.

There is evidence that dendritic cells (DCs) undergo age-related changes that modulate their function with their key role being priming antigen-specific effector T cells. This occurs once DCs develop into antigen-presenting cells in response to stimuli/danger signals. However, the effects of aging on DC responses to bacterial lipopolysaccharide (LPS), the pro-inflammatory cytokine interferon (IFN)-γ and CD40 ligand (CD40L) have not yet been systematically evaluated.

Class C ARFs evolved before the origin of land plants and antagonize differentiation and developmental transitions in Marchantia polymorpha.

A plethora of developmental and physiological processes in land plants is influenced by auxin, to a large extent via alterations in gene expression by AUXIN RESPONSE FACTORs (ARFs). The canonical auxin transcriptional response system is a land plant innovation, however, charophycean algae possess orthologues of at least some classes of ARF and AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) genes, suggesting that elements of the canonical land plant system existed in an ancestral alga. We reconstructed the phylogenetic relationships between streptophyte ARF and AUX/IAA genes and functionally characterized the solitary class C ARF, MpARF3, in Marchantia polymorpha.

A Case of Attempted Bilateral Self-Enucleation in a Patient with Bipolar Disorder.

Attempted and completed self-enucleation, or removal of one's own eyes, is a rare but devastating form of self-mutilation behavior. It is often associated with psychiatric disorders, particularly schizophrenia, substance induced psychosis, and bipolar disorder. We report a case of a patient with a history of bipolar disorder who gouged his eyes bilaterally as an attempt to self-enucleate himself.

Oncogenic Characterization and Pharmacologic Sensitivity of Activating Fibroblast Growth Factor Receptor (FGFR) Genetic Alterations to the Selective FGFR Inhibitor Erdafitinib.

Fibroblast growth factor receptor (FGFR) genetic alterations are frequently observed in cancer, suggesting that FGFR inhibition may be a promising therapy in patients harboring these lesions. Identification of predictive and pharmacodynamic biomarkers to select and monitor patients most likely to respond to FGFR inhibition will be the key to clinical development of this class of agents. Sensitivity to FGFR inhibition and correlation with FGFR pathway activation status were determined in molecularly annotated panels of cancer cell lines and xenograft models.

Validation of biomarkers to predict response to immunotherapy in cancer: Volume I - pre-analytical and analytical validation.

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successes in a variety of malignancies, responses only typically occur in a minority of patients in any given histology.

Validation of biomarkers to predict response to immunotherapy in cancer: Volume II - clinical validation and regulatory considerations.

There is growing recognition that immunotherapy is likely to significantly improve health outcomes for cancer patients in the coming years. Currently, while a subset of patients experience substantial clinical benefit in response to different immunotherapeutic approaches, the majority of patients do not but are still exposed to the significant drug toxicities. Therefore, a growing need for the development and clinical use of predictive biomarkers exists in the field of cancer immunotherapy.

Active suppression of a leaf meristem orchestrates determinate leaf growth.

Leaves are flat determinate organs derived from indeterminate shoot apical meristems. The presence of a specific leaf meristem is debated, as anatomical features typical of meristems are not present in leaves. Here we demonstrate that multiple NGATHA (NGA) and CINCINNATA-class-TCP (CIN-TCP) transcription factors act redundantly, shortly after leaf initiation, to gradually restrict the activity of a leaf meristem in to marginal and basal domains, and that their absence confers persistent marginal growth to leaves, cotyledons and floral organs.

Auxin-mediated lamina growth in tomato leaves is restricted by two parallel mechanisms.

In the development of tomato compound leaves, local auxin maxima points, separated by the expression of the Aux/IAA protein SlIAA9/ENTIRE (E), direct the formation of discrete leaflets along the leaf margin. The local auxin maxima promote leaflet initiation, while E acts between leaflets to inhibit auxin response and lamina growth, enabling leaflet separation. Here, we show that a group of auxin response factors (ARFs), which are targeted by miR160, antagonizes auxin response and lamina growth in conjunction with E.