DEGAST3D: Learning Deformable 3D Graph Similarity to Track Plant Cells in Unregistered Time Lapse Images.

Tracking plant cells in three-dimensional (3D) tissue captured through light microscopy presents significant challenges due to the large number of densely packed cells, non-uniform growth patterns, and variations in cell division planes across different cell layers. In addition, images of deeper tissue layers are often noisy, and systemic imaging errors further exacerbate the complexity of the task. In this paper, we propose a novel learning-based method DEGAST3D: Learning Deformable 3D GrAph Similarity to Track Plant Cells in Unregistered Time Lapse Images exploits the tightly packed 3D cell structure of plant cells to create a three-dimensional graph for accurate cell tracking.

Targeting the COP9 signalosome overcomes platinum resistance in ovarian cancer through two distinct genome stability mechanisms.

Unlabelled: Tubo-ovarian high-grade serous carcinoma (HGSC) is a leading cause of gynecologic cancer mortality, largely due to the emergence of platinum resistance, which serves as the mainstay of chemotherapy. Here, we identify COPS5 as a therapeutic target and use an available small molecule inhibitor to overcome platinum resistance. A genetic screen for platinum-induced DNA damage in a platinum resistant ovarian cancer model identified COPS5 and COPS6, two components of the COP9 signalosome.

Phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.

BACKGROUNDTreatment of tubo-ovarian high-grade serous carcinoma (HGSC) includes cytoreductive surgery, platinum-based chemotherapy, and often poly(ADP-ribose) polymerase (PARP) inhibitors. While homologous recombination (HR) deficiency is a well-established predictor of therapy sensitivity, over 50% of HR-proficient HGSCs also exhibit sensitivity. Currently, there are no biomarkers to identify which HR-proficient HGSCs will be sensitive to standard-of-care therapy.

A Rh-Catalyzed [4 + 3]-Cycloaddition via the Stereoselective Cyclopropanation of Vinyl Allenes En Route to Oxepino[]indoles and Subsequent Elaboration to Spirooxindole Frameworks.

Oxepino[]indoles were obtained in good to excellent yields employing a [4 + 3]-cycloaddition initiated by a stereo- and regioselective, Rh-catalyzed cyclopropanation between a vinyl allene and diazooxindole to afford an intermediate cyclopropyl allene that engaged the oxindole carbonyl in a spontaneous hetero-[3,3]-rearrangement. A survey of functional group tolerance revealed a diverse array of substrates amenable to oxepino[]indole formation. In addition to the intriguing architecture of the cycloadducts, exposure to either Brønsted acid or base enables the assembly of functionalized spirroxindoles via the unusual conversion of a 5-7 fused ring system to a 5-5 spirocycle.

Replication stress marker phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer.

Background: Ovarian cancer treatment includes cytoreductive surgery, platinum-based chemotherapy, and often poly (ADP-ribose) polymerase (PARP) inhibitors. Homologous recombination (HR)-deficiency is a well-established predictor of therapy sensitivity. However, over 50% of HR-proficient tumors also exhibit sensitivity to standard-of-care treatments.

HAIRY MERISTEM proteins regulate the WUSCHEL protein levels in mediating CLAVATA3 expression.

The precise regulation of stem cells in the shoot apical meristems (SAMs) involves the function of the homeodomain transcription factor (TF)-WUSCHEL (WUS). WUS has been shown to move from the site of production-the rib-meristem (RM), into overlaying cells of the central zone (CZ), where it specifies stem cells and also regulates the transcription of CLAVATA3 (CLV3). The secreted signalling peptide CLV3 activates a receptor kinase signalling that restricts WUS transcription and also regulates the nuclear gradient of WUS by offsetting nuclear export.

A toolkit for a modern gynecologic oncology tissue bank.

Objectives: Tissue banking procedures have evolved to keep pace with precision medicine, technology, emerging understanding of racial disparities, and regulatory requirements. However, there is little published guidance regarding strategies to create and maintain a successful biorepository. Our objective is to describe the infrastructure and protocols used by our Gynecologic Oncology Tissue Bank.

A Proline-Squaraine Ligand Framework (Pro-SqEB) for Stereoselective Rhodium(II)-Catalyzed Cyclopropanations.

A proline-squaraine ligand (Pro-SqEB) that demonstrates high levels of stereoselectivity in olefin cyclopropanations when anchored to a Rh scaffold is introduced. High yields and enantioselectivities were achieved in the cyclopropanation of alkenes with diazo compounds in the presence of Rh(Pro-SqEB). Notably, the unique electronic and steric design of this catalyst enabled the use of polar solvents that are otherwise incompatible with most Rh complexes.

Concentration-dependent transcriptional switching through a collective action of cis-elements.

Gene expression specificity of homeobox transcription factors has remained paradoxical. WUSCHEL activates and represses transcription at lower and higher concentrations, respectively. We use computational modeling and experimental analysis to investigate the properties of the cis-regulatory module.

Combined computational modeling and experimental analysis integrating chemical and mechanical signals suggests possible mechanism of shoot meristem maintenance.

Stem cell maintenance in multilayered shoot apical meristems (SAMs) of plants requires strict regulation of cell growth and division. Exactly how the complex milieu of chemical and mechanical signals interact in the central region of the SAM to regulate cell division plane orientation is not well understood. In this paper, simulations using a newly developed multiscale computational model are combined with experimental studies to suggest and test three hypothesized mechanisms for the regulation of cell division plane orientation and the direction of anisotropic cell expansion in the corpus.

Convergent total synthesis of (+)-calcipotriol: A scalable, modular approach to vitamin D analogs.

A convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described. A complete approach, not wedded to semisynthesis, toward both the A-ring and CD-ring is reported. From a retrosynthetic standpoint, hidden symmetry within the decorated A-ring is disclosed, which allowed for scalable quantities of this advanced intermediate.

Ni-electrocatalytic Csp-Csp doubly decarboxylative coupling.

Cross-coupling between two similar or identical functional groups to form a new C-C bond is a powerful tool to rapidly assemble complex molecules from readily available building units, as seen with olefin cross-metathesis or various types of cross-electrophile coupling. The Kolbe electrolysis involves the oxidative electrochemical decarboxylation of alkyl carboxylic acids to their corresponding radical species followed by recombination to generate a new C-C bond. As one of the oldest known Csp-Csp bond-forming reactions, it holds incredible promise for organic synthesis, yet its use has been almost non-existent.

Generation of Functionalized Azepinone Derivatives via a (4 + 3)-Cycloaddition of Vinyl Ketenes and α-Imino Carbenes Derived from -Sulfonyl-triazoles.

An intermolecular Rh-catalyzed, formal (4 + 3)-cycloaddition between vinyl ketenes and -sulfonyl-1,2,3-triazoles for the construction of azepinone products is described. Employing vinyl ketenes as a 1,4-dipolar surrogate, instead of the more commonly used dienyl moieties, allows for the intermolecular and selective formation of azepinone products over a potential (3 + 2)-cycloadduct under mild reaction conditions allows for the generation of azepinone products in up to 98% yield.

Persistent Pulmonary Hypertension: A Look Into the Future Therapy.

Persistent pulmonary hypertension (PPHN) of the newborn is a lung parenchymal disorder that causes a wide range of hemodynamic changes in the newborn's systemic circulation. Arising from a multifactorial web of etiology, PPHN is one of the most common reasons for neonatal intensive care unit hospitalization and is associated with increased morbidity and mortality. Historically, multiple treatment modalities have been explored, ranging from oxygen and surfactant therapy to newer upcoming medications like magnesium sulfate and adenosine.

Anterior Cruciate Ligament Injury: Conservative Versus Surgical Treatment.

The most frequent type of ligament injury is an anterior cruciate ligament (ACL). The mechanisms of an ACL injury are classified as direct contact, indirect contact, and non-contact. Physical examination for the assessment of the ACL is commonly used in routine care in the evaluation of the knee and is part of the diagnostic process.

Coronary Artery Calcium Score - A Reliable Indicator of Coronary Artery Disease?

Coronary artery disease (CAD) is caused by atheromatous blockage of coronary vessels leading to acute coronary events that usually occur when a plaque ruptures and a thrombus forms. CAD is a known cause of significant cardiovascular events, accounting for more than 50% of the deaths in western countries, and most of the patients with CAD remain asymptomatic. The coronary artery calcium (CAC) score has been created as a measure of coronary atherosclerosis.

Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System.

Deregulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) plays a significant role in developmental brain defects, early-onset neurodegeneration, neuronal cell loss, dementia, and several types of cancer. Herein, we report the discovery of three new classes of N-heterocyclic DYRK1A inhibitors based on the potent, yet toxic kinase inhibitors, harmine and harmol. An initial in vitro evaluation of the small molecule library assembled revealed that the core heterocyclic motifs benzofuranones, oxindoles, and pyrrolones, showed statistically significant DYRK1A inhibition.

Acromegaly and the Colon: Scoping Beyond the Pituitary.

Acromegaly is a complex endocrinological disorder commonly caused by hypersecretion of growth hormone (GH) typically due to pituitary gland tumors. Patients with acromegaly who are successfully treated and biochemically managed have a reasonably average life expectancy. However, it causes a cascade of multi-systemic involvement throughout the patient's life, including cardiovascular, neuropsychiatric, respiratory, metabolic, neurological, neoplastic, and gastrointestinal involvement, resulting in a higher rate of hospitalization, lower quality of life, and a shorter life expectancy.

Celiac Disease, Beyond the Bowel: A Review of Its Neurological Manifestations.

Celiac disease (CD) is a multi-systemic autoimmune condition that causes a hyperinflammatory response when gluten is ingested. There has been a shift in the clinical presentation of CD from a mere malabsorption disorder to an autoimmune condition that affects multiple organ systems, which could increase the rate of hospitalizations and a decreased quality of life. This article has compiled various studies that have explored the neurological manifestations of celiac disease, their epidemiology, possible pathogenic mechanisms, diagnosis, and treatment.

Stroke and Pneumonia: Mechanisms, Risk Factors, Management, and Prevention.

A stroke is a cerebrovascular medical emergency characterized by the sudden loss of neurological function due to interruption to the blood supply. A serious and common complication of stroke is pneumonia. This review article outlined various studies in order to understand the pathogenesis pathways that lead to the development of stroke-associated pneumonia, as well as therapeutic and preventive options to reduce pneumonia.

Myelodysplastic Syndromes and Modalities of Treatment: An Updated Literature Review.

Myelodysplastic syndromes (MDS) represent a large group of rare and diverse clonal stem cell disorders. These are classified into several different phenotypes and typically arise following a multistep genetic process, whereby genetic mutations alter the DNA damage and cellular stress responses, impacting transcription, RNA splicing, epigenetics, and cytokine signaling. However, despite the advances made regarding molecular pathophysiology and prognostic criteria and the influx of new treatment modalities, management is primarily based on prognostic scores, such as the Revised International Prognostic Scoring System.

CLAVATA3 mediated simultaneous control of transcriptional and post-translational processes provides robustness to the WUSCHEL gradient.

Regulation of the homeodomain transcription factor WUSCHEL concentration is critical for stem cell homeostasis in Arabidopsis shoot apical meristems. WUSCHEL regulates the transcription of CLAVATA3 through a concentration-dependent activation-repression switch. CLAVATA3, a secreted peptide, activates receptor kinase signaling to repress WUSCHEL transcription.

Compact Bandwidth Enhanced Cavity-Backed Magneto-Electric Dipole Antenna with Outer Γ-Shaped Probe for GNSS Bands.

In this paper, a wideband small cavity-backed magneto-electric (ME) antenna is proposed. This antenna is linearly polarized and designed to cover all the Global Navigation Satellite System (GNSS) bands. It exhibits small external dimensions of 90 × 90 × 40 mm (0.