Delving into the Latest Updates on 99mTc-APA with Synapse

Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones - signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A's alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5' caps in Escherichia coli. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5'-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in Bacillus subtilis. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions.

01 Aug 2023·Biochemistry

Insights into Enzymatic Catalysis from Binding and Hydrolysis of Diadenosine Tetraphosphate by E. coli Adenylate Kinase.

Article

Author: Wolf-Watz, Magnus ; Tischlik, Sonja ; Drescher, Malte ; Rogne, Per ; Sauer-Eriksson, A Elisabeth ; Oelker, Melanie

Adenylate kinases play a crucial role in cellular energy homeostasis through the interconversion of ATP, AMP, and ADP in all living organisms. Here, we explore how adenylate kinase (AdK) from Escherichia coli interacts with diadenosine tetraphosphate (AP4A), a putative alarmone associated with transcriptional regulation, stress, and DNA damage response. From a combination of EPR and NMR spectroscopy together with X-ray crystallography, we found that AdK interacts with AP4A with two distinct modes that occur on disparate time scales. First, AdK dynamically interconverts between open and closed states with equal weights in the presence of AP4A. On a much slower time scale, AdK hydrolyses AP4A, and we suggest that the dynamically accessed substrate-bound open AdK conformation enables this hydrolytic activity. The partitioning of the enzyme into open and closed states is discussed in relation to a recently proposed linkage between active site dynamics and collective conformational dynamics.

01 Oct 2021·Eating and Weight Disorders - Studies on Anorexia, Bulimia and ObesityQ3 · MEDICINE

Parental perceptions of actual and ideal body weight in early childhood prospectively predict adolescent perceptions of actual and ideal body weight among a low-income population

Q3 · MEDICINE

Article

Author: Weeks, Heidi M ; Barry, Mikayla R ; Miller, Alison L ; Hahn, Samantha L ; Sonneville, Kendrin R ; Lumeng, Julie C

PURPOSETo examine the longitudinal associations between parental perceptions of their child's actual weight (PPCA = parental perception of child's actual) and ideal weight (PPCI = parental perception of child ideal) in early childhood and the child's own perceptions of their actual weight (APA = adolescent perceived actual) and ideal weight (API = adolescent perceived ideal) during early adolescence among a low-income population.METHODSUsing a longitudinal study design, 136 child/parent pairs were asked to assess the child's actual and ideal weight using figure rating scales. When children were 4-7 years old, parents reported on their perception of their child's weight; when children were 10-12 years old, the child reported on their own weight perceptions. Actual weight, ideal weight, and the difference between ideal and actual weight perception were assessed at the respective timepoints. Regressions were used to examine the relationship between parental weight perceptions (PPCA and PPCI) and later adolescent weight perception (APA and API).RESULTSOn average, PPCI was higher than PPCA, whereas API was lower than APA. We found a positive relationship between PPCI and API (β = 0.309, p = .029). PPCA was positively associated with API (β = 0.304, p = .015) and marginally positively associated with the APA (β = 0.242, p = .077). However, the difference between PPCI and PPCA did not predict either APA or API.CONCLUSIONSParental perception of their child's weight may relate to the adolescent's weight perception, particularly ideal weight. However, several null and marginal associations suggest that parental weight perception in early childhood may not be the most salient factor in determining weight perception in early adolescence.LEVEL OF EVIDENCELevel III, well-designed longitudinal cohort study.

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News (Medical) associated with 99mTc-APA

06 Jun 2023

·www.prnewswire.com

PathomIQ's AI-powered tool shows promise in assessing risk for metastasis in non-metastatic castration-resistant prostate cancer (nmCRPC)

CUPERTINO, Calif., June 6, 2023 /PRNewswire/ -- New data released today at the American Society of Clinical Oncology (ASCO) Annual Meeting highlighted the application of PathomIQ Inc.'s PATHOMIQ_PRAD AI test to assess the risk for metastasis in non-metastatic castration-resistant prostate cancer (nmCRPC). PathomIQ is a leading provider of AI-enabled solutions that leverage digitized H&E slides to discover novel biomarkers that predict response to therapy, inform drug discovery, de-risk clinical trials and enable precision medicine in clinical practice. PATHOMIQ_PRAD was developed as an AI-enabled prognostic algorithm that predicts the risk of metastasis from Whole Slide Images (WSIs) of H&E-stained core biopsies or radical prostatectomy specimens. Most patients with prostate cancer treated with androgen deprivation therapy (ADT) for progressive disease will experience progression to CRPC. APA (ERLEADA®)* is approved for the treatment of patients with nmCRPC and metastatic castration sensitive prostate cancer (mCSPC). The objective of this study was to determine the risk for metastasis in patients with nmCRPC based on PATHOMIQ_PRAD risk categories. Patients in the Phase 3 SPARTAN clinical trial with available H&E-stained slides from their primary diagnosis were included in this study. The study showed that PATHOMIQ_PRAD score could have prognostic value in identifying patients at high risk of metastatic progression in nmCRPC setting. All patients receiving APA + ADT had significantly improved metastasis-free survival (MSF) compared with patients receiving ADT alone. "We are honored to be collaborating with Janssen and working closely with their team to evaluate H&E-based AI as a potential tool for prognostic risk stratification in nmCRPC patients. Our PATHOMIQ_PRAD AI model has been successfully validated at multiple medical institutions, and we are working to make it clinically available in the near future," said Dr George Wilding, Chief Medical Officer, PathomIQ Inc. The results were shared at the poster session Genitourinary Cancer – Prostate, Testicular, and Penile Abstract #5027, Poster Board #121, "AI-enabled analysis of H&E-stained prostate cancer tissue images: Assessing risk for metastasis prior to apalutamide (APA) treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC)." To learn more about PathomIQ Inc., please visit * ERLEADA (apalutamide) is a product of Janssen Biotech, Inc. SOURCE PathomIQ Inc.

Phase 3Clinical ResultASCODrug Approval

06 Jun 2023

·www.biospace.com

PathomIQ's AI-powered tool shows promise in assessing risk for metastasis in non-metastatic castration-resistant prostate cancer (nmCRPC)

CUPERTINO, Calif., June 6, 2023 /PRNewswire/ -- New data released today at the American Society of Clinical Oncology (ASCO) Annual Meeting highlighted the application of PathomIQ Inc.'s PATHOMIQ_PRAD AI test to assess the risk for metastasis in non-metastatic castration-resistant prostate cancer (nmCRPC). PathomIQ is a leading provider of AI-enabled solutions that leverage digitized H&E slides to discover novel biomarkers that predict response to therapy, inform drug discovery, de-risk clinical trials and enable precision medicine in clinical practice. PATHOMIQ_PRAD was developed as an AI-enabled prognostic algorithm that predicts the risk of metastasis from Whole Slide Images (WSIs) of H&E-stained core biopsies or radical prostatectomy specimens. Most patients with prostate cancer treated with androgen deprivation therapy (ADT) for progressive disease will experience progression to CRPC. APA (ERLEADA®)* is approved for the treatment of patients with nmCRPC and metastatic castration sensitive prostate cancer (mCSPC). The objective of this study was to determine the risk for metastasis in patients with nmCRPC based on PATHOMIQ_PRAD risk categories. Patients in the Phase 3 SPARTAN clinical trial with available H&E-stained slides from their primary diagnosis were included in this study. The study showed that PATHOMIQ_PRAD score could have prognostic value in identifying patients at high risk of metastatic progression in nmCRPC setting. All patients receiving APA + ADT had significantly improved metastasis-free survival (MSF) compared with patients receiving ADT alone. "We are honored to be collaborating with Janssen and working closely with their team to evaluate H&E-based AI as a potential tool for prognostic risk stratification in nmCRPC patients. Our PATHOMIQ_PRAD AI model has been successfully validated at multiple medical institutions, and we are working to make it clinically available in the near future," said Dr George Wilding, Chief Medical Officer, PathomIQ Inc. The results were shared at the poster session Genitourinary Cancer – Prostate, Testicular, and Penile Abstract #5027, Poster Board #121, "AI-enabled analysis of H&E-stained prostate cancer tissue images: Assessing risk for metastasis prior to apalutamide (APA) treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC)." To learn more about PathomIQ Inc., please visit * ERLEADA (apalutamide) is a product of Janssen Biotech, Inc.

Phase 3Clinical ResultASCODrug Approval

100 Deals associated with 99mTc-APA

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