Bacterial microcompartment utilization in the human commensal Nissle 1917.

Unlabelled: Bacterial microcompartments (BMCs) are self-assembled protein structures often utilized by bacteria as a modular metabolic unit, enabling the catalysis and utilization of less common carbon and nitrogen sources within a self-contained compartment. The BMC has been widely demonstrated in enteropathogens, such as , and current research is exploring its activity in the commensal species that populate the human gut. Nissle 1917 (EcN) is a strong colonizer and probiotic in gut microbial communities and has been used extensively for microbiome engineering.

Conflict during learning reconfigures the neural representation of positive valence and approach behavior.

Punishing and rewarding experiences can change the valence of sensory stimuli and guide animal behavior in opposite directions, resulting in avoidance or approach. Often, however, a stimulus is encountered with both positive and negative experiences. How is such conflicting information represented in the brain and resolved into a behavioral decision? We address this question by dissecting a circuit for sexual conditioning in C.

Bexotegrast in people with idiopathic pulmonary fibrosis (IPF): a plain language summary of publication of the INTEGRIS-IPF study.

This plain language summary shares results from a clinical study called INTEGRIS-IPF that was published in the in 2024. This study looked at a medicine called (beck-so-teh-grast) as a possible treatment for (i-dee-uh-pa-thick pul-muh-ner-ee fie-bro-sis; IPF). is an investigational medicine, which means that it is being studied and has not yet been approved by the US Food and Drug Administration (FDA), for people with IPF to take as a treatment.

Bexotegrast Shows Dose-dependent Integrin αβ Receptor Occupancy in Lungs of Participants with Idiopathic Pulmonary Fibrosis: A Phase 2, Open-Label Clinical Trial.

: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by dyspnea and loss of lung function. Transforming growth factor-beta (TGF-β) activation mediated by α integrins is central to the pathogenesis of IPF. Bexotegrast (PLN 74809) is an oral, once-daily, dual-selective inhibitor of αβ and αβ integrins under investigation for the treatment of IPF.

Negative feedback control of hypothalamic feeding circuits by the taste of food.

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here, we show that hunger-promoting agouti-related peptide (AgRP) neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety.

A bacteriocin expression platform for targeting pathogenic bacterial species.

Bacteriocins are antimicrobial peptides that are naturally produced by many bacteria. They hold great potential in the fight against antibiotic resistant bacteria, including ESKAPE pathogens. Engineered live biotherapeutic products (eLBPs) that secrete bacteriocins can be created to deliver targeted bacteriocin production.

Emergent digital bio-computation through spatial diffusion and engineered bacteria.

Biological computing is a promising field with potential applications in biosafety, environmental monitoring, and personalized medicine. Here we present work on the design of bacterial computers using spatial patterning to process information in the form of diffusible morphogen-like signals. We demonstrate, mathematically and experimentally, that single, modular, colonies can perform simple digital logic, and that complex functions can be built by combining multiple colonies, removing the need for further genetic engineering.

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Clinical Trial.

Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease that causes progressive cough, exertional dyspnea, impaired quality of life, and death. Bexotegrast (PLN-74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. This Phase-2a multicenter, clinical trial randomized participants with IPF to receive, orally and once daily, bexotegrast at 40 mg, 80 mg, 160 mg, or 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks.

Differences in Pain Experience Among Different Racial and Ethnic Groups.

Objective: The objective of this study was to examine the role of pain catastrophizing and pain self-efficacy as possible mediators of race-based differences in pain intensity and to evaluate the possible moderating role of race on the relationship between pain catastrophizing and pain self-efficacy with pain outcomes among persons with chronic spinal pain receiving physical therapy.

Methods: This study was a secondary analysis of a cluster-randomized trial. Participants were persons with chronic spinal pain in outpatient physical therapy clinics who consented to complete assessments at baseline and after 2 weeks and 12 weeks.

Negative feedback control of hunger circuits by the taste of food.

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here we show that hunger-promoting AgRP neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety.

Automated sulfur-[F]fluoride exchange radiolabelling of a prostate specific membrane antigen (PSMA) targeted ligand using the GE FASTlab™ cassette-based platform.

Sulfur-[F]fluoride exchange radiochemistry is a rapid and convenient method for incorporating fluorine-18 into biologically active molecules. We report a fully automated radiolabelling procedure for the synthesis of a [F]SOF-bearing prostate specific membrane antigen (PSMA) targeted ligand ([F]5) using the GE FASTLab™ cassette-based platform in a 25.0 ± 2.

Sequential appetite suppression by oral and visceral feedback to the brainstem.

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated, but how the cNTS processes ingestive feedback during behaviour is unknown.

Evaluation of [F]AlF-EMP-105 for Molecular Imaging of C-Met.

C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a Ga-labelled peptide, [Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [F]AlF-labelled analogue, [F]AlF-EMP-105, for c-Met imaging by positron emission tomography.

Automated design of gene circuits with optimal mushroom-bifurcation behavior.

Recent advances in synthetic biology are enabling exciting technologies, including the next generation of biosensors, the rational design of cell memory, modulated synthetic cell differentiation, and generic multifunctional biocircuits. These novel applications require the design of gene circuits leading to sophisticated behaviors and functionalities. At the same time, designs need to be kept minimal to avoid compromising cell viability.

Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B.

Long-term efficacy and safety of the extended half-life recombinant factor IX Fc fusion protein (rFIXFc) has been established among previously treated patients with severe hemophilia B in 2 phase 3 trials (B-LONG [#NCT01027364] and Kids B-LONG [#NCT01440946]) and a long-term extension study (B-YOND [#NCT01425723]). In this study, we report post hoc analyses of pooled longitudinal data for up to 6.5 years for rFIXFc prophylaxis.

A randomized, double-blind, placebo-controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis.

Background: This study assessed the efficacy and safety of velusetrag-a 5-HT agonist with pan-gastrointestinal prokinetic activity-for gastroparesis symptom management and gastric emptying (GE).

Methods: In this multicenter, double-blind, randomized, placebo-controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7-day mean Gastroparesis Cardinal Symptom Index 24-h composite score (GCSI-24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs).

Yeast or water: producing wine with lower alcohol levels in a warming climate: a review.

Climate change effects over the last century have seen grape wine growers being faced with earlier budburst and shorter seasons. One effect is higher sugar levels in the grape berries, resulting in wines with higher than typical alcohol concentrations. Winemakers, both in Australia and globally, need to reassess their wine making approaches to address the challenges associated with warmer drier conditions.

Deep reinforcement learning for optimal experimental design in biology.

The field of optimal experimental design uses mathematical techniques to determine experiments that are maximally informative from a given experimental setup. Here we apply a technique from artificial intelligence-reinforcement learning-to the optimal experimental design task of maximizing confidence in estimates of model parameter values. We show that a reinforcement learning approach performs favourably in comparison with a one-step ahead optimisation algorithm and a model predictive controller for the inference of bacterial growth parameters in a simulated chemostat.

Phenotypic plasticity and genetic control in colorectal cancer evolution.

Genetic and epigenetic variation, together with transcriptional plasticity, contribute to intratumour heterogeneity. The interplay of these biological processes and their respective contributions to tumour evolution remain unknown. Here we show that intratumour genetic ancestry only infrequently affects gene expression traits and subclonal evolution in colorectal cancer (CRC).

Design, synthesis, and evaluation of a novel PET imaging agent targeting lipofuscin in senescent cells.

Promoting a senescent phenotype to suppress tumour progression may present an alternative strategy for treating cancer and encourages the development of positron emission tomography (PET) imaging biomarkers for assessing response to treatment. The accumulation of lipofuscin deposits in senescent cells is visualised using the pathology stain Sudan Black B (SBB) which is an emerging biomarker of senescence. We describe the design, synthesis and evaluation of [F]fluoroethyltriazole-SBB ([F]FET-SBB), a fluorine-18 radiolabelled derivative of SBB.

Chaos in synthetic microbial communities.

Predictability is a fundamental requirement in biological engineering. As we move to building coordinated multicellular systems, the potential for such systems to display chaotic behaviour becomes a concern. Therefore understanding which systems show chaos is an important design consideration.