Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.

BACKGROUND: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. METHODS AND RESULTS: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. CONCLUSIONS: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.

The first occurrence of machimosaurid crocodylomorphs from the Oxfordian of south-central Poland provides new insights into the distribution of macrophagous teleosauroids.

Teleosauroid thalattosuchians were a clade of semi-aquatic crocodylomorphs that achieved a broad geographic distribution during the Mesozoic. While their fossils are well documented in Western European strata, our understanding of teleosauroids (and thalattosuchians in general) is notably poorer in Central-Eastern Europe, and from Poland in particular. Herein, we redescribe a teleosauroid rostrum (MZ VIII Vr-72) from middle Oxfordian strata of Zalecze Wielkie, in south-central Poland. Until now, the specimen has been largely encased in a block of limestone. After preparation, its rostral and dental morphology could be evaluated, showing the specimen to be a non-machimosaurin machimosaurid, similar in morphology to taxa Neosteneosaurus edwardsi and Proexochokefalos heberti. The well-preserved teeth enable us to study the specimen feeding ecology through the means of comparing its teeth to other teleosauroids through PCoA analysis. Comparisons with inferred closely related taxa suggest that the referred specimen was a macrophagous generalist. Notably, MZ VIII Vr-72 displays a prominent pathological distortion of the anterior rostrum, in the form of lateral bending. The pathology affects the nasal passage and tooth size and position, and is fully healed, indicating that, despite its macrophagous diet, it did not prevent the individual from food acquisition.

Distinct Escherichia coli transcriptional profiles in the guts of recurrent UTI sufferers revealed by pangenome hybrid selection.

Low-abundance members of microbial communities are difficult to study in their native habitats. This includes Escherichia coli , a minor, but common inhabitant of the gastrointestinal tract and opportunistic pathogen, including of the urinary tract, where it is the primary pathogen. While multi-omic analyses have detailed critical interactions between uropathogenic Escherichia coli (UPEC) and the bladder that mediate UTI outcome, comparatively little is known about UPEC in its pre-infection reservoir, partly due to its low abundance there (<1% relative abundance). To accurately and sensitively explore the genomes and transcriptomes of diverse E. coli in gastrointestinal communities, we developed E. coli PanSelect which uses a set of probes designed to specifically recognize and capture E. coli 's broad pangenome from sequencing libraries. We demonstrated the ability of E. coli PanSelect to enrich, by orders of magnitude, sequencing data from diverse E. coli using a mock community and a set of human stool samples collected as part of a cohort study investigating drivers of recurrent urinary tract infections (rUTI). Comparisons of genomes and transcriptomes between E. coli residing in the gastrointestinal tracts of women with and without a history of rUTI suggest that rUTI gut E. coli are responding to increased levels of oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of native in vivo biology of E. coli in other environments where it is at low relative abundance, and the framework described here has broad applicability to other highly diverse, low abundance organisms.

New-Onset Intermittent Deceleration-Dependent Left Bundle Branch Block Following Induction of General Anesthesia in a Healthy Patient: A Case Report.

This case report aims to highlight an atypical presentation of deceleration-dependent aberrancy (DDA) following the induction of general anesthesia in a patient with no known cardiac history. It emphasizes the critical role of intraoperative monitoring and the potential effects of anesthetic agents on the cardiac conduction system. A 46-year-old Hispanic male with no significant past medical or surgical history presented for surgical repair of a comminuted radial fracture. Following anesthesia induction with propofol, midazolam, and fentanyl, he developed a transient left bundle branch block (LBBB) exhibiting deceleration-dependent characteristics. Despite stable hemodynamics, the LBBB pattern appeared at heart rates below 60 beats per minute and resolved with heart rates above 90 beats per minute. This was managed intraoperatively with glycopyrrolate. Postoperative evaluations, including a 12-lead ECG, echocardiogram, and nuclear stress test, indicated normal biventricular function with a small to moderate reversible perfusion defect. The patient did not report cardiac symptoms postoperatively and did not prefer to undergo a coronary angiogram. This report underscores the importance of recognizing rate-dependent LBBB as a potential intraoperative complication, even in patients without pre-existing cardiac conditions. The transient nature of DDA, influenced by anesthetic agents and managed through careful monitoring and pharmacological intervention, highlights the necessity for vigilance in perioperative settings. This case contributes to a growing body of evidence suggesting that anesthetic management may require tailored approaches for patients experiencing or at risk for conduction abnormalities. This case illustrates the complexities of cardiac conduction disturbances such as DDA in the context of general anesthesia, serving as a reminder of the importance of thorough monitoring and the judicious use of rate-modifying drugs. It fosters a deeper understanding of the interaction between anesthesia and cardiac electrophysiology. Further research is needed to explore the mechanisms and management strategies for anesthetic-related cardiac conduction abnormalities.

Water temperature at the time of the catch-and-release event is a better predictor of survival in Atlantic salmon (Salmo salar) than acute water temperature changes before and after.

Despite studies on the effect of catch-and-release on the survival of Atlantic salmon (Salmo salar) being widespread in the literature, studies to date have failed to evaluate the potential role of thermal history. Herein, we show that despite cooler conditions post-release, 4/18 (22%) salmon died when caught-and-released at water temperatures ≥20°C, whereas 1/13 (8%) salmon caught-and-released at water temperatures ≤20°C, but who encountered mean water temperatures ≥20°C post-release, died. We conclude water temperature at time of the catch-and-release event remains the most suitable predictor of post-release survival.

Seasonally increasing parasite load is associated with microbiome dysbiosis in wild bumblebees.

The microbiome is increasingly recognized for its complex relationship with host fitness. Bumblebees are host to a characteristic gut microbiome community that is derived and reinforced through social contact between individuals. The bumblebee microbiome is species-poor, and primarily composed from a small number of core taxa that are associated with the greater tribe of corbiculate bees. Experimental findings support a role for the core bumblebee microbiome in resistance to severe infections by a common trypanosomal parasite, Crithidia bombi. However, most studies have been small in scale, often considering just one or two bumblebee species, or making use of commercially-reared bees. To better understand the microbiome diversity of wild populations, we have deeply sampled field populations of ten sympatric species found throughout central and down east Maine in a three-year microbiome field survey. We have used 16S amplicon sequencing to produce microbiome community profiles, and qPCR to screen samples for infections by Crithidia bombi. The breadth of our dataset has enabled us to test for seasonal and interspecific trends in the microbiome community. Controlling for these external sources of variation, we have identified microbial factors associated with infection and parasite load that support the role of the core microbiome in resistance to severe infection.

Structure of the Lysinibacillus sphaericus Tpp49Aa1 pesticidal protein elucidated from natural crystals using MHz-SFX.

The Lysinibacillus sphaericus proteins Tpp49Aa1 and Cry48Aa1 can together act as a toxin toward the mosquito Culex quinquefasciatus and have potential use in biocontrol. Given that proteins with sequence homology to the individual proteins can have activity alone against other insect species, the structure of Tpp49Aa1 was solved in order to understand this protein more fully and inform the design of improved biopesticides. Tpp49Aa1 is naturally expressed as a crystalline inclusion within the host bacterium, and MHz serial femtosecond crystallography using the novel nanofocus option at an X-ray free electron laser allowed rapid and high-quality data collection to determine the structure of Tpp49Aa1 at 1.62 Å resolution. This revealed the packing of Tpp49Aa1 within these natural nanocrystals as a homodimer with a large intermolecular interface. Complementary experiments conducted at varied pH also enabled investigation of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals-a crucial step in its mechanism of action. To better understand the cooperation between the two proteins, assays were performed on a range of different mosquito cell lines using both individual proteins and mixtures of the two. Finally, bioassays demonstrated Tpp49Aa1/Cry48Aa1 susceptibility of Anopheles stephensi, Aedes albopictus, and Culex tarsalis larvae-substantially increasing the potential use of this binary toxin in mosquito control.

Reappraisal of the thalattosuchian crocodylomorph record from the Middle-Upper Jurassic Rosso Ammonitico Veronese of northeastern Italy: Age calibration, new specimens and taphonomic biases.

Despite their extremely rare and fragmentary record, aquatic crocodylomorphs from the Middle to Upper Jurassic (Bajocian-Tithonian) Rosso Ammonitico Veronese (RAV) of northeastern Italy have sparked interest since the late 18th century. Among marine reptiles, Thalattosuchia is by far one of the best represented groups from the RAV units, especially in the Middle Jurassic. Although some specimens have been the subject of multiple studies in recent times, most of them still lack precise stratigraphic assignment and taphonomic assessment, while others remain undescribed. Here we provide a comprehensive revision of the thalattosuchian record from the RAV, alongside the most up-to-date age determination, by means of calcareous nannofossils, when available. Three new metriorhynchoid specimens are described for the first time from the Middle Jurassic of Asiago Plateau (Vicenza province). While the taphonomy of the newly described specimens hampers any taxonomic attribution below superfamily/family level, all three were confidently assigned to a precise interval between the upper Bajocian and the upper Bathonian. This revised record has major paleobiogeographical implications: the new specimens confirm an early origin and distribution of Metriorhynchoidea in the Tethys area and suggest a fast colonization of the open-ocean environment since the upper Bajocian.

To automate or not to automate: advocating the 'cliff-edge' principle.

We reflect briefly on the last forty years or so of ergonomics and human factors research in automation, observing that many of the issues being discussed today are the same as all those decades ago. In this paper, we explicate one of the key arguments regarding the application of automation in complex safety-critical domains, which proposes restraining the capabilities of automation technology until it is able to fully and completely take over the task at hand. We call this the 'cliff-edge' principle of automation design. Instead, we espouse a use for the technology in a more problem-driven, human-centred way. These are not entirely new ideas and such a philosophy is already gaining traction in ergonomics and human factors. The point is that in a given system, tasks should be controlled either by human or by automation; anything in between only causes problems for system performance.

Human factors problems with automation have been with us for over forty years, and have changed little in that time. This brief review shows a groundswell of opinion that points to what we call the cliff-edge automation principle ­ restraining the full capabilities of technology until it is ready to fully and completely take over the task. This approach improves human performance in the system by keeping the person in the loop and in control. Researchers and practitioners in ergonomics and human factors should continue to push this message to the designers and manufacturers of automated systems.

Thalattosuchian crocodylomorphs from European Russia, and new insights into metriorhynchid tooth serration evolution and their palaeolatitudinal distribution.

From the Middle Jurassic to the Early Cretaceous, metriorhynchid crocodylomorphs inhabited marine ecosystems across the European archipelago. Unfortunately, European metriorhynchids are only well known from Germany, France, and the UK, with the Eastern European fossil record being especially poor. This hinders our understanding of metriorhynchid biodiversity across these continuous seaways, and our ability to investigate provincialism. Here we describe eleven isolated tooth crowns and six vertebrae referable to Metriorhynchidae from the Callovian, Oxfordian, Volgian (Tithonian), and Ryazanian (Berriasian) or Valanginian of European Russia. We also describe an indeterminate thalattosuchian tooth from the lower Bajocian of the Volgograd Oblast, the first discovery of a marine reptile from the Bajocian strata of European Russia. These rare fossils, along with previous reports of Russian thalattosuchians, indicate that thalattosuchians have been common in the Middle Russian Sea since it was formed. Palaeolatitude calculations for worldwide metriorhynchid-bearing localities demonstrate that the occurrences in European Russia are the most northern, located mainly between 44-50 degrees north. However, metriorhynchids appear to be rare at these palaeolatitudes, and are absent from palaeolatitudes higher than 50°. These observations support the hypothesis that metriorhynchids evolved an elevated metabolism but were not endo-homeothermic, especially as endo-homeothermic marine reptiles (ichthyosaurs and plesiosaurs) remained abundant at much higher palaeolatitudes.

Distinguishing different surface interactions for nucleotides adsorbed onto hematite and goethite particle surfaces through ATR-FTIR spectroscopy and DFT calculations.

Geochemical interfaces can impact the fate and transport of aqueous species in the environment including biomolecules. In this study, we investigate the surface chemistry of adsorbed nucleotides on two different minerals, hematite and goethite, using infrared spectroscopy and density functional theory (DFT) calculations. Attenuated total reflectance-Fourier transform infrared spectroscopy is used to probe the adsorption of deoxyadenosine monophosphate (dAMP), deoxyguanosine monophosphate (dGMP), deoxycytidine monophosphate (dCMP), and deoxythymidine monophosphate (dTMP) onto either hematite or goethite particle surfaces. The results show preferential adsorption of the phosphate group to either surface. Remarkably, surface adsorption of the four nucleotides onto either hematite or goethite have nearly identical experimental spectra in the phosphate region (900 to 1200 cm-1) for each mineral surface yet are distinctly different between the two minerals, suggesting differences in binding of these nucleotides to the two mineral surfaces. The experimental absorption frequencies in the phosphate region were compared to DFT calculations for nucleotides adsorbed through the phosphate group to binuclear clusters in either a monodentate or bidentate bridging coordination. Although the quality of the fits suggests that both binding modes may be present, the relative amounts differ on the two surfaces with preferential bonding suggested to be monodentate coordination on hematite and bidentate bridging on goethite. Possible reasons for these differences are discussed.

Post-Intensification Poaceae Cropping: Declining Soil, Unfilled Grain Potential, Time to Act.

The status and sustainability of Poaceae crops, wheat and barley, were examined in an Atlantic zone climate. Intensification had caused yield to rise 3-fold over the last 50 years but had also degraded soil and biodiversity. Soil carbon and nitrogen were compared with current growth and yield of crops. The yield gap was estimated and options considered for raising yield. Organic carbon stores in the soil (C-soil) ranged from <2% in intensified systems growing long-season wheat to >4% in low-input, short-season barley and grass. Carbon acquisition by crops (C-crop) was driven mainly by length of season and nitrogen input. The highest C-crop was 8320 kg ha-1 C in long-season wheat supported by >250 kg ha-1 mineral N fertiliser and the lowest 1420 kg ha-1 in short-season barley fertilised by livestock grazing. Sites were quantified in terms of the ratio C-crop to C-soil, the latter estimated as the mass of carbon in the upper 0.25 m of soil. C-crop/C-soil was <1% for barley in low-input systems, indicating the potential of the region for long-term carbon sequestration. In contrast, C-crop/C-soil was >10% in high-input wheat, indicating vulnerability of the soil to continued severe annual disturbance. The yield gap between the current average and the highest attainable yield was quantified in terms of the proportion of grain sink that was unfilled. Intensification had raised yield through a 3- to 4-fold increase in grain number per unit field area, but the potential grain sink was still much higher than the current average yield. Filling the yield gap may be possible but could only be achieved with a major rise in applied nitrogen. Sustainability in Poaceae cropping now faces conflicting demands: (a) conserving and regenerating soil carbon stores in high-input systems, (b) reducing GHG emissions and other pollution from N fertiliser, (c) maintaining the yield or closing the yield gap, and (d) readjusting production among food, feed, and alcohol markets. Current cropping systems are unlikely to satisfy these demands. Transitions are needed to alternative systems based on agroecological management and biological nitrogen fixation.

Primary Gastric Mucosal Melanoma: A Rare Etiology of Iron Deficiency Anemia.

Iron deficiency anemia is a concerning finding, particularly in males and post-menopausal females, and can have numerous underlying causes. When evaluating potential sources of gastrointestinal blood loss, bidirectional endoscopy is often necessary. We report the case of an 89-year-old female with multiple comorbidities, including atrial fibrillation treated with apixaban, who presented with symptomatic iron deficiency anemia. Extensive dermatological and radiological assessments ruled out a primary source, and subsequent endoscopy identified a rare etiology: primary gastric mucosal melanoma. This case highlights the importance of thorough evaluation in identifying uncommon causes of iron deficiency anemia such as unsuspected malignancies, hereditary conditions, and different autoimmune conditions amongst other etiologies.

CryoEM structure and Alphafold molecular modelling of a novel molluscan hemocyanin.

Hemocyanins are multimeric oxygen transport proteins present in the blood of arthropods and molluscs, containing up to 8 oxygen-binding functional units per monomer. In molluscs, hemocyanins are assembled in decamer 'building blocks' formed of 5 dimer 'plates', routinely forming didecamer or higher-order assemblies with d5 or c5 symmetry. Here we describe the cryoEM structures of the didecamer (20-mer) and tridecamer (30-mer) forms of a novel hemocyanin from the slipper limpet Crepidula fornicata (SLH) at 7.0 and 4.7 Å resolution respectively. We show that two decamers assemble in a 'tail-tail' configuration, forming a partially capped cylinder, with an additional decamer adding on in 'head-tail' configuration to make the tridecamer. Analysis of SLH samples shows substantial heterogeneity, suggesting the presence of many higher-order multimers including tetra- and pentadecamers, formed by successive addition of decamers in head-tail configuration. Retrieval of sequence data for a full-length isoform of SLH enabled the use of Alphafold to produce a molecular model of SLH, which indicated the formation of dimer slabs with high similarity to those found in keyhole limpet hemocyanin. The fit of the molecular model to the cryoEM density was excellent, showing an overall structure where the final two functional units of the subunit (FU-g and FU-h) form the partial cap at one end of the decamer, and permitting analysis of the subunit interfaces governing the assembly of tail-tail and head-tail decamer interactions as well as potential sites for N-glycosylation. Our work contributes to the understanding of higher-order oligomer formation in molluscan hemocyanins and demonstrates the utility of Alphafold for building accurate structural models of large oligomeric proteins.

Evidence for a novel cranial thermoregulatory pathway in thalattosuchian crocodylomorphs.

Thalattosuchian crocodylomorphs were a diverse clade that lived from the Early Jurassic to the Early Cretaceous. The subclade Metriorhynchoidea underwent a remarkable transition, evolving from semi-aquatic ambush predators into fully aquatic forms living in the open oceans. Thalattosuchians share a peculiar palatal morphology with semi-aquatic and aquatic fossil cetaceans: paired anteroposteriorly aligned grooves along the palatal surface of the bony secondary palate. In extant cetaceans, these grooves are continuous with the greater palatine artery foramina, arteries that supply their oral thermoregulatory structures. Herein, we investigate the origins of thalattosuchian palatal grooves by examining CT scans of six thalattosuchian species (one teleosauroid, two early-diverging metriorhynchoids and three metriorhynchids), and CT scans of eleven extant crocodylian species. All thalattosuchians had paired osseous canals, enclosed by the palatines, that connect the nasal cavity to the oral cavity. These osseous canals open into the oral cavity via foramina at the posterior terminus of the palatal grooves. Extant crocodylians lack both the external grooves and the internal canals. We posit that in thalattosuchians these novel palatal canals transmitted hypertrophied medial nasal vessels (artery and vein), creating a novel heat exchange pathway connecting the palatal vascular plexus to the endocranial region. Given the general hypertrophy of thalattosuchian cephalic vasculature, and their increased blood flow and volume, thalattosuchians would have required a more extensive suite of thermoregulatory pathways to maintain stable temperatures for their neurosensory tissues.

Young Adults' Electronic Cigarette Use and Perceptions of Risk.

In the United States, 18.6% of college students between 19-and 22-years old report e-cigarette use in the last 30 days. Information regarding e-cigarette use and perceptions in this age group may assist in understanding how to decrease initiation of e-cigarettes in a population that may otherwise not use nicotine. The purpose of this survey was to determine current e-cigarette use and how e-cigarette use history relates to a college student's perceptions of health risks associated with e-cigarettes. A 33-item questionnaire was sent to students at a Midwestern university in Fall 2018. Overall, 3754 students completed the questionnaire. More than half of the respondents (55.2%) had used e-cigarettes and 23.2% identified as current users of e-cigarettes. Current e-cigarette users were more likely to agree that e-cigarettes are a safe and effective option to quit smoking, while never users were more likely to disagree (safe P < .001, effective P < .001). Current users were less likely to agree that e-cigarettes may harm a person's overall health than never users (P < .001). Young adults continue to be frequent users of e-cigarettes. There are significant differences in perceptions of e-cigarettes associated with use history. Additional research is needed to see how perceptions and use of e-cigarettes have changed considering lung injury reports and increased regulations in the U.S.

Identification of the molecular determinants of antagonist potency in the allosteric binding pocket of human P2X4.

P2X receptors are a family of ATP-gated cation channels comprising seven subtypes in mammals, which play key roles in nerve transmission, pain sensation and inflammation. The P2X4 receptor in particular has attracted significant interest from pharmaceutical companies due to its physiological roles in neuropathic pain and modulation of vascular tone. A number of potent small-molecule P2X4 receptor antagonists have been developed, including the allosteric P2X4 receptor antagonist BX430, which is approximately 30-fold more potent at human P2X4 compared with the rat isoform. A single amino-acid difference between human and rat P2X4 (I312T), located in an allosteric pocket, has previously been identified as critical for BX430 sensitivity, implying that BX430 binds in this pocket. Using a combination of mutagenesis, functional assay in mammalian cells and in silico docking we confirmed these findings. Induced-fit docking, permitting the sidechains of the amino-acids of P2X4 to move, showed that BX430 could access a deeper portion of the allosteric pocket, and that the sidechain of Lys-298 was important for shaping the cavity. We then performed blind docking of 12 additional P2X4 antagonists into the receptor extracellular domain, finding that many of these compounds favored the same pocket as BX430 from their calculated binding energies. Induced-fit docking of these compounds in the allosteric pocket enabled us to show that antagonists with high potency (IC50 ≤ 100 nM) bind deep in the allosteric pocket, disrupting a network of interacting amino acids including Asp-85, Ala-87, Asp-88, and Ala-297, which are vital for transmitting the conformational change following ATP binding to channel gating. Our work confirms the importance of Ile-312 for BX430 sensitivity, demonstrates that the allosteric pocket where BX430 binds is a plausible binding pocket for a series of P2X4 antagonists, and suggests a mode of action for these allosteric antagonists involving disruption of a key structural motif required for the conformational change induced in P2X4 when ATP binds.

The use of Bayesian Belief Networks (BBNs) to probe deeper into railway safety management systems - Two studies from Great Britain and Italy.

The importance of Safety Management Systems (SMS) to the railway industry is underlined by the fact that all organisations operating on UK railways are required by law to have one. Analysing SMSs can provide a reliable systemic tool to identify hazards and weaknesses within complex systems like the railway, making it possible to significantly increase safety, reducing the odds of near misses and accidents. However, there is little empirical research evidence to determine the impact on safety of a structured SMS. The current paper describes two studies which use Bayesian Belief Networks (BBN) to conceptualise SMSs and their impact on front-line performance. The paper presents the usefulness of BBNs to compare complex systems and reconcile cultural differences within the railway industry, identifying factors that are deemed vital within Italy and Britain. The two studies allowed us to identify the most influential factors within a SMS and how they interact with each other, as well as the strength of the identified relationships. A BBN is particularly useful in estimating how changing some of the node states (e.g., by making safety leadership present) affected the other factors. The current study showed that safety leadership has an impact on the SMSs of the British and Italian railway industries.

Environmental management on agricultural land: Cost benefit analysis of an integrated cropping system for provision of environmental public goods.

Agricultural land covers a significant portion of the earths land surface. Although the predominant function of agricultural land is food production, environmental public goods, such as biodiversity or soil maintenance, are also essential for long-term sustainability. In arable farms the type of cropping system used has a major impact on delivery of these environmental goods. Low input, integrated and regenerative cropping systems aim to improve environmental outcomes of arable farming, with the goal of reducing external inputs by supporting internal regulation of system processes. However, the production of environmental goods does not have an immediate market value to the farmer, and often comes at a cost, particularly in the early stages of transition to a more sustainable system. We estimate the on-farm costs and benefits of an integrated cropping system during the first six years of transition from intensive conventional management at the Centre for Sustainable Cropping in north east Scotland. Although integrated cropping had better environmental outcomes, all crops had higher financial margins in the conventional system compared to the integrated system, which suffered a loss of over £500 per ha per year across the full rotation. This indicates that financial incentives are likely to be important to allow farmers to transition towards a more environmentally friendly cropping system.