bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent Validity of Performance-Based Measures of Daily Functioning with Cognitive Measures and Informant Reported Everyday Functioning
Authors: Rahman Aneela , Schmitter-Edgecombe Maureen , Krishnan Anjali , Cunningham Reanne , Pare Nadia , Beadle Janelle , Warren David E , Rabin Laura
Published: September 2024

Objective

Despite the substantial need for reliable and valid assessment of functional ability in older adults, there is currently limited research on the emergence of early functional declines during prodromal dementia stages, such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). This study uses novel performance-based assessments to characterize subtle, yet clinically meaningful, changes in functional ability.

Method

A sample of 93 older adults classified as cognitively unimpaired (CU; n = 30, Mage = 73.57 ± 6.66), SCD (n = 34, Mage = 72.56 ± 6.43), or MCI (n = 29, Mage = 78.28 ± 7.55) underwent neuropsychological testing along with an informant-rated daily functional skills measure (Assessment of Functional Capacity Interview). Participants also completed the Night Out Task (NOT), an open-ended performance-based measure of functional assessment, and the Financial Capacity Instrument–Short Form (FCI-SF) that assesses financial skills.

Results

The MCI group performed worse on the NOT and FCI-SF relative to SCD and CU. NOT and FCI scores were associated with measures of global cognitive function, executive function, processing speed, language and memory, and FCI-SF overall score was correlated with informant-rated functional ability. The NOT and FCI-SF were also predictive of informant-reported daily functioning over and above traditional cognitive data and demographics.

Conclusions

Performance-based measures of IADL may allow for earlier detection of subtle functional changes that might not be adequately captured by traditional measures. The measurement of early functional changes is an important global outcome to evaluate the efficacy of interventions in dementia research.
RetroCaptioner: beyond attention in end-to-end retrosynthesis transformer via contrastively captioned learnable graph representation
Authors: Liu Xiaoyi , Ai Chengwei , Yang Hongpeng , Dong Ruihan , Tang Jijun , Zheng Shuangjia , Guo Fei
Published: September 2024

Motivation

Retrosynthesis identifies available precursor molecules for various and novel compounds. With the advancements and practicality of language models, Transformer-based models have increasingly been used to automate this process. However, many existing methods struggle to efficiently capture reaction transformation information, limiting the accuracy and applicability of their predictions.

Results

We introduce RetroCaptioner, an advanced end-to-end, Transformer-based framework featuring a Contrastive Reaction Center Captioner. This captioner guides the training of dual-view attention models using a contrastive learning approach. It leverages learned molecular graph representations to capture chemically plausible constraints within a single-step learning process. We integrate the single-encoder, dual-encoder, and encoder–decoder paradigms to effectively fuse information from the sequence and graph representations of molecules. This involves modifying the Transformer encoder into a uni-view sequence encoder and a dual-view module. Furthermore, we enhance the captioning of atomic correspondence between SMILES and graphs. Our proposed method, RetroCaptioner, achieved outstanding performance with 67.2% in top-1 and 93.4% in top-10 exact matched accuracy on the USPTO-50k dataset, alongside an exceptional SMILES validity score of 99.4%. In addition, RetroCaptioner has demonstrated its reliability in generating synthetic routes for the drug protokylol.

Availability and implementation

The code and data are available at https://github.com/guofei-tju/RetroCaptioner.
Children’s Social Work Safe Staffing Supply and Workforce Demands Analysis: A Case Study from Northern Ireland
Authors: MacLochlainn Justin , McFadden Paula , McColgan Mary , Naylor Rachel , Schroder Heike , McGrory Susan , Nicholl Patricia , Currie Denise , Kirby Karen , Mallett John
Published: September 2024

The matter of ensuring adequate staffing levels in children’s social work services has become increasingly prominent due to challenges related to retention and staff well-being and exacerbated by limited governmental budgetary investment. Various operational tools and policy guidelines in the UK regulate staffing across different sectors of health and social care. However, frameworks for safe staffing in social work are less developed. This study was based on qualitative and quantitative methodologies and specifically targeted Gateway and Family Intervention child protection teams in Northern Ireland, given the significant caseloads and staffing shortages within these specific team structures. The analysis unveiled systemic issues demanding systemic solutions. Frontline social workers and managers were often contending with overwhelming worker-to-caseload ratios, extensive waitlists and vacancies within teams. This analysis also assisted in defining safe staffing in social work, including service-user safety, and staff well-being and retention. These findings serve as a foundation for evidence-based strategic planning, informing the development and enactment of safer and effective social work policies and legislation in the forthcoming years.
Clustering-based compression for raster time series
Authors: Muñoz Martita , Fuentes-Sepúlveda José , Hernández Cecilia , Navarro Gonzalo , Seco Diego , Silva-Coira Fernando
Published: September 2024

A raster time series is a sequence of independent rasters arranged chronologically covering the same geographical area. These are commonly used to depict the temporal evolution of represented variables. The $T$-$k^{2}$-raster is a compact data structure that performs very well in practice for compact representations for raster time series. This structure classifies each raster as a snapshot or a log and encodes logs concerning their reference snapshots, which are the immediately preceding selected snapshots. An enhanced version of the $T$-$k^{2}$-raster, called Heuristic $T$-$k^{2}$-raster, incorporates a heuristic for automating the selection of snapshots. In this study, we investigate the optimality of the heuristic employed in Heuristic $T$-$k^{2}$-raster by comparing it with a dynamic programming (DP) approach. Our experimental evaluation demonstrates that Heuristic $T$-$k^{2}$-raster is a near-optimal solution, achieving compression performance almost identical to the DP method. These results indicate that variations of the structure that maintain the temporal order of the rasters are unlikely to significantly improve compression. Consequently, we explore an alternative approach based on clustering, where rasters are grouped according to their similarity, regardless of their temporal order. Our experimental evaluation reveals that this clustering-based strategy can enhance compression in scenarios characterized by cyclic behaviour.
A hybrid architecture for secure data sharing in multi-clouds system
Authors: Hajlaoui Nasreddine , Bejaoui Chaima , Ismail Tayssir , Ghanmi Houaida , Touati Haifa
Published: September 2024

Cloud computing is one of the most cutting-edge technologies around the world that plays a major role in IT industries and personal use. Several sectors are showing efforts in adopting cloud computing to their services, considering the provided cost reduction and process efficiency. However, outsourcing users’ sensitive data increases the concerns regarding the security, privacy and integrity of stored data. Therefore, there is a need to build a trusting relationship between users and cloud systems. Hence, in this paper, we propose a privacy-preserving framework, called Hybrid and Secure Data Sharing Architecture (HSDSA), for secure data storage in cloud systems. The basic idea of HSDSA is to improve data security in a multi-cloud environment using a combination of cryptography techniques. These techniques ensure that the user has total control over the data generation and management of the decryption without relying on a trusted authority. HSDSA provides removal of centralized file storage distribution and ensures data integrity in the recovery process. We evaluate our contribution under Cloudera, and the results demonstrate the efficiency of HSDSA compared with the existing system.
Distal esophageal spasm and gastroesophageal reflux disease: re-examining the association
Authors: Seltzer Emily S , Sehmbhi Mantej , Sandhu Robinderpal , Cavaliere Kimberly , Luo Yuying , Smith Michael S , Jodorkovsky Daniela
Published: September 2024

Distal esophageal spasm (DES) is a rare motility disorder presenting with dysphagia or chest pain. Although studies suggest a link between DES and gastroesophageal reflux disease (GERD), data supporting a distinct GERD-related phenotype are limited. This study aims to investigate demographic, symptomatic, and physiologic differences between DES subjects with and without GERD. A retrospective cohort analysis of DES patients determined by high resolution manometry (HRM) was conducted between February 2020 and January 2023. Demographics, medications, symptoms, and quantitative reflux testing data were collected. DES subjects with reflux (R-DES) were defined by presence of Los Angeles Grade B/C/D esophagitis, Barrett’s metaplasia, or abnormal pH testing. DES subjects without reflux (NR-DES) had normal parameters. Statistical analysis employed two-sided or Wilcoxon Rank-Sum, Chi-squared, or Fisher’s exact tests, and multivariate logistic regression. Of 69 DES subjects, 32 (46.3%) had GERD. R-DES and NR-DES patients had similar demographic variables except for higher BMI in R-DES (30.41 vs. 26.88, P = 0.01). R-DES and NR-DES shared similar symptom profiles (heartburn P = 0.67, dysphagia P = 0.448, chest pain P = 0.32). Proton pump inhibitor use was similar between groups (78.1% vs. 91.9%, P = 0.202). HRM metrics were comparable except for basal LES tone (20.7 mmHg vs. 32.99 mmHg, P = 0.03) and median IRP 11.82 mmHg versus 17.20 mmHg, P = 0.017). This study found no distinguishing clinical or physiologic differences between DES patients with and without GERD, challenging the historical emphasis of GERD in DES pathogenesis. The impact of GERD management on the natural history of DES remains uncertain.
Production of hybrid macrolide antibiotics by exploiting the specific substrate recognition characteristics of multifunctional cytochrome P450 enzyme MycG
Authors: Iizaka Yohei , Yamada Mari , Koshino Suirei , Takahashi Sawa , Saito Ryota , Sherman David H , Anzai Yojiro
Published: September 2024

Macrolide antibiotics are biosynthesized via enzymatic modifications, including glycosylation, methylation, and oxidation, after the core macro-lactone ring is generated by a polyketide synthase system. This study explored the diversification of macrolides by combining biosynthetic enzymes and reports an approach to produce unnatural hybrid macrolide antibiotics. The cytochrome (CYP) P450 monooxygenase MycG exhibits bifunctional activity, catalyzing late-stage hydroxylation at C-14 followed by epoxidation at C-12/13 during mycinamicin biosynthesis. The mycinose sugar of mycinamicin serves as a key molecular recognition element for binding to MycG. Thus, we subjected the hybrid macrolide antibiotic 23-O-mycinosyl-20-deoxo-20-dihydro-12,13-deepoxyrosamicin (IZI) to MycG, and confirmed that MycG catalyzed hydroxylation at C-22 and epoxidation at C-12/13 in IZI. In addition, the introduction of mycinose biosynthesis-related genes and mycG into rosamicin-producing Micromonospora rosaria enabled the fermentative production of 22-hydroxylated and 12,13-epoxidized forms of IZI. Interestingly, MycG catalyzed the sequential oxidation of hydroxylation and epoxidation in mycinamicin biosynthesis, but only single reactions in IZI. These findings highlight the potential for expanding the application of the multifunctional P450 monooxygenase MycG for the production of unnatural compounds.
Optimal protein allocation controls the inhibition of GltA and AcnB in Neisseria gonorrhoeae
Authors: Shahreen Nabia , Chowdhury Niaz Bahar , Saha Rajib
Published: September 2024

Neisseria gonorrhea (Ngo) is a major concern for global public health due to its severe implications for reproductive health. Understanding its metabolic phenotype is crucial for comprehending its pathogenicity. Despite Ngo’s ability to encode tricarboxylic acid (TCA) cycle proteins, GltA and AcnB, their activities are notably restricted. To investigate this phenomenon, we used the iNgo_557 metabolic model and incorporated a constraint on total cellular protein content. Our results indicate that low cellular protein content severely limits GltA and AcnB activity, leading to a shift toward acetate overflow for Adenosine triphosphate (ATP) production, which is more efficient in terms of protein usage. Surprisingly, increasing cellular protein content alleviates this restriction on GltA and AcnB and delays the onset of acetate overflow, highlighting protein allocation as a critical determinant in understanding Ngo’s metabolic phenotype. These findings underscore the significance of Ngo’s metabolic adaptation in light of optimal protein allocation, providing a blueprint to understand Ngo’s metabolic landscape.
Healthcare Expenditures Among Older Immigrants in the United States With Alzheimer’s Disease and Related Dementias: Population-Based Study Between 2007 and 2020
Authors: Jang Seyeon , Qin Xuanzi , Park Sungchul , McCoy Rozalina G , Chen Jie
Published: September 2024

Objectives

Using nationally representative data sets, this study examined differences in healthcare expenditures between U.S.-born and foreign-born individuals aged 65 and above by the presence of Alzheimer’s disease and related dementias (ADRD) and cognitive limitations (CL). This study further examined whether healthcare expenditures among foreign-born individuals vary by their duration of residence in the United States.

Methods

The study used the 2007–2020 Medical Expenditure Panel Survey and employed generalized linear regression models to estimate differences in healthcare expenditures between U.S.-born and foreign-born older adults with ADRD, CL, and without ADRD or CL. Survey weights were applied to all estimates.

Results

Our study identified significant differences in healthcare expenditures among older adults by the presence of ADRD/CL and immigrant status. Having ADRD/CL had a more pronounced impact on high healthcare expenditures among foreign-born older adults than U.S.-born adults with ADRD/CL, thereby diminishing the difference in healthcare expenditures by U.S. nativity status for the older adults with ADRD or CL. In the analysis further distinguishing immigrants by their duration of residence, lower healthcare expenditures were primarily observed among foreign-born individuals with ADRD or CL who had lived in the United States for less than 10 years.

Discussion

Our results suggest potential shifts in costs resulting from delayed access to, and diagnosis or treatment of ADRD at a younger age, leading to increased healthcare needs and expenses among U.S. foreign-born older adults.
A closer look at individual collisions of dust aggregates: material mixing and exchange on microscopic scales
Authors: Krijt Sebastiaan , Arakawa Sota , Oosterloo Mark , Tanaka Hidekazu
Published: September 2024

Collisions between aggregates with different histories and compositions are expected to be commonplace in dynamically active protoplanetary discs. None the less, relatively little is known about how collisions themselves may contribute to the resulting mixing of material. Here, we use state-of-the-art granular dynamics simulations to investigate mixing between target/projectile material in a variety of individual aggregate-aggregate collisions, and use the results to discuss the efficiency of collisional mixing in protoplanetary environments. We consider sticking collisions (up to 10–20 m s–1 for our set-up) and disruptive collisions (40 m s–1) of ballistic particle–cluster aggregation (BPCA) and ballistic cluster–cluster aggregation (BCCA) clusters, and quantify mixing in the resulting fragments on both individual fragment and sub-aggregate levels. We find that the mass fraction of material that can be considered to be ‘well-mixed’ (i.e. locally made up of a mix of target and projectile material) to be limited, typically between 3 and 6 per cent for compact BPCA precursors, and increasing to 20–30 per cent for more porous BCCA clusters. The larger fragments produced in disruptive collisions are equally heterogeneous, suggesting aggregate–aggregate collisions are a relatively inefficient way of mixing material with different origins on small scales.
Growing planet envelopes in spite of recycling flows
Authors: Bailey Avery P , Zhu Zhaohuan
Published: September 2024

The hydrodynamic exchange of a protoplanet’s envelope material with the background protoplanetary disc has been proposed as one mechanism to account for the diversity of observed planet envelopes that range in mass fractions from $\sim\!\! 1{{\ \rm per\, cent}}$ for super-Earths to $\sim\!\! 90{{\ \rm per\, cent}}$ for giants. Here, we present 3D radiation-hydrodynamics models of protoplanet envelopes applicable to gas-giant cores at intermediate distances and a subset of close-in super-Earths in hot or low-density discs. We analyse how hydrodynamic mass and energy exchange impact the formation process. Our protoplanet envelope simulations show an exchange of material bringing the outer $\gtrsim\!\! 0.4R_\mathrm{ b}$ envelope to steady state. This exchange provides a continuous source of energy, which acts to increase the observed luminosity beyond that inferred from the binding energy liberated from Kelvin–Helmholtz contraction alone – a finding important for potential protoplanet observations. The inner envelope at $\lesssim\!\! 0.4R_\mathrm{ b}$ remains insulated, however – growing in accordance with 1D quasi-static theory. We incorporate these 3D hydrodynamic effects into an extensible 1D framework with a physically motivated three-layer recycling parametrization. Specializing to the case of Jupiter, recycling produces minimal changes to the growth rate with the planet still entering runaway accretion and becoming a gas giant in $\sim\!\! 1$ Myr. Even in the inner disc (0.1 au), our 1D models suggest that recycling is not so robust and ubiquitous as to stop all cores from becoming giants. At the same time, however, this recycling can delay a runaway phase by an order of magnitude depending on the inner disc conditions and core mass.
The relation between black hole spin and molecular gas in massive galaxies
Authors: Chen Yongyun , Gu Qiusheng , Fan Junhui , Yu Xiaoling , Ding Nan , Guo Xiaotong , Xiong Dingrong
Published: September 2024

Molecular gas is the key probe for the complex interaction between the accretion of black holes and star formation of the host galaxy of active galactic nuclei (AGN). The molecular gas discovered around the AGN indicates that this gas is providing fuel for the AGN. According to the theoretical model of the relativistic jet, the spin of a black hole enhances the relativistic jet of AGN. The spin of the black hole is used as an indicator of AGN activity. Therefore, we study the relationship between the activity of AGN and molecular gas. We find a significant strong correlation between molecular gas fraction and CO luminosity and black hole spin for the early-type galaxies. However, there is no correlation between molecular gas fraction and CO luminosity and black hole spin for the late-type galaxies. These results indicate that the spin of black holes mainly regulates the accretion of molecular gas in massive early-type galaxies. The activity of AGN depends on the amount of gas.
Extremely low lattice thermal conductivity in light-element solid materials
Authors: Ma Ni , Liu Lu , Wu Runhua , Xu Juping , Yin Wen , Li Kai , Bai Wei , Yang Jiong , Xiao Chong , Xie Yi
Published: September 2024

Lattice thermal conductivity (κl) is of great importance in basic sciences and in energy conversion applications. However, low-κl crystalline materials have only been obtained from heavy elements, which typically exhibit poor stability and possible toxicity. Thus, low-κl materials composed of light elements should be explored. Herein, light elements with hierarchical structures in a simple square-net lattice as well as a small discrepancy in atomic mass and radius exhibit low κl. The hierarchical structure exhibits various chemical bonds and asymmetric geometry of building units, resulting in flat phonon branches and strong phonon–phonon interactions similar to those observed in heavy-element materials. These phenomena generate a large phonon anharmonicity, which is the prerequisite for achieving extremely low κl. For example, KCu4Se3 exhibits an extremely low κl of 0.12 W/(m·K) at 573 K, which is lower than that of most heavy-element materials. These findings can reshape our fundamental understanding of thermal transport properties of materials and advance the design of low-κl solids comprising light elements.
Select U.S. cross-border planning pitfalls: a deeper dive
Authors: Warshaw Melvin A
Published: September 2024

This article focuses on the use of pre-immigration “drop-off” trusts and “pre-expatriation” trusts. The author explores whether the “drop-off” trust should be a U.S. or foreign trust and some of the pitfalls of utilizing a foreign trust. The balance of the article is focused on how to draft a “pre-expatriation” trust and discusses some of the legal and tax considerations the draftsperson must discuss with the client. Finally, there is commentary around the use of “indirect” gifts under the U.S. inheritance tax laws.
The intentionally defective grantor trust: a strategy for Swiss resident US persons engaging in US gift tax exemption planning
Authors: Berlin Matthew , Grisel Guillaume
Published: September 2024

US Persons (including foreign residents) should prepare for the reduction in the US estate and gift tax lifetime exemption scheduled for 2026. A common planning strategy is to set up irrevocable trusts to divest themselves of part of their wealth. However, for US Persons living abroad, a transfer into trust can result in double taxation of income with no treaty relief. An intentionally defective trust can thread this needle, constituting a completed gift for US lifetime exemption purposes while allowing the application of mechanisms to prevent double taxation of income.
Intracorporeal anastomosis versus extracorporeal anastomosis following laparoscopic right hemicolectomy: Surgical outcomes of a single-center observational study
Authors: Elhoofy Ahmed , Nagy Mostafa , Elghandour Abdelrahman M.
Published: September 2024

Background

The Enhanced Recovery After Surgery protocol strongly recommends minimally invasive approach to colon cancer for rapid recovery, lower complication rate, and wound-related complications. Intracorporeal anastomosis (ICA) is believed to offer better patient outcome compared with extracorporeal anastomosis (ECA).

Materials and Methods

From January 2021 to January 2022, a prospective observational study comparing ICA with ECA in patients after elective right hemicolectomy at a local surgical hospital was conducted. We included all patients ≥18 years old who underwent elective right hemicolectomy. Primary outcome was difference in the incidence of surgical site infection and anastomotic leakage postoperatively.

Results

Seventy-one patients had ICA with a mean age of 52 ± 9.8 years, whereas 67 patients had ECA with a mean age 54.2 ± 8.7 years. Mean overall operative time was longer after ICA (169.1 ± 35.7 minutes) compared with the ECA group (147 ± 36.9 minutes), P = 0.0001. Difference in estimated blood loss (P = 0.60), tumor size (P = 0.57), number of excised lymph nodes (P = 0.19), stage (P = 0.66), and pathology of specimen (P = 0.53) between ICA and ECA was nonsignificant. Patients with ICA after right hemicolectomy had a quicker recovery of bowel function and time to pass stool (ICA: 3.74 ± 0.6 days vs ECA: 4 ± 0.5 days, P = 0.009), early commencement of oral intake (ICA: 2.6 ± 1.1 days vs ECA days: 3.6 ± 1.1, P = 0.0001), and fewer days in hospital (ICA: 4.8 ± 1.1 vs ECA: 6.2 ± 1.4, P = 0.0001) compared with patients with ECA, respectively. There were no significant differences in postoperative complications and causes of readmission between the two groups.

Conclusions

ICA offers comparable postoperative complications to ECA but has enhanced patient outcomes in terms of recovery.
Comparative Analysis of Coagulation Activation in Rheumatoid Arthritis Patients Treated With TNF Inhibitors Versus JAK Inhibitors
Authors: Hansildaar Romy , Raadsen Reinder , Gerritsen Martijn , Nagy Magdolna , Dijkshoorn Bas , Spronk H.M.H. , ten Cate Hugo , Nurmohamed M.T.
Published: September 2024

Objectives

This study aims to investigate the activation of the coagulation system of RA patients and assess changes during anti-inflammatory treatment with tumor necrosis factor blockers (anti-TNF) and Janus kinase inhibitors (JAKi).

Methods

Biomarkers for the coagulation system, including D-dimer, fibrinogen, prothrombin time, activated partial thrombin time, prothrombin fragment 1 + 2, thrombin-antithrombin complex (TAT), activated factor IX, antithrombin complex, and von Willebrand factor (vWF), were longitudinally measured in 83 RA patients treated with anti-TNF and 38 RA patients with JAKi. Data were collected at baseline, after 1, 3, and 6 months.

Results

The mean age was 57 (±14) years; 76% was female. The mean DAS28-CRP was 3.6 (±1.3) for anti-TNF users and 4.1 (±1.4) for JAKi users at baseline and declined in both groups. Baseline coagulation markers levels were comparable between groups. In anti-TNF users, D-dimer and fibrinogen levels significantly declined (−0.31 mg/L, p = 0.01 and −0.71 g/L, p < 0.001, respectively), whereas TAT significantly increased after 6 months follow-up (1.46 μg/L, p = 0.03) and no effect on vWF (p = 0.98). In JAKi users, vWF declined significantly during the 6 months follow-up (−37.41%, p < 0.001); additionally, there were reductions of D-dimer, fibrinogen, and TAT that did not reach significance (−0.17 mg/L, p = 0.59; −0.49 g/L, p = 0.12; and 0.68 μg/L, p = 0.27, respectively).

Conclusions

The prothrombotic tendency in active RA declined during effective treatment with both anti-TNF and JAKi. Altogether, the biomarkers used in this study suggest that an increased VTE risk in the first 6 months due to either treatment with anti-TNF or JAKi is unlikely.
Phylogenomic and synteny analysis of BAHD and SCP/SCPL gene families reveal their evolutionary histories in plant specialized metabolism
Authors: Naake Thomas , D'Auria John C. , Fernie Alisdair R. , Scossa Federico
Published: September 2024

Plant chemical diversity is largely owing to a number of enzymes which catalyse reactions involved in the assembly, and in the subsequent chemical modifications, of the core structures of major classes of plant specialized metabolites. One such reaction is acylation. With this in mind, to study the deep evolutionary history of BAHD and the serine-carboxypeptidase-like (SCPL) acyltransferase genes, we assembled phylogenomic synteny networks based on a large-scale inference analysis of orthologues across whole-genome sequences of 126 species spanning Stramenopiles and Archaeplastida, including
Arabidopsis thaliana
, tomato (
Solanum lycopersicum
) and maize (
Zea mays
). As such, this study combined the study of genomic location with changes in gene sequences. Our analyses revealed that serine-carboxypeptidase (SCP)/serine-carboxypeptidase-like (SCPL) genes had a deeper evolutionary origin than BAHD genes, which expanded massively on the transition to land and with the development of the vascular system. The two gene families additionally display quite distinct patterns of copy number variation across phylogenies as well as differences in cross-phylogenetic syntenic network components. In unlocking the above observations, our analyses demonstrate the possibilities afforded by modern phylogenomic (syntenic) networks, but also highlight their current limitations, as demonstrated by the inability of phylogenetic methods to separate authentic SCPL acyltransferases from standard SCP peptide hydrolases.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Plant sesquiterpene lactones
Authors: Agatha Olivia , Mutwil-Anderwald Daniela , Tan Jhing Yein , Mutwil Marek
Published: September 2024

Sesquiterpene lactones (STLs) are a prominent group of plant secondary metabolites predominantly found in the Asteraceae family and have multiple ecological roles and medicinal applications. This review describes the evolutionary and ecological significance of STLs, highlighting their roles in plant defence mechanisms against herbivory and as phytotoxins, alongside their function as environmental signalling molecules. We also cover the substantial role of STLs in medicine and their mode of action in health and disease. We discuss the biosynthetic pathways and the various modifications that make STLs one of the most diverse groups of metabolites. Finally, we discuss methods for identifying and predicting STL biosynthesis pathways.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Evolution of aromatic amino acid metabolism in plants: a key driving force behind plant chemical diversity in aromatic natural products
Authors: Yokoyama Ryo
Published: September 2024

A diverse array of plant aromatic compounds contributes to the tremendous chemical diversity in the plant kingdom that cannot be seen in microbes or animals. Such chemodiversity of aromatic natural products has emerged, occasionally in a lineage-specific manner, to adopt to challenging environmental niches, as various aromatic specialized metabolites play indispensable roles in plant development and stress responses (e.g. lignin, phytohormones, pigments and defence compounds). These aromatic natural products are synthesized from aromatic amino acids (AAAs),
l
-tyrosine,
l
-phenylalanine and
l
-tryptophan. While amino acid metabolism is generally assumed to be conserved between animals, microbes and plants, recent phylogenomic, biochemical and metabolomic studies have revealed the diversity of the AAA metabolism that supports efficient carbon allocation to downstream biosynthetic pathways of AAA-derived metabolites in plants. This review showcases the intra- and inter-kingdom diversification and origin of committed enzymes involved in plant AAA biosynthesis and catabolism and their potential application as genetic tools for plant metabolic engineering. I also discuss evolutionary trends in the diversification of plant AAA metabolism that expands the chemical diversity of AAA-derived aromatic natural products in plants.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Presence of vitamin B
12
metabolism in the last common ancestor of land plants
Authors: Dorrell Richard G. , Nef Charlotte , Altan-Ochir Setsen , Bowler Chris , Smith Alison G.
Published: September 2024

Vitamin B
12
, also known as cobalamin, is an essential organic cofactor for methionine synthase (METH), and is only synthesized by a subset of bacteria. Plants and fungi have an alternative methionine synthase (METE) that does not need B
12
and are typically considered not to utilize it. Some algae facultatively utilize B
12
because they encode both METE and METH, while other algae are dependent on B
12
as they encode METH only. We performed phylogenomic analyses of METE, METH and 11 further proteins involved in B
12
metabolism across more than 1600 plant and algal genomes and transcriptomes (e.g. from OneKp), demonstrating the presence of B
12
-associated metabolism deep into the streptophytes. METH and five further accessory proteins (MTRR, CblB, CblC, CblD and CblJ) were detected in the hornworts (Anthocerotophyta), and two (CblB and CblJ) were identified in liverworts (Marchantiophyta) in the bryophytes, suggesting a retention of B
12
-metabolism in the last common land plant ancestor. Our data further show more limited distributions for other B
12
-related proteins (MCM and RNR-II) and B
12
dependency in several algal orders. Finally, considering the collection sites of algae that have lost B
12
metabolism, we propose freshwater-to-land transitions and symbiotic associations to have been constraining factors for B
12
availability in early plant evolution.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Evolution of phosphate scouting in the terrestrial biosphere
Authors: Abel Steffen , Naumann Christin
Published: September 2024

Chemistry assigns phosphorus and its most oxidized form, inorganic phosphate, unique roles for propelling bioenergetics and metabolism in all domains of life, possibly since its very origin on prebiotic Earth. For plants, access to the vital mineral nutrient profoundly affects growth, development and vigour, thus constraining net primary productivity in natural ecosystems and crop production in modern agriculture. Unlike other major biogenic elements, the low abundance and uneven distribution of phosphate in Earth’s crust result from the peculiarities of phosphorus cosmochemistry and geochemistry. Here, we trace the chemical evolution of the element, the geochemical phosphorus cycle and its acceleration during Earth’s history until the present (Anthropocene) as well as during the evolution and rise of terrestrial plants. We highlight the chemical and biological processes of phosphate mobilization and acquisition, first evolved in bacteria, refined in fungi and algae and expanded into powerful phosphate-prospecting strategies during land plant colonization. Furthermore, we review the evolution of the genetic and molecular networks from bacteria to terrestrial plants, which monitor intracellular and extracellular phosphate availabilities and coordinate the appropriate responses and adjustments to fluctuating phosphate supply. Lastly, we discuss the modern global phosphorus cycle deranged by human activity and the challenges imposed ahead.

This article is part of the theme issue ‘Evolution and diversity of plant metabolism’.
Zygospore formation in Zygnematophyceae predates several land plant traits
Authors: Permann Charlotte , Holzinger Andreas
Published: September 2024

Recent research on a special type of sexual reproduction and zygospore formation in Zygnematophyceae, the sister group of land plants, is summarized. Within this group, gamete fusion occurs by conjugation. Zygospore development in
Mougeotia, Spirogyra
and
Zygnema
is highlighted, which has recently been studied using Raman spectroscopy, allowing chemical imaging and detection of changes in starch and lipid accumulation. Three-dimensional reconstructions after serial block-face scanning electron microscopy (SBF-SEM) or focused ion beam SEM (FIB-SEM) made it possible to visualize and quantify cell wall and organelle changes during zygospore development. The zygospore walls undergo strong modifications starting from uniform thin cell walls to a multilayered structure. The mature cell wall is composed of a cellulosic endospore and exospore and a central mesospore built up by aromatic compounds. In
Spirogyra
, the exospore and endospore consist of thick layers of helicoidally arranged cellulose fibrils, which are otherwise only known from stone cells of land plants. While starch is degraded during maturation, providing building blocks for cell wall formation, lipid droplets accumulate and fill large parts of the ripe zygospores, similar to spores and seeds of land plants. Overall, data show similarities between streptophyte algae and embryophytes, suggesting that the genetic toolkit for many land plant traits already existed in their shared algal ancestor.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Plant terrestrialization: an environmental pull on the evolution of multi-sourced streptophyte phenolics
Authors: Kunz Cäcilia F. , de Vries Sophie , de Vries Jan
Published: September 2024

Phenolic compounds of land plants are varied: they are chemodiverse, are sourced from different biosynthetic routes and fulfil a broad spectrum of functions that range from signalling phytohormones, to protective shields against stressors, to structural compounds. Their action defines the biology of land plants as we know it. Often, their roles are tied to environmental responses that, however, impacted already the algal progenitors of land plants, streptophyte algae. Indeed, many streptophyte algae successfully dwell in terrestrial habitats and have homologues for enzymatic routes for the production of important phenolic compounds, such as the phenylpropanoid pathway. Here, we synthesize what is known about the production of specialized phenolic compounds across hundreds of millions of years of streptophyte evolution. We propose an evolutionary scenario in which selective pressures borne out of environmental cues shaped the chemodiversity of phenolics in streptophytes.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Understanding metabolic diversification in plants: branchpoints in the evolution of specialized metabolism
Authors: Ji Wenjuan , Osbourn Anne , Liu Zhenhua
Published: September 2024

Plants are chemical engineers par excellence. Collectively they make a vast array of structurally diverse specialized metabolites. The raw materials for building new pathways (genes encoding biosynthetic enzymes) are commonly recruited directly or indirectly from primary metabolism. Little is known about how new metabolic pathways and networks evolve in plants, or what key nodes contribute to branches that lead to the biosynthesis of diverse chemicals. Here we review the molecular mechanisms underlying the generation of biosynthetic branchpoints. We also consider examples in which new metabolites are formed through the joining of precursor molecules arising from different biosynthetic routes, a scenario that greatly increases both the diversity and complexity of specialized metabolism. Given the emerging importance of metabolic gene clustering in helping to identify new enzymes and pathways, we further cover the significance of biosynthetic gene clusters in relation to metabolic networks and dedicated biosynthetic pathways. In conclusion, an improved understanding of the branchpoints between metabolic pathways will be key in order to be able to predict and illustrate the complex structure of metabolic networks and to better understand the plasticity of plant metabolism.

This article is part of the theme issue ‘The evolution of plant metabolism’.
The evolution of flavonoid biosynthesis
Authors: Davies Kevin M. , Andre Christelle M. , Kulshrestha Samarth , Zhou Yanfei , Schwinn Kathy E. , Albert Nick W. , Chagné David , van Klink John W. , Landi Marco , Bowman John L.
Published: September 2024

The flavonoid pathway is characteristic of land plants and a central biosynthetic component enabling life in a terrestrial environment. Flavonoids provide tolerance to both abiotic and biotic stresses and facilitate beneficial relationships, such as signalling to symbiont microorganisms, or attracting pollinators and seed dispersal agents. The biosynthetic pathway shows great diversity across species, resulting principally from repeated biosynthetic gene duplication and neofunctionalization events during evolution. Such events may reflect a selection for new flavonoid structures with novel functions that enable occupancy of varied ecological niches. However, the biochemical and genetic diversity of the pathway also likely resulted from evolution along parallel trends across land plant lineages, producing variant compounds with similar biological functions. Analyses of the wide range of whole-plant genome sequences now available, particularly for archegoniate plants, have enabled proposals on which genes were ancestral to land plants and which arose within the land plant lineages. In this review, we discuss the emerging proposals for how the flavonoid pathway may have evolved and diversified.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Biotic interactions, evolutionary forces and the pan-plant specialized metabolism
Authors: de Vries Sophie , Feussner Ivo
Published: September 2024

Plant specialized metabolism has a complex evolutionary history. Some aspects are conserved across the green lineage, but many metabolites are unique to certain lineages. The network of specialized metabolism continuously diversified, simplified or reshaped during the evolution of streptophytes. Many routes of pan-plant specialized metabolism are involved in plant defence. Biotic interactions are recalled as major drivers of lineage-specific metabolomic diversification. However, the consequences of this diversity of specialized metabolism in the context of plant terrestrialization and land plant diversification into the major lineages of bryophytes, lycophytes, ferns, gymnosperms and angiosperms remain only little explored. Overall, this hampers conclusions on the evolutionary scenarios that shaped specialized metabolism. Recent efforts have brought forth new streptophyte model systems, an increase in genetically accessible species from distinct major plant lineages, and new functional data from a diversity of land plants on specialized metabolic pathways. In this review, we will integrate the recent data on the evolution of the plant immune system with the molecular data of specialized metabolism and its recognition. Based on this we will provide a contextual framework of the pan-plant specialized metabolism, the evolutionary aspects that shape it and the impact on adaptation to the terrestrial environment.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Cytochromes P450 evolution in the plant terrestrialization context
Authors: Werck-Reichhart Danièle , Nelson David R. , Renault Hugues
Published: September 2024

Plants started to colonize land around 500 million years ago. It meant dealing with new challenges like absence of buoyancy, water and nutrients shortage, increased light radiation, reproduction on land, and interaction with new microorganisms. This obviously required the acquisition of novel functions and metabolic capacities. Cytochrome P450 (CYP) monooxygenases form the largest superfamily of enzymes and are present to catalyse critical and rate-limiting steps in most plant-specific pathways. The different families of CYP enzymes are typically associated with specific functions. CYP family emergence and evolution in the green lineage thus offer the opportunity to obtain a glimpse into the timing of the evolution of the critical functions that were required (or became dispensable) for the plant transition to land. Based on the analysis of currently available genomic data, this review provides an evolutionary history of plant CYPs in the context of plant terrestrialization and describes the associated functions in the different lineages. Without surprise it highlights the relevance of the biosynthesis of antioxidants and UV screens, biopolymers, and critical signalling pathways. It also points to important unsolved questions that would deserve to be answered to improve our understanding of plant adaptation to challenging environments and the management of agricultural traits.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Evolution of the biochemistry underpinning purine alkaloid metabolism in plants
Authors: Jia Xinxin , Luo Shijie , Ye Xiali , Liu Lin , Wen Weiwei
Published: September 2024

Purine alkaloids are naturally occurring nitrogenous methylated derivatives of purine nucleotide degradation products, having essential roles in medicine, food and various other aspects of our daily lives. They are generated through convergent evolution in different plant species. The pivotal reaction steps within the purine alkaloid metabolic pathways have been largely elucidated, and the convergent evolution of purine alkaloids has been substantiated through bioinformatic, biochemical and other research perspectives within
S
-adenosyl-ʟ-methionine-dependent
N
-methyltransferases. Currently, the biological and ecological roles of purine alkaloids, further refinement of the purine alkaloid metabolic pathways and the investigation of purine alkaloid adaptive evolutionary mechanisms continue to attract widespread research interest. The exploration of the purine alkaloid metabolic pathways also enhances our comprehension of the biochemical mechanism, providing insights into inter-species interactions and adaptive evolution and offering potential value in drug development and agricultural applications. Here, we review the progress of research in the distribution, metabolic pathway elucidation and regulation, evolutionary mechanism and ecological roles of purine alkaloids in plants. The opportunities and challenges involved in elucidating the biochemical basis and evolutionary mechanisms of the purine alkaloid metabolic pathways, as well as other research aspects, are also discussed.

This article is part of the theme issue ‘The evolution of plant meta­bolism’.
Evolution of small molecule-mediated regulation of arbuscular mycorrhiza symbiosis
Authors: Delaux Pierre-Marc , Gutjahr Caroline
Published: September 2024

The arbuscular mycorrhizal (AM) symbiosis formed by most extant land plants with symbiotic fungi evolved 450 Ma. AM promotes plant growth by improving mineral nutrient and water uptake, while the symbiotic fungi obtain carbon in return. A number of plant genes regulating the steps leading to an efficient symbiosis have been identified; however, our understanding of the metabolic processes involved in the symbiosis and how they were wired to symbiosis regulation during plant evolution remains limited. Among them, the exchange of chemical signals, the activation of dedicated biosynthesis pathways and the production of secondary metabolites regulating late stages of the AM symbiosis begin to be well described across several land plant clades. Here, we review our current understanding of these processes and propose future directions to fully grasp the phylogenetic distribution and role played by small molecules during this ancient plant symbiosis.

This article is part of the theme issue ‘The evolution of plant metabolism’.
Conserved carotenoid pigmentation in reproductive organs of Charophyceae
Authors: Rieseberg Tim P. , Holzhausen Anja , Bierenbroodspot Maaike J. , Zhang Wanchen , Abreu Ilka N. , de Vries Jan
Published: September 2024

Sexual reproduction in Charophyceae abounds in complex traits. Their gametangia develop as intricate structures, with oogonia spirally surrounded by envelope cells and richly pigmented antheridia. The red—probably protectant—pigmentation of antheridia is conserved across Charophyceae.
Chara tomentosa
is, however, unique in exhibiting this pigmentation and also in vegetative tissue. Here, we investigated the two sympatric species,
C. tomentosa
and
Chara baltica
, and compared their molecular chassis for pigmentation. Using reversed phase C
30
high performance liquid chromatography (RP-C
30
-HPLC), we uncover that the major pigments are β-carotene, δ-carotene and γ-carotene; using headspace solid-phase microextraction coupled to gas chromatography equipped with a mass spectrometer (HS-SPME-GC-MS), we pinpoint that the unusually large carotenoid pool in
C. tomentosa
gives rise to diverse volatile apocarotenoids, including abundant 6-methyl-5-hepten-2-one. Based on transcriptome analyses, we uncover signatures of the unique biology of Charophycaee and genes for pigment production, including monocyclized carotenoids. The rich carotenoid pool probably serves as a substrate for diverse carotenoid-derived metabolites, signified not only by (i) the volatile apocarotenoids we detected but (ii) the high expression of a gene coding for a cytochrome P450 enzyme related to land plant proteins involved in the biosynthesis of carotenoid-derived hormones. Overall, our data shed light on a key protection strategy of sexual reproduction in the widespread group of macroalgae. The genetic underpinnings of this are shared across hundreds of millions of years of plant and algal evolution.

This article is part of the theme issue ‘The evolution of plant metabolism’.