Mechanisms controlling metabolite concentrations of the Calvin Benson Cycle.

Maintaining proper metabolite levels in a complex metabolic network is crucial for maintaining a high flux through the network. In this paper, we discuss major regulatory mechanisms over the Calvin Benson Cycle (CBC) with regard to their roles in conferring homeostasis of metabolite levels in CBC. These include: 1) Redox regulation of enzymes in the CBC on one hand ensures that metabolite levels stay above certain lower bounds under low light while on the other hand increases the flux through the CBC under high light. 2) Metabolite regulations, especially allosteric regulations of major regulatory enzymes, ensure the rapid up-regulation of fluxes to ensure sufficient amount of triose phosphate is available for end product synthesis and concurrently avoid phosphate limitation. 3) A balanced activities of enzymes in the CBC help maintain balanced flux through CBC; some innate product feedback mechanisms, in particular the ADP feedback regulation of GAPDH and F6P feedback regulation of FBPase, exist in CBC to achieve such a balanced enzyme activities and hence flux distribution in the CBC for greater photosynthetic efficiency. Transcriptional regulation and natural variations of enzymes controlling CBC metabolite homeostasis should be further explored to maximize the potential of engineering CBC for greater efficiency.

The legacy environmental footprints of manufactured capital.

The foundations of today's societies are provided by manufactured capital accumulation driven by investment decisions through time. Reconceiving how the manufactured assets are harnessed in the production-consumption system is at the heart of the paradigm shifts necessary for long-term sustainability. Our research integrates 50 years of economic and environmental data to provide the global legacy environmental footprint (LEF) and unveil the historical material extractions, greenhouse gas emissions, and health impacts accrued in today's manufactured capital. We show that between 1995 and 2019, global LEF growth outpaced GDP and population growth, and the current high level of national capital stocks has been heavily relying on global supply chains in metals. The LEF shows a larger or growing gap between developed economies (DEs) and less-developed economies (LDEs) while economic returns from global asset supply chains disproportionately flow to DEs, resulting in a double burden for LDEs. Our results show that ensuring best practice in asset production while prioritizing well-being outcomes is essential in addressing global inequalities and protecting the environment. Achieving this requires a paradigm shift in sustainability science and policy, as well as in green finance decision-making, to move beyond the focus on the resource use and emissions of daily operations of the assets and instead take into account the long-term environmental footprints of capital accumulation.

Individual Optimization of Reproductive Investment and the Cost of Incubation in a Wild Songbird.

AbstractDespite avid interest in life history trade-offs and the costs of reproduction, evidence that increased parental allocation reduces subsequent breeding productivity is mixed. This uncertainty may be attributable to environmental heterogeneity in space and time, necessitating experiments across a range of ecological contexts. Over three breeding seasons, we cross-fostered clutches between nests to manipulate incubation duration in a wild population of Carolina wrens, a species in which only females incubate, to test for a cost of incubation on current and future reproduction. Prolonged incubation affected maternal productivity in a manner dependent on the current environment and initial investment in eggs, suggesting that incubation is optimized according to other components of reproduction and individual quality. Effects of incubation duration on foster nestling condition varied between years, being costly in one, beneficial in another, and neutral in the third. The proportion of young fledged, females' probability of breeding again within seasons, and subsequent clutch sizes all declined with increasing incubation effort-effects that became more pronounced as seasons progressed. Therefore, costs of incubation were almost entirely dependent on maternal quality and environmental variation, illustrating the importance of conducting experiments across a range of environmental settings for understanding the costs of reproduction and evolution of life histories.

Evolutionary trade-offs between testes size and parenting in Neotropical glassfrogs.

In males, large testes size signifies high sperm production and is commonly linked to heightened sperm competition levels. It may also evolve as a response to an elevated risk of sperm depletion due to multiple mating or large clutch sizes. Conversely, weapons, mate or clutch guarding may allow individuals to monopolize mating events and preclude sperm competition, thereby reducing the selection of large testes. Herein, we examined how paternal care, sexual size dimorphism (SSD), weaponry and female fecundity are linked to testes size in glassfrogs. We found that paternal care was associated with a reduction in relative testes size, suggesting an evolutionary trade-off between testes size and parenting. Although females were slightly larger than males and species with paternal care tended to have larger clutches, there was no significant relationship between SSD, clutch size and relative testes size. These findings suggest that the evolution of testes size in glassfrogs is influenced by sperm competition risk, rather than sperm depletion risk. We infer that clutch guarding precludes the risk of fertilization by other males and consequently diminishes selective pressure for larger testes. Our study highlights the prominent role of paternal care in the evolution of testes size in species with external fertilization.

Acclimation of intertidally reproducing sea-snails protects embryos from lethal effects of transient hyperthermia.

Embryos of Ilyanassa obsoleta (from Massachusetts and Florida) and Phrontis vibex (from Florida) were exposed to temperatures from 33 to 37°C. In both species, very young embryos are especially sensitive to thermal stress. Brief early heat shock did not disturb spiral cleavage geometry but led to variable, typically severe defects in larval morphogenesis and tissue differentiation. In Ilyanassa but not P. vibex, early heat shock resulted in immediate slowing or arrest of interphase progression during early cleavage. This reversible arrest was correlated with improved prognosis for larval development and (in Massachusetts snails, at least) depended on parental acclimation to warm temperature (~25.5°C). Embryos from Massachusetts snails housed at lower temperature (16°C) exhibited cytokinesis failure when briefly incubated at 33°C during early cleavage, and tissue differentiation failure during incubation at 33°C begun at later stages. This preliminary study reveals a case in which stress-conditioned parents may endow embryos with protection against potentially lethal thermal stress during the most vulnerable stages of life.

Return on investment of fracture liaison services: a systematic review and analysis.

Fracture liaison services (FLS) have been proven clinically effective and cost-effective in preventing subsequent fractures among patients with an existing fragility fracture. Little is known about their monetary benefits such as their return on investment (ROI). This systematic review aimed to investigate the ROI of FLS and identify the FLS characteristics with better ROI. Studies on the cost-effectiveness of FLS published between January 2000 and December 2022 were searched from MEDLINE, EMBASE, PubMed, and Cochrane Central. Two independent reviewers conducted study selection and data extraction. ROI was calculated based on the difference between monetary benefits and FLS costs divided by the FLS costs. Subgroup analysis of ROI was performed across FLS types and FLS design details. A total of 23 FLS were included in this review. The majority of them were targeting patients aged over 50 years having fractures without identified sites. The mean ROI of these FLS was 10.49 (with a median ROI of 7.57), and 86.96% of FLS had positive ROI. FLS making treatment recommendations yielded the highest ROI (with a mean ROI of 18.39 and a median of 13.60). Incorporating primary care providers (with a mean ROI of 16.04 and a median of 13.20) or having them as program leaders (with a mean ROI of 12.07 and a median of 12.07) has demonstrated a high ROI. FLS for specific fracture sites had great monetary return. Intensive FLS such as type A and B FLS programs had higher ROI than non-intensive type C and D FLS. This review revealed a 10.49-fold monetary return of FLS. Identified characteristics contributing to greater economic return informed value-for-money FLS designs. Findings highlight the importance of FLS and the feasibility of expanding their contribution in mitigating the economic burden of osteoporotic fracture and are conducive to the promotion of FLS internationally.

Cell and gene therapy investment: evolution and future outlook on investor perspectives.

BACKGROUND AIMS: To better understand the attitudes and behaviors of investors involved in funding cell and gene therapy (CGT) businesses, the Business Development and Finance) subcommittee of International Society for Cell and Gene Therapy, in collaboration with Truist Securities, conducted a broad survey of the investment community in late 2021. METHODS: This survey follows a similar study that this group executed in 2018, and the longitudinal comparisons between the two time periods provide insights into how investor behavior in the CGT field has evolved. RESULTS: The vast majority of investor respondents are specialist biotech investors who are primarily active in deploying capital in North America and Europe. There was a notable increase in the proportion of investors actively deploying capital in China and Japan between 2018 and 2021. The percentage of respondents' portfolios dedicated to CGT companies has also increased in this period, reflecting a noteworthy trend in the therapeutic landscape. CONCLUSIONS: Clinically significant data remain the dominant force behind investment decisions, whereas competition from other drug modalities has now emerged as the most-cited barrier to making a CGT investment, eclipsing safety concerns as the most significant barrier to investment in 2018. Concerns around manufacturing and scale-up have also increased in prominence amongst the investment community. Gene-editing technologies are attracting investors as the most compelling new CGT technology. This survey also revealed that most investors expect to increase their level of investment in allogeneic technologies relative to autologous products in the coming years.

The fecundity costs of building domed nests in birds.

Animal nests provide a beneficial environment for offspring development and as such contribute to fitness. Gathering and transporting materials to construct nests is energetically costly, but the life history trade-offs associated with the types of nests built are largely unknown. Who contributes to building the nest could also mediate these trade-offs, as building a nest as a couple is expected to be less costly per individual than building alone. Using a comparative analysis on 227 songbird species globally, we found a fecundity cost associated with the type of nest a species builds. Species that build domed nests produce fewer broods per year than species building cups or platforms. Dome nesting species also have larger clutch sizes than open nesting species, but only when the nest is built by a couple and not when females build nests alone. This suggests that building domed nests represents a trade-off with investment in young, especially when females are solely responsible for nest building. More broadly, our results could explain macroevolutionary patterns, such as the recent finding that females, building on their own, more often build open cup rather than domed nests.

Food environment research in Canada: a rapid review of methodologies and measures deployed between 2010 and 2021.

Numerous research methodologies have been used to examine food environments. Existing reviews synthesizing food environment measures have examined a limited number of domains or settings and none have specifically targeted Canada. This rapid review aimed to 1) map research methodologies and measures that have been used to assess food environments; 2) examine what food environment dimensions and equity related-factors have been assessed; and 3) identify research gaps and priorities to guide future research. A systematic search of primary articles evaluating the Canadian food environment in a real-world setting was conducted. Publications in English or French published in peer-reviewed journals between January 1 2010 and June 17 2021 and indexed in Web of Science, CAB Abstracts and Ovid MEDLINE were considered. The search strategy adapted an internationally-adopted food environment monitoring framework covering 7 domains (Food Marketing; Labelling; Prices; Provision; Composition; Retail; and Trade and Investment). The final sample included 220 articles. Overall, Trade and Investment (1%, n = 2), Labelling (7%, n = 15) and, to a lesser extent, Prices (14%, n = 30) were the least studied domains in Canada. Among Provision articles, healthcare (2%, n = 1) settings were underrepresented compared to school (67%, n = 28) and recreation and sport (24%, n = 10) settings, as was the food service industry (14%, n = 6) compared to grocery stores (86%, n = 36) in the Composition domain. The study identified a vast selection of measures employed in Canada overall and within single domains. Equity-related factors were only examined in half of articles (n = 108), mostly related to Retail (n = 81). A number of gaps remain that prevent a holistic and systems-level analysis of food environments in Canada. As Canada continues to implement policies to improve the quality of food environments in order to improve dietary patterns, targeted research to address identified gaps and harmonize methods across studies will help evaluate policy impact over time.

Plant physical defenses contribute to a latitudinal gradient in resistance to insect herbivory within a widespread perennial grass.

PREMISE: Herbivore pressure can vary across the range of a species, resulting in different defensive strategies. If herbivory is greater at lower latitudes, plants may be better defended there, potentially driving a latitudinal gradient in defense. However, relationships that manifest across the entire range of a species may be confounded by differences within genetic subpopulations, which may obscure the drivers of these latitudinal gradients. METHODS: We grew plants of the widespread perennial grass Panicum virgatum in a common garden that included genotypes from three genetic subpopulations spanning an 18.5° latitudinal gradient. We then assessed defensive strategies of these plants by measuring two physical resistance traits-leaf mass per area (LMA) and leaf ash, a proxy for silica-and multiple measures of herbivory by caterpillars of the generalist herbivore fall armyworm (Spodoptera frugiperda). RESULTS: Across all genetic subpopulations, low-latitude plants experienced less herbivory than high-latitude plants. Within genetic subpopulations, however, this relationship was inconsistent-the most widely distributed and phenotypically variable subpopulation (Atlantic) exhibited more consistent latitudinal trends than either of the other two subpopulations. The two physical resistance traits, LMA and leaf ash, were both highly heritable and positively associated with resistance to different measures of herbivory across all subpopulations, indicating their importance in defense against herbivores. Again, however, these relationships were inconsistent within subpopulations. CONCLUSIONS: Defensive gradients that occur across the entire species range may not arise within localized subpopulations. Thus, identifying the drivers of latitudinal gradients in herbivory defense may depend on adequately sampling the diversity within a species.

The cuckoldry conundrum.

Concerns about cuckoldry are a dominant theme in evolutionary studies of mating, frequently used to explain sex differences in reproductive strategies. However, studies in nonhuman species have shown that cuckoldry can be associated with important benefits. These insights have not been well integrated with the human literature, which continues to focus on anticuckoldry tactics and negative repercussions for men. I evaluate two key assumptions central to human models of cuckoldry: (1) men are being tricked into investing in nonbiological offspring and (2) investment in nonbiological offspring is wasted. The ethnographic data on fatherhood shows that the concepts of pater and genitor are complex and locally constructed ideas that often include explicit knowledge of extra-pair paternity, countering the idea that nonpaternity results from trickery. Furthermore, rather than being a "waste," paternity loss can be associated with important gains for men, helping to explain why men invest in nonbiological offspring.

Investing in midwifery for sustainable development goals in low- and middle-income countries: a cost-benefit analysis.

BACKGROUND: Maternal and neonatal mortality in low- and middle-income countries is frequently caused by inadequate management of obstetric and neonatal complications and a shortage of skilled health workers. The availability of these workers is essential for effective and high-quality healthcare. To meet the needs of sexual, reproductive, maternal, new-born, child, and adolescent health by 2030, more than one million health workers, including 900 000 midwives, are required globally. Despite this, uncertainty persists regarding the return on investment in the health workforce. METHODS: The objective of this research was to determine the cost-benefit ratio of increasing investment in midwifery in Morocco from 2021 to 2030. A comparative analysis was conducted between scenarios "with" and "without" the additional investment. The costs and benefits were estimated using relevant data from national and international sources. RESULTS: Following the International Confederation of Midwives' recommendations, it is advised that Morocco recruit 760 midwives annually to achieve 95% of universal health coverage. This increase in midwifery could result in saving 120 593 lives by 2030, including reducing maternal deaths by 3 201, stillbirths by 48 399, and neonatal deaths by 68 993. The estimated economic benefit of investing in midwives was US$ 10 152 287 749, while the total cost was US$ 638 288 820. Consequently, the cost-benefit ratio was calculated as 15.91, indicating that investing in midwifery would provide 16 times more benefits than costs. CONCLUSION: Increasing investment in midwifery appears to be an efficient strategy for achieving comprehensive maternal and child health coverage in low- and middle-income countries.

Return on investment in science: twenty years of European Commission funded research in Alzheimer's dementia, breast cancer and prostate cancer.

Alzheimer's disease (AD), breast cancer (BC) and prostate cancer (PC) continue to be high in the research and innovation agenda of the European Commission (EC). This is due to their exceptionally large burden to the national health systems, the profound economic effects of opportunity costs attributable to decreased working ability, premature mortality and the ever-increasing demand for both hospital and home-based medical care. Over the last two decades, the EC has been steadily increasing both the number of proposals being funded and the amounts of financial resources being allocated to these fields of research. This trend has continued throughout four consecutive science funding cycles, namely framework programme (FP)5, FP6, FP7 and Horizon 2020 (H2020). We performed a retrospective assessment of the outputs and outcomes of EC funding in AD, BC and PC research over the 1999-2019 period by means of selected indicators. These indicators were assessed for their ability to screen the past, present and future for an array of causal relationships and long-term trends in clinical, epidemiological and public health sphere, while considering also the broader socioeconomic impact of funded research on the society at large. This analysis shows that public-private partnerships with large industry and university-based consortia have led to some of the most impactful proposals being funded over the analysed time period. New pharmaceuticals, small molecules and monoclonal antibodies alike, along with screening and prevention, have been the most prominent sources of innovation in BC and PC, extending patients' survival and enhancing their quality of life. Unlike oncology, dementia drug development has been way less successful, with only minor improvements related to the quality of supportive medical care for symptoms and more sensitive diagnostics, without any ground-breaking disease-modifying treatment(s). Significant progresses in imaging diagnostics and nanotechnology have been largely driven by the participation of medical device industry multinational companies. Clinical trials funded by the EC were conducted, leading to the development of brand-new drug molecules featuring novel mechanisms of action. Some prominent cases of breakthrough discoveries serve as evidence for the European capability to generate cutting-edge technological innovation in biomedicine. Less productive areas of research may be reconsidered as priorities when shaping the new agenda for forthcoming science funding programmes.

The Spherical Tokamak for Energy Production (STEP) in context: UK public sector approach to fusion energy.

The UK's fusion energy approach has developed over the past 5 years to include government policy initiatives and a range of public sector investments designed to be delivered in partnership with the private sector. These have aimed to create an environment that stimulates innovation and investment to deliver economic as well as scientific and environmental benefits throughout the lifetime of the public sector fusion energy programme. The Spherical Tokamak for Energy Production acts as a focus and anchor for both public and private sector efforts to develop fusion energy, developing the supply chain and potential for Intellectual Property development and export opportunities well ahead of the anticipated STEP completion date of 2040. This is maximized by the UK's approach to a holistic research and innovation programme backed up by a regulatory and skills programme. This article is part of the theme issue 'Delivering Fusion Energy - The Spherical Tokamak for Energy Production (STEP)'.

Specification of the health production function and its behavioral implications.

The health production function of the canonical health-capital model is generalized to allow the state of health to affect the total and marginal products of health investment. If the total and marginal products of health investment are nonincreasing functions of the state of health, then the solution of the generalized model is locally qualitatively identical to that of the canonical model. Moreover, and in contrast to the canonical model, the generalized model is able to rationalize the cycling of the state of health and health investment observed in some individuals. The necessary conditions on the health production function for cyclical behavior are identified as well.

An analysis of a rural hospital's investment decision under different payment systems.

From an economic perspective, large investments in medical equipment are justifiable only when many patients benefit. Although rural hospitals play a crucial role locally, the treatments they can offer are limited. In this study, I characterize investment level that maximizes the total surplus, encompassing patients' welfare and producer surplus, and subtracting treatment costs. Specifically, I account for economic externalities generated by the investment in the rural hospital and for different utility losses that patients suffer when they cannot be treated locally. I demonstrate that the optimal investment level can be implemented if the Health Authority has the power to set specific prices for each disease. Additionally, I explore a decentralized situation wherein the investment decision lies with the rural hospital manager, and the Health Authority can only make a discrete decision between two payment systems: Fee-for-service, which covers all treatment costs, or Diagnosis-Related-Groups, which reimburses a price per patient based on the overall average cost. I find that the Diagnosis-Related-Groups system outperforms the Fee-for-service in terms of total surplus when the treatment cost at the rural hospital is lower. However, when the rural hospital has higher costs and the Health Authority seeks to incentivize investment, the Fee-for-service system is superior.

Technoeconomic assessment for the viable exploitation of biomass residues by an innovative pyrolysis-anaerobic digestion processing plant.

In Greece, there is no organized practice in agricultural and animal wastes management. Their exploitation is still set aside, due mainly to economic reasons and lack of incentives for their efficient utilization. Therefore, in the present work a technoeconomic assessment for the environmentally friendly useful exploitation of biomass residues produced in the Prefectures of Ilia and Achaia (Western Greece) for the generation of energy by an integrated anaerobic digestion (AD)-pyrolysis processing plant was carried out. The processed biomass of the AD unit is corn residues and cattle manure, while the feedstock of pyrolysis unit is olive tree prunings. The residues will be transferred to collection areas by field tractors. Then an integrated harvester is used and afterwards, the residues are discharged from the lifting bin of the harvester to trucks and are transported to the processing unit. The total fixed capital for a capacity of 328,716 t/y is equal to 11.5 M€, while the initial working capital is equal to 2.1 M€. The total operational cost of this investment is estimated at 18.3 M€/y, the projected revenues amount to 21.4 M€/y and the net profit is equal to 3.1 M€/y. The return on investment is estimated at 23% and the payback period becomes equal to 4.4 years. From the sensitivity analysis becomes apparent that the capacity, the incentive cost, the fuel price, the products price and the total fixed capital affect significantly the investment characteristics of the proposed AD-pyrolysis processing unit. The amount of the expected profit is considered quite significant, and the evaluation criteria (return on investment and payback period) advocate for a more detailed examination of the investment plan, in the direction of undertaking the project.

Carbon emissions prediction considering environment protection investment of 30 provinces in China.

In the backdrop of carbon peaking and carbon neutrality, carbon emissions have always been a major concern. The approach of the heterogeneity grey model is proposed, aiming to predict carbon emissions of 30 provinces in China. This model combines the manta ray foraging optimization algorithm to search for the optimal heterogeneity coefficient. By using the heterogeneity grey model, the carbon emissions are analyzed in 30 provinces of China from 2022 to 2030 considering different environmental protection investment scenarios. The results indicate that in 19 provinces from 2022 to 2030, there is a significant decrease in carbon emissions as government investment increases. In 11 provinces during the same period, there is a rising trend in carbon emissions with the increase of government investment. Hence, achieving a reduction in carbon emissions necessitates not only relying on government investment in environmental protection but also exploring alternative approaches to mitigate carbon emissions. The methodologies and conclusions proposed in this study can provide technical references and making decision references for provincial carbon emission efforts.

Religious Involvement Is Associated With Higher Fertility and Lower Maternal Investment, but More Alloparental Support Among Gambian Mothers.

OBJECTIVES: Human childrearing is cooperative, with women often able to achieve relatively high fertility through help from many individuals. Previous work has documented tremendous socioecological variation in who supports women in childrearing, but less is known about the intracultural correlates of variation in allomaternal support. In the highly religious, high-fertility setting of The Gambia, we studied whether religious mothers have more children and receive more support with their children. METHODS: We randomly sampled 395 mothers and 745 focal children enrolled in the Kiang West (The Gambia) Longitudinal Population Study cohort. Structured interviews asked mothers who and how often people invest in their children, and about their religious practices. Data were collected at participants' homes on electronic tablet-based long-form surveys and analyzed using the Bayesian hierarchical models. RESULTS: Religiosity was weakly associated with women's higher age-adjusted fertility. Maternal religiosity was negatively related to maternal investment in focal children, but positively associated with total allomaternal support. Specifically, a woman's religiosity was positively associated with allomaternal support from matrilineal kin, other offspring, and affinal kin, but unrelated to paternal, patrilineal, and non-kin investment. CONCLUSIONS: These results suggest that higher fertility among religious mothers may be supported by high levels of investment from biological and affinal kin. Matrilineal kin, other siblings, and affinal kin seem to be the most responsive to a woman's religiosity. Our findings cast doubt on interpretations of women's religious behaviors as signals of fidelity, and instead suggest they may be part of strategies to enable collective allomaternal resources and higher relative fertility.

From discovery to innovation in animal health: Maturing emerging technologies for industrial development.

The Discovery to Innovation in Animal Health Conference (DIAH) was organised to bridge the gap between early developers, including academia, regulators, research organizations, and spin-offs/start-ups on one side, and medium-to large-sized companies on the other. The DIAH Conference confronted and aligned vision from academia, industry and regulators, emphasizing the need for early collaboration, careful IP management, and strategic planning for successful product development and partnerships. Recent breakthroughs in vaccinology have not only accelerated the vaccine production process but have also improved antigen quality significantly. These novel technologies are likely to transform vaccine development and play a crucial role in addressing both immediate health challenges (such as cancer vaccines) and ensuring preparedness for future pandemics. The potential and pitfalls of leveraging AI to drive forward R&I activities in the field of animal health were also discussed. Researchers and entrepreneurs looking for collaboration or investment presented a series of new technologies and start-ups, respectively. A market analysis showed that the animal health industry, while highly consolidated, also shows great diversity, ranging from big pharma to companies offering diagnostics, nutritional health services, wearables, feed additives, animal feed and genetic analyses. An analysis of the investment landscape, although subject to external factors, showed that the chances for success are high when good science, a well established regulatory pathways, with a clearly defined market need can be combined with experienced management and a strong investor consortium.