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Global efforts for biodiversity protection and land use-based greenhouse gas mitigation call for increases in the effectiveness and efficiency of environmental conservation. Incentive-based policy instruments are key tools for meeting these goals, yet their effectiveness might be undermined by such factors as social norms regarding whether payments are considered fair. We investigated the causal link between equity and conservation effort with a randomized real-effort experiment in forest conservation with 443 land users near a tropical forest national park in the Vietnamese Central Annamites, a global biodiversity hotspot. The experiment introduced unjustified payment inequality based on luck, in contradiction of local fairness norms that were measured through responses to vignettes. Payment inequality was perceived as less fair than payment equality. In agreement with our preregistered hypotheses, participants who were disadvantaged by unequal payments exerted significantly less conservation effort than other participants receiving the same payment under an equal distribution. No effect was observed for participants advantaged by inequality. Thus, equity effects on effort can have consequences for the effectiveness and efficiency of incentive-based conservation instruments. Furthermore, we show that women exerted substantially more conservation effort than men, and that increasing payment size unexpectedly reduced effort. This emphasizes the need to consider social comparisons, local equity norms, and gender in environmental policies using monetary incentives to motivate behavioral change.

The regulation of autophagy-dependent lysosome homeostasis in vivo is unclear. We showed that the inositol polyphosphate 5-phosphatase INPP5K regulates autophagic lysosome reformation (ALR), a lysosome recycling pathway, in muscle. INPP5K hydrolyzes phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol 4-phosphate [PI(4)P], and INPP5K mutations cause muscular dystrophy by unknown mechanisms. We report that loss of INPP5K in muscle caused severe disease, autophagy inhibition, and lysosome depletion. Reduced PI(4,5)P2 turnover on autolysosomes in Inpp5k-/- muscle suppressed autophagy and lysosome repopulation via ALR inhibition. Defective ALR in Inpp5k-/- myoblasts was characterized by enlarged autolysosomes and the persistence of hyperextended reformation tubules, structures that participate in membrane recycling to form lysosomes. Reduced disengagement of the PI(4,5)P2 effector clathrin was observed on reformation tubules, which we propose interfered with ALR completion. Inhibition of PI(4,5)P2 synthesis or expression of WT INPP5K but not INPP5K disease mutants in INPP5K-depleted myoblasts restored lysosomal homeostasis. Therefore, bidirectional interconversion of PI(4)P/PI(4,5)P2 on autolysosomes was integral to lysosome replenishment and autophagy function in muscle. Activation of TFEB-dependent de novo lysosome biogenesis did not compensate for loss of ALR in Inpp5k-/- muscle, revealing a dependence on this lysosome recycling pathway. Therefore, in muscle, ALR is indispensable for lysosome homeostasis during autophagy and when defective is associated with muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice. Dystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01)). Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001). Glycogen synthase activity was 12% higher (P<0.05) but glycogen branching enzyme activity was 70% lower (P<0.01) in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01) in mdx mice resulting from a 24% reduction in PKA activity (P<0.01). In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001) together with starch-binding domain protein 1 (219% higher; P<0.01). In addition, mdx mice were glucose intolerant (P<0.01) and had 30% less liver glycogen (P<0.05) compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05) as a possible cause of this phenotype. We identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen.

Collective action of resource users is essential for sustainability. Yet, often user groups are socioculturally heterogeneous, which requires cooperation to be established across salient group boundaries. We explore the effect of this type of heterogeneity on resource extraction in lab-in-the-field Common Pool Resource (CPR) experiments in Zanzibar, Tanzania. We create heterogeneous groups by mixing fishers from two neighbouring fishing villages which have distinct social identities, a history of conflict and diverging resource use practices and institutions. Additionally, we analyse between-village differences in extraction behaviour in the heterogeneous setting to assess if out-group cooperation in a CPR dilemma is associated with a community's institutional scope in the economic realm (e.g., degree of market integration). We find no aggregate effect of heterogeneity on extraction. However, this is because fishers from the two villages behave differently in the heterogeneity treatment. We find support for the hypothesis that cooperation under sociocultural heterogeneity is higher for fishers from the village with larger institutional scope. In line with this explanation, cooperation under heterogeneity also correlates with a survey measure of individual fishers' radius of trust. We discuss implications for resource governance and collective action research.

The COVID-19 pandemic has had a profound impact on societies, with possible consequences for their fundamental values. Inglehart’s revised modernization theory links societal values to the underlying subjective sense of existential security in a given society (scarcity hypothesis), while also claiming that influences on values diminish once individuals reach adulthood (socialization hypothesis). An acute existential crisis such as the COVID-19 pandemic offers a rare opportunity to test these assumptions. We analyze data from representative surveys conducted in Japan shortly before and after the onset of the pandemic. Remaining survey sample differences are statistically controlled via propensity score weighting and regression adjustment, while post-stratification weights allow conclusions about the Japanese population. In three sets of analyses, we reveal that the pandemic and the experienced psychological distress are negatively associated with emancipative and secular values, entailing a reversal to traditionalism, intolerance, and religiosity. First, we document a substantial decline in both emancipative and secular values in the first months of the pandemic compared to five months earlier. This decline remained stable a year later. Second, we find that value change was stronger in prefectures more severely affected by the pandemic. Third, individuals who experienced higher psychological distress emphasized the same values more strongly, as evident in two surveys from May 2020 and April 2021. In contrast to the socialization hypothesis, our study provides evidence that, under extraordinary environmental conditions, values can shift even within a negligibly short time period.

Background Inpatient safety can benefit from effective policies for hospital quality assurance. Following legal reform to put quality of care more center stage in hospital capacity planning, a new quality assurance program was introduced in Germany in 2017. The program was based on pre-existing quality indicators and included new policy design components emphasizing hospital accountability. Learning if the policy was effective is important, but challenging in the observational setting. Methods We adapt a quasi-experimental difference-in-differences approach to estimate the causal effect of the program on quality of care in the 4 years after program onset. A control group of indicators from other clinical areas is carefully selected to compare trends in process quality. Results Results show a relevant reduction in risk of adverse care events nationally in the affected patient population relative to a counterfactual scenario of no program adoption. The effect emerged over the first two program years before plateauing. Conclusion The study allows to learn about important design components in healthcare quality assurance. Among our discussed mechanisms for the documented improvement in process quality are the initial announcements of legal consequences and high public attention. These led hospitals to initiate quality improvement, to seek dialogue with state agencies, and to put more efforts into submitting correct quality data. Methodologically, we show how to adapt rigorous study designs to quality assurance evaluation, considering also their assumptions and limitations.

Increasing the expression of intramuscular heat shock protein 72 preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy, suggesting a promising way forward for the treatment of muscular dystrophy. Hsp72 in muscular dystrophy The absence of the membrane-stabilizing protein dystrophin in patients with Duchenne muscular dystrophy results in a highly fragile muscle-cell membrane, abnormal handling of cytoplasmic calcium ions and muscle degeneration. Gehrig et al . tested the idea that enhanced intramuscular expression of heat shock protein 72 (Hsp72) might reduce the pathophysiology of muscular dystrophy in two mouse models. They found that treatment with BGP-15 — an Hsp72 inducer in clinical trials for diabetes — improved muscle function and whole body strength in mdx dystrophic mice. Activity of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase was reduced in both mouse models, and was restored by BGP-15. This work raises the prospect that BGP-15 and other therapies targeting Hsp72 might be beneficial in people with muscular dystrophy. Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin 1 , 2 , 3 . Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca 2+ , which activates inflammatory and muscle degenerative pathways 4 , 5 , 6 . At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death 7 , 8 , BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase (SERCA, the main protein responsible for the removal of intracellular Ca 2+ ) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.

Biodiversity conservation is a “crisis discipline,” with funds often directed toward urgent needs rather than evaluations. Accordingly, researchers tasked with an impact evaluation in conservation can face the evaluator's dilemma: determining the potential impacts of project activities while lacking an ideal study design. Using as an example a USAID‐funded intervention to improve pastoralist communal rangeland health in Northern Tanzania, we show how methods relatively novel to the field of conservation evaluation—directed acyclic graphs and item response theory—can help to mitigate this dilemma. We find that the perceived quality of rangeland commons governance after project completion is positively associated with, and potentially causally related to, positive outcomes in the perceived successes of management and remotely sensed assessments of changes in bare land cover pre and post intervention. This is consistent with the development partner's theory of change and extends our knowledge of which factors mediate whether and how commons management interventions work. Our methodological tools demonstrate how messy and complex data can be productively leveraged, and why unequivocal causal effects cannot always be determined. More broadly, we demonstrate valuable additions to the evaluator's toolkit that can improve the validity of inferences when resources allocated to evaluation are constrained. We demonstrate how directed acyclic graphs and item response theory can help mitigate the evaluator's dilemma—that of identifying project impacts in contexts of limited funding and absence of an ideal study design. In our case study, using these methods, we find that the perceived quality of rangeland commons governance after project completion is positively associated with, and potentially causally related to, positive outcomes for commons rangeland conditions.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease with no effective treatment. The genetic cause of FSHD is complex and the primary pathogenic insult underlying the muscle disease is unknown. Several disease candidate genes have been proposed including DUX4 and FRG1. Expression analysis studies of FSHD report the deregulation of genes which mediate myoblast differentiation and fusion. Transgenic mice overexpressing FRG1 recapitulate the FSHD muscular dystrophy phenotype. Our current study selectively examines how increased expression of FRG1 may contribute to myoblast differentiation defects. We generated stable C2C12 cell lines overexpressing FRG1, which exhibited a myoblast fusion defect upon differentiation. To determine if myoblast fusion defects contribute to the FRG1 mouse dystrophic phenotype, this strain was crossed with skeletal muscle specific FHL1-transgenic mice. We previously reported that FHL1 promotes myoblast fusion in vitro and FHL1-transgenic mice develop skeletal muscle hypertrophy. In the current study, FRG1 mice overexpressing FHL1 showed an improvement in the dystrophic phenotype, including a reduced spinal kyphosis, increased muscle mass and myofiber size, and decreased muscle fibrosis. FHL1 expression in FRG1 mice, did not alter satellite cell number or activation, but enhanced myoblast fusion. Primary myoblasts isolated from FRG1 mice showed a myoblast fusion defect that was rescued by FHL1 expression. Therefore, increased FRG1 expression may contribute to a muscular dystrophy phenotype resembling FSHD by impairing myoblast fusion, a defect that can be rescued by enhanced myoblast fusion via expression of FHL1.

Microfinance is an economic development tool that provides loans to low-income borrowers to stimulate economic growth and reduce financial hardship. Lenders typically require joint liability, where multiple borrowers share the responsibility of repaying a group loan. We propose that this lending practice creates a cooperation dilemma similar to that faced by humans and other organisms in nature across many domains. This could offer a real-world test case for evolutionary theories of cooperation from the biological sciences. In turn, such theories could provide new insights into loan repayment behaviour. We first hypothesise how group loan repayment efficacy should be affected by mechanisms of assortment from the evolutionary literature on cooperation, i.e. common ancestry (kin selection), prior interaction (reciprocity), partner choice, similarity of tags, social learning, and ecology and demography. We then assess selected hypotheses by reviewing 41 studies from 32 countries on micro-borrowers’ loan repayment, evaluating which characteristics of borrowers are associated with credit repayment behaviour. Surprisingly, we find that kinship is mostly negatively associated with repayment efficacy, but prior interaction and partner choice are both more positively associated. Our work highlights the scope of evolutionary theory to provide systematic insight into how humans respond to novel economic institutions and interventions.