A diffuse, pustular eruption in a neonate: Recognizing SAMD9L-associated autoinflammatory disease (SAAD).

A 3-week-old baby with hydrops fetalis, acute respiratory failure, and shock of unknown etiology developed a diffuse, pustular rash with worsening inflammatory markers and respiratory status despite antimicrobials. Whole exome sequencing revealed a de novo, frameshift mutation in the SAM9DL gene, leading to the diagnosis of SAMD9L-associated autoinflammatory disease.

Quinoa, potatoes, and llamas fueled emergent social complexity in the Lake Titicaca Basin of the Andes.

The Lake Titicaca basin was one of the major centers for cultural development in the ancient world. This lacustrine environment is unique in the high, dry Andean altiplano, and its aquatic and terrestrial resources are thought to have contributed to the florescence of complex societies in this region. Nevertheless, it remains unclear to what extent local aquatic resources, particularly fish, and the introduced crop, maize, which can be grown in regions along the lakeshores, contributed to facilitating sustained food production and population growth, which underpinned increasing social political complexity starting in the Formative Period (1400 BCE to 500 CE) and culminating with the Tiwanaku state (500 to 1100 CE). Here, we present direct dietary evidence from stable isotope analysis of human skeletal remains spanning over two millennia, together with faunal and floral reference materials, to reconstruct foodways and ecological interactions in southern Lake Titicaca over time. Bulk stable isotope analysis, coupled with compound-specific amino acid stable isotope analysis, allows better discrimination between resources consumed across aquatic and terrestrial environments. Together, this evidence demonstrates that human diets predominantly relied on C3 plants, particularly quinoa and tubers, along with terrestrial animals, notably domestic camelids. Surprisingly, fish were not a significant source of animal protein, but a slight increase in C4 plant consumption verifies the increasing importance of maize in the Middle Horizon. These results underscore the primary role of local terrestrial food resources in securing a nutritious diet that allowed for sustained population growth, even in the face of documented climate and political change across these periods.

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.

Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4.

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022. METHODS: ADNI4 will recruit URPs using community-engaged approaches. An online portal will screen 20,000 participants, 4000 of whom (50-60% URPs) will be tested for plasma biomarkers and APOE. From this, 500 new participants will undergo in-clinic assessment joining 500 ADNI3 rollover participants. Remaining participants (∼3500) will undergo longitudinal plasma and digital cognitive testing. ADNI4 will add MRI sequences and new PET tracers. Project 1 will optimize biomarkers in AD clinical trials. RESULTS AND DISCUSSION: ADNI4 will improve generalizability of results, use remote digital and blood screening, and continue providing longitudinal clinical, biomarker, and autopsy data to investigators.

Comproportionation of CO2 and Cellulose to Formate Using a Floating Semiconductor-Enzyme Photoreforming Catalyst.

Formate production via both CO2 reduction and cellulose oxidation in a solar-driven process is achieved by a semi-artificial biohybrid photocatalyst consisting of immobilized formate dehydrogenase on titanium dioxide (TiO2 |FDH) producing up to 1.16±0.04 mmolformate g TiO 2 ${{_{\ {\rm TiO}{_{2}}}}}$ -1 in 24 hours at 30 °C and 101 kPa under anaerobic conditions. Isotopic labeling experiments with 13 C-labeled substrates support the mechanism of stoichiometric formate formation through both redox half-reactions. TiO2 |FDH was further immobilized on hollow glass microspheres to perform more practical floating photoreforming allowing vertical solar light illumination with optimal light exposure of the photocatalyst to real sunlight. Enzymatic cellulose depolymerization coupled to the floating photoreforming catalyst generates 0.36±0.04 mmolformate per m2 irradiation area after 24 hours. This work demonstrates the synergistic solar-driven valorization of solid and gaseous waste streams using a biohybrid photoreforming catalyst in aqueous solution and will thus provide inspiration for the development of future semi-artificial waste-to-chemical conversion strategies.

Engineering Electro- and Photocatalytic Carbon Materials for CO2 Reduction by Formate Dehydrogenase.

Semiartificial approaches to renewable fuel synthesis exploit the integration of enzymes with synthetic materials for kinetically efficient fuel production. Here, a CO2 reductase, formate dehydrogenase (FDH) from Desulfovibrio vulgaris Hildenborough, is interfaced with carbon nanotubes (CNTs) and amorphous carbon dots (a-CDs). Each carbon substrate, tailored for electro- and photocatalysis, is functionalized with positive (-NHMe2+) and negative (-COO-) chemical surface groups to understand and optimize the electrostatic effect of protein association and orientation on CO2 reduction. Immobilization of FDH on positively charged CNT electrodes results in efficient and reversible electrochemical CO2 reduction via direct electron transfer with >90% Faradaic efficiency and -250 µA cm-2 at -0.6 V vs SHE (pH 6.7 and 25 °C) for formate production. In contrast, negatively charged CNTs only result in marginal currents with immobilized FDH. Quartz crystal microbalance analysis and attenuated total reflection infrared spectroscopy confirm the high binding affinity of active FDH to CNTs. FDH has subsequently been coupled to a-CDs, where the benefits of the positive charge (-NHMe2+-terminated a-CDs) were translated to a functional CD-FDH hybrid photocatalyst. High rates of photocatalytic CO2 reduction (turnover frequency: 3.5 × 103 h-1; AM 1.5G) with dl-dithiothreitol as the sacrificial electron donor were obtained after 6 h, providing benchmark rates for homogeneous photocatalytic CO2 reduction with metal-free light absorbers. This work provides a rational basis to understand interfacial surface/enzyme interactions at electrodes and photosensitizers to guide improvements with catalytic biohybrid materials.

Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America.

Over several millennia, various native plant species in South America have been used for their healing and psychoactive properties. Chemical analysis of archaeological artifacts provides an opportunity to study the use of psychoactive plants in the past and to better understand ancient botanical knowledge systems. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze organic residues from a ritual bundle, radiocarbon dated to approximately 1,000 C.E., recovered from archaeological excavations in a rock shelter located in the Lípez Altiplano of southwestern Bolivia. The site is located at an elevation of ∼3,900 m above sea level and contains evidence of intermittent human occupations during the last 4,000 years. Chemical traces of bufotenine, dimethyltryptamine, harmine, and cocaine, including its degradation product benzoylecgonine, were identified, suggesting that at least three plants containing these compounds were part of the shamanic paraphernalia dating back 1,000 years ago, the largest number of compounds recovered from a single artifact from this area of the world, to date. This is also a documented case of a ritual bundle containing both harmine and dimethyltryptamine, the two primary ingredients of ayahuasca. The presence of multiple plants that come from disparate and distant ecological areas in South America suggests that hallucinogenic plants moved across significant distances and that an intricate botanical knowledge was intrinsic to pre-Columbian ritual practices.

Microbial Fermentation of Polyethylene Terephthalate (PET) Plastic Waste for the Production of Chemicals or Electricity.

Ideonella sakaiensis (I. sakaiensis) can grow on polyethylene terephthalate (PET) as the major carbon and energy source. Previous work has shown that PET conversion in the presence of oxygen released carbon dioxide and water while yielding adenosine triphosphate (ATP) through oxidative phosphorylation. This study demonstrates that I. sakaiensis is a facultative anaerobe that ferments PET to the feedstock chemicals acetate and ethanol in the absence of oxygen. In addition to PET, the pure monomer ethylene glycol (EG), the intermediate product ethanol, and the carbohydrate fermentation test substance maltose can also serve as fermenting substrates. Co-culturing of I. sakaiensis with the electrogenic and acetate-consuming Geobacter sulfurreducens produced electricity from PET or EG. This newly identified plastic fermentation process by I. sakaiensis provides thus a novel biosynthetic route to produce high-value chemicals or electricity from plastic waste streams.

Collegian help seeking: the role of self-compassion and self-coldness.

BACKGROUND: Researchers have identified a two-factor structure of self-compassion (i.e. self-compassion and self-coldness). To date, no research has examined each of these constructs' role in collegian professional help-seeking intention. AIM: The current study sought to assess the role of self-compassion and self-coldness in collegian professional help-seeking intention, accounting for other theoretically and empirically-supported help-seeking constructs. METHOD: Participants included 9349 collegians recruited as part of the national 2015-2016 Healthy Minds Study archival dataset. A logistic regression was conducted to examine the unique contributions of self-compassion and self-coldness in predicting professional help-seeking intention, controlling for key help-seeking variables. RESULTS: A test of the full model against a constant only model was statistically significant, which indicated that the predictors collectively distinguished between collegians who intended to seek help from a professional clinician compared to those who did not. The Wald criterion indicated that both self-compassion and self-coldness were uniquely associated with intention to seek professional help. Self-compassion increased and self-coldness decreased the probability of seeking professional help. CONCLUSIONS: The study highlights the importance of self-compassion and self-coldness in collegian help-seeking intention. These findings can inform specific outreach efforts targeting both self-compassion and self-coldness.

Raising girls and boys in early China: Stable isotope data reveal sex differences in weaning and childhood diets during the eastern Zhou era.

OBJECTIVES: Using stable isotope analysis of incremental dentin segments, we reconstruct breastfeeding, weaning, and childhood dietary patterns of Eastern Zhou period (771-221 BC) individuals from the Central Plains of China. Previous isotopic research on the Eastern Zhou demonstrated dietary difference between male and female diets in adulthood via bone collagen analysis. To understand the development of gendered dietary patterns we must examine the early life period. We aim to identify the timing of the weaning process, whether childhood diets were the same as adulthood diets, and if there were differences between the diets of boys and girls during childhood. MATERIALS AND METHODS: We present incremental dentin and bone collagen δ13 C and δ15 N isotope data from 23 individuals from two Eastern Zhou archaeological sites (Xiyasi and Changxinyuan ). RESULTS: Weaning was completed between ages 2.5 and 4 years. Females were weaned slightly earlier than males. Early childhood diets show significant incorporation of C3 foods, such as wheat and soybean, for almost all children, while later adulthood diets indicate greater incorporation of C4 foods (millets), particularly for males. DISCUSSION: Childhood diets included greater amounts of C3 foods than expected, suggesting that grains such as wheat may have been adopted in these communities as foods for children. Nevertheless, dietary differentiation between females and males began in childhood, with boys eating more millets (C4 foods) than girls. The findings suggest that feeding children was a significant aspect of socialization and cultural gendering of individuals in ancient China.

Herpes associated erythema multiforme: A retrospective study.

BACKGROUND: Erythema multiforme (EM), an acute dermatologic condition frequently encountered in the Emergency Department, classically presents with a targetoid rash. We reviewed all recent EM cases seen at the LAC-USC County Hospital in order to ascertain the proportion of Herpes associated EM (HAEM) cases and to inform the diagnostic workup of these patients. METHODS: ICD-9 and ICD-10 codes were used to extract a list of EM cases at our institution from 2013 to 2019. Two non-blinded abstractors screened records to confirm an EM diagnosis and entered patient data utilizing a standardized data abstraction form. Cohen's kappa statistic was used to measure inter-rater reliability on various variables. Kappa (κ) values ranged from 0.803 to 1.0. RESULTS: 70 pediatric and 56 adult EM patients were included in the study. A likely etiology was ascribed to 63% of pediatric and adult EM cases. Pediatric EM was most commonly attributed to upper respiratory infection (URI) (n = 23; 33%), Mycoplasma pneumoniae infection (n = 5; 7%), and medications (n = 4; 6%). Adult EM was most commonly attributed to HSV infection (n = 11; 20%), medications (n = 5; 9%), URIs (n = 4; 7%), and other infections (n = 4; 7%). CONCLUSION: HSV-1/2 serologic testing should be considered in most EM patients to potentially prevent repeated ED visits. In EM cases not clearly attributable to herpes or drug exposure, physicians can consider further workup: Mycoplasma serology, nasal PCR, and a respiratory viral panel in pediatric patients. Identification of an etiologic cause may suggest a different treatment approach and prevent mislabeling of medication allergies in patient charts.

Inward- and Outward-Directed Violence in the Lives of Urban Minority Adults Followed from Middle School into Their Thirties.

This study explores connections between inward-directed violence and outward-directed violence using data from the Reach for Health sample, which was originally recruited in the 1990s from three middle schools in economically distressed, predominantly African American neighborhoods of New York City. Now in their thirties, participants (N = 595) completed surveys assessing current suicidal thoughts and behaviors as well as other violence involvements, including intimate partner violence victimization and perpetration. About 10% of males and females reported any suicidal ideation or attempt in the past 12 months. In logistic regression analyses adjusting for sociodemographics, prior reports of feeling blue in middle school (OR: 1.12, CI: 1.02-4.39) and young adult suicidality (OR: 2.54, CI: 1.30-4.95) are significantly related to later suicidality. So are concurrent aggressive behaviors, including reports of physical fighting outside the home (OR: 2.70, CI: 1.29-5.67) and IPV perpetration (OR: 2.09, CI: 1.11-3.94). Neither IPV victimization nor witnessing neighborhood violence is correlated. Findings shed light on the persistence of suicidality in the lives of those who come of age, and often remain, in communities with high levels of poverty, and confirm linkages of suicidality with externally directed aggression. Life-stage interventions are needed to counter the interwoven causes and consequences of multiple forms of violence.

An Implementation Study of Relationship Checkups as Home Visitations for Low-Income At-Risk Couples.

Couples with the greatest need for relationship health maintenance and intervention are often least able to afford and access it; therefore, accessible, affordable, effective, and brief interventions are needed to improve relationship health for those who need it most. Consequently, this paper examined whether a brief relationship intervention could be effectively implemented with a low-income, underserved population. All enrolled participants (N = 1,312) received the Relationship Checkup, which consists of an assessment and a feedback session delivered in their homes or at a local clinic at their request. Measures assessed relationship satisfaction, communication, psychological and physical aggression, and intimacy at baseline and 1-month follow-up, and program and relationship satisfaction at 6-month follow-up. All participants reported significant improvements on all outcomes with small effect sizes. However, moderation analyses suggested that distressed couples reported significantly larger effects across the board. Overall, participants reported that they were highly satisfied with the intervention both immediately after its delivery and 6 months later. Findings provide preliminary support for the effectiveness of this brief checkup and point to the utility of offering these kinds of low-cost brief interventions in flexible formats for those who might have the most difficulty accessing them.

Las parejas más necesitadas de mantenimiento e intervención para la salud de sus relaciones son con frecuencia las menos equipadas para costear y obtenerlos; por lo tanto, las intervenciones accesibles, asequibles, efectivas y breves son necesarias para mejorar la salud de las relaciones de aquéllos que más lo necesitan. Por consiguiente, este artículo examinó si sería posible implementar una intervención breve para relaciones con una población subatendida de bajo ingreso. Todos los participantes inscritos (N = 1312) recibieron un Control de Relación, que consiste en una evaluación y una sesión de comentarios realizadas en sus hogares o en una clínica local a petición de ellos. Las medidas evaluaron la satisfacción en la relación, comunicación, agresión psicológica y física, e intimidad en la línea de base y en un seguimiento después de un mes, así como satisfacción con el programa y con la relación en un seguimiento después de seis meses. Todos los participantes informaron mejoras sustanciales en todos los resultados con tamaños de efecto pequeños. Sin embargo, análisis de moderación sugirieron que las parejas angustiadas informaron efectos considerablemente mayores en todos los renglones. En general, los participantes informaron que estaban sumamente satisfechos con la intervención tanto inmediatamente después de realizarse como seis meses después. Los hallazgos proporcionan apoyo preliminar a la efectividad de este control breve y señalan la utilidad de ofrecer estos tipos de intervenciones breves de bajo costo en formatos flexibles para aquéllos que podrían tener mayores dificultades para obtenerlos.

Interfacing Formate Dehydrogenase with Metal Oxides for the Reversible Electrocatalysis and Solar-Driven Reduction of Carbon Dioxide.

The integration of enzymes with synthetic materials allows efficient electrocatalysis and production of solar fuels. Here, we couple formate dehydrogenase (FDH) from Desulfovibrio vulgaris Hildenborough (DvH) to metal oxides for catalytic CO2 reduction and report an in-depth study of the resulting enzyme-material interface. Protein film voltammetry (PFV) demonstrates the stable binding of FDH on metal-oxide electrodes and reveals the reversible and selective reduction of CO2 to formate. Quartz crystal microbalance (QCM) and attenuated total reflection infrared (ATR-IR) spectroscopy confirm a high binding affinity for FDH to the TiO2 surface. Adsorption of FDH on dye-sensitized TiO2 allows for visible-light-driven CO2 reduction to formate in the absence of a soluble redox mediator with a turnover frequency (TOF) of 11±1 s-1 . The strong coupling of the enzyme to the semiconductor gives rise to a new benchmark in the selective photoreduction of aqueous CO2 to formate.

Expert opinion on existing and developing drugs to treat female sexual dysfunction.

INTRODUCTION: Female sexual dysfunction (FSD) is a highly prevalent, yet commonly underdiagnosed and undertreated condition. This paper reviews the diagnostic terminology for FSD, and basic sexual physiology in women. The Food and Drug Administration (FDA) approved drugs for FSD are discussed, followed by investigational drugs for FSD currently in phase 2 or 3 clinical trials, reasons for failure of drug development, and potential future drug targets. Areas covered: A literature review was conducted for available treatments for FSD: flibanserin, estrogen, ospemifene and prasterone. Potential treatments are assessed, as was the Pharmaprojects database which includes clinical trial information. Testosterone, bremelanotide, bupropion-trazodone, PDE-5 inhibitors, prostaglandins, tibolone and combination therapies, and the theoretical basis of potential drug targets are discussed. Expert opinion: The lack of established endpoints for phase 3 studies of FSD has impeded approval of new treatments, and required additional studies for validation, resulting in proposed changes to the FDA draft guidance for FSD clinical trials in October 2016. Current DSM-5 diagnostic nosology also fails to capture the full range of symptomology. Several promising compounds have shown no movement for several years limiting women's options. Overcoming socio-cultural bias against women's sexual and reproductive health will be critical in the approval of new treatments for FSD.

The daily grind: Sex- and age-related activity patterns inferred from cross-sectional geometry of long bones in a pre-Columbian muisca population from Tibanica, Colombia.

OBJECTIVES: Daily activities involve biomechanical strains acting on skeletal structures. This study identifies differences in activity patterns between males and females, and between young, middle, and older aged individuals within an excavated Muisca skeletal sample from the Eastern Andes region of Northern South America. MATERIALS AND METHODS: The Tibanica archaeological site (AD 1000-1400) is located at 2600 masl on the Sabana de Bogotá, Colombia. Cross-sectional geometric analysis of femurs from 63 individuals and paired-humerii from 33 individuals was used to examine bone size (TA), strength (J) and diaphyseal shape (Imax /Imin , Ix /Iy ). RESULTS: The findings indicate both age- and sex-related differences in activity patterns. An emphasis on upper body strength and robusticity was observed in the females, while males performed more strenuous work using their lower bodies, suggesting gender-based differences in labor. Men showed significant asymmetry in their humerii, with most showing right-hand dominance for upper body activities, while females showed high levels of humeral symmetry indicating similar levels of biomechanical stress for both arms. Female femoral diaphyseal shape changes with age, suggesting more mobility in youth and decreased mobility in middle and older ages. DISCUSSION: These results suggest that daily life may have been structured through patterns of routine labor that united and divided particular age and sex groups. Cross-sectional geometry data indicate women likely spent significant time and energy preparing food, especially grinding maize or other foods, while men may have done more long-distance walking potentially to work in agricultural fields or procure other resources.

Ionic Conductivity Measurements-A Powerful Tool for Monitoring Polyol Reduction Reactions.

The reduction of metal precursors during the polyol synthesis of metal nanoparticles was monitored by ex situ ionic conductivity measurements. Using commonly used platinum precursors (K2PtCl6, H2PtCl6, and K2PtCl4) as well as iridium and ruthenium precursors (IrCl3 and RuCl3), we demonstrate that their reduction in ethylene glycol at elevated temperatures is accompanied by a predictable change in ionic conductivity, enabling a precise quantification of the onset temperature for their reduction. This method also allows detecting the onset temperature for the further reaction of ethylene glycol with HCl produced by the reduction of chloride-containing metal precursors (at ≈120 °C). On the basis of these findings, we show that the conversion of the metal precursor to reduced metal atoms/clusters can be precisely quantified, if the reaction occurs below 120 °C, which also enables a distinction between the stages of metal particle nucleation and growth. The latter is demonstrated by the reduction of H2PtCl6 in ethylene glycol, comparing ionic conductivity measurements with transmission electron microscopy analysis. In summary, ionic conductivity measurements are a simple and straightforward tool to quantify the reduction kinetics of commonly used metal precursors in the polyol synthesis.

Fully Automated RNAscope In Situ Hybridization Assays for Formalin-Fixed Paraffin-Embedded Cells and Tissues.

Biomarkers such as DNA, RNA, and protein are powerful tools in clinical diagnostics and therapeutic development for many diseases. Identifying RNA expression at the single cell level within the morphological context by RNA in situ hybridization provides a great deal of information on gene expression changes over conventional techniques that analyze bulk tissue, yet widespread use of this technique in the clinical setting has been hampered by the dearth of automated RNA ISH assays. Here we present an automated version of the RNA ISH technology RNAscope that is adaptable to multiple automation platforms. The automated RNAscope assay yields a high signal-to-noise ratio with little to no background staining and results comparable to the manual assay. In addition, the automated duplex RNAscope assay was able to detect two biomarkers simultaneously. Lastly, assay consistency and reproducibility were confirmed by quantification of TATA-box binding protein (TBP) mRNA signals across multiple lots and multiple experiments. Taken together, the data presented in this study demonstrate that the automated RNAscope technology is a high performance RNA ISH assay with broad applicability in biomarker research and diagnostic assay development. J. Cell. Biochem. 117: 2201-2208, 2016. © 2016 Wiley Periodicals, Inc.

Carbon source-dependent alteration of Puf3p activity mediates rapid changes in the stabilities of mRNAs involved in mitochondrial function.

The Puf family of RNA-binding proteins regulates gene expression primarily by interacting with the 3' untranslated region (3' UTR) of targeted mRNAs and inhibiting translation and/or stimulating decay. Physical association and computational analyses of yeast Puf3p identified >150 potential mRNA targets involved in mitochondrial function. However, only COX17 has been established as a target of Puf3p-mediated deadenylation and decapping. We have identified 10 new targets that are rapidly degraded in a Puf3p-dependent manner. We also observed changes in Puf3p activity in response to environmental conditions. Puf3p promotes rapid degradation of mRNA targets in the fermentable carbon source dextrose. However, Puf3p-mediated decay activity is inhibited in carbon sources that require mitochondrial function for efficient cell growth. In addition, the activity of Puf3p is rapidly altered by changing the carbon source. PUF3 expression is not decreased at the RNA or protein level by different carbon sources and localization is not significantly altered, suggesting that Puf3p activity is regulated posttranslationally. Finally, under conditions when Puf3p is unable to stimulate decay, Puf3p can still bind its target mRNAs. Together, these experiments provide insight into the carbon source-specific control of Puf3p activity and how such alterations allow Puf3p to dynamically regulate mitochondrial function.