Dynamic Regulation of Mitochondrial Import by the Ubiquitin System.

Mitochondria import nearly their entire proteome from the cytoplasm by translocating precursor proteins through the translocase of the outer membrane (TOM) complex. Here, we show dynamic regulation of mitochondrial import by the ubiquitin system. Acute pharmacological inhibition or genetic ablation of the mitochondrial deubiquitinase (DUB) USP30 triggers accumulation of Ub-substrates that are normally localized inside the mitochondria. Mitochondrial import of USP30 substrates is impaired in USP30 knockout (KO) cells, suggesting that deubiquitination promotes efficient import. Upstream of USP30, the E3 ligase March5 ubiquitinates mitochondrial proteins whose eventual import depends on USP30. In USP30 KOs, exogenous March5 expression induces accumulation of unimported translocation intermediates that are degraded by the proteasomes. In USP30 KO mice, TOM subunits have reduced abundance across multiple tissues. Together these data highlight how protein import into a subcellular compartment can be regulated by ubiquitination and deubiquitination by E3 ligase and DUB machinery positioned at the gate.

Life after a fiery death: Fire and plant biomass loading affect dissolved organic matter in experimental ponds.

Drier and hotter conditions linked with anthropogenic climate change can increase wildfire frequency and severity, influencing terrestrial and aquatic carbon cycles at broad spatial and temporal scales. The impacts of wildfire are complex and dependent on several factors that may increase terrestrial deposition and the influx of dissolved organic matter (DOM) from plants into nearby aquatic systems, resulting in the darkening of water color. We tested the effects of plant biomass quantity and its interaction with fire (burned vs. unburned plant biomass) on dissolved organic carbon (DOC) concentration and degradation (biological vs. photochemical) and DOM composition in 400 L freshwater ponds using a gradient experimental design. DOC concentration increased nonlinearly with plant biomass loading in both treatments, with overall higher concentrations (>56 mg/L) in the unburned treatment shortly after plant addition. We also observed nonlinear trends in fluorescence and UV-visible absorbance spectroscopic indices as a function of fire treatment and plant biomass, such as greater humification and specific UV absorbance at 254 nm (a proxy for aromatic DOM) over time. DOM humification occurred gradually over time with less humification in the burned treatment compared to the unburned treatment. Both burned and unburned biomass released noncolored, low molecular weight carbon compounds that were rapidly consumed by microbes. DOC decomposition exhibited a unimodal relationship with plant biomass, with microbes contributing more to DOC loss than photodegradation at intermediate biomass levels (100-300 g). Our findings demonstrate that the quantity of plant biomass leads to nonlinear responses in the dynamics and composition of DOM in experimental ponds that are altered by fire, indicating how disturbances interactively affect DOM processing and its role in aquatic environments.

Fire transforms effects of terrestrial subsidies on aquatic ecosystem structure and function.

Fire can lead to transitions between forest and grassland ecosystems and trigger positive feedbacks to climate warming by releasing CO2 into the atmosphere. Climate change is projected to increase the prevalence and severity of wildfires. However, fire effects on the fate and impact of terrestrial organic matter (i.e., terrestrial subsidies) in aquatic ecosystems are unclear. Here, we performed a gradient design experiment in freshwater pond mesocosms adding 15 different amounts of burned or unburned plant detritus and tracking the chronology of detritus effects at 10, 31, 59, and 89 days. We show terrestrial subsidies had time- and mass-dependent, non-linear impacts on ecosystem function that influenced dissolved organic carbon (DOC), ecosystem metabolism (net primary production and respiration), greenhouse gas concentrations (carbon dioxide [CO2 ], methane [CH4 ]), and trophic transfer. These impacts were shifted by fire treatment. Burning increased the elemental concentration of detritus (increasing %N, %P, %K), with cascading effects on ecosystem function. Mesocosms receiving burned detritus had lower [DOC] and [CO2 ] and higher dissolved oxygen (DO) through Day 59. Fire magnified the effects of plant detritus on aquatic ecosystem metabolism by stimulating photosynthesis and respiration at intermediate detritus-loading through Day 89. The effect of loading on DO was similar for burned and unburned treatments (Day 10); however, burned-detritus in the highest loading treatments led to sustained hypoxia (through Day 31), and long-term destabilization of ecosystem metabolism through Day 89. In addition, fire affected trophic transfer by increasing autochthonous nitrogen source utilization and reducing the incorporation of 15 N-labeled detritus into plankton biomass, thereby reducing the flux of terrestrial subsidies to higher trophic levels. Our results indicate fire chemically transforms plant detritus and alters the role of aquatic ecosystems in processing and storing carbon. Wildfire may therefore induce shifts in ecosystem functions that cross the boundary between aquatic and terrestrial habitats.

Increased Rates of Late Periprosthetic Fractures in Larger Hydroxyapatite-Coated Cementless Stems: Are Collared Stems a Better Alternative for Total Hip Arthroplasty?

BACKGROUND: Cementless hip stems are widely used for total hip arthroplasty (THA) and have demonstrated excellent survivorship. This study aimed to investigate the effects of stem size and calcar collars on rates of revision due to periprosthetic fracture. METHODS: All primary THA procedures recorded by the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) from September 1999 to December 2021 for a diagnosis of osteoarthritis using a single cementless hip stem with modern bearings were included. The primary outcome measure was revision due to periprosthetic fracture. Stems were divided into 2 groups for comparison, large (size 14 to 20) and small-medium (6 to 13). A subanalysis was performed for collared stems. A total of 59,518 primary THA procedures were included. RESULTS: The cumulative percent revision for periprosthetic fracture was significantly higher for large stems compared to small-medium stems (hazard ratio [HR] = 1.57 [95% confidence interval {CI} 1.18, 2.09] P = .002). Furthermore, collared stems had significantly lower revision rates due to late periprosthetic fracture compared to collarless variants (2 week + HR = 4.55 [95% CI 3.23, 6.42], P < .001). Large collarless stems were found to have greater revision rates due to fracture compared to small-medium collarless stems (HR = 1.55 [95% CI 1.13, 2.12] P = .006), but no difference was found between collared groups (HR = 1.37 [95% CI 0.68, 2.78] P = .382). CONCLUSION: Large cementless hip stems have a higher rate of revision due to periprosthetic fracture compared to small-medium stems. Using a collared stem reduces the rate of periprosthetic fracture.

Lower Revision Rates and Improved Stability With a Monoblock Ceramic Acetabular Cup.

BACKGROUND: Monoblock ceramic cups are designed to accommodate large-diameter femoral heads. This has the potential to offer the advantages of an increased range of motion and enhanced joint stability. These features could benefit younger and high-demand patients in need of total hip arthroplasty. The aim of this study was to assess the survival rate and the reasons for revision of the DeltaMotion cup. METHODS: Data from the AOANJRR were analyzed for all patients who had undergone a primary conventional THA performed between January 1, 2001 and December 31, 2021. Only prostheses with ceramic/ceramic, ceramic/XLPE, metal/XLPE, or CM/XLPE bearing surfaces were included. The primary outcome measure was the cumulative percent revision for all causes. Secondary outcome measures were revision for dislocation/instability, ceramic breakage, or noise. A subanalysis for cup size was also performed. RESULTS: There were 486,946 primary conventional THA procedures undertaken for any reason. Of these, 4,033 used the DeltaMotion cup and 482,913 were modular designs. The DeltaMotion cup had the lowest CPR for all diagnoses compared to the modular bearings at all time points, had a significantly lower revision rate for prosthesis dislocation and no revisions for squeaking compared to other modular bearings. There were 175 ceramic breakages recorded in the modular bearing group and 1 ceramic breakage in the DeltaMotion group. CONCLUSIONS: The DeltaMotion cup had a low rate of all-cause revision, and for dislocation, ceramic breakage, and noise. Although this cup is no longer manufactured, ongoing follow-up of newer monoblock ceramic cups will determine their suitability for younger and more active patients.

Mitochondrial respiratory chain dysfunction alters ER sterol sensing and mevalonate pathway activity.

Mitochondrial dysfunction induces a strong adaptive retrograde signaling response; however, many of the downstream effectors of this response remain to be discovered. Here, we studied the shared transcriptional responses to three different mitochondrial respiratory chain inhibitors in human primary skin fibroblasts using QuantSeq 3'-RNA-sequencing. We found that genes involved in the mevalonate pathway were concurrently downregulated, irrespective of the respiratory chain complex affected. Targeted metabolomics demonstrated that impaired mitochondrial respiration at any of the three affected complexes also had functional consequences on the mevalonate pathway, reducing levels of cholesterol precursor metabolites. A deeper study of complex I inhibition showed a reduced activity of endoplasmic reticulum-bound sterol-sensing enzymes through impaired processing of the transcription factor Sterol Regulatory Element-Binding Protein 2 and accelerated degradation of the endoplasmic reticulum cholesterol-sensors squalene epoxidase and HMG-CoA reductase. These adaptations of mevalonate pathway activity affected neither total intracellular cholesterol levels nor the cellular free (nonesterified) cholesterol pool. Finally, measurement of intracellular cholesterol using the fluorescent cholesterol binding dye filipin revealed that complex I inhibition elevated cholesterol on intracellular compartments. Taken together, our study shows that mitochondrial respiratory chain dysfunction elevates intracellular free cholesterol levels and therefore attenuates the expression of mevalonate pathway enzymes, which lowers endogenous cholesterol biosynthesis, disrupting the metabolic output of the mevalonate pathway. We conclude that intracellular disturbances in cholesterol homeostasis may alter systemic cholesterol management in diseases associated with declining mitochondrial function.

Obesity is associated with an increased risk of undergoing shoulder arthroplasty in Australia.

BACKGROUND: The aim of this study was to examine the incidence of overweight and obesity in patients undergoing primary total shoulder arthroplasty (TSA) for osteoarthritis (OA) in Australia compared to the incidence of obesity in the general population. MATERIALS AND METHODS: A 2017/18 cohort consisting of 2997 patients from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) who underwent TSA were compared with matched controls from the Australian Bureau of Statistics (ABS) National Health Survey from the same time period. The 2 groups were analyzed according to body mass index (BMI) category, sex, and age. RESULTS: According to the 2017/18 National Health Survey, 35.6% of Australian adults were overweight and 31.3% were obese. Of the primary TSA cases performed, 34.9% were overweight and 50.1% were obese. The relative risk of requiring TSA for OA increased with increasing BMI category. Class III obese females, aged 55-64, were 8.6 times more likely to receive a TSA compared to their normal weight counterparts. Males in the same age and BMI category were 2.5 times more likely. Class III obese patients underwent TSA 4 years (female) and 6 years (male) younger than their normal weight counterparts. CONCLUSION: Obesity significantly increases the risk of requiring TSA. The association appears to be particularly strong for younger females.

Perception of Perioperative Risk for Arthroplasty Patients: A Poll of Australian Orthopedic Surgeons.

BACKGROUND: There is growing interest in the perioperative management of patients who have indications for hip and knee arthroplasty in the setting of modifiable risk factors such as morbid obesity, poorly controlled diabetes, and smoking. A recent survey of the American Association of Hip and Knee Surgeons (AAHKS) found that 95% of respondents address modifiable risk factors prior to surgery. The aim of this study was to poll Australian arthroplasty surgeons regarding their approach to patients who have modifiable risk factors. METHODS: The survey tool used in the AAHKS study was adapted for use in the Australian context and distributed to the membership of the Arthroplasty Society of Australia via SurveyMonkey. There were 77 responses received, representing a response rate of 64%. RESULTS: The majority of respondents were experienced, high volume arthroplasty surgeons. Overall, 91% of respondents restricted access to arthroplasty for patients who have modifiable risk factors. There were 72% restricting access for excessive body mass index, 85% for poor diabetic control, and 46% for smoking. Most respondents made decisions based on personal experience or literature review rather than hospital or departmental pressures. While 49% of surgeons believed that current payment systems did not impair their ability to achieve good outcomes, 58% believed that certain arthroplasty patients would benefit from additional intervention, based on their socioeconomic status. CONCLUSION: Over 90% of surgeons who responded address modifiable risk factors prior to surgery. This finding aligns with the practice patterns of AAHKS members, despite differences in healthcare systems.

The International Initiative to Measure Perceived Risk in Arthroplasty: The Results From a Multinational Survey.

BACKGROUND: There is an inherent moral imperative to avoid complications from arthroplasty. Doing so at ideal cost is also associated with surgeon reputation, and, increasingly in health care delivery systems that measure and competitively score outcomes, reimbursement to the surgeons and their hospitals. As a result, patients who are perceived to be in higher risk comorbidity groups, such as the obese and diabetics, as well as those challenged by socioeconomic factors may face barriers to access elective arthroplasty. METHODS: In this initiative, surveys were sent to surgeons in 8 different countries, each adapted for their own unique payment, remuneration, and punitive models. The questions in the surveys pertained to surgeons' perception of risk regarding medical and socioeconomic factors in patients indicated for total hip or knee arthroplasty. This paper primarily reports on the results from Canada, Ireland, and the United Kingdom. RESULTS: The health care systems varied between a universal/state funded health care system (Canada) to those that were almost exclusively private (India). Some health care systems have "bundled" payment with retention of fees for postoperative complications requiring readmission/reoperation and including some with public publication of outcome data (United States and the United Kingdom), whereas others had none (Canada). There were some major discrepancies across different countries regarding the perceived risk of diabetic patients, who have variable Hemoglobin A1c cut-offs, if any used. However, overall the perception of risk for age, body mass index, age, sex, socioeconomic, and social situations remained surprisingly consistent throughout the health care systems. Any limitations set were primarily driven by surgeon decision making and not external demands. CONCLUSION: Surgeons will understandably try and optimize the health status of patients who have reversible risks as shown by best available evidence. The evidence is of variable quality, and, especially for irreversible social risk factors, limited due to concerns over cost and quality outcomes that can be influenced by experience-driven perceptions of risk. The results show that perceptions of risk do have such influence on access across many health care delivery environments. The authors recommend better risk-adjustment models for medical and socioeconomic risk factors with possible stratification/exclusions regarding reimbursement adjustments and reporting to help reverse disparities of access to arthroplasty.

Core arbuscular mycorrhizal fungi are predicted by their high abundance-occupancy relationship while host-specific taxa are rare and geographically structured.

Habitat restoration may depend on the recovery of plant microbial symbionts such as arbuscular mycorrhizal (AM) fungi, but this requires a better understanding of the rules that govern their community assembly. We examined the interactions of soil and host-associated AM fungal communities between remnant and restored patches of subtropical montane forests. While AM fungal richness did not differ between habitat types, community membership did and was influenced by geography, habitat and host. These differences were largely driven by rare host-specific AM fungi that displayed near-complete turnover between forest types, while core AM fungal taxa were highly abundant and ubiquitous. The bipartite networks in the remnant forest were more specialized and hosts more specific than in the restored forest. Host-associated AM fungal communities nested within soil communities in both habitats, but only significantly so in the restored forest. Our results provide evidence that restored and remnant forests harbour the same core fungal symbionts, while rare host-specific taxa differ, and that geography, host identity and taxonomic resolution strongly affect the observed distribution patterns of these fungi. We suggest that host-specific interactions with AM fungi, as well as spatial processes, should be explicitly considered to effectively re-establish target host and symbiont communities.

Distal Femoral Replacement for Periprosthetic Fractures After TKA: Australian Orthopaedic Association National Joint Replacement Registry Review.

BACKGROUND: Distal femoral replacement (DFR) is a potential treatment option following periprosthetic fracture (PPF) of a total knee arthroplasty (TKA). However, there is limited literature regarding implant survivorship and complication rates. The aim of this study was to examine patient demographics and trends in usage, implant survivorship and modes of failure, and patient mortality following DFR for PPF captured by a national joint replacement registry. METHODS: A retrospective registry review was performed using data from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). In total, 306 DFR were performed for PPF of a known primary TKA. Eighty-five percent of patients were female, and the mean age was 76.4 years. Kaplan-Meier estimates of implant and patient survivorship were performed. RESULTS: The number of DFR performed for PPF has doubled over the past five years. The cumulative percent second revision rate at six years was 12%. The most common indications for revision were infection (37%) and aseptic loosening (33%). Patient survivorship after DFR was 97% and 83% at five and ten years, respectively. CONCLUSION: A national registry review has identified the increasing prevalence of DFR for PPF after primary TKA and demonstrated implant survivorship of 88% at midterm follow-up. Surgeons may consider DFR as an acceptable and durable treatment option. LEVEL OF EVIDENCE: Level III - Case Series.

Amino acid δ13C and δ15N analyses reveal distinct species-specific patterns of trophic plasticity in a marine symbiosis.

Compound-specific isotope analyses (CSIA) and multivariate "isotope fingerprinting" track biosynthetic sources and reveal trophic interactions in food webs. However, CSIA have not been widely applied in the study of marine symbioses. Here, we exposed a reef coral (Montipora capitata) in symbiosis with Symbiodiniaceae algae to experimental treatments (autotrophy, mixotrophy, heterotrophy) to test for trophic shifts and amino acid (AA) sources using paired bulk (δ13C, δ15N) and AA-CSIA (δ13CAA, δ15NAA). Treatments did not influence carbon or nitrogen trophic proxies, thereby not supporting nutritional plasticity. Instead, hosts and symbionts consistently overlapped in essential- and nonessential-δ13CAA (11 of 13 amino acids) and trophic- and source-δ15NAA values (9 of 13 amino acids). Host and symbiont trophic-δ15NAA values positively correlated with a plankton end-member, indicative of trophic connections and dietary sources for trophic-AA nitrogen. However, mass balance of AA-trophic positions (TPGlx-Phe) revealed heterotrophic influences to be highly variable (1-41% heterotrophy). Linear discriminant analysis using M. capitata mean-normalized essential-δ13CAA with previously published values (Pocillopora meandrina) showed similar nutrition isotope fingerprints (Symbiodiniaceae vs. plankton) but revealed species-specific trophic strategies. Montipora capitata and Symbiodiniaceae shared identical AA-fingerprints, whereas P. meandrina was assigned to either symbiont or plankton nutrition. Thus, M. capitata was 100% reliant on symbionts for essential-δ13CAA and demonstrated autotrophic fidelity and contrasts with trophic plasticity reported in P. meandrina. While M. capitata AA may originate from host and/or symbiont biosynthesis, AA carbon is Symbiodiniaceae-derived. Together, AA-CSIA/isotope fingerprinting advances the study of coral trophic plasticity and are powerful tools in the study of marine symbioses.

Three decades post-reforestation has not led to the reassembly of arbuscular mycorrhizal fungal communities associated with remnant primary forests.

The negative effects of deforestation can potentially be ameliorated through ecological restoration. However, reforestation alone may not reassemble the same ecological communities or functions as primary forests. In part, this failure may be owed to forest ecosystems inherently involving complex interactions among guilds of organisms. Plants, which structure forest food webs, rely on intimate associations with symbiotic microbes such as root-inhabiting mycorrhizal fungi. Here, we leverage a large-scale reforestation project on Hawai'i Island underway for over three decades to assess whether arbuscular mycorrhizal (AM) fungal communities have concurrently been restored. The reference ecosystem for this restoration project is a remnant montane native Hawaiian forest that provides critical habitat for endangered birds. We sampled soils from 12 plots within remnant and restored forest patches and characterized AM fungal communities using high-throughput amplicon sequencing. While some AM fungal community metrics were comparable between remnant and restored forest (e.g. species richness), other key characteristics were not. Specifically, community membership and the identity of AM fungal keystone species differed between the two habitat types, as well as the primary environmental factors influencing community composition. Remnant forest AM fungal communities were strongly associated with soil chemical properties, especially pH, while restored forest communities were influenced by the spatial proximity to remnant forests. We posit that combined, these differences in soil AM fungal communities could be negatively affecting the recruitment of native plant hosts and that future restoration efforts should consider plant-microbe interactions as an important facet of forest health.

High light alongside elevated PCO2 alleviates thermal depression of photosynthesis in a hard coral (Pocillopora acuta).

The absorbtion of human-emitted CO2 by the oceans (elevated PCO2 ) is projected to alter the physiological performance of coral reef organisms by perturbing seawater chemistry (i.e. ocean acidification). Simultaneously, greenhouse gas emissions are driving ocean warming and changes in irradiance (through turbidity and cloud cover), which have the potential to influence the effects of ocean acidification on coral reefs. Here, we explored whether physiological impacts of elevated PCO2  on a coral-algal symbiosis (Pocillopora acuta-Symbiodiniaceae) are mediated by light and/or temperature levels. In a 39 day experiment, elevated PCO2  (962 versus 431 µatm PCO2 ) had an interactive effect with midday light availability (400 versus 800 µmol photons m-2 s-1) and temperature (25 versus 29°C) on areal gross and net photosynthesis, for which a decline at 29°C was ameliorated under simultaneous high-PCO2  and high-light conditions. Light-enhanced dark respiration increased under elevated PCO2  and/or elevated temperature. Symbiont to host cell ratio and chlorophyll a per symbiont increased at elevated temperature, whilst symbiont areal density decreased. The ability of moderately strong light in the presence of elevated PCO2  to alleviate the temperature-induced decrease in photosynthesis suggests that higher substrate availability facilitates a greater ability for photochemical quenching, partially offsetting the impacts of high temperature on the photosynthetic apparatus. Future environmental changes that result in moderate increases in light levels could therefore assist the P. acuta holobiont to cope with the 'one-two punch' of rising temperatures in the presence of an acidifying ocean.

Trophic Ecology of the Tropical Pacific Sponge Mycale grandis Inferred from Amino Acid Compound-Specific Isotopic Analyses.

Many sponges host abundant and active microbial communities that may play a role in the uptake of dissolved organic matter (DOM) by the sponge holobiont, although the mechanism of DOM uptake and metabolism is uncertain. Bulk and compound-specific isotopic analysis of whole sponge, isolated sponge cells, and isolated symbiotic microbial cells of the shallow water tropical Pacific sponge Mycale grandis were used to elucidate the trophic relationships between the host sponge and its associated microbial community. δ15N and δ13C values of amino acids in M. grandis isolated sponge cells are not different from those of its bacterial symbionts. Consequently, there is no difference in trophic position of the sponge and its symbiotic microbes indicating that M. grandis sponge cell isolates do not display amino acid isotopic characteristics typical of metazoan feeding. Furthermore, both the isolated microbial and sponge cell fractions were characterized by a similarly high ΣV value-a measure of bacterial-re-synthesis of organic matter calculated from the sum of variance among individual δ15N values of trophic amino acids. These high ΣV values observed in the sponge suggest that M. grandis is not reliant on translocated photosynthate from photosymbionts or feeding on water column picoplankton, but obtains nutrition through the uptake of amino acids of bacterial origin. Our results suggest that direct assimilation of bacterially synthesized amino acids from its symbionts, either in a manner similar to translocation observed in the coral holobiont or through phagotrophic feeding, is an important if not primary pathway of amino acid acquisition for M. grandis.

Novel Positron Emission Tomography Tracers for Imaging Vascular Inflammation.

PURPOSE OF REVIEW: To provide a focused update on recent advances in positron emission tomography (PET) imaging in vascular inflammatory diseases and consider future directions in the field. RECENT FINDINGS: While PET imaging with 18F-fluorodeoxyglucose (FDG) can provide a useful marker of disease activity in several vascular inflammatory diseases, including atherosclerosis and large-vessel vasculitis, this tracer lacks inflammatory cell specificity and is not a practical solution for imaging the coronary vasculature because of avid background myocardial signal. To overcome these limitations, research is ongoing to identify novel PET tracers that can more accurately track individual components of vascular immune responses. Use of these novel PET tracers could lead to a better understanding of underlying disease mechanisms and help inform the identification and stratification of patients for newly emerging immune-modulatory therapies. Future research is needed to realise the true clinical translational value of PET imaging in vascular inflammatory diseases.

Spatial variation in the biochemical and isotopic composition of corals during bleaching and recovery.

Ocean warming and the increased prevalence of coral bleaching events threaten coral reefs. However, the biology of corals during and following bleaching events under field conditions is poorly understood. We examined bleaching and postbleaching recovery in Montipora capitata and Porites compressa corals that either bleached or did not bleach during a 2014 bleaching event at three reef locations in Kane'ohe Bay, O'ahu, Hawai'i. We measured changes in chlorophylls, tissue biomass, and nutritional plasticity using stable isotopes (δ 13C, δ 15N). Coral traits showed significant variation among periods, sites, bleaching conditions, and their interactions. Bleached colonies of both species had lower chlorophyll and total biomass, and while M. capitata chlorophyll and biomass recovered 3 months later, P. compressa chlorophyll recovery was location dependent and total biomass of previously bleached colonies remained low. Biomass energy reserves were not affected by bleaching, instead M. capitata proteins and P. compressa biomass energy and lipids declined over time and P. compressa lipids were site specific during bleaching recovery. Stable isotope analyses did not indicate increased heterotrophic nutrition in bleached colonies of either species, during or after thermal stress. Instead, mass balance calculations revealed that variations in δ 13C values reflect biomass compositional change (i.e., protein : lipid : carbohydrate ratios). Observed δ 15N values reflected spatiotemporal variability in nitrogen sources in both species and bleaching effects on symbiont nitrogen demand in P. compressa. These results highlight the dynamic responses of corals to natural bleaching and recovery and identify the need to consider the influence of biomass composition in the interpretation of isotopic values in corals.

High-fat diet and FGF21 cooperatively promote aerobic thermogenesis in mtDNA mutator mice.

Mitochondria are highly adaptable organelles that can facilitate communication between tissues to meet the energetic demands of the organism. However, the mechanisms by which mitochondria can nonautonomously relay stress signals remain poorly understood. Here we report that mitochondrial mutations in the young, preprogeroid polymerase gamma mutator (POLG) mouse produce a metabolic state of starvation. As a result, these mice exhibit signs of metabolic imbalance including thermogenic defects in brown adipose tissue (BAT). An unexpected benefit of this adaptive response is the complete resistance to diet-induced obesity when POLG mice are placed on a high-fat diet (HFD). Paradoxically, HFD further increases oxygen consumption in part by inducing thermogenesis and mitochondrial biogenesis in BAT along with enhanced expression of fibroblast growth factor 21 (FGF21). Collectively, these findings identify a mechanistic link between FGF21, a long-known marker of mitochondrial disease, and systemic metabolic adaptation in response to mitochondrial stress.

Treatments and Services Provided to Children Diagnosed with Bipolar Disorder.

To better understand the types and quantity of mental health services and medication usage for youth diagnosed with bipolar disorder (BD) within an integrated healthcare system, medical records were reviewed from 2000 to 2011. Eighty-five youth diagnosed with BD were identified and healthcare services (medication and psychotherapy follow-up appointments, emergency room (ER) visits, admissions, phone contacts) and visit-related details (medication usage) were abstracted for 2 years after initial BD diagnosis. Despite complex medication regimens (91.7 and 81.2 % received mood stabilizers and antipsychotic agents, respectively), medication appointments were infrequent, averaging 1 visit every 2 months. Only 36 (42 %) of 85 youth were noted to receive psychotherapy services following BD diagnosis, also averaging 1 visit every 2 months. Most (58.8 %) patients needed one or more hospitalizations during the follow-up period; nearly half (48.2 %) had psychiatric ER visits. The relative lack of psychotherapy and infrequent follow-up visits suggests need for improvement to optimize healthcare delivery.