[The subanalysis of Rheuma-VOR demonstrates a considerable need for rheumatological care]. / Die Subanalyse von Rheuma-VOR zeigt den erheblichen Bedarf der rheumatologischen Versorgung auf.

BACKGROUND: Early diagnosis and treatment of inflammatory rheumatic diseases can prevent consequential damage such as permanently limited mobility and joint or organ damage. Simultaneously, there is an increasing deficit in medical care owing to the lack of rheumatological capacity. Rural regions are particularly affected. OBJECTIVES: The available unconfirmed diagnoses of the study Rheuma-VOR were analysed regarding another definitive inflammatory rheumatic disease. MATERIALS AND METHODS: The returned questionnaires of the rheumatologists participating in Rheuma-VOR were screened for definitive inflammatory rheumatic diseases other than the required diagnosis of rheumatoid arthritis, psoriatic arthritis or spondyloarthritis. RESULTS: Of 910 unconfirmed diagnoses, in 245 patients another definitive diagnosis could be confirmed. A total of 29.8% of the diagnoses corresponded to degenerative joint changes or chronic pain syndrome, whereas 26.1% involved different forms of inflammatory arthritis. The majority of diagnoses (40.5%) were collagenosis or vasculitis, DISCUSSION: The available data show that a rheumatological presentation was indicated for the majority of patients. Owing to the increasing deficits in medical care a prior selection of the patients is crucial to make optimal use of restricted rheumatological capacities.

The application of epiphenotyping approaches to DNA methylation array studies of the human placenta.

BACKGROUND: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. RESULTS: Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry-informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, as well as over very long placental processing times. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. CONCLUSIONS: This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. We further demonstrate the specific utility of epiphenotyping tools developed for use with placental DNAme data, and show that these variables (i) provide an independent check of clinically obtained data and (ii) provide a robust approach to compare variables across different datasets. Finally, we present a general framework for the processing and analysis of placental DNAme data, integrating the epiphenotype variables discussed here.

[Nonpharmacological treatment measures, rehabilitation services and membership in patient support groups in axial spondylarthritis (The ATTENTUS axSpA study)]. / Nichtmedikamentöse Therapiemaßnahmen, Rehabilitationsleistungen und Mitgliedschaft in Selbsthilfeorganisationen bei axialer Spondyloarthritis (Die ATTENTUS axSpA-Studie).

BACKGROUND: The treatment of axial spondylarthritis (axSpA) includes pharmacological treatment measures (PTM) and nonpharmacological treatment measures (NPTM) as well as supporting resources, such as rehabilitation services (RS) and membership in patient support groups (PSG). Nevertheless, there are significant participation restrictions in patients with axSpA in Germany. OBJECTIVE: Investigation of functional deficits, participation restrictions and utilization of PTM, NPTM, RS and PSG membership in patients with axSpA. MATERIAL AND METHODS: Multicentric, observational study of 770 axSpA patients in Germany (ATTENTUS-axSpA). RESULTS: Substantial functional deficits and participation restrictions were observed in axSpA patients. Of the patients 39% did not receive treatment with biological disease-modifying antirheumatic drugs (bDMARD). In the NPTM 54% received physiotherapy less than once per week and 29% once per week. Physical activities were regularly performed by 86% of patients, mainly in the form of home exercises. Training in a gym (14%) or sports club (7%) was carried out much less frequently. Of the patients 54% received RS, one third had the last rehabilitation more than 5 years ago and 13% of the patients were members in a PSG. A significantly higher utilization of NPTM and rehabilitation was found in this group. CONCLUSION: Treatment options and resources were often utilized to a small extent and/or in low intensity by axSpA patients, which could be a possible explanation for persisting restrictions of participation. Membership in a PSG was associated with an increased utilization of NPTM and RS.

Mission statement from rheumatologists in the German Society of Rheumatology (DGRh e. V.) : We live rheumatology.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.

[Mission statement from rheumatologists in the German Society of Rheumatology (DGRh e. V.) : We live rheumatology. German version]. / Leitbild der Rheumatologinnen und Rheumatologen in der Deutschen Gesellschaft für Rheumatologie e. V. (DGRh e. V.) : Wir sind die Rheumatologie.

Systemic disease demands systemic thinkers. In this mission statement we define rheumatology, describe the role of the German Society of Rheumatology and the rheumatologist's spirit to their discipline. Rheumatologists are dedicated to improving the quality of life of their acute, chronic, and rehabilitative patients on the basis of up to date evidence and strong physician-patient relations. We think, act and interact systemically, scientifically, consistently, transparently, reliably, inclusively, innovatively and enthusiastically.

Construction of lactic acid overproducing Clostridium thermocellum through enhancement of lactate dehydrogenase expression.

Rapid expansion of global market of lactic acid (LA) has prompted research towards cheaper and more eco-friendly strategies for its production. Nowadays, LA is produced mainly through fermentation of simple sugars or starchy biomass (e.g. corn) and its price is relatively high. Lignocellulose could be an advantageous alternative feedstock for LA production owing to its high abundance and low cost. However, the most effective natural producers of LA cannot directly ferment lignocellulose. So far, metabolic engineering aimed at developing microorganisms combining efficient LA production and cellulose hydrolysis has been generally based on introducing designer cellulase systems in natural LA producers. In the present study, the approach consisted in improving LA production in the natural cellulolytic bacterium Clostridium thermocellum DSM1313. The expression of the native lactate dehydrogenase was enhanced by functional replacement of its original promoter with stronger ones resulting in a 10-fold increase in specific activity, which resulted in a 2-fold increase of LA yield. It is known that eliminating allosteric regulation can also increase lactic acid production in C. thermocellum, however we were unable to insert strong promoters upstream of the de-regulated ldh gene. A strategy combining these regulations and inactivation of parasitic pathways appears essential for developing a homolactic C. thermocellum.

A "Global Safety Net" to reverse biodiversity loss and stabilize Earth's climate.

Global strategies to halt the dual crises of biodiversity loss and climate change are often formulated separately, even though they are interdependent and risk failure if pursued in isolation. The Global Safety Net maps how expanded nature conservation addresses both overarching threats. We identify 50% of the terrestrial realm that, if conserved, would reverse further biodiversity loss, prevent CO2 emissions from land conversion, and enhance natural carbon removal. This framework shows that, beyond the 15.1% land area currently protected, 35.3% of land area is needed to conserve additional sites of particular importance for biodiversity and stabilize the climate. Fifty ecoregions and 20 countries contribute disproportionately to proposed targets. Indigenous lands overlap extensively with the Global Safety Net. Conserving the Global Safety Net could support public health by reducing the potential for zoonotic diseases like COVID-19 from emerging in the future.

Clostridium thermocellum: A microbial platform for high-value chemical production from lignocellulose.

Second generation biorefining, namely fermentation processes based on lignocellulosic feedstocks, has attracted tremendous interest (owing to the large availability and low cost of this biomass) as a strategy to produce biofuels and commodity chemicals that is an alternative to oil refining. However, the innate recalcitrance of lignocellulose has slowed progress toward economically viable processes. Consolidated bioprocessing (CBP), i.e., single-step fermentation of lignocellulose may dramatically reduce the current costs of 2nd generation biorefining. Metabolic engineering has been used as a tool to develop improved microbial strains supporting CBP. Clostridium thermocellum is among the most efficient cellulose degraders isolated so far and one of the most promising host organisms for application of CBP. The development of efficient and reliable genetic tools has allowed significant progress in metabolic engineering of this strain aimed at expanding the panel of growth substrates and improving the production of a number of commodity chemicals of industrial interest such as ethanol, butanol, isobutanol, isobutyl acetate and lactic acid. The present review aims to summarize recent developments in metabolic engineering of this organism which currently represents a reference model for the development of biocatalysts for 2nd generation biorefining.

The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

[Early recognition and screening consultation: a necessary way to improve early detection and treatment in rheumatology? : Overview of the early recognition and screening consultation models for rheumatic and musculoskeletal diseases in Germany]. / Früh- und Screeningsprechstunden: Ein notwendiger Weg zur besseren Frühversorgung in der internistischen Rheumatologie? : Rheumatologische Früh- und Screeningsprechstundenmodelle in Deutschland.

In order to reduce the prognostically relevant time interval between the initial manifestation of a rheumatic and musculoskeletal disease and diagnosis as well as the consecutive initiation of an appropriate treatment, several rheumatological centers in Germany have improved the access to initial rheumatologic evaluation by establishing early recognition/screening clinics at their respective sites. Corresponding models located at Altoetting·Burghausen, Bad Pyrmont, Berlin Buch, Duesseldorf, Heidelberg, Herne, Mannheim as well as supraregional/multicenter initiatives Rheuma Rapid, RhePort and Rheuma-VOR are presented in this overview along with the respective characteristics, potential advantages and disadvantages, but also first evaluation results of several models. The aim of this publication is to promote early detection of rheumatic and musculoskeletal diseases as one of the most important challenges in current rheumatology by encouraging further rheumatologic centers and practices to launch their own early recognition/screening consultation model on the basis of aspects presented herein.

A Global Deal For Nature: Guiding principles, milestones, and targets.

The Global Deal for Nature (GDN) is a time-bound, science-driven plan to save the diversity and abundance of life on Earth. Pairing the GDN and the Paris Climate Agreement would avoid catastrophic climate change, conserve species, and secure essential ecosystem services. New findings give urgency to this union: Less than half of the terrestrial realm is intact, yet conserving all native ecosystems-coupled with energy transition measures-will be required to remain below a 1.5°C rise in average global temperature. The GDN targets 30% of Earth to be formally protected and an additional 20% designated as climate stabilization areas, by 2030, to stay below 1.5°C. We highlight the 67% of terrestrial ecoregions that can meet 30% protection, thereby reducing extinction threats and carbon emissions from natural reservoirs. Freshwater and marine targets included here extend the GDN to all realms and provide a pathway to ensuring a more livable biosphere.

Recent Canadian efforts to develop population-level pregnancy intervention studies to mitigate effects of natural disasters and other tragedies.

The preconception, pregnancy and immediate postpartum and newborn periods are times for mothers and their offspring when they are especially vulnerable to major stressors - those that are sudden and unexpected and those that are chronic. Their adverse effects can transcend generations. Stressors can include natural disasters or political stressors such as conflict and/or migration. Considerable evidence has accumulated demonstrating the adverse effects of natural disasters on pregnancy outcomes and developmental trajectories. However, beyond tracking outcomes, the time has arrived for gathering more information related to identifying mechanisms, predicting risk and developing stress-reducing and resilience-building interventions to improve outcomes. Further, we need to learn how to encapsulate both the quantitative and qualitative information available and share it with communities and authorities to mitigate the adverse developmental effects of future disasters, conflicts and migrations. This article briefly reviews prenatal maternal stress and identifies three contemporary situations (wildfire in Fort McMurray, Alberta, Canada; hurricane Harvey in Houston, USA and transgenerational and migrant stress in Pforzheim, Germany) where current studies are being established by Canadian investigators to test an intervention. The experiences from these efforts are related along with attempts to involve communities in the studies and share the new knowledge to plan for future disasters or tragedies.

Short communication: Influence of an aqueous myrrh suspension on yogurt culture bacteria over yogurt shelf life.

Myrrh is an essential oil and natural flavoring approved by the US Food and Drug Administration, and it has antibacterial and antifungal activity against pathogens. Our objective was to determine the effect of an aqueous myrrh suspension on Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus counts in peptone solution and yogurt, as well as pH and titratable acidity of yogurt during 5 wk of storage at 1 to 4°C. The myrrh suspension (10% wt/vol) was prepared and incorporated into a pure culture dilution in peptone and into yogurt mix at a 1% (vol/vol) level. A control with no myrrh was also prepared, and 3 replications were conducted. Streptococcus thermophilus were enumerated using Streptococcus thermophilus agar with aerobic incubation at 37°C for 24 h, and Lactobacillus delbrueckii ssp. bulgaricus were enumerated using de Man, Rogosa, and Sharpe agar adjusted to pH 5.2, with anaerobic incubation at 43°C for 72 h. During the 8-h period after inoculation, S. thermophilus and L. delbrueckii ssp. bulgaricus counts in peptone solution at 37°C and 43°C, respectively, were not significantly different in the presence or absence of the aqueous myrrh suspension. Counts of S. thermophilus in yogurt containing myrrh (mean ± SD; 4.96 ± 0.58 log cfu/mL) were not significantly different from those in the control yogurt (4.87 ± 0.39 log cfu/mL). The log counts for L. delbrueckii ssp. bulgaricus in yogurt containing myrrh (5.04 ± 1.44 log cfu/mL) and those of the control (5.52 ± 1.81 log cfu/mL) did not differ, and the counts remained within 1 log of each other throughout 5 wk of storage. The pH of the yogurts containing the aqueous myrrh suspension was not significantly different from that of the control yogurts, and their pH values were within 0.1 pH unit of each other in any given week. Titratable acidity values remained steady around 1.1 to 1.2% lactic acid for both yogurt types throughout the storage period, with no significant differences between them. Yogurt culture bacteria can survive in the presence of a myrrh suspension in yogurt with no significant change in pH or titratable acidity. Therefore, it may be beneficial to add an aqueous myrrh suspension to yogurt.

Childhood stress, grown-up brain networks: corticolimbic correlates of threat-related early life stress and adult stress response.

BACKGROUND: Exposure to threat-related early life stress (ELS) has been related to vulnerability for stress-related disorders in adulthood, putatively via disrupted corticolimbic circuits involved in stress response and regulation. However, previous research on ELS has not examined both the intrinsic strength and flexibility of corticolimbic circuits, which may be particularly important for adaptive stress responding, or associations between these dimensions of corticolimbic dysfunction and acute stress response in adulthood. METHODS: Seventy unmedicated women varying in history of threat-related ELS completed a functional magnetic resonance imaging scan to evaluate voxelwise static (overall) and dynamic (variability over a series of sliding windows) resting-state functional connectivity (RSFC) of bilateral amygdala. In a separate session and subset of participants (n = 42), measures of salivary cortisol and affect were collected during a social-evaluative stress challenge. RESULTS: Higher severity of threat-related ELS was related to more strongly negative static RSFC between amygdala and left dorsolateral prefrontal cortex (DLPFC), and elevated dynamic RSFC between amygdala and rostral anterior cingulate cortex (rACC). Static amygdala-DLPFC antagonism mediated the relationship between higher severity of threat-related ELS and blunted cortisol response to stress, but increased dynamic amygdala-rACC connectivity weakened this mediated effect and was related to more positive post-stress mood. CONCLUSIONS: Threat-related ELS was associated with RSFC within lateral corticolimbic circuits, which in turn was related to blunted physiological response to acute stress. Notably, increased flexibility between the amygdala and rACC compensated for this static disruption, suggesting that more dynamic medial corticolimbic circuits might be key to restoring healthy stress response.

Atomic-scale age resolution of planetary events.

Resolving the timing of crustal processes and meteorite impact events is central to understanding the formation, evolution and habitability of planetary bodies. However, identifying multi-stage events from complex planetary materials is highly challenging at the length scales of current isotopic techniques. Here we show that accurate U-Pb isotopic analysis of nanoscale domains of baddeleyite can be achieved by atom probe tomography. Within individual crystals of highly shocked baddeleyite from the Sudbury impact structure, three discrete nanostructural domains have been isolated yielding average 206Pb/238U ages of 2,436±94 Ma (protolith crystallization) from homogenous-Fe domains, 1,852±45 Ma (impact) from clustered-Fe domains and 1,412±56 Ma (tectonic metamorphism) from planar and subgrain boundary structures. Baddeleyite is a common phase in terrestrial, Martian, Lunar and asteroidal materials, meaning this atomic-scale approach holds great potential in establishing a more accurate chronology of the formation and evolution of planetary crusts.

Glucose challenge test screening for prediabetes and early diabetes.

AIMS: To test the hypothesis that a 50-g oral glucose challenge test with 1-h glucose measurement would have superior performance compared with other opportunistic screening methods. METHODS: In this prospective study in a Veterans Health Administration primary care clinic, the following test performances, measured by area under receiver-operating characteristic curves, were compared: 50-g oral glucose challenge test; random glucose; and HbA1c level, using a 75-g oral glucose tolerance test as the 'gold standard'. RESULTS: The study population was comprised of 1535 people (mean age 56 years, BMI 30.3 kg/m2 , 94% men, 74% black). By oral glucose tolerance test criteria, diabetes was present in 10% and high-risk prediabetes was present in 22% of participants. The plasma glucose challenge test provided area under receiver-operating characteristic curves of 0.85 (95% CI 0.78-0.91) to detect diabetes and 0.76 (95% CI 0.72-0.80) to detect high-risk dysglycaemia (diabetes or high-risk prediabetes), while area under receiver-operating characteristic curves for the capillary glucose challenge test were 0.82 (95% CI 0.75-0.89) and 0.73 (95% CI 0.69-0.77) for diabetes and high-risk dysglycaemia, respectively. Random glucose performed less well [plasma: 0.76 (95% CI 0.69-0.82) and 0.66 (95% CI 0.62-0.71), respectively; capillary: 0.72 (95% CI 0.65-0.80) and 0.64 (95% CI 0.59-0.68), respectively], and HbA1c performed even less well [0.67 (95% CI 0.57-0.76) and 0.63 (95% CI 0.58-0.68), respectively]. The cost of identifying one case of high-risk dysglycaemia with a plasma glucose challenge test would be $42 from a Veterans Health Administration perspective, and $55 from a US Medicare perspective. CONCLUSIONS: Glucose challenge test screening, followed, if abnormal, by an oral glucose tolerance test, would be convenient and more accurate than other opportunistic tests. Use of glucose challenge test screening could improve management by permitting earlier therapy.

Towards a standard for the dynamic measurement of pressure based on laser absorption spectroscopy.

We describe an approach for creating a standard for the dynamic measurement of pressure based on the measurement of fundamental quantum properties of molecular systems. From the linewidth and intensities of ro-vibrational transitions we plan on making an accurate determination of pressure and temperature. The goal is to achieve an absolute uncertainty for time-varying pressure of 5 % with a measurement rate of 100 kHz, which will in the future serve as a method for the traceable calibration of pressure sensors used in transient processes. To illustrate this concept we have used wavelength modulation spectroscopy (WMS), due to inherent advantages over direct absorption spectroscopy, to perform rapid measurements of carbon dioxide in order to determine the pressure. The system records the full lineshape profile of a single ro-vibrational transition of CO2 at a repetition rate of 4 kHz and with a systematic measurement uncertainty of 12 % for the linewidth measurement. A series of pressures were measured at a rate of 400 Hz (10 averages) and from these measurements the linewidth was determined with a relative uncertainty of about 0.5 % on average. The pressures measured using WMS have an average difference of 0.6 % from the absolute pressure measured with a capacitance diaphragm sensor.

Partial recovery of senescence and differentiation disturbances in CD8+ T cell effector-memory cells in HIV-1 infection after initiation of anti-retroviral treatment.

Immune senescence as well as disturbed CD8+ T cell differentiation are a hallmark of chronic HIV infection. Here, we investigated to what extent immune senescence is reversible after initiation of anti-retroviral treatment (ART). Peripheral blood mononuclear cells (PBMCs) from a cohort of HIV patients with different disease courses, including untreated viral controllers (n = 10), viral non-controllers (n = 16) and patients on ART (n = 20), were analysed and compared to uninfected controls (n = 25) by flow cytometry on bulk and HIV-specific major histocompatibility complex (MHC) class I tetramer+ CD8+ T cells for expression of the memory markers CCR7 and CD45RO, as well as the senescence marker CD57 and the differentiation and survival marker CD127. Furthermore, a subset of patients was analysed longitudinally before and after initiation of ART. Frequencies of CD57+ CD8+ T cells decreased after initiation of ART in central memory (Tcm) but not in effector memory T cell populations (TemRO and TemRA). The frequency of CD127+ CD8+ cells increased in Tcm and TemRO. We observed a reduction of CD127- T cells in Tcm, TemRO and partially in TemRA subsets after initiation of ART. Importantly, HIV-specific CD8+ TemRO cells predominantly displayed a CD127- CD57+ phenotype in untreated HIV-patients, whereas the CD127+ CD57- phenotype was under-represented in these patients. The frequency of the CD127+ CD57- CD8+ T cell subpopulation correlated strongly with absolute CD4+ counts in HIV-infected patients before and after initiation of ART. These findings can be interpreted as a phenotypical correlate of CD8+ memory T cell differentiation and the premature 'ageing' of the immune system, which was even observed in successfully virally suppressed HIV patients.

Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

UNLABELLED: Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. INTRODUCTION: Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. METHODS: Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. RESULTS: C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. CONCLUSIONS: Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies utilizing mice as preclinical models for osteoporosis.

Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.