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Abstract According to GNSS/INSAR measurements, the Konya Basin in Central Anatolia is undergoing rapid subsidence within an uplifting orogenic plateau. Further, geophysical studies reveal thickened crust under the basin and a fast seismic wave speed anomaly in the underlying mantle, in addition to a localised depression in calculated residual topography (down to 280 m) over the Konya Basin, based on gravity-topography considerations. Using scaled laboratory (analogue) experiments we show that the active formation of the Konya Basin may be accounted for by the descent of a mantle lithospheric drip causing local circular-shaped surface subsidence. We interpret that the Konya Basin is developing through a secondary drip pulse that is contemporaneous with broad plateau uplift caused by a larger-scale lithospheric drip since the Miocene. The research reveals that basin evolution and plateau uplift may be linked in a multistage process of lithospheric removal during episodic development of orogenic systems.

Abstract The spatiotemporal interaction of large‐ and regional‐scale upper mantle forces can prevail in collisional settings. To better understand the role of these forces on post‐subduction tectonics, we focus on mantle dynamics in the East Anatolian Plateau, a well‐documented segment of the Arabian‐Eurasian continental collision zone. Specifically, we analyze multiple forces in the upper mantle, which have not been considered in previous studies in this region. To this end, we use a state‐of‐the‐art 3D instantaneous geodynamic model to quantify the dynamics of thermally defined upper mantle structures derived from seismic tomography data. Results reveal a prominent SW‐NE‐oriented mantle flow from the Arabian foreland to the Greater Caucasus–a plumelet–through a lithospheric channel under the East Anatolian Plateau. This plumelet induces localized dynamic topography (∼500 m) around the extensional Lake Van province, favoring NE‐directed compression and westward escape of the Anatolian plate. We suggest that the Lake Van region is an active magma‐rich intraplate rift in the Africa‐Arabia‐Anatolian plume‐rift system. The rift zone was probably initiated by Neotethyan subduction‐related forces and has been reactivated and/or sustained by the plumelet‐induced convective support. Our findings are consistent with numerous observations, including the recent low‐ultralow seismic velocities with a SW‐NE splitting anisotropy pattern, geochemical and petrological studies, and local kinematics showing upper mantle‐induced extensional tectonics in the collisional region.

Abstract Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPARα in C. elegans. Untargeted metabolomics of a β-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a β-cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a β-methyl fatty acid, bemeth#1, which mimics the activity of microbiota-dependent becyp#1 but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated β-oxidation pathway, while the endogenous bemeth#1 is metabolized via α-oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPARα to regulate fat desaturation.

Abstract Inherited retinal degenerations (IRDs) are a heterogeneous group of predominantly monogenic disorders with over 300 causative genes identified. Short-read exome sequencing is commonly used to genotypically diagnose patients with clinical features of IRDs, however, in up to 30% of patients with autosomal recessive IRDs, one or no disease-causing variants are identified. Furthermore, chromosomal maps cannot be reconstructed for allelic variant discovery with short-reads. Long-read genome sequencing can provide complete coverage of disease loci and a targeted approach can focus sequencing bandwidth to a genomic region of interest to provide increased depth and haplotype reconstruction to uncover cases of missing heritability. We demonstrate that targeted adaptive long-read sequencing on the Oxford Nanopore Technologies (ONT) platform of the USH2A gene from three probands in a family with the most common cause of the syndromic IRD, Usher Syndrome, resulted in greater than 12-fold target gene sequencing enrichment on average. This focused depth of sequencing allowed for haplotype reconstruction and phased variant identification. We further show that variants obtained from the haplotype-aware genotyping pipeline can be heuristically ranked to focus on potential pathogenic candidates without a priori knowledge of the disease-causing variants. Moreover, consideration of the variants unique to targeted long-read sequencing that are not covered by short-read technology demonstrated higher precision and F1 scores for variant discovery by long-read sequencing. This work establishes that targeted adaptive long-read sequencing can generate targeted, chromosome-phased data sets for identification of coding and non-coding disease-causing alleles in IRDs and can be applicable to other Mendelian diseases.

Abstract The paradigm of plate tectonics holds that ocean plates are rigid during drift and only experience tectonic deformation at subduction zones, but new findings from the Pacific challenge this idea. Geological and geophysical evidence from the Ontong Java, Shatsky, Hess, and Manihiki oceanic plateaux indicates that extensional deformation during plate drift is a widespread phenomenon across the Pacific plate. These anomalously thick oceanic plateaux are weaker regions of the ocean lithosphere and more prone to tectonic deformation. Numerical geodynamic models demonstrate that a slab pull force from distant subduction plate boundaries can be effectively transmitted to oceanic plateaux through strong ocean lithosphere and cause substantial extension during plate drift. Our findings reveal that a wide expanse of the Pacific has experienced syn‐drift plate tectonics linked to pull from the western Pacific subduction factory.

The ocular surface microbiome, unlike that of the skin or gut, has not been well characterized. Culture experiments historically suggested a nearly sterile ocular surface, but initial application of molecular methods such as 16S ribosomal RNA and high-throughput sequencing demonstrated a surprisingly rich ocular surface microbiome. However, a major limitation in studying such a low-biomass niche is the potential for artifactual results when amplification-based techniques such as ribosomal polymerase chain reaction and shotgun sequencing are used. It will be essential to establish standards across the field for sample collection, positive and negative controls, and limitation of contamination in both the laboratory setting and computational analysis. New developments in ocular microbiome research, including the generation of reference reagents and fluoroscopic imaging techniques, provide improved means to validate sequencing results and to visualize complex interactions between host cells and bacteria. Through more thorough characterization of the ocular surface microbiome, the connections between a dysregulated surface and ophthalmic disease may be better understood. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Biological sex affects all aspects of animal physiology. Using the model C. elegans, the authors show that metabolomes are highly sex-specific and include a vast space of yet unidentified metabolites that may control development and lifespan.

Abstract In the first millennia of the Holocene, human communities in the Fertile Crescent experienced drastic cultural and technological transformations that modified social and human-environments interactions, ultimately leading to the rise of complex societies. The potential influence of climate on this “Neolithic Revolution” has long been debated. Here we present a speleothem record from the Kurdistan Region of Iraq, covering from Early Neolithic to Early Chalcolithic periods (~ 11 to 7.3 ka, 9000–5300 BCE). The record reveals the influence of the Siberian High on regional precipitation, and shows large hydroclimatic variability at the multicentennial scale. In particular, it highlights wetter conditions between 9.7 and 9.0 ka, followed by an abrupt reduction of precipitation between 9.0 and 8.5 ka, and a wetter interval between 8.5 and 8.0 ka. A comparison with regional and local archaeological data demonstrates an influence of recorded hydroclimatic changes on settlement patterns (size, distribution, permanent vs. seasonal occupation) and on the exploitation of water resources by Neolithic to Chalcolithic populations. Our record does not show prominent hydroclimatic changes at 9.3 and 8.2 ka, thus not supporting direct influence of such rapid and widespread events on the process of Neolithization and its cultural dispersal.

With climate change predicted to alter water column stability and mixing across the world’s oceans, a mesocosm experiment was designed to ascertain how a natural phytoplankton community would respond to these changes. As a departure from other mesocosm experiments, we used heating and cooling to produce four different climate-inspired mixing scenarios ranging from well-mixed water columns representative of typical open turbulence (ϵ = 3 x 10-8 m2/s3) through to a quiescent water column with stable stratification (ϵ = 5 x 10-10 m2/s3). This method of turbulence generation is an improvement on previous techniques (e.g., grid, shaker, and aeration) which tend to produce excessive dissipation rates inconsistent with oceanic turbulence observations. Profiles of classical physical parameters used to describe turbulence and mixing (turbulent dissipation rate, buoyancy frequency, turbulent eddy diffusivity, Ozmidov scale) were representative of the profiles found in natural waters under similar mixing conditions. Chlorophyll-a profiles and cell enumeration showed a clear biological response to the different turbulence scenarios. However, the responses of specific phytoplankton groups (diatoms and dinoflagellates) did not conform to the usual expectations: diatoms are generally expected to thrive under convective, turbulent regimes, while dinoflagellates are expected to thrive in converse conditions, i.e., in stable, stratified conditions. Our results suggest that responses to mixing regimes are taxon-specific, with no overwhelming physical effect of the turbulence regime. Rather, each taxon seemed to very quickly reach a given vertical distribution that it managed to hold, whether actively or passively, with a high degree of success. Future studies on the effects of climate change on phytoplankton vertical distribution should thus focus on the factors and mechanisms that combine to determine the specific distribution of species within taxa. Our convection-based mesocosm approach, because it uses a primary physical force that generates turbulence in open waters, should prove a valuable tool in this endeavor.

The presence of pollen and charcoal in radiometrically dated speleothems suggest the Naracoorte Cave Complex, South Australia, has been open to the atmosphere for the past 600,000 years, placing an upper limit on the accumulation of fossils inside the caves.

Several central Andean basins may have formed from the coupling of crustal deformation to dripping of the upper mantle lithosphere, according to three- dimensional scaled analogue experiments

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production. In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines. There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.

Abstract Purpose The purpose of this study was to identify modifiable medical comorbidities, laboratory markers and flaws in perioperative management that increase the risk of acute dislocation in total hip arthroplasty (THA) patients. Methods All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Demographic data, preoperative laboratory values, recorded past medical history, operative details as well as outcome and complication information were collected. The study population was divided into two cohorts: non‐dislocation and dislocation patients. Statistics were performed to compare the characteristics of both cohorts and to identify risk factors for prosthetic dislocation (α

Objective: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes. Design: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis. Participants: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study. Methods: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods. Main Outcome Measures: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures. Results: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83% for Clade 1 to 46% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases (P = 1.5 × 10−5). Prediction was dependent on ensemble groups of polymorphisms across multiple genes. Conclusions: Adenovirus D8 has ≥ 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity.

Purpose: To report monozygotic twin 4-year-old boys with chronic bilateral anterior uveitis with simultaneous onset. Observations: Here we report monozygotic twin 4-year-old boys with chronic bilateral anterior uveitis. The boys had simultaneous onset of uveitis and identical features. Evaluation, including whole exome sequencing (WES), failed to reveal a specific causative etiology. Each patient responded well to immune modulation and achieved uveitis remission on methotrexate monotherapy off topical glucocorticoids. Conclusions and Importance: From this case of monozygotic twin boys presenting with chronic uveitis, we conclude that monozygotic twins may warrant evaluation in the setting of idiopathic uveitis, especially in young patients unable to express an adequate history.

Abstract The human ocular surface hosts a paucibacterial resident microbiome and virome. The factors contributing to homeostasis of this mucosal community are presently unknown. To determine the impact of ocular enucleation and prosthesis placement on the ocular surface microbiome, we sampled conjunctival swabs from 20 anophthalmic and 20 fellow-eye intact conjunctiva. DNA was extracted and subjected to quantitative 16S rDNA PCR, biome representational karyotyping (BRiSK), and quantitative PCR (qPCR) confirmation of specific organisms. 16S ribosomal qPCR revealed equivalent bacterial loads between conditions. Biome representational in silico karyotyping (BRiSK) demonstrated comparable bacterial fauna between anophthalmic and intact conjunctiva. Both torque teno virus and Merkel cell polyoma virus (MCPyV) were detected frequently in healthy and anophthalmic conjunctiva. By qPCR, MCPyV was detected in 19/20 anophthalmic samples compared with 5/20 fellow eyes. MCPyV copy number averaged 891 copies/ng in anophthalmic conjunctiva compared with 193 copies/ng in fellow eyes (p

Abstract The COVID-19 epidemic of 2019–20 is due to the novel coronavirus SARS-CoV-2. Following first case description in December, 2019 this virus has infected over 10 million individuals and resulted in at least 500,000 deaths world-wide. The virus is undergoing rapid mutation, with two major clades of sequence variants emerging. This study sought to determine whether SARS-CoV-2 sequence variants are associated with differing outcomes among COVID-19 patients in a single medical system. Whole genome SARS-CoV-2 RNA sequence was obtained from isolates collected from patients registered in the University of Washington Medicine health system between March 1 and April 15, 2020. Demographic and baseline clinical characteristics of patients and their outcome data including their hospitalization and death were collected. Statistical and machine learning models were applied to determine if viral genetic variants were associated with specific outcomes of hospitalization or death. Full length SARS-CoV-2 sequence was obtained 190 subjects with clinical outcome data. 35 (18.4%) were hospitalized and 14 (7.4%) died from complications of infection. A total of 289 single nucleotide variants were identified. Clustering methods demonstrated two major viral clades, which could be readily distinguished by 12 polymorphisms in 5 genes. A trend toward higher rates of hospitalization of patients with Clade 2 infections was observed (p = 0.06, Fisher’s exact). Machine learning models utilizing patient demographics and co-morbidities achieved area-under-the-curve (AUC) values of 0.93 for predicting hospitalization. Addition of viral clade or sequence information did not significantly improve models for outcome prediction. In summary, SARS-CoV-2 shows substantial sequence diversity in a community-based sample. Two dominant clades of virus are in circulation. Among patients sufficiently ill to warrant testing for virus, no significant difference in outcomes of hospitalization or death could be discerned between clades in this sample. Major risk factors for hospitalization and death for either major clade of virus include patient age and comorbid conditions.

Photopharmacological compounds such as azobenzene-based photoswitches have been shown to control the conductivity of ionic channels in a light-dependent manner and are considered a potential strategy to restore vision in patients with end-stage photoreceptor degeneration. Here, we report the effects of DENAQ, a second-generation azobenzene-based photoswitch on retinal ganglion cells (RGC) in canine retinas using multi-electrode array (MEA) recordings (from nine degenerated and six WT retinas). DENAQ treatment conferred increased light sensitivity to RGCs in degenerated canine retinas. RGC light responses were observed in degenerated retinas following ex vivo application of 1 mM DENAQ (n = 6) or after in vivo DENAQ injection (n = 3, 150 μL, 3–10 mM) using 455 nm light at intensities as low as 0.2 mW/cm2. The number of light-sensitive cells and the per cell response amplitude increased with light intensity up to the maximum tested intensity of 85 mW/cm2. Application of DENAQ to degenerated retinas with partially preserved cone function caused appearance of DENAQ-driven responses both in cone-driven and previously non-responsive RGCs, and disappearance of cone-driven responses. Repeated stimulation slowed activation and accelerated recovery of the DENAQ-driven responses. The latter is likely responsible for the delayed appearance of a response to 4 Hz flicker stimulation. Limited aqueous solubility of DENAQ results in focal drug aggregates associated with ocular toxicity. While this limits the therapeutic potential of DENAQ, more potent third-generation photoswitches may be more promising, especially when delivered in a slow-release formulation that prevents drug aggregation.

Objective This study aimed to investigate emerging trends and increasing costs in the National Residency Matching Program (NRMP) and San Francisco Residency and Fellowship Match Services (SF Match) associated with the current applicant/program Gale–Shapley-type matching algorithms. Design A longitudinal observational study of behavioral trends in national residency matching systems with modeling of match results with alternative parameters. Patients and Methods We analyzed publicly available data from the SF Match and NRMP websites from 1985 to 2020 for trends in the total number of applicants and available positions, as well the average number of applications and interviews per applicant for multiple specialties. To understand these trends and the algorithms' effect on the residency programs and applicants, we analyzed anonymized rank list and match data for ophthalmology from the SF Match between 2011 and 2019. Match results using current match parameters, as well as under conditions in which applicant and/or program rank lists were truncated with finalized rank lists, were analyzed. Results Both the number of applications and length of programs' rank lists have increased steadily throughout residency programs, particularly those with competitive specialties. Capping student rank lists at seven programs, or less than 80% of the average 8.9 programs currently ranked, results in a 0.71% decrease in the total number of positions filled. Similarly, capping program rank lists at seven applicants per spot, or less than 60% of the average 11.5 applicants ranked per spot, results in a 5% decrease in the total number of positions filled. Conclusion While the number of ophthalmology positions in the United States has increased only modestly, the number of applications under consideration has increased substantially over the past two decades. The current study suggests that both programs and applicants rank more choices than are required for a nearly complete and stable match, creating excess cost and work for both applicants and programs. “Stable-marriage” type algorithms induce applicants and programs to rank as many counterparties as possible to maximize individual chances of optimizing the match.

Hepatocellular carcinoma (HCC) is the sixth most common and the fourth most deadly cancer worldwide. The development cost of new therapeutics is a major limitation in patient outcomes. Importantly, there is a paucity of preclinical HCC models in which to test new small molecules. Herein, we implemented potentially novel patient-derived organoid (PDO) and patient-derived xenografts (PDX) strategies for high-throughput drug screening. Omacetaxine, an FDA-approved drug for chronic myelogenous leukemia (CML), was found to be a top effective small molecule in HCC PDOs. Next, omacetaxine was tested against a larger cohort of 40 human HCC PDOs. Serial dilution experiments demonstrated that omacetaxine is effective at low (nanomolar) concentrations. Mechanistic studies established that omacetaxine inhibits global protein synthesis, with a disproportionate effect on short–half-life proteins. High-throughput expression screening identified molecular targets for omacetaxine, including key oncogenes, such as PLK1. In conclusion, by using an innovative strategy, we report — for the first time to our knowledge — the effectiveness of omacetaxine in HCC. In addition, we elucidate key mechanisms of omacetaxine action. Finally, we provide a proof-of-principle basis for future studies applying drug screening PDOs sequenced with candidate validation in PDX models. Clinical trials could be considered to evaluate omacetaxine in patients with HCC.

We present stable carbon (δ13C) and oxygen (δ18O) isotope records from two partially coeval speleothems from Manita peć Cave, Croatia. The cave is located close to the Adriatic coast (3.7 km) at an elevation of 570 m a.s.l. The site experienced competing Mediterranean and continental climate influences throughout the last glacial cycle and was situated close to the ice limit during the glacial phases. U-Th dating constrains the growth history from Marine Isotope Stage (MIS) 5 to MIS 3 and the transition from MIS 2 to MIS 1. 14C dating was used to estimate the age of the youngest part of one stalagmite found to be rich in detrital thorium and thus undatable by U-Th. On a millennial scale, δ18O variations partly mimic the Dansgaard–Oeschger interstadials recorded in Greenland ice cores (Greenland Interstadials, GI) from GI 22 to GI 13. We interpret our δ18O record as a proxy for variations in precipitation amount and/or moisture sources, and the δ13C record is interpreted as a proxy for changes in soil bioproductivity. The latter indicates a generally reduced vegetation cover towards MIS 3–MIS 4, with shifts of ~8‰ and approaching values close to those of the host rock. However, even during the coldest phases, when a periglacial setting and enhanced aridity sustained long-residence-time groundwater, carbonic-acid dissolution remains the driving force of the karstification processes. Speleothem morphology follows changes in environmental conditions and complements regional results of submerged speleothems findings. Specifically, narrow sections of light porous spelaean calcite precipitated during the glacial/stadial sea-level lowstands, while the warmer and wetter conditions were marked with compact calcite and hiatuses in submerged speleothems due to sea-level highstands. Presumably, the transformation of this littoral site to a continental one with somewhat higher amounts of orographic precipitation was a site-specific effect that masked regional environmental changes.

The recycling of continental lithosphere and rapid plateau uplift is believed to be the result of lithospheric drips, but natural examples are missing. Here, the authors use geodynamic models to suggest that the folding and thickening of the Central Anatolian arc caused lithospheric dripping of the arc root.

Contributions of iron sources to Southern Ocean CO2sequestration during the last glacial period remain uncertain. Here, based on the biogeochemical analysis of subglacial calcites, the authors propose Antarctic volcanism, via subglacial drainage of Fe-rich waters, as a key contributor.

Summary: Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, and the circadian system, in which light entrains a physiological clock. Here we describe a light response pathway in mice that employs encephalopsin (OPN3, a 480 nm, blue-light-responsive opsin) to regulate the function of adipocytes. Germline null and adipocyte-specific conditional null mice show a light- and Opn3-dependent deficit in thermogenesis and become hypothermic upon cold exposure. We show that stimulating mouse adipocytes with blue light enhances the lipolysis response and, in particular, phosphorylation of hormone-sensitive lipase. This response is Opn3 dependent. These data establish a key mechanism in which light-dependent, local regulation of the lipolysis response in white adipocytes regulates energy metabolism. : White adipocytes activate the lipolysis pathway to produce the free fatty acids that are used as heating fuel by brown adipose tissue. Nayak et al. show that Opsin 3 is required for blue-light-enhanced activation of the lipolysis pathway. This explains the low body temperature of Opn3 mutant mice. Keywords: OPN3, encephalopsin, opsin, light, thermogenesis, adipocyte, lipolysis, metabolism, mitochondria

Interdecadal modes of tropical Pacific ocean-atmosphere circulation have a strong influence on global temperature. Here, the authors present a 2000-year hydroclimate record from the Indo-Pacific, which suggests that century-scale variations in these modes are also linked with global temperature variability.

The causes of intraplate deformation remain poorly constrained. Heron et al. use numerical models to show that ancient plate tectonic processes produce mantle lithosphere structures that may be reactivated to generate intraplate deformation.

Abstract Mammals receive light information through the eyes, which perform two major functions: image forming vision to see objects and non-image forming adaptation of physiology and behavior to light. Cone and rod photoreceptors form images and send the information via retinal ganglion cells to the brain for image reconstruction. In contrast, nonimage-forming photoresponses vary widely from adjustment of pupil diameter to adaptation of the circadian clock. nonimage-forming responses are mediated by retinal ganglion cells expressing the photopigment melanopsin. Melanopsin-expressing cells constitute 1–2% of retinal ganglion cells in the adult mammalian retina, are intrinsically photosensitive, and integrate photic information from rods and cones to control nonimage-forming adaptation. Action spectra of ipRGCs and of melanopsin photopigment peak around 480 nm blue light. Understanding melanopsin function lets us recognize considerable physiological effects of blue light, which is increasingly important in our modern society that uses light-emitting diode. Misalignment of circadian rhythmicity is observed in numerous conditions, including aging, and is thought to be involved in the development of age-related disorders, such as depression, diabetes, hypertension, obesity, and cancer. The appropriate regulation of circadian rhythmicity by proper lighting is therefore essential. This perspective introduces the potential risks of excessive blue light for human health through circadian rhythm disruption and sleep deprivation. Knowing the positive and negative aspects, this study claims the importance of being exposed to light at optimal times and intensities during the day, based on the concept of the circadian clock, ultimately to improve quality of life to have a healthy and longer life.

The development of the tourist trail in the side passage Rov Novih Podpisov of Postojna Cave in 2001 exposed an over four metres thick sedimentary succession characterised by horizontal flowstone layers intercalated between fine-grained fluvial sediments, and gravel deposits that record past environmental changes. The time of the flowstone deposition was determined by radiocarbon and uranium-thorium dating techniques. The results yielded three distinctive age groups of flowstone facies of 33 ka, 103 ka and 153 ka. These results also indicate that flowstone deposition has not been limited solely to periods of warm climate, which suggests that environmental conditions during glacial periods in south-western Slovenia supported flowstone deposition.

Introduction: Very little quantitative data on occupational burnout and exposure to critical incidents are available from contemporary United States emergency medical services (EMS) cohorts. Given that burnout has been associated positively with turnover intentions and absenteeism in EMS workers, studies that uncover correlates of burnout may be integral to combating growing concerns around retention in the profession. Methods: We administered a 167-item electronic survey that included the Maslach Burnout Inventory (MBI) and a modified version of the Critical Incident History Questionnaire (n=29 incident types) to paramedics, emergency medical technicians (EMTs), and dispatchers of a single ambulance service. We defined the presence of burnout as a high score on either the emotional exhaustion or depersonalization subscales of the MBI. Results: Survey respondents who provided regular 911 response at the time of the survey and completed the MBI portion of the survey were included in our analysis (190 paramedics/EMTs, 19 dispatchers; 54% response). The overall prevalence of burnout was 18%, with prevalence reaching 32% among dispatchers. The seven pediatric critical incident types presented in the survey accounted for seven of the top eight rated most difficult to cope with, and severity ratings for pediatric critical incidents did not differ by parental status (all p>0.30). A significant number of respondents reported that they had been threatened with a gun/weapon (43%) or assaulted by a patient (68%) at least once while on duty. Being over the age of 50, a parent, or in a committed relationship was associated with reduced odds of burnout in unadjusted models; however, these associations did not remain statistically significant in multivariate analysis. Increasing tertile of career exposure to critical incidents was not associated with burnout. Conclusion: Medical dispatchers may be an EMS subgroup particularly susceptible to burnout. These data also demonstrate quantitatively that in this EMS agency, responders find pediatric critical incidents especially distressing and that violence against responders is commonplace. In this study, a simple measure of career exposure to potentially critical incidents was not associated with burnout; however, individual reactions to incidents are heterogeneous, and assessment tools that more accurately enumerate encounters that result in distress are needed.