Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction.

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

Experimental demonstration of novel beam characterization using a polarizable X-band transverse deflection structure.

The PolariX TDS (Polarizable X-Band Transverse Deflection Structure) is an innovative TDS-design operating in the X-band frequency-range. The design gives full control of the streaking plane, which can be tuned in order to characterize the projections of the beam distribution onto arbitrary transverse axes. This novel feature opens up new opportunities for detailed characterization of the electron beam. In this paper we present first measurements of the Polarix TDS at the FLASHForward beamline at DESY, including three-dimensional reconstruction of the charge-density distribution of the bunch and slice emittance measurements in both transverse directions. The experimental results open the path toward novel and more extensive beam characterization in the direction of multi-dimensional-beam-phase-space reconstruction.

Juno Observations of Heavy Ion Energization During Transient Dipolarizations in Jupiter Magnetotail.

Transient magnetic reconnection and associated fast plasma flows led by dipolarization fronts play a crucial role in energetic particle acceleration in planetary magnetospheres. Despite large statistical observations on this phenomenon in the Earth's magnetotail, many important characteristics (e.g., mass or charge dependence of acceleration efficiency and acceleration scaling with the spatial scale of the system) of transient reconnection cannot be fully investigated with the limited parameter range of the Earth's magnetotail. The much larger Jovian magnetodisk, filled by a mixture of various heavy ions and protons, provides a unique opportunity for such investigations. In this study, we use recent Juno observations in Jupiter's magnetosphere to examine the properties of reconnection associated dipolarization fronts and charged particle acceleration. High-energy fluxes of sulfur, oxygen, and hydrogen ions show clear mass-dependent acceleration with energy ~ m 1/3. We compare Juno observations with similar observations in the Earth's magnetotail and discuss possible mechanism for the observed ion acceleration.

Intestinal insulin/IGF1 signalling through FoxO1 regulates epithelial integrity and susceptibility to colon cancer.

Obesity promotes the development of insulin resistance and increases the incidence of colitis-associated cancer (CAC), but whether a blunted insulin action specifically in intestinal epithelial cells (IECs) affects CAC is unknown. Here, we show that obesity impairs insulin sensitivity in IECs and that mice with IEC-specific inactivation of the insulin and IGF1 receptors exhibit enhanced CAC development as a consequence of impaired restoration of gut barrier function. Blunted insulin signalling retains the transcription factor FOXO1 in the nucleus to inhibit expression of Dsc3, thereby impairing desmosome formation and epithelial integrity. Both IEC-specific nuclear FoxO1ADA expression and IEC-specific Dsc3 inactivation recapitulate the impaired intestinal integrity and increased CAC burden. Spontaneous colonic tumour formation and compromised intestinal integrity are also observed upon IEC-specific coexpression of FoxO1ADA and a stable Myc variant, thus suggesting a molecular mechanism through which impaired insulin action and nuclear FOXO1 in IECs promotes CAC.

Mars's Dayside Upper Ionospheric Composition Is Affected by Magnetic Field Conditions.

Previous observations have shown that electron density and temperature in the dayside ionosphere of Mars vary between strongly and weakly magnetized regions of the planet. Here we use data from the Neutral Gas and Ion Mass Spectrometer (NGIMS) on the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft to examine whether dayside ion densities and ionospheric composition also vary. We find that O+, O 2 + , and CO 2 + densities above ~200 km are greater in strongly magnetized regions than in weakly magnetized regions. Fractional abundances of ion species are also affected. The O + / O 2 + ratio at 300-km altitude increases from ~0.5 in strongly magnetized regions to ~0.8 in weakly magnetized regions. Consequently, the plasma reservoir available for escape is fundamentally different between strongly magnetized and weakly magnetized regions.

Prenatally Diagnosed Isolated Coronary Arterial Fistula Leading to Severe Complications at Birth.

Prenatal diagnosis of a huge coronary artery fistula between the left coronary artery and the right ventricle was made by Doppler echocardiography at 22 weeks of gestation. Progression of the dilated fistula was monitored throughout pregnancy. The size of the fistula increased enormously up to 11 mm. Death occurred at birth. Monitoring of these fetuses is essential as severe complications can occur during pregnancy or at birth.

Sterility and Safety Validation for Transport Packaging of Organs and Tissues.

The bags used in the transport of organs and tissues must be sterile, nontoxic, pyrogen free, and must serve as a barrier throughout their useful life. The goal of this study was to show the sterility, safety, and functionality of the bags subjected to irradiation, through validated procedures and techniques. The selected sterilization method was the use of gamma radiation. The sterilization dose was determined based on validated standards for the sterilization of medical products, ISO 11137-2: 2013 and ISO/TS 13004: 2013, using the Verification Dose Maximum method on samples belonging to 3 manufacturing lots. The ISO 10993-5: 2009 standard was used in the cytotoxicity tests, by means of extracts test and quantitative technique of MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The tests to determine the expiration date of the kit were performed by ASTM F1980, accelerated aging, and ASTM D3078 to evaluate hermeticity. The irradiation dose validated to reach the required sterility safety level was 22.5 kGy. The constituent materials and the sterilization method do not generated cellular toxicity, and the product was not modified during the simulated time of 5 years. Sterilization by irradiation is a method that leaves no residue, does not harm the properties of the material because it is conducted in cold, and as the sterilizing agent, the energy absorbed by the product is highly penetrating and can be treated in its final packaging, with no risk of postcontamination. It is for this reason that it is prioritized over other methods of sterilization.

Synthesis, characterization and Pd(ii)-coordination chemistry of the ligand tris(quinolin-8-yl)phosphite. Application in the catalytic aerobic oxidation of amines.

The synthesis and characterization of the ligand tris(quinolin-8-yl)phosphite, (P(Oquin)3), are described and its coordination chemistry toward the metal precursor [Pd(COD)Cl2] (COD = 1,5-cyclooctadiene, C8H12) is reported. A new Pd(ii)-P(Oquin)3 metal complex was isolated and fully characterized ([Pd{P(Oquin)3}Cl2]), and its X-ray diffraction analysis shows that the phosphite ligand coordinates as a bidentate P-N chelate. This complex is an efficient catalyst for the solvent-free mild oxidative coupling of primary amines to imines using air as an oxidant, obtaining moderate to good yields (up to 99%) and turnover numbers (TONs up to 230). This catalyst can be recovered from the reaction mixture and reused in a subsequent run without a significant loss of activity. Kinetic measurements of the oxidation of benzylamine suggest that the rate law is r = kapp[BnNH2][cat] ([BnNH2] = molar concentration of benzylamine, [cat] = molar concentration of [Pd{P(Oquin)3}Cl2], kapp = k[O2]c = 0.756 L mol-1 h-1 = apparent rate constant). In situ NMR tests were performed to gain some insight into the reactivity of the Pd(ii)-P(Oquin)3 complex toward benzylamine.

Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-κB signaling.

The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-κB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-κB and tumor suppressor gene CYLD regulates the pool of CD5+ B cells through sustained canonical NF-κB signaling. Reinforced canonical NF-κB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5+ B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-like mouse model represents an appropriate tool for studying ubiquitination-driven canonical NF-κB activation in CLL. Thus, inhibition of alternative splicing of this negative regulator is essential for preventing NF-κB-driven clonal CD5+ B-cell expansion and ultimately CLL-like disease.

[A 44 year old patient presenting with Ewing's sarcoma of the big toe]. / 44-jährige Patientin mit Ewing­Sarkom der Großzehengrundphalanx.

We present the case of a patient with osseous Ewing's sarcoma of the big toe occurring during the healing process after a fracture of the little toe, which significantly delayed diagnosis, despite striking findings on imaging. We subsequently performed further diagnostics, neoadjuvant chemotherapy, tumor resection in the form of a resection of the first ray, and adjuvant chemotherapy. This case shows that the occurrence of a secondary disease should always be considered in untypical courses of healing.

Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency.

BACKGROUND: Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined. OBJECTIVE: To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB. DESIGN: Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA. RESULTS: More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median <3%, range 0-32.6) in both patient groups. The proportion with IDA and hepcidin concentration â©¿ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median <3%, range 0-15.1). CONCLUSIONS: ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.

Potential in two types of collagen scaffolds for urological tissue engineering applications - Are there differences in growth behaviour of juvenile and adult vesical cells?

The aging society has a deep impact on patient care in urology. The number of patients in need of partial or whole bladder wall replacement is increasing simultaneously with the number of cancer incidents. Therefore, urological research requires a model of bladder wall replacement in adult and elderly people. Two types of porcine collagen I/III scaffolds were used in vitro for comparison of cell growth of two different pig breeds at different growth stages. Scaffolds were characterised with scanning electron and laser scanning microscopy. Urothelial and detrusor smooth muscle cells were isolated from 15 adult Göttingen minipigs and 15 juvenile German Landrace pigs. Growth behaviour was examined in cell culture and seeded onto the collagen scaffolds via immunohistochemistry, two-photon laser scanning microscopy and a viability assay. The collagen scaffolds showed different structured surfaces which are appropriate for seeding of the two different cell types. Moisturisation of the scaffolds resulted in a change of the structure. Cell growth of German Landrace urothelial cells and smooth muscle cells was significantly higher than cell growth of the Göttingen minipig cells. Seeding of scaffolds with both cell types from both pig races was possible which could be shown by immunohistochemistry and two-photon laser scanning microscopy. Growth behaviour on the scaffolds was significantly increased for the German Landrace compared to Göttingen minipig. Nevertheless, seeding with the adult Göttingen minipig cells resulted in a closed layer on the surface and urothelial cells and smooth muscle cells showed increasing growth until day 14. The results show that these collagen scaffolds are adequate for the seeding with vesical cells. Moreover, they seem appropriate for the use as an in vitro model for the adult or elderly as the cells of the adult Göttingen minipig too, show good growth behaviour.

Minocycline does not evoke anxiolytic and antidepressant-like effects in C57BL/6 mice.

Minocycline is a broad-spectrum tetracycline antibiotic with multiple actions, including anti-inflammatory and neuroprotective effects, that was proposed as novel treatment for several psychiatric disorders including schizophrenia and depression. However, there are contradictory results regarding antidepressant effects of minocycline in rodent models. Additionally, the possible anxiolytic effect of minocycline is still poorly investigated. Therefore, we aimed to clarify in the present study the influence of minocycline on behavioral correlates of mood disorders in standard tests for depression and anxiety, the Porsolt Forced Swim Test (FST), Elevated O-Maze, Dark-Light Box Test and Openfield Test in adult C57BL/6 mice. We found, unexpectedly, that mice treated with minocycline (20-40mg/kg, i.p.) did not display antidepressant- or anxiolytic-like behavioral changes in contrast to mice treated with diazepam (0.5mg/kg, anxiety tests) or imipramine (20mg/kg, depressive-like behavior). These results are relevant for future studies, considering that C57BL/6 mice, the most widely used strain in pharmacological and genetic animal models, did not react as expected to the treatment regime applied.

Low-valent iron: an Fe(I) ate compound as a building block for a linear trinuclear Fe cluster.

A low-valent trinuclear iron complex with an unusual linear Fe(I)-Fe(II)-Fe(I) unit is presented. It is accessed in a rational approach using a salt metathesis reaction between a new anionic Fe(I) containing heterocycle and FeCl2. Its electronic structure was studied by single crystal XRD analysis, EPR and Mössbauer spectroscopy, and magnetic susceptibility measurements.

Effects of Rest Interval on Strength Recovery in Breast Cancer Survivors.

The purpose of this study was to compare the acute effect of 2 different resting intervals (RI) between sets of isokinetic knee extension exercise on peak torque (PT) and total work (TW) in breast cancer survivors (BCS) and control group (CNT). 16 BCS (52±4 years) and 14 CNT (53±6 years) performed 3 sets of 10 unilateral isokinetic knee extension repetitions at 60°.s(- 1) on 2 separate days with 2 different RI between sets (1 and 2 min). There was a significant interaction between groups vs. exercise sets (p=0.03) and RI vs. exercise sets (p<0.001) for PT. PT was greater in CNT at 1(st) and 2(nd) sets compared to BCS group (CNT, 133.4±20.8 and BCS 107.6±19.9 Nm, p=0.012 and CNT, 118.9±19.6 and BCS, 97.1±15.9 Nm, p=0.045, respectively). The TW of the knee extensor was significant greater in CNT than BCS group for all 3 knee extension exercise sets. In conclusion, the present study suggests that Breast Cancer Survivors women may need a longer rest interval (longer than 2 min) to be able to fully recover during a 3 sets of isokinetic knee extension exercise training session.

Immobilization stress sensitizes rat dorsal horn neurons having input from the low back.

BACKGROUND: Stress is known to promote several forms of muscle pain including non-specific low back pain. However, the question if stress alone activates nociceptive central neurons has not been studied systematically. Here, we investigated the influence of repeated immobilization stress on dorsal horn neurons and behaviour in the rat. METHODS: The stress consisted of immobilization in a narrow tube for 1 h on 12 days. Single dorsal horn neurons were recorded with microelectrodes introduced into the spinal segment L2. In this segment, about 14% of the neurons responded to mechanical stimulation of the subcutaneous soft tissues of the low back in naïve rats. The neurons often behaved like wide dynamic range cells in that they had a low mechanical threshold and showed graded responses to noxious stimuli. RESULTS: The stress-induced changes in neuronal response behaviour were (1) appearance of new receptive fields in the deep tissues of the hindlimb, (2) increased input from deep soft tissues, but unchanged input from the skin and (3) significant increase in resting activity. Surprisingly, the pressure-pain threshold of the low back remained unchanged, although dorsal horn neurons were sensitized. In the open field test, the rats showed signs of increased anxiety. CONCLUSIONS: This study shows that stress alone is sufficient to sensitize dorsal horn neurons. The data may explain the enhanced pain low back patients report when they are under stress. The increased resting discharge may lead to spontaneous pain.

Implications of p75NTR for dentate gyrus morphology and hippocampus-related behavior revisited.

The pan-neurotrophin receptor p75NTR is expressed in the adult brain in a discrete pattern. Although numerous studies have addressed its implications for hippocampal functions, the generated sets of data are surprisingly conflicting. We have therefore set out to re-investigate the impact of a deletion of the full-length p75NTR receptor on several parameters of the dentate gyrus (DG), including neurogenesis and hippocampus-related behavior by using p75NTR(ExIII) knockout mice. Moreover, we investigated further parameters of the DG (cholinergic innervation, dendritic spines). In addition, we analyzed on the morphological level the impact of aging by comparing adult and aged p75NTR(ExIII) mice and their age-matched littermates. Adult (4-6 months old), but not aged (20 months old), p75NTR(ExIII) knockout mice display an enhanced volume of the DG. However, adult neurogenesis within the adult DG was unaffected in both adult and aged p75NTR(ExIII) knockout mice. We could further demonstrate that the change in the volume of the DG was accompanied by an increased cholinergic innervation and increased spine densities of granule cells in adult, but not aged p75NTR deficient mice. These morphological changes in the adult p75NTR deficient mice were accompanied by specific alterations in their behavior, including altered behavior in the Morris water maze test, indicating impairments in spatial memory retention.

Cardiac Adaptation of the Maternal Heart During Pregnancy: A Color-Coded Tissue Doppler Imaging Study--Feasibility, Reproducibility and Course during Pregnancy.

PURPOSE: Tissue Doppler imaging (TDI) allows the noninvasive quantification of global and regional myocardial function. Since there are changing loading conditions during pregnancy, this study aimed to determine maternal myocardial adaptation in normal pregnancy with TDI and tracking of the heart cycle. PATIENTS AND METHODS: 106 pregnant women, mean age of 33.4 years at baseline, prospectively underwent a total of 161 color-coded tissue Doppler echocardiography samples throughout pregnancy. In further offline analysis of the global and regional myocardial function of the basal segments, maximum tissue velocities at systole (Sm), in the early filling phase of diastole (Em) and during atrial contraction (Am) were assessed. RESULTS: From those stored samples, S-wave, E-wave and A-wave velocities could be obtained with a feasibility of 94.8 % and with good inter- and intra-observer variability. S-wave velocity first showed an increase during early pregnancy followed by a decline to baseline characteristics at the 3 rd trimester. The E-wave velocity declined throughout pregnancy. The A-wave velocity increased continuously. These alterations result in a continuous decline of Em/Am ratio as pregnancy advances. CONCLUSION: Alterations in tissue velocities during pregnancy reflect maturational changes that mimic "diastolic dysfunction". Based on an understanding of those normal physiological changes, TDI may therefore assist in the monitoring and/or detecting of subclinical myocardial dysfunction during pregnancy.

Characteristics and treatment outcomes of 69 cases with early prosthetic joint infections of the hip and knee.

PURPOSE: Early prosthetic joint infection (PJI) can be treated with an intensive surgical debridement and implant retention (DAIR) of the prosthesis if (1) the prosthesis is stable, (2) the pathogen is not a difficult-to-treat microorganism, (3) symptoms have lasted for <3 weeks and (4) a sinus tract is absent. METHODS: We retrospectively evaluated the treatment outcome of early PJI in the hip and knee in a single orthopaedic centre. An early PJI was defined as a prosthesis infection within 3 months after primary implantation or revision surgery for a non-infectious cause. RESULTS: We identified 69 patients with confirmed early PJI, with a median age of 71 (range 33-84) years. Only 64 % presented with ≥2 acute signs of infection. The most commonly isolated bacteria were coagulase-negative staphylococci (38 %) and Staphylococcus aureus (25 %). Surgical procedures included DAIR (50 cases, 69 %) and two-stage exchange (19 cases, 31 %). At last follow-up, five of remaining living 67 patients (7.5 %) had a relapse of infection. The overall relapse-free survival of the prosthesis after 2 years was 92.3 % (95 % confidence interval 82-97 %) with no significant difference between DAIR and exchange of prosthesis. CONCLUSION: Our data suggest that an early PJI should be treated with DAIR as a less invasive procedure whenever possible according to the established treatment algorithm.