Circulating luteinizing hormone receptor inhibitor(s) in boys with chronic renal failure

Circulating luteinizing hormone receptor inhibitor(s) in boys with chronic renal failure. Patients with chronic renal failure frequently have hypogonadism. To elucidate the molecular mechanisms involved, we tested the ability of serum from these patients to inhibit recombinant human luteinizing hormone receptors. Using a cell line expressing functional human luteinizing hormone receptors, we found that adenosine 3′,5′-monophosphate (cAMP) production was markedly inhibited by sera from the patients, but not by sera from healthy subjects. Inhibition of cAMP production was associated with inhibition of 125I-human chorionic gonadotropin binding. Inhibition of LH receptors by sera from patients correlated with the glomerular filtration rate and after renal allograft transplantation, decreased. Fractionation of serum samples indicated the receptor-inhibiting activity in proteins of molecular weights from 30,000 to 60,000 Daltons. When characterized and purified, the factor responsible may well be a new LH receptor antagonist of clinical significance

Optimization of immunomagnetic separation for cord blood-derived hematopoietic stem cells

BACKGROUND: There is a growing interest in cord blood as a source of primitive stem cells with the capacity for multilineage differentiation. Pure cell fractions are needed for the characterization and in vitro expansion of stem cells as well as for their use in preclinical research. However, enrichment of stem cells is challenging due to the lack of stem cell-specific markers and gentle protocols for the isolation of highly pure stem cell fractions. Protocols developed for the enrichment of peripheral blood-derived stem cells have been found to be suboptimal for cord blood. RESULTS: In this study, immunomagnetic cell sorting protocols to purify CD34+, CD133+ and Lin- cells from fresh and cryopreserved cord blood were optimized. Reproducible purities of up to 97% were reached. The selected cells were highly viable having substantial colony-forming potential. CONCLUSION: The optimized protocols enable rapid enrichment of highly pure hematopoietic stem cells from both fresh and cryopreserved cord blood

Improving Yasso15 soil carbon model estimates with ensemble adjustment Kalman filter state data assimilation

Model-calculated forecasts of soil organic carbon (SOC) are important for approximating global terrestrial carbon pools and assessing their change. However, the lack of detailed observations limits the reliability and applicability of these SOC projections. Here, we studied whether state data assimilation (SDA) can be used to continuously update the modeled state with available total carbon measurements in order to improve future SOC estimations. We chose six fallow test sites with measurement time series spanning 30 to 80 years for this initial test. In all cases, SDA improved future projections but to varying degrees. Furthermore, already including the first few measurements impacted the state enough to reduce the error in decades-long projections by at least 1 tCha(-1). Our results show the benefits of implementing SDA methods for forecasting SOC as well as highlight implementation aspects that need consideration and further research.Peer reviewe

Calibrating the sqHIMMELI v1.0 wetland methane emission model with hierarchical modeling and adaptive MCMC

Estimating methane (CH4) emissions from natural wetlands is complex, and the estimates contain large uncertainties. The models used for the task are typically heavily parameterized and the parameter values are not well known. In this study, we perform a Bayesian model calibration for a new wetland CH4 emission model to improve the quality of the predictions and to understand the limitations of such models. The detailed process model that we analyze contains descriptions for CH4 production from anaerobic respiration, CH4 oxidation, and gas transportation by diffusion, ebullition, and the aerenchyma cells of vascular plants. The processes are controlled by several tunable parameters. We use a hierarchical statistical model to describe the parameters and obtain the posterior distributions of the parameters and uncertainties in the processes with adaptive Markov chain Monte Carlo (MCMC), importance resampling, and time series analysis techniques. For the estimation, the analysis utilizes measurement data from the Siikaneva flux measurement site in southern Finland. The uncertainties related to the parameters and the modeled processes are described quantitatively. At the process level, the flux measurement data are able to constrain the CH4 production processes, methane oxidation, and the different gas transport processes. The posterior covariance structures explain how the parameters and the processes are related. Additionally, the flux and flux component uncertain-ties are analyzed both at the annual and daily levels. The parameter posterior densities obtained provide information regarding importance of the different processes, which is also useful for development of wetland methane emission models other than the square root HelsinkI Model of MEthane buiLd- up and emIssion for peatlands (sqHIMMELI). The hierarchical modeling allows us to assess the effects of some of the parameters on an annual basis. The results of the calibration and the cross validation suggest that the early spring net primary production could be used to predict parameters affecting the annual methane production. Even though the calibration is specific to the Siikaneva site, the hierarchical modeling approach is well suited for larger-scale studies and the results of the estimation pave way for a regional or global- scale Bayesian calibration of wetland emission models.Peer reviewe

Electric field navigated 1-Hz rTMS for poststroke motor recovery: The E-FIT randomized controlled trial

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training-related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil. METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial). The sham coil appearance mimicked the active coil but without the weak electric field in the NICHE trial sham coil. Outcomes measured 1 week, and 1, 3, and 6 months after the end of treatment included the following: upper extremity Fugl-Meyer (primary, 6 months after end of treatment), Action Research Arm Test, National Institutes of Health Stroke Scale, quality of life (EQ-5D), and safety. RESULTS: Of 60 participants randomized, 58 completed treatment and were included for analysis. Bayesian analysis of combined data from the E-FIT and the NICHE trials indicated that active treatment was not superior to sham at the primary end point (posterior mean odds ratio of 1.94 [96% credible interval of 0.61-4.80]). For the E-FIT intent-to-treat population, upper extremity Fugl-Meyer improvement ≥ 5 pts occurred in 60% (18/30) active group and 50% (14/28) sham group. Participants enrolled 3 to 6 months following stroke had a 67% (31%-91% CI) response rate in the active group at the 6-month end point versus 50% in the sham group (21.5%-78.5% CI). There were significant improvements from baseline to 6 months for both active and sham groups in upper extremity Fugl-Meyer, Action Research Arm Test, and EQ-5D (P\u3c0.05). Improvement in National Institutes of Health Stroke Scale was observed only in the active group (P=0.004). Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P=0.72). CONCLUSIONS: Intensive motor rehabilitation 3 to 12 months after stroke improved clinical impairment, function, and quality of life; however, 1 Hz-repetitive transcranial magnetic stimulation was not an effective treatment adjuvant in the present sample population with mixed lesion location and extent. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03010462

Rakennetaan humalatarha: Suomalaisen humalan (Humulus lupulus) viljelystä

Humala on Suomessa vanha viljelykasvi, joka on ollut unohduksissa vuosikymmeniä. Erikoiskasvitutkimuksen, viljelyn erikoistumisen, suomalaisten vanhojen puutarhakasvien geenivaratyön ja pienpanimobuumin myötä se on noussut yhdeksi mielenkiintoisimmista viljelykasveista. Luonnonvarakeskus on tutkinut suomalaista humalaa intensiivisesti yli kymmenen vuotta, ja tieto uniikeista humalakasvikannoistamme lisääntyy koko ajan. Humalakuulutuksessa Luke pyysi kansalaisia ilmiantamaan pihapiiriensä vanhoja humalia. Ilmoituksia tuli koko Suomesta yli 1400, ja lehti- ja käpynäytteitä tutkittiin noin tuhannesta ilmoitetusta kasvista. Käpyjen kemiallisten ominaisuuksien ja humalan viljelyhistorian perusteella valittiin reilu parikymmentä geneettisesti keskenään erilaista humalakantaa. Kasvit käytiin keräämässä ja niistä lisättiin solukkoviljelyn avulla taimimateriaalia, joka istutettiin kesällä 2020 viljelykokeiksi Lukelle Piikkiöön Varsinais-Suomeen, Jamille Kurejoelle Etelä-Pohjanmaalle sekä Lappialle Louelle Lappiin. Tähän julkaisuun on koottu ohjeet humalatarhan rakentamisesta sekä ensivuosien havainnot suomalaisten humalakantojen kasvusta ja kehittymisestä perustetuissa pilottitarhoissa. Mukana kantavertailussa on ollut myös yksityisiä viljelijöitä Etelä-Pohjanmaan ja Lapin alueilta. Humalatarhan malli on tuttu keskieurooppalaisilta humalatiloilta. Julkaisussamme esitetään yksityiskohtaiset rakennusohjeet ja tarvikelista noin sadan köynnöksen kokoisen tarhan rakentamiseen. Kokemuksia ja tietoa viljelytekniikasta kertyy maastamme lisää sitä mukaa, kun tätä vanhaa kulttuurikasvia aletaan ammattimaisesti viljellä isommalla alalla. Ensihavaintojen mukaan humala vaatii kasvaakseen hyvää rikkakasvien hallintaa, kastelua ja lannoitusta. Eri humalakantojen kasvurytmissä ja kukintakehityksessä on eroja: myöhäinen kukinta tarkoittaa myös myöhäistä sadonkorjuuajankohtaa. Kovin myöhään syksyllä valmistuvan käpysadon laatu on riskialtis sääoloille. Humalien biomassa ja sadontuottokyky kasvoivat kokeessa ensivuosina. Tuhoojista erityisesti kirvoja havaittiin jonkin verran. Viljelykokeet jatkuvat ja niiden myötä taimituotantoon tullaan valitsemaan Lukessa muutamia suomalaisia humalakantoja, jotka mahdollisesti sopivat viljelyyn ja panimoiden raaka-aineeksi. Raportti on kirjoitettu osana HopUp – Suomalaisen humalan tuotannon käynnistäminen hanketta (1.4.2020-31.12.2022), jota ovat rahoittaneet Lapin ja Etelä-Pohjanmaan ELY-keskukset, Euroopan maaseudun kehittämisen maatalousrahasto sekä Maiju ja Yrjö Rikalan puutarhasäätiö

Electric Field Navigated 1-Hz rTMS for Poststroke Motor Recovery: The E-FIT Randomized Controlled Trial

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training–related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil. METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial). The sham coil appearance mimicked the active coil but without the weak electric field in the NICHE trial sham coil. Outcomes measured 1 week, and 1, 3, and 6 months after the end of treatment included the following: upper extremity Fugl-Meyer (primary, 6 months after end of treatment), Action Research Arm Test, National Institutes of Health Stroke Scale, quality of life (EQ-5D), and safety. RESULTS: Of 60 participants randomized, 58 completed treatment and were included for analysis. Bayesian analysis of combined data from the E-FIT and the NICHE trials indicated that active treatment was not superior to sham at the primary end point (posterior mean odds ratio of 1.94 [96% credible interval of 0.61–4.80]). For the E-FIT intent-to-treat population, upper extremity Fugl-Meyer improvement ≥5 pts occurred in 60% (18/30) active group and 50% (14/28) sham group. Participants enrolled 3 to 6 months following stroke had a 67% (31%–91% CI) response rate in the active group at the 6-month end point versus 50% in the sham group (21.5%–78.5% CI). There were significant improvements from baseline to 6 months for both active and sham groups in upper extremity Fugl-Meyer, Action Research Arm Test, and EQ-5D (P\u3c0.05). Improvement in National Institutes of Health Stroke Scale was observed only in the active group (P=0.004). Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P=0.72). CONCLUSIONS: Intensive motor rehabilitation 3 to 12 months after stroke improved clinical impairment, function, and quality of life; however, 1 Hz-repetitive transcranial magnetic stimulation was not an effective treatment adjuvant in the present sample population with mixed lesion location and extent. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03010462

Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as N-6-methyl-adenosine (m6A) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on m6A and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of m6A and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets

Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG

Peer reviewe