Revealing historic insect damage of P.sylvestris L. in the northeast lowlands of Germany by means of the Needle Trace Method (NTM)

Informationen zu historischen Fraßschäden durch Forstinsekten konnten in der Vergangenheit allein über die Anlage von Langzeituntersuchungsflächen erhoben oder mit Hilfe von Jahrringanalysen abgeschätzt werden. Ein Langzeitmonitoring, wie es auch seit 1984 auf Level II - Flächen in Bundesforsten durchgeführt wird, ist allerdings mit hohem zeitlichen und finanziellem Aufwand verbunden und deckt zudem nur einen kurzen Zeitraum ab. Mittels Jahrringanalysen erhält man zwar weiter zurückreichende Informationen, diese sind jedoch mit einer gewissen Unsicherheit behaftet, da nur über ein Ausschlußverfahren klimatische bzw. abiotische Ursachen für Zuwachsstörungen ausgeschlossen werden. Eine Methode, mit der man direkt dort ansetzen kann, wo der Schaden passiert – an der Belaubung eines Baumes – war in der Vergangenheit nicht gegeben. Seit Anfang der 1990er Jahre ist dies jedoch mit dem sog. Nadelspurverfahren (KURKELA & JALKANEN 1990) möglich. Mit Hilfe dieser Technik kann die Benadelung von Koniferen retrospektiv entlang von Hauptachsen (Stamm, Äste) über das gesamte Lebensalter eines Baumes aufgedeckt werden, wobei die erhobenen Benadelungsparameter eine direkte Auskunft über Auffälligkeiten im enadelungsmuster geben (JALKANEN 1995, SANDER 1997) können.Until recently, information on historic insect damage to forest trees could not be obtained unless exact documentations, e.g. by the forest service existed. The needle trace method, NTM, reveals the past needle retention of conifers over a trees lifetime (KURKELA & JALKANEN 1990). These needle parameters can be used for dendro-ecological research as well as for the detection of insect outbreaks in forest stands (INSINNA et.al. 2004). In 2004, a Scots pine (Pinus sylvestris L.) stand in north eastern Germany near Müllrose was investigated. We demonstrate that the long-term needle age and needle loss patterns can be correlated with recorded historical outbreaks of Bupalus piniarius L., Lymantria monacha L. (Lepidoptera) and Diprion pini L. (Hymenoptera). A differentiation between biotic (insect) and abiotic (e.g. drought) damage is possible with NTM, but not by use of the previously applied tree ring analysis. The average needle age correlates well with the outbreak situation of a defoliator as documented in the records of the local forest service. Years of insect damage can also be identified by calculating the percentage of needle loss. We conclude from our results that NTM is a suitable tool for the detection of insect damage for example in areas where no records are available. An identification of specific insect species responsible for the damage is possible

Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis

Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD

Impaired Progesterone-Responsiveness of CD11c+ Dendritic Cells Affects the Generation of CD4+ Regulatory T Cells and Is Associated With Intrauterine Growth Restriction in Mice

Up to 10% of pregnancies in Western societies are affected by intrauterine growth restriction (IUGR). IUGR reduces short-term neonatal survival and impairs long-term health of the children. To date, the molecular mechanisms involved in the pathogenesis of IUGR are largely unknown, but the failure to mount an adequate endocrine and immune response during pregnancy has been proposed to facilitate the occurrence of IUGR. A cross talk between the pregnancy hormone progesterone and innate immune cell subsets such as dendritic cells (DCs) is vital to ensure adequate placentation and fetal growth. However, experimental strategies to pinpoint distinct immune cell subsets interacting with progesterone in vivo have long been limited. In the present study, we have overcome this limitation by generating a mouse line with a specific deletion of the progesterone receptor (PR) on CD11c+ DCs. We took advantage of the cre/loxP system and assessed reproductive outcome in Balb/c-mated C57Bl/6 PRflox/floxCD11ccre/wt females. Balb/c-mated C57Bl/6 PRwt/wtCD11ccre/wt females served as controls. In all dams, fetal growth and development, placental function and maternal immune and endocrine adaptation were evaluated at different gestational time points. We observed a significantly reduced fetal weight on gestational day 13.5 and 18.5 in PRflox/floxCD11ccre/wt females. While frequencies of uterine CD11c+ cells were similar in both groups, an increased frequency of co-stimulatory molecules was observed on DCs in PRflox/floxCD11ccre/wt mice, along with reduced frequencies of CD4+ FoxP3+ and CD8+ CD122+ regulatory T (Treg) cells. Placental histomorphology revealed a skew toward increased junctional zone at the expense of the labyrinth in implantations of PRflox/floxCD11ccre/wt females, accompanied by increased plasma progesterone concentrations. Our results support that DCs are highly responsive to progesterone, subsequently adapting to a tolerogenic phenotype. If such cross talk between progesterone and DCs is impaired, the generation of pregnancy-protective immune cells subsets such as CD4+ and CD8+ Treg cells is reduced, which is associated with poor placentation and IUGR in mice

High resolution monitoring of valvular interstitial cell driven pathomechanisms in procalcific environment using label-free impedance spectroscopy

IntroductionFibro-calcific aortic valve disease has high prevalence and is associated with significant mortality. Fibrotic extracellular matrix (ECM) remodeling and calcific mineral deposition change the valvular microarchitecture and deteriorate valvular function. Valvular interstitial cells (VICs) in profibrotic or procalcifying environment are frequently used in vitro models. However, remodeling processes take several days to weeks to develop, even in vitro. Continuous monitoring by real-time impedance spectroscopy (EIS) may reveal new insights into this process.MethodsVIC-driven ECM remodeling stimulated by procalcifying (PM) or profibrotic medium (FM) was monitored by label-free EIS. Collagen secretion, matrix mineralization, viability, mitochondrial damage, myofibroblastic gene expression and cytoskeletal alterations were analyzed.Results and DiscussionEIS profiles of VICs in control medium (CM) and FM were comparable. PM reproducibly induced a specific, biphasic EIS profile. Phase 1 showed an initial impedance drop, which moderately correlated with decreasing collagen secretion (r = 0.67, p = 0.22), accompanied by mitochondrial membrane hyperpolarization and cell death. Phase 2 EIS signal increase was positively correlated with augmented ECM mineralization (r = 0.97, p = 0.008). VICs in PM decreased myofibroblastic gene expression (p < 0.001) and stress fiber assembly compared to CM. EIS revealed sex-specific differences. Male VICs showed higher proliferation and in PM EIS decrease in phase 1 was significantly pronounced compared to female VICs (male minimum: 7.4 ± 4.2%, female minimum: 26.5 ± 4.4%, p < 0.01). VICs in PM reproduced disease characteristics in vitro remarkably fast with significant impact of donor sex. PM suppressed myofibroblastogenesis and favored ECM mineralization. In summary, EIS represents an efficient, easy-to-use, high-content screening tool enabling patient-specific, subgroup- and temporal resolution

Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure

BACKGROUND: The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10-15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients.¦METHODOLOGY/PRINCIPAL FINDINGS: We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LOD(max) of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations.¦CONCLUSIONS/SIGNIFICANCE: We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function

Efficacy of UVC-treated, pathogen-reduced platelets versus untreated platelets: a randomized controlled non-inferiority trial

Pathogen reduction (PR) technologies for blood components have been established to reduce the residual risk of known and emerging infectious agents. THERAFLEX UVPlatelets, a novel UVC light-based PR technology for platelet concentrates, works without photoactive substances. This randomized, controlled, double-blind, multicenter, noninferiority trial was designed to compare the efficacy and safety of UVC-treated platelets to that of untreated platelets in thrombocytopenic patients with hematologic-oncologic diseases. Primary objective was to determine non-inferiority of UVC-treated platelets, assessed by the 1-hour corrected count increment (CCI) in up to eight per-protocol platelet transfusion episodes. Analysis of the 171 eligible patients showed that the defined non-inferiority margin of 30% of UVC-treated platelets was narrowly missed as the mean differences in 1-hour CCI between standard platelets versus UVC-treated platelets for intention-to-treat and perprotocol analyses were 18.2% (95% confidence interval [CI]: 6.4%; 30.1) and 18.7% (95% CI: 6.3%; 31.1%), respectively. In comparison to the control, the UVC group had a 19.2% lower mean 24-hour CCI and was treated with an about 25% higher number of platelet units, but the average number of days to next platelet transfusion did not differ significantly between both treatment groups. The frequency of low-grade adverse events was slightly higher in the UVC group and the frequencies of refractoriness to platelet transfusion, platelet alloimmunization, severe bleeding events, and red blood cell transfusions were comparable between groups. Our study suggests that transfusion of pathogen-reduced platelets produced with the UVC technology is safe but non-inferiority was not demonstrated. (The German Clinical Trials Register number: DRKS00011156)