Factors influencing the spatial distribution of forest plant species in hedgerows of North-western Germany

In North-western Germany woodland fragmentation has caused a decline in many forest plant species. Hedgerows partly offer a similar environment as forests and have been identified as potential habitats for forest plants in various studies from North America and Western Europe. The objective of this study was to examine whether this applies also to Central Europe and which variables affect the spatial distribution and abundance of forest plant species in hedgerows on a local scale. Three hedgerow networks north of the city of Bremen, Germany, were selected as study areas and divided into totally 515 hedgerow segments. In each segment we recorded all vascular plants and a large number of explanatory variables relating to structure, spatial configuration, environment and management. Averaged across species there was a predominant effect of environmental factors on the occurrence of forest species in the hedgerows, followed by spatial configuration and management. Hedgerow structure was found to be less important. In general, forest species were favored by low nutrient and light availability as well as high connectivity with other hedgerows or forest; they avoided hedgerows with a west-easterly orientation and an adjacent land use in the form of fields or grasslands. Forest species found and not found in hedgerows did not differ in their environmental preferences or life history traits. The number of threatened forest species in the hedgerows, however, was lower than expected with respect to their overall proportion to the total number of forest species in the region.     

The miRNA-kallikrein axis of interaction: a new dimension in the pathogenesis of prostate cancer

Kallikrein-related peptidases (KLKs) are a family of serine proteases that were shown to be useful cancer biomarkers. KLKs have been shown to be dysregulated in prostate cancer (PCa). microRNAs (miRNAs) are short RNA nucleotides that negatively regulate gene expression and have been reportedly dysregulated in PCa. We compiled a comprehensive list of 55 miRNAs that are differentially expressed in PCa from previous microarray analysis and published literature. Target prediction analyses showed that 29 of these miRNAs are predicted to target 10 KLKs. Eight of these miRNAs were predicted to target more than one KLK. Quantitative real-time (qRT)-PCR demonstrated that there was an inverse correlation pattern in the expression (normal vs. cancer) between dysregulated miRNAs and their target KLKs. In addition, we experientially validated the miRNA-KLK interaction by transfecting miR-331-3p and miR-143 into a PCa cell line. Decreased expression of targets KLK4 and KLK10, respectively, and decreased cellular growth were observed. In addition to KLKs, dysregulated miRNAs were predicted to target other genes involved in the pathogenesis of PCa. These data show that miRNAs can contribute to KLK regulation in PCa. The miRNA-KLK axis of interaction projects a new element in the pathogenesis of PCa that may have therapeutic implications.     

Effects of Land-Use Change on Carbon Stocks in Switzerland

We assessed how consequences of future land-use change may affect size and spatial shifts of C stocks under three potential trends in policy—(a) business-as-usual: continuation of land-use trends observed during the past 15 years; (b) extensification: full extensification of open-land; and (c) liberalization: full reforestation potential. The build-up times for the three scenarios are estimated at 30, 80 and 100 years, respectively. Potential C-stock change rates are derived from the literature. Whereas the business-as-usual scenario would cause marginal changes of 0.5%, liberalization would provoke a 13% increase in C stocks (+62 MtC). Gains of 24% would be expected for forests (+95 MtC), whereas open-land C stock would decrease 27% (−33 MtC). Extensification would lead to a C stock decrease of 3% (−12 MtC). Whereas forest C is expected to increase 12% (+36.5 MtC) at high elevations, stocks of open-land C would decline 38.5% (−48.5 MtC). Most affected are unfavorable grasslands, which increase in area (+59%) but contribute only 14.5% to the C stocks. C sinks would amount to 0.6 MtC y⁻¹ assuming a build-up time of 100 years for the liberalization scenario. C stocks on the current forest area are increasing by 1 MtC y⁻¹. The maximal total C sink of 1.6 MtC might thus suffice to compensate for agricultural greenhouse gases (2004: 1.4 Mt CO₂–C equivalents), but corresponds only to 11–13% of the anthropogenic greenhouse gas emission in Switzerland. Thus, even the largest of the expected terrestrial C stocks under liberalization will be small in comparison with current emissions of anthropogenic greenhouse gases.     

Behavioral genetic approaches to visual system development and function in zebrafish

The zebrafish is a recent vertebrate model system that shows great potential for a genetic analysis of behavior. Early development is extraordinarily rapid, so that larvae already display a range of behaviors 5 days after fertilization. In particular the visual system develops precociously, supporting a number of visually mediated behaviors in the larva. This provides the opportunity to use these visually mediated behaviors to screen chemically mutagenized strains for defects in vision. Larval optokinetic and optomotor responses have already been successfully employed to screen for mutant strains with defects in the visual system. In the adult zebrafish a visually mediated escape response has proved useful for screening for dominant mutations of the visual system. Here, I summarize visually mediated behaviors of both larval and adult zebrafish and their applicability for genetic screens, and present, the approaches and results of visual behavior carried out to date.     

Pyronaridine–artesunate real-world safety,tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm,open-label,cohort event monitoring study

BackgroundIn Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine–artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa.Methods and findingsThis single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine–artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine–artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine–artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated.ConclusionsPyronaridine–artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine–artesunate as an operationally useful addition to the management of acute uncomplicated malaria.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03201770","term_id":"NCT03201770"}}NCT03201770.

Gaston Tona Lutete and co-workers report on safety and effectiveness of the antimalarial drug pyronaridine-artesunate in African countries.     

Tandem-repetitive noncoding DNA: forms and forces

A model of sequence-dependent, unequal crossing-over and gene amplification (slippage replication) has been stimulated in order to account for various structural features of tandemly repeated DNA sequences. It is shown that DNA whose sequence is not maintained by natural selection will exhibit repetitive patterns over a wide range of recombination rates as a result of the interaction of unequal crossing-over and slippage replication, processes that depend on sequence similarity. At high crossing-over frequencies, the nucleotide patterns generated in the simulations are simple and highly regular, with short, nearly identical sequences repeated in tandem. Decreasing recombination rates increase the tendency to longer and more-complex repeat units. Periodicities have been observed down to very low recombination rates (one or more orders of magnitude lower than mutation rate). At such low rates, most of the sequences contain repeats which have an extensive substructure and a high degree of heterogeneity among each other; often higher-order structures are superimposed on a tandem array. These results are compared with various structural properties of tandemly repeated DNAs known from eukaryotes, the spectrum ranging from simple-sequence DNAs, particularly the hypervariable mini-satellites, to the classical satellite DNAs, located in chromosomal regions of low recombination, e.g., heterochromatin.     

The Process-inducing Activity of Transmembrane Agrin Requires Follistatin-like Domains

Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system.