Environmental constraints and call evolution in torrent‐dwelling frogs

Although acoustic signals are important for communication in many taxa, signal propagation is affected by environmental properties. Strong environmental constraints should drive call evolution, favoring signals with greater transmission distance and content integrity in a given calling habitat. Yet, few empirical studies have verified this prediction, possibly due to a shortcoming in habitat characterization, which is often too broad. Here we assess the potential impact of environmental constraints on the evolution of advertisement call in four groups of torrent‐dwelling frogs in the family Ranidae. We reconstruct the evolution of calling site preferences, both broadly categorized and at a finer scale, onto a phylogenetic tree for 148 species with five markers (～3600 bp). We test models of evolution for six call traits for 79 species with regard to the reconstructed history of calling site preferences and estimate their ancestral states. We find that in spite of existing morphological constraints, vocalizations of torrent‐dwelling species are most probably constrained by the acoustic specificities of torrent habitats and particularly their high level of ambient noise. We also show that a fine‐scale characterization of calling sites allows a better perception of the impact of environmental constraints on call evolution.     

A common genetic network underlies substance use disorders and disruptive or externalizing disorders

Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders.     

Environmental impacts of decommissioning nuclear power plants: methodical challenges,case study,and implications

Purpose

Environmental impacts of the decommissioning of nuclear power plants are brought into focus by the nuclear phase-out in Germany and a worldwide growing number of decommissioning projects. So far, life cycle assessments of decommissioning nuclear power plants have been conducted very rarely or are based on rather uncertain assumptions. Against this background, environmental impacts of the ongoing decommissioning of the nuclear power plant in Lubmin (KGR), Germany are examined. Methodological aspects like transferability to other decommissioning projects as well as influence of assumptions about the lifespan of a power plant are discussed.

Methods

A life cycle assessment of the decommissioning according to ISO 14040/44 is conducted. The decommissioning of one power plant (of the assessed KGR) is chosen as functional unit. The system boundaries include removal and demolition of plant components and buildings as well as decontamination, conditioning, interim storage, and final repository of low-level and interim-level nuclear waste together with disposal and recycling of conventional waste. Interim storage and final repository of high-level nuclear waste such as fuel rods are excluded from the system boundaries as they are assigned to the use phase of the plant. Primary data was obtained from the plant decommissioning firm (Energiewerke Nord GmbH, EWN) in Lubmin. The GaBi database was used to model background processes. Environmental impacts are estimated using the CML2001 methodology.

Results and discussion

Environmental impacts are mainly caused by on-site energetic demands of component removal and peripheral tasks. Further significant impacts are caused by the handling, storage, and final repository of low-level and intermediate-level nuclear waste. Recycling conventional, nonradioactive metallic waste has the potential to unburden the process in a significant scale, depending on recycling rates.

Conclusions

The dismantling of nuclear power plants shows a relevant environmental impact. Regarding the environmental impacts per kilowatt-hour assumptions concerning the plant’ lifespan are a crucial factor. Comparing the result from this study to recent datasets for nuclear power poses the question if LCA datasets represent environmental burdens of nuclear power accurately. The transferability of LCA results to other studies using one parameter for scaling is problematic and needs further research.     

Mutations in Smooth Muscle Alpha-Actin (ACTA2) Cause Coronary Artery Disease, Stroke, and Moyamoya Disease, Along with Thoracic Aortic Disease

The vascular smooth muscle cell (SMC)-specific isoform of α-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections (TAAD), but only half of mutation carriers have aortic disease. Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease (CAD) and premature ischemic strokes (including Moyamoya disease [MMD]), as well as previously defined TAAD. Sequencing of DNA from patients with nonfamilial TAAD and from premature-onset CAD patients independently identified ACTA2 mutations in these patients and premature onset strokes in family members with ACTA2 mutations. Vascular pathology and analysis of explanted SMCs and myofibroblasts from patients harboring ACTA2 suggested that increased proliferation of SMCs contributed to occlusive diseases. These results indicate that heterozygous ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, including TAAD, premature CAD, ischemic strokes, and MMD. These data demonstrate that diffuse vascular diseases resulting from either occluded or enlarged arteries can be caused by mutations in a single gene and have direct implications for clinical management and research on familial vascular diseases.     

The first metal complexes bearing ligated 3-iminoisoindolin-1-ones

The reaction between Zn(OAc)₂ · 2H₂O (1) and the 3-iminoisoindolin-1-ones H₂NCNC(O)C₆R¹R²R³R⁴ (R¹-R⁴ = H 2; R¹, R⁴ = H, R², R³ = Cl 3; R¹, R³, R⁴ = H, R² = Me 4) in EtCN at 70 °C for ca. 12 h affords the novel family of complexes [Zn{H₂NCNC(O)C₆R¹R²R³R⁴}₂(OAc)₂] (R¹-R⁴ = H 5; R¹, R⁴ = H, R², R³ = Cl 6; R¹, R³, R⁴ = H, R² = Me 7) in excellent (90% and 93% for 5 and 6, correspondingly) to good (64% for 7) yields. The isolated compounds were characterized by elemental analyses (C, H, N), IR, NMR and ESI⁺-MS. X-ray diffraction data for 2 and 5 indicate that both free (2) and ligated (5) 3-iminoisoindolin-1-ones exist in the zwitterionic form.     

Die submikroskopische Struktur der Assimilatleitbahnen von Polytrichum commune

Summary In the young part of the stem of Polytrichum commune the protoplasts of the two types of conducting cells, the leptoids and parenchyma cells, are nearly identically equipped with cell organelles and cytoplasmic structures. Both types contain a nucleus, chloroplasts, mitochondria, and dictyosomes. The endoplasmic reticulum builds characteristic cisterns in form of hollow cylinders extending from one end wall to the other. The cisterns are connected with many plasmodesmata, which occur only in the end walls. Leptoids have oblique end walls with 16 to 20 plasmodesmata per m², and parenchyma cells show cross walls perpendicular to the axis with 9 to 12 plasmodesmata per m².Since the leptoids are supposed to be the pathways for the longitudinal transport of assimilates (Eschrich and Steiner, 1967, 1968), it is of interest that early in their development these elements undergo a change in their protoplasmatic structure. Two to 3 cm below the apical cell the protoplasts degenerate and show lysosome-like structures. The endoplasmic reticulum and other structures are deformed or dissolved; the plasmodesmata are constricted by callose deposits. At the same level the parenchyma cells still retain the original structure of their protoplasts.Thus, assimilates moving upward in one row of leptoids may penetrate the whole lumen of the leptoids at lower levels, but they are restricted to the cisterns of the endoplasmic reticulum at higher levels of the stem.     

Correlation of Perfusion MRI and 18F-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

ObjectivesTo investigate a multimodal, multiparametric perfusion MRI / ¹⁸F-fluoro-deoxyglucose-(¹⁸F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.ResultsRegorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05).ConclusionsA multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and ¹⁸F-FDG-PET validated by immunohistochemistry.     

An Inactivated Cell Culture Japanese Encephalitis Vaccine (JE-ADVAX) Formulated with Delta Inulin Adjuvant Provides Robust Heterologous Protection against West Nile Encephalitis via Cross-Protective Memory B Cells and Neutralizing Antibody

West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a mosquito-borne flavivirus and member of the Japanese encephalitis (JE) serocomplex. There is currently no approved human WNV vaccine, and treatment options remain limited, resulting in significant mortality and morbidity from human infection. Given the availability of approved human JE vaccines, this study asked whether the JE-ADVAX vaccine, which contains an inactivated cell culture JE virus antigen formulated with Advax delta inulin adjuvant, could provide heterologous protection against WNV infection in wild-type and β2-microglobulin-deficient (β2m^−/−) murine models. Mice immunized twice or even once with JE-ADVAX were protected against lethal WNV challenge even when mice had low or absent serum cross-neutralizing WNV titers prior to challenge. Similarly, β2m^−/− mice immunized with JE-ADVAX were protected against lethal WNV challenge in the absence of CD8⁺ T cells and prechallenge WNV antibody titers. Protection against WNV could be adoptively transferred to naive mice by memory B cells from JE-ADVAX-immunized animals. Hence, in addition to increasing serum cross-neutralizing antibody titers, JE-ADVAX induced a memory B-cell population able to provide heterologous protection against WNV challenge. Heterologous protection was reduced when JE vaccine antigen was administered alone without Advax, confirming the importance of the adjuvant to induction of cross-protective immunity. In the absence of an approved human WNV vaccine, JE-ADVAX could provide an alternative approach for control of a major human WNV epidemic.     

The Conserved PFT1 Tandem Repeat Is Crucial for Proper Flowering in Arabidopsis thaliana

It is widely appreciated that short tandem repeat (STR) variation underlies substantial phenotypic variation in organisms. Some propose that the high mutation rates of STRs in functional genomic regions facilitate evolutionary adaptation. Despite their high mutation rate, some STRs show little to no variation in populations. One such STR occurs in the Arabidopsis thaliana gene PFT1 (MED25), where it encodes an interrupted polyglutamine tract. Although the PFT1 STR is large (∼270 bp), and thus expected to be extremely variable, it shows only minuscule variation across A. thaliana strains. We hypothesized that the PFT1 STR is under selective constraint, due to previously undescribed roles in PFT1 function. We investigated this hypothesis using plants expressing transgenic PFT1 constructs with either an endogenous STR or synthetic STRs of varying length. Transgenic plants carrying the endogenous PFT1 STR generally performed best in complementing a pft1 null mutant across adult PFT1-dependent traits. In stark contrast, transgenic plants carrying a PFT1 transgene lacking the STR phenocopied a pft1 loss-of-function mutant for flowering time phenotypes and were generally hypomorphic for other traits, establishing the functional importance of this domain. Transgenic plants carrying various synthetic constructs occupied the phenotypic space between wild-type and pft1 loss-of-function mutants. By varying PFT1 STR length, we discovered that PFT1 can act as either an activator or repressor of flowering in a photoperiod-dependent manner. We conclude that the PFT1 STR is constrained to its approximate wild-type length by its various functional requirements. Our study implies that there is strong selection on STRs not only to generate allelic diversity, but also to maintain certain lengths pursuant to optimal molecular function.