Rapid population decline in red knots: fitness consequences of decreased refuelling rates and late arrival in Delaware Bay

Most populations of migrant shorebirds around the world are in serious decline, suggesting that vital condition-dependent rates such as fecundity and annual survival are being affected globally. A striking example is the red knot (Calidris canutus rufa) population wintering in Tierra del Fuego, which undertakes marathon 30,000 km hemispheric migrations annually. In spring, migrant birds forage voraciously on horseshoe crab eggs in Delaware Bay in the eastern USA before departing to breed in Arctic polar deserts. From 1997 to 2002 an increasing proportion of knots failed to reach threshold departure masses of 180-200 g, possibly because of later arrival in the Bay and food shortage from concurrent over-harvesting of crabs. Reduced nutrient storage, especially in late-arriving birds, possibly combined with reduced sizes of intestine and liver during refuelling, had severe fitness consequences for adult survival and recruitment of young in 2000-2002. From 1997 to 2002 known survivors in Delaware Bay were heavier at initial capture than birds never seen again, annual survival of adults decreased by 37% between May 2000 and May 2001, and the number of second-year birds in wintering flocks declined by 47%. Population size in Tierra del Fuego declined alarmingly from 51,000 to 27,000 in 2000-2002, seriously threatening the viability of this subspecies. Demographic modelling predicts imminent endangerment and an increased risk of extinction of the subspecies without urgent risk-averse management.     

Major Changes in the Ecology of the Wadden Sea: Human Impacts, Ecosystem Engineering and Sediment Dynamics

Shallow soft-sediment systems are mostly dominated by species that, by strongly affecting sediment dynamics, modify their local environment. Such ecosystem engineering species can have either sediment-stabilizing or sediment-destabilizing effects on tidal flats. They interplay with abiotic forcing conditions (wind, tide, nutrient inputs) in driving the community structure and generating spatial heterogeneity, determining the composition of different communities of associated species, and thereby affecting the channelling of energy through different compartments in the food web. This suggests that, depending on local species composition, tidal flats may have conspicuously different geomorphology and biological functions under similar external conditions. Here we use a historical reconstruction of benthic production in the Wadden Sea to construct a framework for the relationships between human impacts, ecosystem engineering and sediment dynamics. We propose that increased sediment disturbances by human exploitation interfere with biological controls of sediment dynamics, and thereby have shifted the dominant compartments of both primary and secondary production in the Wadden Sea, transforming the intertidal from an internally regulated and spatially heterogeneous, to an externally regulated and spatially homogenous system. This framework contributes to the general understanding of the interaction between biological and environmental control of ecosystem functioning, and suggests a general framework for predicting effects of human impacts on soft-bottom ecosystems.     

Extramuscular myofascial force transmission alters substantially the acute effects of surgical aponeurotomy: assessment by finite element modeling

Effects of extramuscular myofascial force transmission on the acute effects of aponeurotomy were studied using finite element modeling and implications of such effects on surgery were discussed. Aponeurotomized EDL muscle of the rat was modeled in two conditions: (1) fully isolated (2) with intact extramuscular connections. The specific goal was to assess the alterations in muscle length-force characteristics in relation to sarcomere length distributions and to investigate how the mechanical mechanism of the intervention is affected if the muscle is not isolated. Major effects of extramuscular myofascial force transmission were shown on muscle length-force characteristics. In contrast to the identical proximal and distal forces of the aponeurotomized isolated muscle, substantial proximo-distal force differences were shown for aponeurotomized muscle with extramuscular connections (for all muscle lengths F (dist) > F (prox) after distal muscle lengthening). Proximal optimal length did not change whereas distal optimal length was lower (by 0.5 mm). The optimal forces of the aponeurotomized muscle with extramuscular connections exerted at both proximal and distal tendons were lower than that of isolated muscle (by 15 and 7%, respectively). The length of the gap separating the two cut ends of the intervened aponeurosis decreases substantially due to extramuscular myofascial force transmission. The amplitude of the difference in gap length was muscle length dependent (maximally 11.6% of the gap length of the extramuscularly connected muscle). Extramuscular myofascial force transmission has substantial effects on distributions of lengths of sarcomeres within the muscle fiber populations distal and proximal to the location of intervention: (a) Within the distal population, the substantial sarcomere shortening at the proximal ends of muscle fibers due to the intervention remained unaffected however, extramuscular myofascial force transmission caused a more pronounced serial distribution towards the distal ends of muscle fibers. (b) In contrast, extramuscular myofascial force transmission limits the serial distribution of sarcomere lengths shown for the aponeurotomized isolated muscle in the proximal population. Fiber stress distributions showed that extramuscular myofascial force transmission causes most sarcomeres within the aponeurotomized muscle to attain lengths favorable for higher force exertion. It is concluded that acute effects of aponeurotomy on muscular mechanics are affected greatly by extramuscular myofascial force transmission. Such effects have important implications for the outcome of surgery performed to improve impeded function since muscle in vivo is not isolated both anatomically and mechanically.     

Exome sequencing reveals a <Emphasis Type="Italic">nebulin</Emphasis> nonsense mutation in a dog model of nemaline myopathy

Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bulldogs (ABDs); rod bodies in muscle biopsies established this as NM. Using SNP profiles from the nuclear family, we evaluated inheritance patterns at candidate loci and prioritized TNNT1 and NEB for further investigation. Whole exome sequencing of the dam, two affected littermates, and an unaffected littermate revealed a nonsense mutation in NEB (g.52734272 C>A, S8042X). Whole tissue gel electrophoresis and western blots confirmed a lack of full-length NEB in affected tissues, suggesting nonsense-mediated decay. The pathogenic variant was absent from 120 dogs of 24 other breeds and 100 unrelated ABDs, suggesting that it occurred recently and may be private to the family. This study presents the first molecularly characterized large animal model of NM, which could provide new opportunities for therapeutic approaches.     

17 years of grassland management leads to parallel local and regional biodiversity shifts among a wide range of taxonomic groups

Conservation management is expected to increase local biodiversity, but uniform management may lead to biotic homogenization and diversity losses at the regional scale. We evaluated the effects of renewed grazing and cutting management carried out across a whole region, on the diversity of plants and seven arthropod groups. Changes in occurrence over 17 years of intensive calcareous grassland management were analysed at the species level, which gave insight into the exact species contributing to regional homogenization or differentiation. Reponses were compared between species differing in habitat affinity, dispersal ability, food specialisation and trophic level. Local species richness increased over the sampling period for true bugs and millipedes, while carabid beetles and weevils declined in local species richness. Species richness remained unchanged for plants, woodlice, ants and spiders. Regional diversity and compositional variation generally followed local patterns. Diversity shifts were only to a limited extent explained by species’ habitat affinity, dispersal ability, trophic level and food specialisation. We conclude that implementation of relatively uniform conservation management across a region did not lead to uniform changes in local species composition. This is an encouraging result for conservation managers, as it shows that there is not necessarily a conflict of interest between local and regional conservation goals. Our study also demonstrates that shifts in diversity patterns differ markedly between taxonomic groups. Single traits provide only limited understanding of these differences. This highlights the need for a wide taxonomic scope when evaluating conservation management and demonstrates the need to understand the mechanisms underlying occurrence shifts.     

B-cell expansion in the presence of the novel 293-CD40L-sCD40L cell line allows the generation of large numbers of efficient xenoantigen-free APC

BACKGROUND: CD40-activated B lymphocytes have been used successfully as potent APC for the induction of T-cell responses. However, the 3T3-CD40L cell line, regularly used for engagement of CD40 on the B-cell surface, is a potential source of xenoantigens. This may affect the specificity of T cells stimulated with CD40-activated B cells, especially when generation of T-cell lines specific for endogenously processed Ag is desired. METHODS: To develop a system that allows efficient expansion of B cells in the absence of sources of xenoantigens, we created a human 293-CD40L-sCD40L cell line that produces soluble CD40L and expresses CD40L on the cell surface. B cells from patients with hematologic malignancies were expanded on the 293-CD40L-sCD40L cells and used for stimulation of either naive or in vivo primed donor T cells in three HLA-identical patient-donor combinations. RESULTS: The 293-CD40L-sCD40L cell line was able to stimulate B-cell growth with an efficiency superior to that of the commonly used 3T3-CD40L cell line. In all cases T-cell lines and, subsequently, T-cell clones were generated that showed reactivity against patient and not donor B cells, suggesting their specificity for minor histocompatibility antigens (mHAg). DISCUSSION: B cells activated with GMP grade 293-CD40L-sCD40L can be used in a variety of applications. In particular, they may be suitable for ex vivo stimulation of T cells prior to donor lymphocyte infusion (DLI), which may enhance its graft versus leukemia (GvL) effect.     

Alterations of plasma lipids in mice via adenoviral-mediated hepatic overexpression of human ABCA1

ATP binding cassette transporter A1 (ABCA1) is a widely expressed lipid transporter essential for the generation of HDL. ABCA1 is particularly abundant in the liver, suggesting that the liver may play a major role in HDL homeostasis. To determine how hepatic ABCA1 affects plasma HDL cholesterol levels, we treated mice with an adenovirus (Ad)-expressing human ABCA1 under the control of the cytomegalovirus promoter. Treated mice showed a dose-dependent increase in hepatic ABCA1 protein, ranging from 1.2-fold to 8.3-fold using doses from 5 x 108 to 1.5 x 109 pfu, with maximal expression observed on Day 3 posttreatment. A selective increase in HDL cholesterol occurred at Day 3 in mice treated with 5 x 108 pfu Ad-ABCA1, but higher doses did not further elevate HDL cholesterol levels. In contrast, total cholesterol, triglycerides, phospholipids, non-HDL cholesterol, and apolipoprotein B levels all increased in a dose-dependent manner, suggesting that excessive overexpression of hepatic ABCA1 in the absence of its normal regulatory sequences altered total lipid homeostasis. At comparable expression levels, bacterial artificial chromosome transgenic mice, which express ABCA1 under the control of its endogenous regulatory sequences, showed a greater and more specific increase in HDL cholesterol than Ad-ABCA1-treated mice. Our results suggest that appropriate regulation of ABCA1 is critical for a selective increase in HDL cholesterol levels.     

Inhibition of Mushroom Formation and Induction of Glycerol Release—Ecological Strategies of Burkholderia terrae BS001 to Create a Hospitable Niche at the Fungus Lyophyllum sp. Strain Karsten

We investigated the ecological strategies exerted by the soil bacterium Burkholderia terrae BS001 at the hyphae of the soil saprotrophic fungus Lyophyllum sp. strain Karsten. Recently, this bacterium has been reported to form biofilms around, and to comigrate with, growing hyphae of Lyophyllum sp. strain Karsten. In addition, it was found to be able to utilize fungal metabolites. Here, we extend this work to shed some light on the interactions between the bacterial and fungal partner which allow ecological success for the former. In standing liquid microcosms inoculated with Lyophyllum sp. strain Karsten, we detected, upon prolonged incubation, the formation of a mycelial mat at the liquid–air interface. From this mat, primordia were formed after 4–6 weeks, which eventually resulted in mushrooms. However, upon addition of strain BS001 to the bulk liquid, mushroom formation from the fungal mat was clearly inhibited, as evidenced by (1) the formation of significantly lower numbers of primordia and (2) a delay of the onset of primordia formation. Moreover and importantly, the presence of strain BS001 caused the fungus to secrete large amounts of exudates at the mycelial mat, whereas such exudation was absent from control (uninoculated) or Escherichia coli K12- or Variovorax paradoxus BS64-inoculated microcosms. In the exudates, glycerol was the main carbonaceous component, and this compound could be easily utilized by strain BS001. Thus, in different experimental set-ups with the fungal partner, strain BS001 was shown to grow in the fungal exudates on the mat. The two fungal-interactive phenotypes were specific for B. terrae strain BS001, as the other bacteria used in our study, i.e. E. coli K12 and V. paradoxus BS64, did not exhibit any of these phenomena.     

A phase-II study of pegylated interferon alfa-2b for patients with metastatic renal cell carcinoma and removal of the primary tumor

Twenty-two patients with metastatic renal cell carcinoma and removal of the primary tumor were treated with subcutaneous pegylated interferon alfa-2b (PEG-Intron) to evaluate toxicity and efficacy. Start dose was 3.0 g/kg/week, escalated to 6.0 g/kg/week. After 2 months, therapy was extended in case of response or stable disease (SD) until progressive disease (PD) or relapse for a maximum of 2 years. National Cancer Institute common toxicity criteria (NCI-CTC) were monitored every 2–4 weeks. After 2 months, nine patients did not continue (8 PD, 1 SD with grade 4 CTC) and 13 extended treatment [three partial response (PR), 10 SD], of these, 11 progressed. One patient with PR developed a durable complete response later. Overall response rate was 13.6% (3/22). Median overall survival is 13 months (range 3–35 months). Dosage was escalated to 6 g/kg/week in three patients . NCI-CTC grade 2 and 3 required dose attenuation in 12 patients during escalation, and reduction in 10 during the trial. Three patients discontinued because of grade 4 CTC (two fatigue, one hyperglycemia). Fatigue was the major dose-limiting toxicity. These results suggest an efficacy and toxicity of PEG-Intron comparable to standard interferon alfa-2b in patients with mRCC and removal of the primary tumor.Author disclosure declaration: None of the authors has a relationship with pharmaceutical companies, biomedical device manufacturers or other corporations whose products or services are related to the subject matter of the submission, nor do the authors have financial interests such as investments, licensing, or other commercial interest in any drugs, goods, or services in connection with the matter under consideration.