Successful reintroduction of species: improving on windows of opportunity for biodiversity repair

To overcome resistance of degraded ecological communities to restorative interventions, we need to understand windows of opportunity—limited time frames when species reintroduction attempts are still successful. More specifically, we need to understand what makes these windows close, as this may enable us to stretch or reopen them. We investigated this using models of simple food web modules. We show how joint changes of bottom–up and top–down control may be applied to change windows of opportunity and increase reintroduction success. Which reintroduction densities were most effective seemed system-specific. A more general result is that reintroduction success was strongly enhanced by low to intermediate carrying capacities of basal species (e.g. periphyton and other algae in streams). This can be seen as equivalent to low to intermediate nutrient levels. When these were too high, almost any combination of restorative measures was rendered ineffective. Interestingly, reintroducing primarily and secondarily lost species at the same time was more effective than sequential reintroductions that first attempted to fix secondary extinctions. We could further enhance the success of species reintroductions by reducing the carrying capacities of basal species before the reintroduction of primarily and secondarily lost species. We discuss our results in the light of empirical work on macro-invertebrates in streams. This serves to exemplify how our results can be applied in the practice of ecological restoration.     

Functional Dissection of the Nascent Polypeptide-Associated Complex in Saccharomyces cerevisiae

Both the yeast nascent polypeptide-associated complex (NAC) and the Hsp40/70-based chaperone system RAC-Ssb are systems tethered to the ribosome to assist cotranslational processes such as folding of nascent polypeptides. While loss of NAC does not cause phenotypic changes in yeast, the simultaneous deletion of genes coding for NAC and the chaperone Ssb (nacΔssbΔ) leads to strongly aggravated defects compared to cells lacking only Ssb, including impaired growth on plates containing L-canavanine or hygromycin B, aggregation of newly synthesized proteins and a reduced translational activity due to ribosome biogenesis defects. In this study, we dissected the functional properties of the individual NAC-subunits (α-NAC, β-NAC and β’-NAC) and of different NAC heterodimers found in yeast (αβ-NAC and αβ’-NAC) by analyzing their capability to complement the pleiotropic phenotype of nacΔssbΔ cells. We show that the abundant heterodimer αβ-NAC but not its paralogue αβ’-NAC is able to suppress all phenotypic defects of nacΔssbΔ cells including global protein aggregation as well as translation and growth deficiencies. This suggests that αβ-NAC and αβ’-NAC are functionally distinct from each other. The function of αβ-NAC strictly depends on its ribosome association and on its high level of expression. Expression of individual β-NAC, β’-NAC or α-NAC subunits as well as αβ’-NAC ameliorated protein aggregation in nacΔssbΔ cells to different extents while only β-NAC was able to restore growth defects suggesting chaperoning activities for β-NAC sufficient to decrease the sensitivity of nacΔssbΔ cells against L-canavanine or hygromycin B. Interestingly, deletion of the ubiquitin-associated (UBA)-domain of the α-NAC subunit strongly enhanced the aggregation preventing activity of αβ-NAC pointing to a negative regulatory role of this domain for the NAC chaperone activity in vivo.     

Environmental influences on the production of pre-implantation embryos

Generation and cryopreservation of transgenic mice depend on reliable and continuous production of pre-implantation embryos. To suppress circannual and circadian rhythms driving the physiological and sexual behaviour of free living animals, laboratory animals are housed under standardized conditions. It remains to be elucidated if the artificial climate can cover all environmental effects. Here, we report that the humidity in an animal facility affects the embryo yield. The weather at the location of the facility, especially the temperature, influences the climate within an animal facility; weather peaks are obviously covered in part only, even if the facility is equipped with a powerful air-conditioning supply. Subsequently, external weather changes interact with the environment within the facility, influencing the production of embryos. Furthermore, noise and/or vibrations as generated by construction works, negatively affect the embryo yield.     

Inhibition of 5-lipoxygenase by U73122 is due to covalent binding to cysteine 416

U73122 which was originally identified as a phospholipase C inhibitor represents a potent direct inhibitor of purified 5-lipoxygenase (5-LO) with an IC50 value of 30 nM. 5-LO catalyzes the conversion of arachidonic acid (AA) into leukotrienes which represent mediators involved in inflammatory and allergic reactions and in host defense reactions against microorganisms. Since the efficient inhibition of the human 5-LO enzyme depended on the thiol reactivity of the maleinimide group of U73122, we used this property to identify cysteine residues in the 5-LO protein that are important for 5-LO inhibition by U73122. We found by MALDI-MS that U73122 covalently binds to cysteine residues 99, 159, 248, 264, 416 and 449. Mutation of Cys416 to serine strongly reduces inhibition of 5-LO by U73122 and the additional mutation of three cysteines close to Cys416 further impairs 5-LO inhibition by the compound. Wash out experiments with U73122 and 5-LO indicated an irreversible binding of U73122. Together, our data suggest that the area around Cys416 which is close to the proposed AA entry channel to the active site is an interesting target for the development of new 5-LO inhibitors.     

The historical development of zoo elephant survivorship

In the discussion about zoo elephant husbandry, the report of Clubb et al. (2008, Science 322: 1649) that zoo elephants had a “compromised survivorship” compared to certain non-zoo populations is a grave argument, and was possibly one of the triggers of a large variety of investigations into zoo elephant welfare, and changes in zoo elephant management. A side observation of that report was that whereas survivorship in African elephants (Loxodonta africana) improved since 1960, this was not the case in Asian elephants (Elephas maximus). We used historical data (based on the Species360 database) to revisit this aspect, including recent developments since 2008. Assessing the North American and European populations from 1910 until today, there were significant improvements of adult (≥10 years) survivorship in both species. For the period from 1960 until today, survivorship improvement was significant for African elephants and close to a significant improvement in Asian elephants; Asian elephants generally had a higher survivorship than Africans. Juvenile (<10 years) survivorship did not change significantly since 1960 and was higher in African elephants, most likely due to the effect of elephant herpes virus on Asian elephants. Current zoo elephant survivorship is higher than some, and lower than some other non-zoo populations. We discuss that in our view, the shape of the survivorship curve, and its change over time, are more relevant than comparisons with specific populations. Zoo elephant survivorship should be monitored continuously, and the expectation of a continuous trend towards improvement should be met.     

Proteolytic Processing Regulates Placental Growth Factor Activities

Placental growth factor (PlGF) is a critical mediator of blood vessel formation, yet mechanisms of its action and regulation are incompletely understood. Here we demonstrate that proteolytic processing regulates the biological activity of PlGF. Specifically, we show that plasmin processing of PlGF-2 yields a protease-resistant core fragment comprising the vascular endothelial growth factor receptor-1 binding site but lacking the carboxyl-terminal domain encoding the heparin-binding domain and an 8-amino acid peptide encoded by exon 7. We have identified plasmin cleavage sites, generated a truncated PlGF118 isoform mimicking plasmin-processed PlGF, and explored its biological function in comparison with that of PlGF-1 and -2. The angiogenic responses induced by the diverse PlGF forms were distinct. Whereas PlGF-2 increased endothelial cell chemotaxis, vascular sprouting, and granulation tissue formation upon skin injury, these activities were abrogated following plasmin digestion. Investigation of PlGF/Neuropilin-1 binding and function suggests a critical role for heparin-binding domain/Neuropilin-1 interaction and its regulation by plasmin processing. Collectively, here we provide new mechanistic insights into the regulation of PlGF-2/Neuropilin-1-mediated tissue vascularization and growth.     

Role of ion channels in heart failure and channelopathies

Heart failure (HF) is a complication of multiple cardiac diseases and is characterized by impaired contractile and electric function. Patients with HF are not only limited by reduced contractile function but are also prone to life-threatening ventricular arrhythmias. HF itself leads to remodeling of ion channels, gap junctions, and intracellular calcium handling abnormalities that in combination with structural remodeling, e.g., fibrosis, produce a substrate for an arrhythmogenic disorders. Not only ventricular life-threatening arrhythmias contribute to increased morbidity and mortality but also atrial arrhythmias, especially atrial fibrillation (AF), are common in HF patients and contribute to morbidity and mortality. The distinct ion channel remodeling processes in HF and in channelopathies associated with HF will be discussed. Further basic research and clinical studies are needed to identify underlying molecular pathways of HF pathophysiology to provide the basis for improved patient care and individualized therapy based on individualized ion channel composition and remodeling.     

Inhibition of 5-lipoxygenase by U73122 is due to covalent binding to cysteine 416

U73122 which was originally identified as a phospholipase C inhibitor represents a potent direct inhibitor of purified 5-lipoxygenase (5-LO) with an IC50 value of 30 nM. 5-LO catalyzes the conversion of arachidonic acid (AA) into leukotrienes which represent mediators involved in inflammatory and allergic reactions and in host defense reactions against microorganisms. Since the efficient inhibition of the human 5-LO enzyme depended on the thiol reactivity of the maleinimide group of U73122, we used this property to identify cysteine residues in the 5-LO protein that are important for 5-LO inhibition by U73122. We found by MALDI-MS that U73122 covalently binds to cysteine residues 99, 159, 248, 264, 416 and 449. Mutation of Cys416 to serine strongly reduces inhibition of 5-LO by U73122 and the additional mutation of three cysteines close to Cys416 further impairs 5-LO inhibition by the compound. Wash out experiments with U73122 and 5-LO indicated an irreversible binding of U73122. Together, our data suggest that the area around Cys416 which is close to the proposed AA entry channel to the active site is an interesting target for the development of new 5-LO inhibitors.