Species richness and evenness respond to diverging land‐use patterns – a cross‐border study of dry tropical woodlands in southern Africa

Cross‐border studies offer unique situations to study the impact of different land‐use regimes on ecosystems. Along the Angolan and Namibian border formed by the Okavango River, the environmental conditions and traditional land‐use practises are the same on either side of the river. However, decades of civil war in Angola led to a stagnant development while political stability in Namibia fostered a recent socio‐economic transformation. We investigated the impact of spatially diffuse land use on plant diversity of the dry tropical woodlands covering the vast, sandy hinterlands of the river. As accessibility is the major factor governing land use, we used distance to road as a proxy for land‐use intensity. Based on 58 vegetation plots sized 20 m × 50 m, we showed that species richness increased with distance to road in Angola while in Namibia it remained constant on a lower level. Evenness showed an inverse pattern to species richness and Shannon diversity index showed no response. Analysing diversity patterns according to life forms revealed that these patterns are primarily driven by woody species. The study showed that spatially diffuse land use has a measurable effect on plant diversity and illustrates that roads act as vectors of change.     

Mitochondrial DNA of pre‐last glacial maximum red deer from NW Spain suggests a more complex phylogeographical history for the species

The major climatic oscillations that characterized the Quaternary had a great influence on the evolution and distribution of several species. During cold periods, the distribution of temperate‐adapted species became fragmented with many surviving in southern refugia (Iberian, Italian, and Balkan Peninsulas). Red deer was one of the species that contracted its original range to southern refugia. Currently, two main lineages have been described for the species: western and eastern. We have analyzed fossils pre‐dating the last glacial maximum (LGM) from Liñares cave (NW Spain) that belongs to the peripheral range of the western clade, and fossils from the Danish Holocene belonging to the central part of the same clade. Phylogenetic analyses place our samples in the western clade. However, some specimens from Liñares represent an early split in the tree along with other pre‐LGM western samples from previous studies. Despite low bootstrap values in the Bayesian phylogenies, haplotype networks connect these foreign haplotypes to the eastern clade. We suggest a mixed phylogeographical model to explain this pattern with range expansions from the east during the expansion phase after the cold periods in marine isotope stage 3. We find slight isolation by distance in post‐LGM populations that could be a consequence of the recolonization from southern refugia after the LGM.     

Protein O-Mannosyltransferases Associate with the Translocon to Modify Translocating Polypeptide Chains

O-Mannosylation and N-glycosylation are essential protein modifications that are initiated in the endoplasmic reticulum (ER). Protein translocation across the ER membrane and N-glycosylation are highly coordinated processes that take place at the translocon-oligosaccharyltransferase (OST) complex. In analogy, it was assumed that protein O-mannosyltransferases (PMTs) also act at the translocon, however, in recent years it turned out that prolonged ER residence allows O-mannosylation of un-/misfolded proteins or slow folding intermediates by Pmt1-Pmt2 complexes. Here, we reinvestigate protein O-mannosylation in the context of protein translocation. We demonstrate the association of Pmt1-Pmt2 with the OST, the trimeric Sec61, and the tetrameric Sec63 complex in vivo by co-immunoprecipitation. The coordinated interplay between PMTs and OST in vivo is further shown by a comprehensive mass spectrometry-based analysis of N-glycosylation site occupancy in pmtΔ mutants. In addition, we established a microsomal translation/translocation/O-mannosylation system. Using the serine/threonine-rich cell wall protein Ccw5 as a model, we show that PMTs efficiently mannosylate proteins during their translocation into microsomes. This in vitro system will help to unravel mechanistic differences between co- and post-translocational O-mannosylation.     

Role of IL1A rs1800587, IL1B rs1143627 and IL1RN rs2234677 Genotype Regarding Development of Chronic Lumbar Radicular Pain; a Prospective One-Year Study

Previous studies indicate that lumbar radicular pain following disc herniation may be associated with release of several pro-inflammatory mediators, including interleukin-1 (IL1). In the present study, we examined how genetic variability in IL1A (rs1800587 C>T), IL1B (rs1143627 T>C) and IL1RN (rs2234677 G>A) influenced the clinical outcome the first year after disc herniation. Patients (n = 258) with lumbar radicular pain due to disc herniation were recruited from two hospitals in Norway. Pain and disability were measured by visual analogue scale (VAS) and Oswestry Disability Index (ODI) over a 12 month period. The result showed that patients with the IL1A T allele, in combination with the IL1RN A allele had more pain and a slower recovery than other patients (VAS p = 0.049, ODI p = 0.059 rmANOVA; VAS p = 0.003, ODI p = 0.050 one-way ANOVA at 12 months). However, regarding the IL1B/IL1RN genotype, no clear effect on recovery was observed (VAS p = 0.175, ODI p = 0.055 rmANOVA; VAS p = 0.105, ODI p = 0.214 one-way ANOVA at 12 months). The data suggest that the IL1A T/IL1RN A genotype, but not the IL1B T/IL1RN A genotype, may increase the risk of a chronic outcome in patients following disc herniation.     

4E10-Resistant HIV-1 Isolated from Four Subjects with Rare Membrane-Proximal External Region Polymorphisms

Human antibody 4E10 targets the highly conserved membrane-proximal external region (MPER) of the HIV-1 transmembrane glycoprotein, gp41, and has extraordinarily broad neutralizing activity. It is considered by many to be a prototype for vaccine development. In this study, we describe four subjects infected with viruses carrying rare MPER polymorphisms associated with resistance to 4E10 neutralization. In one case resistant virus carrying a W680G substitution was transmitted from mother to infant. We used site-directed mutagenesis to demonstrate that the W680G substitution is necessary for conferring the 4E10-resistant phenotype, but that it is not sufficient to transfer the phenotype to a 4E10-sensitive Env. Our third subject carried Envs with a W680R substitution causing variable resistance to 4E10, indicating that residues outside the MPER are required to confer the phenotype. A fourth subject possessed a F673L substitution previously associated with 4E10 resistance. For all three subjects with W680 polymorphisms, we observed additional residues in the MPER that co-varied with position 680 and preserved charged distributions across this region. Our data provide important caveats for vaccine development targeting the MPER. Naturally occurring Env variants described in our study also represent unique tools for probing the structure-function of HIV-1 envelope.     

Activity-dependent α-Cleavage of Nectin-1 Is Mediated by A Disintegrin and Metalloprotease 10 (ADAM10)

Nectin-1 is known to undergo ectodomain shedding by α-secretase and subsequent proteolytic processing by γ-secretase. How secretase-mediated cleavage of nectin-1 is regulated in neuronal cells and how nectin-1 cleavage affects synaptic adhesion is poorly understood. We have investigated α-and γ-secretase-mediated processing of nectin-1 in primary cortical neurons and identified which protease acts as a α-secretase. We report here that NMDA receptor activation, but not stimulation of AMPA or metabotropic glutamate receptors, resulted in robust α- and γ-secretase cleavage of nectin-1 in mature cortical neurons. Cleavage of nectin-1 required influx of Ca²⁺ through the NMDA receptor, and activation of calmodulin, but was not dependent on calcium/calmodulin-dependent protein kinase II (CaMKII) activation. We found that ADAM10 is the major secretase responsible for nectin-1 ectodomain cleavage in neurons and the brain. These observations suggest that α- and γ-secretase processing of nectin-1 is a Ca²⁺/calmodulin-regulated event that occurs under conditions of activity-dependent synaptic plasticity and ADAM10 and γ-secretase are responsible for these cleavage events.     

Mba1, a membrane-associated ribosome receptor in mitochondria

The genome of mitochondria encodes a small number of very hydrophobic polypeptides that are inserted into the inner membrane in a cotranslational reaction. The molecular process by which mitochondrial ribosomes are recruited to the membrane is poorly understood. Here, we show that the inner membrane protein Mba1 binds to the large subunit of mitochondrial ribosomes. It thereby cooperates with the C-terminal ribosome-binding domain of Oxa1, which is a central component of the insertion machinery of the inner membrane. In the absence of both Mba1 and the C-terminus of Oxa1, mitochondrial translation products fail to be properly inserted into the inner membrane and serve as substrates of the matrix chaperone Hsp70. We propose that Mba1 functions as a ribosome receptor that cooperates with Oxa1 in the positioning of the ribosome exit site to the insertion machinery of the inner membrane.