Dental topography indicates ecological contraction of lemur communities

Understanding the paleoecology of extinct subfossil lemurs requires reconstruction of dietary preferences. Tooth morphology is strongly correlated with diet in living primates and is appropriate for inferring dietary ecology. Recently, dental topographic analysis has shown great promise in reconstructing diet from molar tooth form. Compared with traditionally used shearing metrics, dental topography is better suited for the extraordinary diversity of tooth form among subfossil lemurs and has been shown to be less sensitive to phylogenetic sources of shape variation. Specifically, we computed orientation patch counts rotated (OPCR) and Dirichlet normal energy (DNE) of molar teeth belonging to 14 species of subfossil lemurs and compared these values to those of an extant lemur sample. The two metrics succeeded in separating species in a manner that provides insights into both food processing and diet. We used them to examine the changes in lemur community ecology in Southern and Southwestern Madagascar that accompanied the extinction of giant lemurs. We show that the poverty of Madagascar's frugivore community is a long-standing phenomenon and that extinction of large-bodied lemurs in the South and Southwest resulted not merely in a loss of guild elements but also, most likely, in changes in the ecology of extant lemurs.     

Novel role for surfactant protein A in gastrointestinal graft-versus-host disease

Graft-versus-host disease (GVHD) is a severe and frequent complication of allogeneic bone marrow transplantation (BMT) that involves the gastrointestinal (GI) tract and lungs. The pathobiology of GVHD is complex and involves immune cell recognition of host Ags as foreign. We hypothesize a central role for the collectin surfactant protein A (SP-A) in regulating the development of GVHD after allogeneic BMT. C57BL/6 (H2b; WT) and SP-A-deficient mice on a C57BL/6 background (H2b; SP-A(-/-)) mice underwent allogeneic or syngeneic BMT with cells from either C3HeB/FeJ (H2k; SP-A-deficient recipient mice that have undergone an allogeneic BMT [SP-A(-/-)alloBMT] or SP-A-sufficient recipient mice that have undergone an allogeneic BMT) or C57BL/6 (H2b; SP-A-deficient recipient mice that have undergone a syngeneic BMT or SP-A-sufficient recipient mice that have undergone a syngeneic BMT) mice. Five weeks post-BMT, mice were necropsied, and lung and GI tissue were analyzed. SP-A(-/-) alloBMT or SP-A-sufficient recipient mice that have undergone an allogeneic BMT had no significant differences in lung pathology; however, SP-A(-/-)alloBMT mice developed marked features of GI GVHD, including decreased body weight, increased tissue inflammation, and lymphocytic infiltration. SP-A(-/-)alloBMT mice also had increased colon expression of IL-1β, IL-6, TNF-α, and IFN-γ and as well as increased Th17 cells and diminished regulatory T cells. Our results demonstrate the first evidence, to our knowledge, of a critical role for SP-A in modulating GI GVHD. In these studies, we demonstrate that mice deficient in SP-A that have undergone an allogeneic BMT have a greater incidence of GI GVHD that is associated with increased Th17 cells and decreased regulatory T cells. The results of these studies demonstrate that SP-A protects against the development of GI GVHD and establishes a role for SP-A in regulating the immune response in the GI tract.     

Reduced activity of juvenile hormone esterase in microsporidia-infected Lymantria dispar larvae

Infection of the fat body of Lymantria dispar (Lep.: Lymantriinae) larvae with the microsporidium Vairimorpha disparis has severe effects on juvenile hormone (JH) metabolism of the host. Beginning 8 days postinfection, activity of the JH degrading enzyme JH-esterase was significantly lower in the hemolymph of infected than uninfected larvae. Activity remained low as microsporidiosis progressed. JH titers were slightly elevated in infected larvae; the difference was not significant in most cases. This disturbance of JH metabolism may be due to generally impaired fat body functions and high demand for resources by the developing pathogen.     

MUF1/Leucine-Rich Repeat Containing 41 (LRRC41), a Substrate of RhoBTB-Dependent Cullin 3 Ubiquitin Ligase Complexes, Is a Predominantly Nuclear Dimeric Protein

RhoBTB (BTB stands for broad-complex, tramtrack, bric à brac) proteins are tumor suppressors involved in the formation of cullin 3 (Cul3)-dependent ubiquitin ligase complexes. However, no substrates of RhoBTB-Cul3 ubiquitin ligase complexes have been identified. We identified MUF1 (LRRC41, leucine-rich repeat containing 41) as a potential interaction partner of RhoBTB3 in a two-hybrid screening on a mouse brain cDNA library. MUF1 is a largely uncharacterized protein containing a leucine-rich repeat and, interestingly, a BC-box that serves as a linker in multicomponent, cullin 5 (Cul5)-based ubiquitin ligases. We confirmed the interaction of MUF1 with all three mammalian RhoBTB proteins using immunoprecipitation. We characterized MUF1 in terms of expression profile and subcellular localization, the latter also with respect to RhoBTB proteins. We found out that MUF1 is a ubiquitously expressed nuclear protein that, upon coexpression with RhoBTB, partially retains in the cytoplasm, where both proteins colocalize. We also show that MUF1 is able to dimerize similarly to other leucine-rich repeat-containing proteins. To explore the significance of MUF1-RhoBTB interaction within Cul-ligase complexes and the mechanism of MUF1 degradation, we performed a protein stability assay and found that MUF1 is degraded in the proteasome in a Cul5-independent manner by RhoBTB3-Cul3 ubiquitin ligase complex. Finally, we explored a possible heterodimerization of Cul3 and Cul5 and indeed discovered that these two cullins are capable of forming heterodimers. Thus, we have identified MUF1 as the first substrate for RhoBTB-Cul3 ubiquitin ligase complexes. Identification of substrates of these complexes will result in better understanding of the tumor suppressor function of RhoBTB.     

Ca++/CaMKII switches nociceptor‐sensitizing stimuli into desensitizing stimuli

Many extracellular factors sensitize nociceptors. Often they act simultaneously and/or sequentially on nociceptive neurons. We investigated if stimulation of the protein kinase C epsilon (PKCε) signaling pathway influences the signaling of a subsequent sensitizing stimulus. Central in activation of PKCs is their transient translocation to cellular membranes. We found in cultured nociceptive neurons that only a first stimulation of the PKCε signaling pathway resulted in PKCε translocation. We identified a novel inhibitory cascade to branch off upstream of PKCε, but downstream of Epac via IP3‐induced calcium release. This signaling branch actively inhibited subsequent translocation and even attenuated ongoing translocation. A second ‘sensitizing’ stimulus was rerouted from the sensitizing to the inhibitory branch of the signaling cascade. Central for the rerouting was cytoplasmic calcium increase and CaMKII activation. Accordingly, in behavioral experiments, activation of calcium stores switched sensitizing substances into desensitizing substances in a CaMKII‐dependent manner. This mechanism was also observed by in vivo C‐fiber electrophysiology corroborating the peripheral location of the switch. Thus, we conclude that the net effect of signaling in nociceptors is defined by the context of the individual cell's signaling history.     

Epstein-Barr virus BPLF1 deubiquitinates PCNA and attenuates polymerase η recruitment to DNA damage sites

PCNA is monoubiquitinated in response to DNA damage and fork stalling and then initiates recruitment of specialized polymerases in the DNA damage tolerance pathway, translesion synthesis (TLS). Since PCNA is reported to associate with Epstein-Barr virus (EBV) DNA during its replication, we investigated whether the EBV deubiquitinating (DUB) enzyme encoded by BPLF1 targets ubiquitinated PCNA and disrupts TLS. An N-terminal BPLF1 fragment (a BPLF1 construct containing the first 246 amino acids [BPLF1 1-246]) associated with PCNA and attenuated its ubiquitination in response to fork-stalling agents UV and hydroxyurea in cultured cells. Moreover, monoubiquitinated PCNA was deubiquitinated after incubation with purified BPLF1 1-246 in vitro. BPLF1 1-246 dysregulated TLS by reducing recruitment of the specialized repair polymerase polymerase η (Polη) to the detergent-resistant chromatin compartment and virtually abolished localization of Polη to nuclear repair foci, both hallmarks of TLS. Expression of BPLF1 1-246 decreased viability of UV-treated cells and led to cell death, presumably through deubiquitination of PCNA and the inability to repair damaged DNA. Importantly, deubiquitination of PCNA could be detected endogenously in EBV-infected cells in comparison with samples expressing short hairpin RNA (shRNA) against BPLF1. Further, the specificity of the interaction between BPLF1 and PCNA was dependent upon a PCNA-interacting peptide (PIP) domain within the N-terminal region of BPLF1. Both DUB activity and PIP sequence are conserved in the members of the family Herpesviridae. Thus, deubiquitination of PCNA, normally deubiquitinated by cellular USP1, by the viral DUB can disrupt repair of DNA damage by compromising recruitment of TLS polymerase to stalled replication forks. PCNA is the first cellular target identified for BPLF1 and its deubiquitinating activity.     

A suite of citrate-derived siderophores from a marine Vibrio species isolated following the Deepwater Horizon oil spill

Nearly all microbes require iron for growth. The low concentration of iron found in the ocean makes iron acquisition a particularly difficult task. In response to these low iron conditions, many bacteria produce low-molecular-weight iron-binding molecules called siderophores to aid in iron uptake. We report herein the isolation and structural characterization of a suite of amphiphilic siderophores called the ochrobactins-OH, which are produced by a Vibrio species isolated from the Gulf of Mexico after the 2010 Deepwater Horizon oil spill. The citrate-based ochrobactins-OH are derivatives of aerobactin, replacing the acetyl groups with fatty acid appendages ranging in size from C8 to C12, and are distinctly different from the ochrobactins in that the fatty acid appendages are hydroxylated rather than unsaturated. The discovery of the marine amphiphilic ochrobactin-OH suite of siderophores increases the geographic and phylogenetic diversity of siderophore-producing bacteria.     

Effect of nutrient loading on biogeochemical processes in tropical tidal creeks

The effect of increased nutrient loads on biogeochemical processes in macrotidal, mangrove-lined creeks was studied in tropical Darwin Harbour, Australia. This study uses an integrative approach involving multiple benthic and pelagic processes as measures of ecosystem function, and provides a comparison of these processes in three tidal creeks receiving different loads of treated sewage effluent. There were significant differences in process rates between Buffalo Creek (BC) (hypereutrophic), which receives the largest sewage loads; Myrmidon Creek (MC) (oligotrophic–mesotrophic) which receives smaller sewage inputs; and Reference Creek (RC) (oligotrophic) which is comparatively pristine. Benthic nutrient fluxes and denitrification were more than an order of magnitude higher and lower, respectively, in BC and denitrification efficiency (DE) was <10%. Pelagic primary production rates were also much higher in BC but respiration exceeded primary production resulting in severe drawdown of O₂ concentrations at night. Hypoxic conditions released oxide-bound phosphorus and inhibited coupled nitrification–denitrification, enhancing benthic nitrogen and phosphorus fluxes, leading to a build-up of excess nutrients in the water column. Poor water quality in BC was exacerbated by limited tidal flushing imposed by a narrow meandering channel and sandbar across the mouth. In contrast to BC, the effect of the sewage load in MC was confined to the water column, and the impact was temporary and highly localized. This is attributed to the effective flushing of the sewage plume with each tidal cycle. Denitrification rates in MC and RC were high (up to 6.83 mmol N m^?2 day^?1) and DE was approximately 90%. This study has identified denitrification, benthic nutrient fluxes and pelagic primary production as the biogeochemical processes most affected by nutrient loading in these tidal creek systems. Physical process play a key role and the combined influence of nutrient loading and poor tidal flushing can have serious consequences for ecosystem functioning.