Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema

Purpose

A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function.

Method

Nine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts.

Principal Findings

PPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups.

Conclusions

The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an increased sensitivity for detecting heterogeneous lung disorders was found. This indicated that the technique has potential for early detection of lung dysfunction–before global changes occur.     

Breaking Through Disciplinary Barriers: Human–Wildlife Interactions and Multispecies Ethnography

One of the main challenges when integrating biological and social perspectives in primatology is overcoming interdisciplinary barriers. Unfamiliarity with subject-specific theory and language, distinct disciplinary-bound approaches to research, and academic boundaries aimed at “preserving the integrity” of subject disciplines can hinder developments in interdisciplinary research. With growing interest in how humans and other primates share landscapes, and recognition of the importance of combining biological and social information to do this effectively, the disparate use of terminology is becoming more evident. To tackle this problem, we dissect the meaning of what the biological sciences term studies in “human–wildlife conflict” or more recently “human–wildlife interactions” and compare it to what anthropology terms “multispecies ethnography.” In the biological sciences, human–wildlife interactions are the actions resulting from people and wild animals sharing landscapes and resources, with outcomes ranging from being beneficial or harmful to one or both species. In the social sciences, human–nonhuman relationships have been explored on a philosophical, analytical, and empirical level. Building on previous work, we advocate viewing landscapes through an interdisciplinary “multispecies lens” in which humans are observed as one of multiple organisms that interact with other species to shape and create environments. To illustrate these interconnections we use the case study of coexistence between people of the Nalu ethnic group and Critically Endangered western chimpanzees (Pan troglodytes verus) at Cantanhez National Park in Guinea-Bissau, to demonstrate how biological and social research approaches can be complementary and can inform conservation initiatives at the human–primate interface. Finally, we discuss how combining perspectives from ethnoprimatology with those from multispecies ethnography can advance the study of ethnoprimatology to aid productive discourse and enhance future interdisciplinary research.     

Open‐access platform to synthesize knowledge of ape conservation across sites

Despite the large body of literature on ape conservation, much of the data needed for evidence‐based conservation decision‐making is still not readily accessible and standardized, rendering cross‐site comparison difficult. To support knowledge synthesis and to complement the IUCN SSC Ape Populations, Environments and Surveys database, we created the A.P.E.S. Wiki ( https://apeswiki.eva.mpg.de ), an open‐access platform providing site‐level information on ape conservation status and context. The aim of this Wiki is to provide information and data about geographical ape locations, to curate information on individuals and organizations active in ape research and conservation, and to act as a tool to support collaboration between conservation practitioners, scientists, and other stakeholders. To illustrate the process and benefits of knowledge synthesis, we used the momentum of the update of the conservation action plan for western chimpanzees (Pan troglodytes verus) and began with this critically endangered taxon. First, we gathered information on 59 sites in West Africa from scientific publications, reports, and online sources. Information was compiled in a standardized format and can thus be summarized using a web scraping approach. We then asked experts working at those sites to review and complement the information (20 sites have been reviewed to date). We demonstrate the utility of the information available through the Wiki, for example, for studying species distribution. Importantly, as an open‐access platform and based on the well‐known wiki layout, the A.P.E.S. Wiki can contribute to direct and interactive information sharing and promote the efforts invested by the ape research and conservation community. The Section on Great Apes and the Section on Small Apes of the IUCN SSC Primate Specialist Group will guide and support the expansion of the platform to all small and great ape taxa. Similar collaborative efforts can contribute to extending knowledge synthesis to all nonhuman primate species.     

Treponema denticola PurE Is a bacterial AIR carboxylase

De novo purine biosynthesis proceeds by two divergent paths. In bacteria, yeasts, and plants, 5-aminoimidazole ribonucleotide (AIR) is converted to 4-carboxy-AIR (CAIR) by two enzymes: N(5)-carboxy-AIR (N(5)-CAIR) synthetase (PurK) and N(5)-CAIR mutase (class I PurE). In animals, the conversion of AIR to CAIR requires a single enzyme, AIR carboxylase (class II PurE). The CAIR carboxylate derives from bicarbonate or CO(2), respectively. Class I PurE is a promising antimicrobial target. Class I and class II PurEs are mechanistically related but bind different substrates. The spirochete dental pathogen Treponema denticola lacks a purK gene and contains a class II purE gene, the hallmarks of CO(2)-dependent CAIR synthesis. We demonstrate that T. denticola PurE (TdPurE) is AIR carboxylase, the first example of a prokaryotic class II PurE. Steady-state and pre-steady-state experiments show that TdPurE binds AIR and CO(2) but not N(5)-CAIR. Crystal structures of TdPurE alone and in complex with AIR show a conformational change in the key active site His40 residue that is not observed for class I PurEs. A contact between the AIR phosphate and a differentially conserved residue (TdPurE Lys41) enforces different AIR conformations in each PurE class. As a consequence, the TdPurE·AIR complex contains a portal that appears to allow the CO(2) substrate to enter the active site. In the human pathogen T. denticola, purine biosynthesis should depend on available CO(2) levels. Because spirochetes lack carbonic anhydrase, the corresponding reduction in bicarbonate demand may confer a selective advantage.     

Assembly of the Bak Apoptotic Pore: A CRITICAL ROLE FOR THE BAK PROTEIN α6 HELIX IN THE MULTIMERIZATION OF HOMODIMERS DURING APOPTOSIS*

Bak and Bax are the essential effectors of the intrinsic pathway of apoptosis. Following an apoptotic stimulus, both undergo significant changes in conformation that facilitates their self-association to form pores in the mitochondrial outer membrane. However, the molecular structures of Bak and Bax oligomeric pores remain elusive. To characterize how Bak forms pores during apoptosis, we investigated its oligomerization under native conditions using blue native PAGE. We report that, in a healthy cell, inactive Bak is either monomeric or in a large complex involving VDAC2. Following an apoptotic stimulus, activated Bak forms BH3:groove homodimers that represent the basic stable oligomeric unit. These dimers multimerize to higher-order oligomers via a labile interface independent of both the BH3 domain and groove. Linkage of the α6:α6 interface is sufficient to stabilize higher-order Bak oligomers on native PAGE, suggesting an important role in the Bak oligomeric pore. Mutagenesis of the α6 helix disrupted apoptotic function because a chimera of Bak with the α6 derived from Bcl-2 could be activated by truncated Bid (tBid) and could form BH3:groove homodimers but could not form high molecular weight oligomers or mediate cell death. An α6 peptide could block Bak function but did so upstream of dimerization, potentially implicating α6 as a site for activation by BH3-only proteins. Our examination of native Bak oligomers indicates that the Bak apoptotic pore forms by the multimerization of BH3:groove homodimers and reveals that Bak α6 is not only important for Bak oligomerization and function but may also be involved in how Bak is activated by BH3-only proteins.     

The Ajanta Caves

Picturing Time Braun, Marta, Picturing Time: The Work of Etienne‐Jules Marey (1830–1904). Chicago, IL.: University of Chicago Press, 1992, 72 pp., 270 halftones, 65 line drawings, $65.00 hardbound.

A Bibliography of Ethnographic Film Husmann, Rolf, Ingrid Wellinger, Johannes Rühl, and Martin Taureg, A Bibliography of Ethnographic Film. Hamburg and Münster: Lit Verlag (Göttinger Kulturwissenschaftliche Schriften, 1), 1992, 340 pp., 5 indexes.     

Tailored Enrichment Strategies and Stereotypic Behavior in Captive Individually Housed Macaques (Macaca spp.)

The welfare of nonhuman animals in captivity is widely dependent on the natural psychological, physical, and behavioral needs of the animals and how adequately these needs are met. Inability to engage in natural behaviors can lead to chronic stress and expression of stereotypic behavior. The majority of research on decreasing stereotypic behavior in captivity addresses problems at the group level and does not account for individual variability in each animal's needs, history, and preferences. This study combined physiological and behavioral measures of well being to comprehensively assess the unique needs of individually housed captive macaques (Macaca spp.) with the aim of developing tailored welfare strategies. Behavioral and hormonal data were collected under 2 conditions: baseline and individualized enrichment. The results showed a significant decrease in stereotypic behavior under the enrichment condition. Additionally, 7 out of 9 individuals showed a decrease in fecal glucocorticoid (stress hormone) levels, indicating a reduction in hypothalamic-pituitary-adrenal activity. Addressing welfare on an individual, rather than group, level allows for a better overall characterization of well being and maximizes the probability of improving the welfare of each animal.     

High-throughput magnetic resonance imaging in murine colonic inflammation

The aim of this study was to investigate if a rapid magnetic resonance imaging (MRI) screening protocol (<5min/mouse) could characterize colonic inflammation in a chronic experimental colitis model. No respiratory triggering or spasmolytic agent was used during MRI-acquisition. Biomarkers assessed in vivo were colon wall thickness and T2w signal intensity (reflecting oedema) and ex vivo inflammatory score, colon weight, and plasma haptoglobin. The inflammation was characterised by significantly higher local and systemic inflammatory markers in the colitic mice compared to healthy mice. MRI-colon wall thickness and T2w signal intensity correlated well with inflammatory score (r=0.95 and 0.94), colon weight (r=0.92 and 0.93) and plasma haptoglobin (r=0.89 and 0.95). Thus, the data showed that in vivo MRI screening could be used to assess colon wall inflammation, suggesting that high-throughput MRI can be used to follow the potential efficacy of new IBD therapies in individual animal in longitudinal studies.     

Protecting important sites for biodiversity contributes to meeting global conservation targets

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as 'important sites'). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45-1.14% annually since 1950 for IBAs and 0.79-1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends.