Global patterns of geographic range size in birds

Large-scale patterns of spatial variation in species geographic range size are central to many fundamental questions in macroecology and conservation biology. However, the global nature of these patterns has remained contentious, since previous studies have been geographically restricted and/or based on small taxonomic groups. Here, using a database on the breeding distributions of birds, we report the first (to our knowledge) global maps of variation in species range sizes for an entire taxonomic class. We show that range area does not follow a simple latitudinal pattern. Instead, the smallest range areas are attained on islands, in mountainous areas, and largely in the southern hemisphere. In contrast, bird species richness peaks around the equator, and towards higher latitudes. Despite these profoundly different latitudinal patterns, spatially explicit models reveal a weak tendency for areas with high species richness to house species with significantly smaller median range area. Taken together, these results show that for birds many spatial patterns in range size described in geographically restricted analyses do not reflect global rules. It remains to be discovered whether global patterns in geographic range size are best interpreted in terms of geographical variation in species assemblage packing, or in the rates of speciation, extinction, and dispersal that ultimately underlie biodiversity.     

Tissue-Specific Differences in PD-1 and PD-L1 Expression during Chronic Viral Infection: Implications for CD8 T-Cell Exhaustion

The PD-1/PD-L pathway plays a major role in regulating T-cell exhaustion during chronic viral infections in animal models, as well as in humans, and blockade of this pathway can revive exhausted CD8⁺ T cells. We examined the expression of PD-1 and its ligands, PD-L1 and PD-L2, in multiple tissues during the course of chronic viral infection and determined how the amount of PD-1 expressed, as well as the anatomical location, influenced the function of exhausted CD8 T cells. The amount of PD-1 on exhausted CD8 T cells from different anatomical locations did not always correlate with infectious virus but did reflect viral antigen in some tissues. Moreover, lower expression of PD-L1 in some locations, such as the bone marrow, favored the survival of PD-1^Hi exhausted CD8 T cells, suggesting that some anatomical sites might provide a survival niche for subpopulations of exhausted CD8 T cells. Tissue-specific differences in the function of exhausted CD8 T cells were also observed. However, while cytokine production did not strictly correlate with the amount of PD-1 expressed by exhausted CD8 T cells from different tissues, the ability to degranulate and kill were tightly linked to PD-1 expression regardless of the anatomical location. These observations have implications for human chronic infections and for therapeutic interventions based on blockade of the PD-1 pathway.Chronic viral infections are often associated with CD8⁺ T-cell dysfunction (30). This dysfunction, termed exhaustion, includes defects in the ability to produce antiviral cytokines, poor cytotoxicity, a loss of antigen-independent self-renewal, and the inability to vigorously re-expand following antigen exposure (30). These functional deficiencies contrast with the highly functional memory CD8⁺ T cells that are generated after acute infection and maintained via interleukin-7 (IL-7)- and IL-15-mediated homeostatic proliferation (30). During chronic viral infections, T-cell exhaustion often correlates with poor control of viral replication (3, 8, 38, 39). Thus, there is considerable interest in developing strategies to reverse exhaustion and restore function in virus-specific CD8⁺ T cells during chronic infections.Recent studies have revealed an important role for the negative regulatory molecule PD-1 in CD8 T-cell exhaustion during chronic viral infections (29). PD-1, a member of the CD28/CTLA-4 family of costimulatory/coinhibitory receptors, contains both ITIM and ITSM motifs in the intracellular tail and can deliver negative signals, at least partly via recruitment of the phosphatase Shp-2 (29). A role for PD-1 in regulating T-cell responses to chronic viral infections was first observed using lymphocytic choriomeningitis virus (LCMV) infection of mice, where PD-1 was found to be highly expressed on exhausted CD8⁺ T cells from chronically infected animals but not on functional memory CD8⁺ T cells from mice that had cleared an acute strain of the virus (3). In vivo blockade of the PD-1 pathway led to a dramatic increase in the number of virus-specific CD8⁺ T cells, improved functionality of these cells, and enhanced control of viral replication (3). These observations were extended to human chronic viral infections, and a series of studies have demonstrated that human immunodeficiency virus (HIV)-, hepatitis C virus (HCV)-, and HBV-specific CD8⁺ T cells upregulate PD-1 in humans compared to CD8⁺ T cells specific for nonpersisting viruses such as influenza virus or vaccinia virus (6-8, 24, 26, 32, 33, 42). Increasing PD-1 expression also correlates with disease status during HIV infection (8, 42). In vitro blockade of PD-1-PD-L interactions can reinvigorate exhausted virus-specific T-cell responses in humans and appears to have a prominent impact on proliferative expansion and/or prevention of apoptosis in these cases (9, 24, 32). Finally, recent results from in vivo blockade in the macaque simian immunodeficiency virus (SIV) infection model demonstrated the effectiveness of blocking PD-1 in primates during chronic viral infection (36). In these studies, PD-1 blockade enhanced virus-specific T and B-cell responses, lowered viral load, and improved the survival of chronically infected animals. Thus, PD-1 has emerged as not only a major regulator of T-cell exhaustion and viral control during chronic infection but also as an important potential therapeutic target.Despite these important studies and the clear impact of PD-1 blockade on the reversal of T-cell exhaustion, important questions remain. For example, previous work has demonstrated that PD-1 expression is not uniform on subsets of exhausted CD8 T cells (4). However, the expression of PD-1 on exhausted CD8 T cells in multiple tissues, and the relationship between PD-1 expression in these tissues to viral load, the PD-1 ligands and function has not been examined. Given the nonlymphoid accumulation of virus-specific CD8 T cells during chronic viral infections (11, 39) and the predilection of many important chronic infections for replicating in anatomically restricted locations (e.g., HCV and the liver, HIV and mucosal tissues, etc.), the dynamics of PD-1 expression by exhausted CD8 T cells outside the blood and spleen could have important therapeutic implications.In the present study we examined these issues using the mouse model of LCMV infection. Our results demonstrate that exhausted CD8 T cells have a wide range of PD-1 expression in different tissues of chronically infected mice. Virus-specific CD8 T cells in some anatomical locations such as the liver, brain, and bone marrow (BM) expressed high PD-1 for substantially longer than virus-specific CD8⁺ T cells from the spleens or blood of the same mice. Although PD-1 expression in the spleen correlated well with reduced gamma interferon (IFN-γ) and tumor necrosis factor (TNF) production, the PD-1^Hi virus-specific CD8⁺ T cells from the BM remained capable of producing antiviral cytokines ex vivo. In contrast, a strong negative correlation between PD-1 expression and cytotoxicity existed for exhausted CD8 T cells from all tissues tested. PD-L1 expression was high in the spleen, whereas in the BM antigen-presenting cell (APC) populations expressed lower amounts of PD-L1. Survival of PD-1^Hi CD8⁺ T cells from the BM was decreased in the presence of splenic APCs, suggesting that different tissue microenvironments in vivo could selectively support the persistence of PD-1^Hi exhausted CD8 T cells. Since PD-1 expression differs by anatomical location, these observations suggest that PD-1 blockade in vivo will have varying impacts on exhausted CD8 T cells from different tissues or anatomical locations. These observations have implications for human chronic infections such as HBV, HCV, and HIV.     

Interactions between Copper-binding Sites Determine the Redox Status and Conformation of the Regulatory N-terminal Domain of ATP7B

Copper-transporting ATPase ATP7B is essential for human copper homeostasis and normal liver function. ATP7B has six N-terminal metal-binding domains (MBDs) that sense cytosolic copper levels and regulate ATP7B. The mechanism of copper sensing and signal integration from multiple MBDs is poorly understood. We show that MBDs communicate and that this communication determines the oxidation state and conformation of the entire N-terminal domain of ATP7B (N-ATP7B). Mutations of copper-coordinating Cys to Ala in any MBD (2, 3, 4, or 6) change the N-ATP7B conformation and have distinct functional consequences. Mutating MBD2 or MBD3 causes Cys oxidation in other MBDs and loss of copper binding. In contrast, mutation of MBD4 and MBD6 does not alter the redox status and function of other sites. Our results suggest that MBD2 and MBD3 work together to regulate access to other metal-binding sites, whereas MBD4 and MBD6 receive copper independently, downstream of MBD2 and MBD3. Unlike Ala substitutions, the Cys-to-Ser mutation in MBD2 preserves the conformation and reduced state of N-ATP7B, suggesting that hydrogen bonds contribute to interdomain communications. Tight coupling between MBDs suggests a mechanism by which small changes in individual sites (induced by copper binding or mutation) result in stabilization of distinct conformations of the entire N-ATP7B and altered exposure of sites for interactions with regulatory proteins.     

Motor neurone responses during a postural reflex in solitarious and gregarious desert locusts

Desert locusts show extreme phenotypic plasticity and can change reversibly between two phases that differ radically in morphology, physiology and behaviour. Solitarious locusts are cryptic in appearance and behaviour, walking slowly with the body held close to the ground. Gregarious locusts are conspicuous in appearance and much more active, walking rapidly with the body held well above the ground. During walking, the excursion of the femoro-tibial (F-T) joint of the hind leg is smaller in solitarious locusts, and the joint is kept more flexed throughout an entire step. Under open loop conditions, the slow extensor tibiae (SETi) motor neurone of solitarious locusts shows strong tonic activity that increases at more extended F-T angles. SETi of gregarious locusts by contrast showed little tonic activity. Simulated flexion of the F-T joint elicits resistance reflexes in SETi in both phases, but regardless of the initial and final position of the leg, the spiking rate of SETi during these reflexes was twice as great in solitarious compared to gregarious locusts. This increased sensory-motor gain in the neuronal networks controlling postural reflexes in solitarious locusts may be linked to the occurrence of pronounced behavioural catalepsy in this phase similar to other cryptic insects such as stick insects.     

Phylogeography and ethnogenesis of aboriginal Southeast Asians

Studying the genetic history of the Orang Asli of Peninsular Malaysia can provide crucial clues to the peopling of Southeast Asia as a whole. We have analyzed mitochondrial DNA (mtDNAs) control-region and coding-region markers in 447 mtDNAs from the region, including 260 Orang Asli, representative of each of the traditional groupings, the Semang, the Senoi, and the Aboriginal Malays, allowing us to test hypotheses about their origins. All of the Orang Asli groups have undergone high levels of genetic drift, but phylogeographic traces nevertheless remain of the ancestry of their maternal lineages. The Semang have a deep ancestry within the Malay Peninsula, dating to the initial settlement from Africa >50,000 years ago. The Senoi appear to be a composite group, with approximately half of the maternal lineages tracing back to the ancestors of the Semang and about half to Indochina. This is in agreement with the suggestion that they represent the descendants of early Austroasiatic speaking agriculturalists, who brought both their language and their technology to the southern part of the peninsula approximately 4,000 years ago and coalesced with the indigenous population. The Aboriginal Malays are more diverse, and although they show some connections with island Southeast Asia, as expected, they also harbor haplogroups that are either novel or rare elsewhere. Contrary to expectations, complete mtDNA genome sequences from one of these, R9b, suggest an ancestry in Indochina around the time of the Last Glacial Maximum, followed by an early-Holocene dispersal through the Malay Peninsula into island Southeast Asia.     

Further differentiation of murine double-positive thymocytes is inhibited in adenosine deaminase-deficient murine fetal thymic organ culture

Murine fetal thymic organ culture (FTOC) was used to investigate the mechanism by which a lack of adenosine deaminase (ADA) leads to a failure of T cell production in the thymus. We previously showed that T cell development was inhibited beginning at the CD4(-)CD8(-)CD25(+)CD44(low) stage in ADA-deficient FTOC initiated at day 15 of gestation when essentially all thymocytes are CD4(-)CD8(-). In the present study, we asked whether thymocytes at later stages of differentiation would also be sensitive to ADA inhibition by initiating FTOC when substantial numbers of CD4(+)CD8(+) thymocytes were already present. dATP was highly elevated in ADA-deficient cultures, and the recovery of alphabeta TCR(+) thymocytes was inhibited by 94%, indicating that the later stages of thymocyte differentiation are also dependent upon ADA. ADA-deficient cultures were partially rescued by the pan-caspase inhibitor carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone or by the use of apoptotic protease-activating factor-1-deficient mice. Rescue was even more dramatic, with 60- to >200-fold increases in the numbers of CD4(+)CD8(+) cells, when FTOC were performed with an inhibitor of adenosine kinase, the major thymic deoxyadenosine phosphorylating enzyme, or with bcl-2 transgenic mice. dATP levels were normalized by treatment with either carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone or an adenosine kinase inhibitor, but not in cultures with fetal thymuses from bcl-2 transgenic mice. These data suggest that ADA deficiency leads to the induction of mitochondria-dependent apoptosis as a consequence of the accumulation of dATP derived from thymocytes failing the positive/negative selection checkpoint.     

Does GARP really fail miserably? A response to Stockman et al. (2006)

Stockman et al. (2006 ) found that ecological niche models built using DesktopGARP ‘failed miserably’ to predict trapdoor spider (genus Promyrmekiaphila) distributions in California. This apparent failure of GARP (Genetic Algorithm for Rule‐Set Production) was actually a failure of the authors’ methods, that is, attempting to build ecological niche models using single data points. In this paper, we present a re‐analysis of their original data using standard methods with the data appropriately partitioned into training/testing subsets. This re‐evaluation generated accurate distributional predictions that we contrast with theirs. We address the consequences of model‐building using single data points and the need for a foundational understanding of the principles of ecological niche modelling.     

A stochastic model for integrating changes in species richness and community similarity across spatial scales

Human activities have elevated the extinction of natural populations as well as the invasion of new areas by non-native species. These dual processes of invasion and extinction may change the richness and similarity of communities, but the form these changes take is likely to depend on the manner in which invasions and extinctions occur and the spatial scale at which the changes are measured. Here, we explore the influence of differing patterns of extinction and invasion on the similarity and richness of a meta-community. In particular, we model simple stochastic processes analogous to realistic modes of human-mediated introduction of non-native species and range expansion by native species. We show that different modes of invasion and extinction can produce very different changes in diversity, and that the relative magnitude of these changes depends both on where in the meta-community diversity is measured and the degree of initial species aggregation. At any spatial scale of measurement, changes in the richness and similarity of communities following invasion and extinction are not necessarily strongly coupled: relatively large increases in richness may or may not also be associated with relatively large increases in similarity among communities. Thus, in real systems, the influence of human-induced invasions and extinctions on diversity will depend on both the precise mode of these processes (especially invasion), and how species populations are distributed across space.     

Variations on a theme: sources of heterogeneity in the form of the interspecific relationship between abundance and distribution

1. A positive interspecific relationship between abundance and distribution is widely considered to be one of the most general patterns in ecology. However, the relationship appears to vary considerably across assemblages, from significant positive to significant negative correlations and all shades in between. 2. This variation has led to the suggestion that the abundance-distribution relationship has multiple forms, with the corollary that different patterns may inform about, or have different, causes. However, this variation has never been formally quantified, nor has it been determined whether the observed variation is indicative of sampling error in estimating a single effect or of real heterogeneity in such relationships. Here, we use the meta-analytical approach to assess variation in abundance-distribution relationships, and to test different hypotheses for it. 3. Analysis of 279 relationships found a mean effect size of 0.655, which was both highly significantly different from zero and indicative of a strong positive association between abundance and distribution. However, effect sizes were highly heterogeneous, supporting the contention that this relationship does indeed have multiple forms. 4. Most notably, relationships vary significantly in strength across realms, with the strongest in the marine and intertidal, intermediate relationships for terrestrial and parasitic assemblages, and the weakest relationships in freshwater systems. Effect sizes in all of the aquatic realms are homogeneous, suggesting that realm is an important source of the heterogeneity observed across all studies. We posit that this may be because the different spatial structure of the environment in each realm affects the opportunity for the dispersal of individuals between sites. 5. Some of the remaining heterogeneity in effect sizes for terrestrial assemblages could be explained by partitioning assemblages by habitat, scale, biogeographical region and taxon, but considerable heterogeneity in effect sizes for terrestrial and parasitic assemblages remained unexplained.