Optimal thermal conditions for corals extend poleward with oceanic warming

Aim

The capacity for poleward range expansions beyond the tropics in corals hinges on ecophysiological constraints and resulting responses to climatic variability. We aimed to determine how future warming will affect coral habitat suitability at the poleward range edges of these foundational species in the Northwest Pacific.

Location

Northwest Pacific.

Methods

We generated models integrating thermal physiological constraints of corals adapted to extreme seasonality in Hong Kong, specifically the minimum annual temperature and the proportion of time annually spent at seasonal extremes. With these models, we projected habitat suitability for five coral species under current and future climatic conditions across the Northwest Pacific.

Results

Climate model projections reveal an easing of thermal constraints on the leading-edge of coral ecophysiological limits with an expansion of thermally suitable habitat poleward by 2°–7° in latitude depending on the coral species and model considered. We also highlight a potential divergence of present and future thermal regimes that may lead to a mismatch in suitability for corals currently inhabiting high latitude reefs.

Main Conclusions

Understanding the thermal constraints on coral distributions and defining the potential range of corals under climate change is critical for adaptive management that focuses on coral conservation and ensuring ecosystem function of existing subtropical and temperate ecosystems.     

A homeotic mutation influences the wing vibration patterns during mating in males of the silkworm moth Bombyx mori

An abnormality in the wing vibration pattern in males of the E^Nc homeotic mutant of Bombyx mori was investigated. The wild-type (+/+) males show a switching of the rhythmic wing vibrations from a sequential pattern to an intermittent pattern during mating, whereas the E^Nc mutants show a sequential pattern both before and during mating. Wing motions in +/+ males became small during mating, but those in +/E^Nc males did not. Ablation of the head ganglia of +/+ and +/E^Nc males during mating caused no change in the motor patterns of wing vibrations. Ablation or cooling of the posterior abdomen in the +/+ males during mating caused sequential wing vibrations, suggesting that the change in wing vibrations is induced by signals from the posterior abdomen. The pterothoracic ganglion in the +/E^Nc males is separated into two ganglia, in contrast to the complete ganglionic fusion in the +/+ males. The neurons in the pterothoracic ganglion stained from abdominal nerve cords are homologus in +/+ and +/E^Nc males, but many of these in +/E^Nc males are elongated along the anteroposterior axis. These results suggest that the wing vibration pattern is restricted by genetic factors through reconstruction of the thoracic nervous system during metamorphosis.     

Identification and Multidimensional Optimization of an Asymmetric Bispecific IgG Antibody Mimicking the Function of Factor VIII Cofactor Activity

In hemophilia A, routine prophylaxis with exogenous factor VIII (FVIII) requires frequent intravenous injections and can lead to the development of anti-FVIII alloantibodies (FVIII inhibitors). To overcome these drawbacks, we screened asymmetric bispecific IgG antibodies to factor IXa (FIXa) and factor X (FX), mimicking the FVIII cofactor function. Since the therapeutic potential of the lead bispecific antibody was marginal, FVIII-mimetic activity was improved by modifying its binding properties to FIXa and FX, and the pharmacokinetics was improved by engineering the charge properties of the variable region. Difficulties in manufacturing the bispecific antibody were overcome by identifying a common light chain for the anti-FIXa and anti-FX heavy chains through framework/complementarity determining region shuffling, and by pI engineering of the two heavy chains to facilitate ion exchange chromatographic purification of the bispecific antibody from the mixture of byproducts. Engineering to overcome low solubility and deamidation was also performed. The multidimensionally optimized bispecific antibody hBS910 exhibited potent FVIII-mimetic activity in human FVIII-deficient plasma, and had a half-life of 3 weeks and high subcutaneous bioavailability in cynomolgus monkeys. Importantly, the activity of hBS910 was not affected by FVIII inhibitors, while anti-hBS910 antibodies did not inhibit FVIII activity, allowing the use of hBS910 without considering the development or presence of FVIII inhibitors. Furthermore, hBS910 could be purified on a large manufacturing scale and formulated into a subcutaneously injectable liquid formulation for clinical use. These features of hBS910 enable routine prophylaxis by subcutaneous delivery at a long dosing interval without considering the development or presence of FVIII inhibitors. We expect that hBS910 (investigational drug name: ACE910) will provide significant benefit for severe hemophilia A patients.     

Expression of truncated Babesia gibsoni thrombospondin-related adhesive proteins in Escherichia coli and evaluation of their diagnostic potential by enzyme-linked immunosorbent assay

Among the previously established enzyme-linked immunosorbent assays (ELISAs), an ELISA using the full length of a recombinant thrombospondin-related adhesive protein of Babesia gibsoni (rBgTRAPf) is considered as the most sensitive diagnostic method for the detection of an antibody to B. gibsoni in dogs. However, the expression of rBgTRAPf in high concentration is poor and, thus, limits its usefulness as a diagnostic antigen. To improve its expression level, we have truncated BgTRAPf into two fragments having either an N- or a C-terminus (BgTRAPn or BgTRAPc, respectively). The expression of BgTRAPc protein in Escherichia coli yielded adequate recombinant protein. The specificity and sensitivity of ELISAs with the truncated proteins were determined using dog sera experimentally infected with B. gibsoni and specific pathogen-free (SPF) dog sera. A total of 254 field dog sera were examined by the ELISA with rBgTRAPn, rBgTRAPc, and rBgTRAPf as well as by an indirect fluorescent antibody test (IFAT). The specificity of rBgTRAPc was the highest (97.15%), and its kappa value was more (0.8003) than rBgTRAPn (0.7083). With a sufficient level of expression as well as higher specificity and reliable sensitivity, rBgTRAPc appears to be a potential candidate antigen for the serodiagnosis of B. gibsoni infection in dogs.     

Generation of infectious molecular clones of simian immunodeficiency virus from fecal consensus sequences of wild chimpanzees

Studies of simian immunodeficiency viruses (SIVs) in their endangered primate hosts are of obvious medical and public health importance, but technically challenging. Although SIV-specific antibodies and nucleic acids have been detected in primate fecal samples, recovery of replication-competent virus from such samples has not been achieved. Here, we report the construction of infectious molecular clones of SIVcpz from fecal viral consensus sequences. Subgenomic fragments comprising a complete provirus were amplified from fecal RNA of three wild-living chimpanzees and sequenced directly. One set of amplicons was concatenated using overlap extension PCR. The resulting clone (TAN1.24) contained intact genes and regulatory regions but was replication defective. It also differed from the fecal consensus sequence by 76 nucleotides. Stepwise elimination of all missense mutations generated several constructs with restored replication potential. The clone that yielded the most infectious virus (TAN1.910) was identical to the consensus sequence in both protein and long terminal repeat sequences. Two additional SIVcpz clones were constructed by direct synthesis of fecal consensus sequences. One of these (TAN3.1) yielded fully infectious virus, while the second one (TAN2.69) required modification at one ambiguous site in the viral pol gene for biological activity. All three reconstructed proviruses produced infectious virions that replicated in human and chimpanzee CD4(+) T cells, were CCR5 tropic, and resembled primary human immunodeficiency virus type 1 isolates in their neutralization phenotype. These results provide the first direct evidence that naturally occurring SIVcpz strains already have many of the biological properties required for persistent infection of humans, including CD4 and CCR5 dependence and neutralization resistance. Moreover, they outline a new strategy for obtaining medically important "SIV isolates" that have thus far eluded investigation. Such isolates are needed to identify viral determinants that contribute to cross-species transmission and host adaptation.     

Molecular Epidemiology of Simian Immunodeficiency Virus Infection in Wild-Living Gorillas

Chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to HIV-1. Phylogenetic analyses showed that gorillas acquired the simian immunodeficiency virus SIVgor from chimpanzees, and viruses from the SIVcpz/SIVgor lineage have been transmitted to humans on at least four occasions, leading to HIV-1 groups M, N, O, and P. To determine the geographic distribution, prevalence, and species association of SIVgor, we conducted a comprehensive molecular epidemiological survey of wild gorillas in Central Africa. Gorilla fecal samples were collected in the range of western lowland gorillas (n = 2,367) and eastern Grauer gorillas (n = 183) and tested for SIVgor antibodies and nucleic acids. SIVgor antibody-positive samples were identified at 2 sites in Cameroon, with no evidence of infection at 19 other sites, including 3 in the range of the Eastern gorillas. In Cameroon, based on DNA and microsatellite analyses of a subset of samples, we estimated the prevalence of SIVgor to be 1.6% (range, 0% to 4.6%), which is significantly lower than the prevalence of SIVcpzPtt in chimpanzees (5.9%; range, 0% to 32%). All newly identified SIVgor strains formed a monophyletic lineage within the SIVcpz radiation, closely related to HIV-1 groups O and P, and clustered according to their field site of origin. At one site, there was evidence for intergroup transmission and a high intragroup prevalence. These isolated hot spots of SIVgor-infected gorilla communities could serve as a source for human infection. The overall low prevalence and sporadic distribution of SIVgor could suggest a decline of SIVgor in wild populations, but it cannot be excluded that SIVgor is still more prevalent in other parts of the geographical range of gorillas.Simian immunodeficiency viruses (SIVs) have been identified in approximately 40 African primate species, but chimpanzees and gorillas are the only nonhuman primates known to harbor viruses closely related to human immunodeficiency virus type 1 (HIV-1) (38). These viruses have been transmitted to humans on at least four occasions, leading to four different HIV-1 groups, M to P (14, 26). West central African chimpanzees (Pan troglodytes troglodytes) in southern Cameroon are recognized as the reservoir of the ancestors of HIV-1 group M, which resulted in the AIDS pandemic, and of HIV-1 group N, which has been identified in only a few individuals in Cameroon (15). Western lowland gorillas (Gorilla gorilla gorilla) are infected with SIVgor, which is closely related to the two other HIV-1 lineages, termed group O, which represents 1% of HIV-1 infections in west central Africa, and group P, recently described from a single Cameroonian patient residing in France (26, 36).The phylogenetic relationships between SIVcpz, SIVgor, and HIV-1 show that chimpanzees are the original reservoir of SIVs found in gorillas and humans (31, 36). Pan troglodytes troglodytes apes were most likely the original source of SIVgor, because SIVgor is significantly more closely related to SIVcpzPtt, from Pan troglodytes troglodytes in west central Africa, than to SIVcpzPts, from Pan troglodytes schweinfurthii in east Africa. In addition, an ancestral SIVcpzPtt lineage from which SIVgor and HIV-1 group O viruses are derived has been identified in the form of mosaic pol fragments in present-day SIVcpzPtt recombinants (2, 31). However, the ways of transmission and the exact origin of SIVgor infection in gorillas are not yet resolved. Because of the extensive overlap in habitat and diet (6, 23, 29, 33, 40), direct encounters between gorillas and chimpanzees seem inevitable, but they have rarely been observed and have been described as primarily nonaggressive (17, 28). The primate source of HIV-1 groups O and P also remains unclear, since current data do not allow one to differentiate between a chimpanzee and a gorilla reservoir, especially for HIV-1 group O (26, 31, 36).To determine the geographic distribution, prevalence, and species association of SIVgor, we performed a comprehensive survey of wild gorilla populations in west central (Gorilla gorilla gorilla) and east (Gorilla beringei graueri) Africa. We found an overall prevalence of SIVgor of 1.6%, with infection confirmed at only three field sites. At two of these sites, however, the prevalence of SIVgor was 4.6%, indicating efficient virus spread within and between different communities. The geographic distribution of SIVgor is thus far limited to only a few sites in Cameroon. However, isolated hot spots of infection do exist, which could serve as a source of human infection.     

Fast DNA Interstrand Cross-Linking Reaction by 6-Vinylpurine

Oligonucleotides that incorporate a reactive moiety to form an interstrand cross-link have been widely studied for their potential toward inhibiting gene expression or as basic tools for chemical biology studies. The 6-vinylpurine (2) newly designed in the current study serves well as a new purine-base moiety for increasing cross-link reactivity to target cytosine. Thus, oligonucleotides containing 6-vinylpurine exhibit a more selective and much smoother DNA cross-linking ability to cytosine than the oligonucleotide analogs derived from 2-amino-6-vinylpurine (1) previously explored.     

Design and synthesis of Rho kinase inhibitors (II)

In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay.