Marine spatial planning makes room for offshore aquaculture in crowded coastal waters.

Marine spatial planning (MSP) seeks to reduce conflicts and environmental impacts, and promote sustainable use of marine ecosystems. Existing MSP approaches have successfully determined how to achieve target levels of ocean area for particular uses while minimizing costs and impacts, but they do not provide a framework that derives analytical solutions in order to co-ordinate siting of multiple uses while balancing the effects of planning on each sector in the system. We develop such a framework for guiding offshore aquaculture (bivalve, finfish, and kelp farming) development in relation to existing sectors and environmental concerns (wild-capture fisheries, viewshed quality, benthic pollution, and disease spread) in California, USA. We identify > 250,000 MSP solutions that generate significant seafood supply and billions of dollars in revenue with minimal impacts (often < 1%) on existing sectors and the environment. We filter solutions to identify candidate locations for high-value, low-impact aquaculture development. Finally, we confirm the expectation of substantial value of our framework over conventional planning focused on maximizing individual objectives.

Persistent spatial structuring of coastal ocean acidification in the California Current System.

The near-term progression of ocean acidification (OA) is projected to bring about sharp changes in the chemistry of coastal upwelling ecosystems. The distribution of OA exposure across these early-impact systems, however, is highly uncertain and limits our understanding of whether and how spatial management actions can be deployed to ameliorate future impacts. Through a novel coastal OA observing network, we have uncovered a remarkably persistent spatial mosaic in the penetration of acidified waters into ecologically-important nearshore habitats across 1,000 km of the California Current Large Marine Ecosystem. In the most severe exposure hotspots, suboptimal conditions for calcifying organisms encompassed up to 56% of the summer season, and were accompanied by some of the lowest and most variable pH environments known for the surface ocean. Persistent refuge areas were also found, highlighting new opportunities for local adaptation to address the global challenge of OA in productive coastal systems.

Regulatory B Cell-Dependent Islet Transplant Tolerance Is Also Natural Killer Cell Dependent.

Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models by using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B cells (Bregs). To elucidate further the mechanism by which Bregs induce tolerance, we investigated the requirement of natural killer (NK) and NKT cells in this model. To do so, hyperglycemic B6, µMT, Beige, or CD1d-/- mice received BALB/c islet grafts and treatment with the tolerance-inducing regimen consisting of anti-CD45RB and anti-TIM1. B6 mice depleted of both NK and NKT cells by anti-NK1.1 antibody and mice deficient in NK activity (Beige) did not develop tolerance after dual-antibody treatment. In contrast, transplant tolerance induction was successful in CD1d-/- recipients (deficient in NKT cells), indicating that NK, but not NKT, cells are essential in B cell-dependent tolerance. In addition, reconstitution of Beige host with NK cells restored the ability to induce transplant tolerance with dual-antibody treatment. Transfer of tolerance by B cells from tolerant mice was also dependent on host Nk1.1+ cells. In conclusion, these results show that regulatory function of B cells is dependent on NK cells in this model of transplantation tolerance.

Antenatal steroid exposure and pulmonary outcomes in adolescents born with very low birth weight.

OBJECTIVE: To compare asthma history and pulmonary function in adolescents born prematurely with very low birth weight with and without antenatal steroid exposure. STUDY DESIGN: We studied 188 fourteen-year olds (94 exposed, 84 male). We used parent report to ascertain asthma and asthma-related symptoms and spirometry to assess pulmonary function. Steroid-exposed and -unexposed groups were compared using Mann-Whitney U-tests (continuous variables), χ(2) analysis (categorical variables) and logistic regression (multivariate analyses). RESULT: The steroid-exposed group had greater prevalence of larger airway obstruction (35% vs 21%), and steroid-exposed adolescents with birth weights <1000 g had 4.5-fold higher odds of larger airway obstruction. Wheezing in the past 12 months was two times as prevalent in steroid-exposed adolescents with birth weights between 1000 and 1500 g. CONCLUSION: Antenatal steroid exposure does not provide long-term benefits for pulmonary outcomes in adolescents born prematurely with very low birth weight in the era of surfactant therapy.

Weight gain in infancy and early childhood is associated with school age body mass index but not intelligence and blood pressure in very low birth weight children.

Rates of weight gain in infancy and early childhood can influence later neurocognitive, metabolic and cardiovascular health. We studied the relationship of weight gain during infancy and early childhood to intelligence quotient (IQ), blood pressure (BP) and body mass index (BMI) at age 9 in children born with very low birth weight (VLBW). Sixty-five children born prematurely with VLBW were followed longitudinally and at 9 years IQ, BP and BMI were measured. The mean weight z-scores at birth, neonatal intensive care discharge, 1 year corrected for prematurity, 5 and 9 years were -0.17, -2.09, -1.3, -0.68 and 0.06, respectively. Weight gain during infancy (discharge to 1 year corrected for prematurity) and early childhood (1 year corrected age to 5 years) was expressed as rate of change in weight, rate of change in weight z-score and interval change in weight z-score. In multiple regression analyses that adjusted for race, gender, maternal education, antenatal steroids, birth weight z-score, major intracranial lesions on ultrasound and chronic lung disease, rates of weight gain in infancy and early childhood were predictive of BMI z-score at 9 years, regression coefficients (95% confidence intervals); 0.19 (0.02, 0.36) and 0.37 (0.11, 0.63), respectively, expressed as change in BMI z-score per 10 g/week weight increase. Rates of weight gain were not predictive of systolic BP z-score, Verbal IQ or Performance IQ. In VLBW infants, more rapid weight gain during infancy, and especially early childhood, is associated with higher BMI at school age.

The postnatal maternal environment influences diabetes development in nonobese diabetic mice.

When nonobese-diabetic (NOD) mouse embryos were implanted into pseudopregnant mothers of a nonautoimmune mouse strain, the progeny had a reduced type 1 diabetes (T1D) incidence, suggesting that transmission of maternal autoantibodies is important for T1D development. Whether eliminating islet autoantibody transmission in utero, or postnatally (through milk), prevented T1D is unknown. Herein, we show that fostering newborn NOD mice on B-cell deficient NOD.Igmu-/- dams does not prevent T1D, demonstrating that postnatally transmitted islet autoantibodies are not required for disease pathogenesis. Additionally, NOD.Igmu-/- mice reared on NOD dams did not develop T1D, indicating that autoantibody transmission to B-cell deficient NOD neonates is insufficient to trigger T1D. Interestingly, newborn NOD mice that were reared by ICR (but not NOD or C57BL/6) dams had reduced T1D incidence, although not as reduced as that reported after embryo transfer to ICR mice, suggesting that both prenatal and postnatal factors contribute to the observed reduction in T1D incidence. Thus, NOD mice have different risks for developing T1D depending on the strain of their foster mother, and both prenatal and postnatal maternal factors, other than islet autoantibodies, influence their T1D incidence. The results may be relevant for understanding the increasing incidence of T1D and designing interventions.

The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

Mycoplasma arthritidis bacteriophage MAV1 prophage integration, deletions, and strain-related polymorphisms.

Temperate bacteriophage MAV1 is found in certain highly virulent strains of Mycoplasma arthritidis. Integration sites, portions of the right and left prophage ends, and flanking DNA from eight prophages in seven M. arthritidis strains were characterized in this study. attb and attp sites conformed for the most part to the consensus sequence TATTTTT, although minor polymorphisms were noted. Prophages were integrated into similar sites in four strains, suggesting that these strains may have had a common ancestor. Two strains had three prophage copies each, and integration sites were identical. Two strains had two copies each. One of these shared two of the integration sites occupied in the three-copy strains, while the other shared one of these sites and harbored a second prophage in a unique site. Integration sites in the two strains with one prophage each were unique. Four MAV1 copies contained extensive substitutions within a region encoding a putative structural protein and the putative repressor protein. A 3-kb fragment was deleted from the right side of two of these copies. It is proposed that polymorphisms within MAV1 prophage integration sites and within the prophages themselves may help to identify phylogenetic relationships among virulent M. arthritidis strains.

The Mouse Genome Database (MGD): integrating biology with the genome.

The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a community database resource for the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about the mouse with experiments and data annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genetic, genotype (sequence) and phenotype information including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent developments in MGD discussed here include an extensive integration of the mouse sequence data and substantial revisions in the presentation, query and visualization of sequence data.

Does one gene determine whether a C57BL/6J-Y(POS) mouse will develop as a female or as an hermaphrodite?

Two studies were conducted to further our understanding of the inherited condition in mice known as C57BL/6J-Y(POS) (B6-Y(POS)) sex reversal. One study determined what proportion of B6 XY(POS) mice develop as females or hermaphrodites. We found that 75% develop as females and the remainder develop as hermaphrodites regardless of whether the analysis is conducted at 14.5-16 days of embryonic development (based on gonad phenotype) or at weaning (based on the appearance of external genitalia and presence of mammary-associated yellow pigmented hair). We also found that 75 % of the gonads in B6 XY(POS) mice develop as ovaries and the remainder develop as ovotestes; none develop as a testis. We conclude that if any testicular tissue develops, sufficient testosterone is produced to cause at least some masculinization of the external genitalia. The second study tested the hypothesis that development of testicular tissue in B6 XY(POS) mice is due to the presence of a POS-derived gene, whereas B6 homozygosity of this gene guarantees ovarian development. The results did not support the POS gene theory. Therefore, we conclude it is a matter of chance that 75 % of B6 XY(POS) mice develop as females and 25 % develop as hermaphrodites.

C57BL/6J-T-associated sex reversal in mice is caused by reduced expression of a Mus domesticus Sry allele.

C57BL/6J-T-associated sex reversal (B6-TAS) in XY mice results in ovarian development and involves (1) hemizygosity for Tas, a gene located in the region of Chromosome 17 deleted in T(hp) and T(Orl), (2) homozygosity for one or more B6-derived autosomal genes, and (3) the presence of the AKR Y chromosome. Here we report results from experiments designed to investigate the Y chromosome component of this sex reversal. Testis development was restored in B6 T(Orl)/+ XY(AKR) mice carrying a Mus musculus Sry transgene. In addition, two functionally different classes of M. domesticus Sry alleles were identified among eight standard and two wild-derived inbred strains. One class, which includes AKR, did not initiate normal testis development in B6 T(Orl)/+ XY mice, whereas the other did. DNA sequence analysis of the Sry ORF and a 5' 800-bp segment divided these inbred strains into the same groups. Finally, we found that Sry is transcribed in B6 T(Orl)/+ XY(AKR) fetal gonads but at a reduced level. These results pinpoint Sry as the Y-linked component of B6-TAS. We hypothesize that the inability of specific M. domesticus Sry alleles to initiate normal testis development in B6 T(Orl)/+ XY(AKR) mice results from a biologically insufficient level of Sry expression, allowing the ovarian development pathway to proceed.

Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism.

Defects in a triad of organelles (melanosomes, platelet granules, and lysosomes) result in albinism, prolonged bleeding, and lysosome abnormalities in Hermansky-Pudlak syndrome (HPS). Defects in HPS1, a protein of unknown function, and in components of the AP-3 complex cause some, but not all, cases of HPS in humans. There have been 15 inherited models of HPS described in the mouse, underscoring its marked genetic heterogeneity. Here we characterize a new spontaneous mutation in the mouse, cappuccino (cno), that maps to mouse chromosome 5 in a region conserved with human 4p15-p16. Melanosomes of cno/cno mice are immature and dramatically decreased in number in the eye and skin, resulting in severe oculocutaneous albinism. Platelet dense body contents (adenosine triphosphate, serotonin) are markedly deficient, leading to defective aggregation and prolonged bleeding. Lysosomal enzyme concentrations are significantly elevated in the kidney and liver. Genetic, immunofluorescence microscopy, and lysosomal protein trafficking studies indicate that the AP-3 complex is intact in cno/cno mice. It was concluded that the cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles. (Blood. 2000;96:4227-4235)

Defective mesonephric cell migration is associated with abnormal testis cord development in C57BL/6J XY(Mus domesticus) mice.

During the critical period of mouse sex determination, mesenchymal cells migrate from the mesonephros into the adjacent developing testis. This process is thought to initiate cord development and is dependent on Sry. The presence of Sry, however, does not always guarantee normal testis development. For example, transfer of certain Mus domesticus-derived Y chromosomes, i.e., M. domesticus Sry alleles, onto the C57BL/6J (B6) inbred mouse strain results in abnormal testis development. We tested the hypothesis that mesonephric cell migration was impaired in three cases representing a range of aberrant testis development: B6 XY(AKR), B6 XY(POS), and (BXD-21 x B6-Y(POS))F1 XY(POS). In each case, mesonephric cell migration was abnormal. Furthermore, the timing, extent, and position of migrating cells in vitro and cord development in vivo were coincident, supporting the hypothesis that mesonephric cells are critical for cord development. Additional experiments indicated that aberrant testis development results from the inability of Sry(M. domesticus) to initiate normal cell migration, but that downstream signal transduction mechanisms are intact. These experiments provide new insight into the mechanism of C57BL/6J-Y(M. domesticus) sex reversal. We present a model incorporating these findings as they relate to mammalian sex determination.

Sry induces cell proliferation in the mouse gonad.

Sry is the only gene on the Y chromosome that is required for testis formation in mammals. One of the earliest morphological changes that occurs as a result of Sry expression is a size increase of the rudimentary XY gonad relative to the XX gonad. Using 5'-bromo-2'-deoxyuridine (BrdU) incorporation to label dividing cells, we found that the size increase corresponds with a dramatic increase in somatic cell proliferation in XY gonads, which is not detected in XX gonads. This male-specific proliferation was observed initially in the cells of the coelomic epithelium and occurred in two distinct stages. During the first stage, proliferation in the XY gonad was observed largely in SF1-positive cells and contributed to the Sertoli cell population. During the second stage, proliferation was observed in SF1-negative cells at and below the coelomic epithelium and did not give rise to Sertoli cells. Both stages of proliferation were dependent on Sry and independent of any other genetic differences between male and female gonads, such as X chromosome dosage or other genes on the Y chromosome. The increase in cell proliferation began less than 24 hours after the onset of Sry expression, before the establishment of male-specific gene expression patterns, and before the appearance of any other known male-specific morphological changes in the XY gonad. Therefore, an increase in cell proliferation in the male coelomic epithelium is the earliest identified effect of Sry expression.

Molecular characterization of Mycoplasma arthritidis membrane lipoprotein MAA1.

Genes encoding the Mycoplasma arthritidis surface-exposed lipoprotein MAA1 were cloned and sequenced from MAA1-expressing strains 158p10p9 and PG6, from a low-adherence (LA) variant derived from 158p10p9 that expresses a truncated version of MAA1 (MAA1Delta) and from two MAA1-negative strains, 158 and H39. The deduced amino acid sequences of maa1 from 158p10p9 and PG6 predicted, respectively, 86.5- and 86.4-kDa basic, largely hydrophilic lipoproteins with 29-amino-acid signal peptides and predicted cleavage sites for signal peptidase II (Ala-Ala-Ala downward arrowCys). The truncation in the LA variant resulted from a G-->T substitution at nucleotide 695, which created a premature stop codon. This, in turn, generated a predicted 26.6-kDa prolipoprotein (23.6 kDa after processing), consistent with an M(r) of approximately 24,000 calculated for MAA1Delta. Similarly, absence of MAA1 expression in H39 and 158 resulted from C-->A substitutions at nucleotide 208, generating premature stop codons at that site in both strains.

Three new allelic mouse mutations that cause skeletal overgrowth involve the natriuretic peptide receptor C gene (Npr3).

In 1979, a BALB/cJ mouse was identified with an exceptionally long body. This phenotype was found to be caused by a recessive mutation, designated longjohn (lgj), that mapped to the proximal region of chromosome 15. Several years later, a mouse with a similarly elongated body was identified in an outbred stock after chemical mutagenesis with ethylnitrosourea. This phenotype also was caused by a recessive mutation, designated strigosus (stri). The two mutations were found to be allelic. A third allele was identified in a DBA/2J mouse and was designated longjohn-2J (lgj(2J)). Analysis of skeletal preparations of stri/stri mice indicated that the endochondral ossification process was slightly delayed, resulting in an extended proliferation zone. A recent study reported that mice overexpressing brain natriuretic peptide, one of the members of the natriuretic peptide family, exhibit a skeletal-overgrowth syndrome with endochondral ossification defects. The Npr3 gene coding for type C receptor for natriuretic peptides (NPR-C), which is mainly involved in the clearance of the natriuretic peptides, mapped in the vicinity of our mouse mutations and thus was a candidate gene. The present study reports that all three mutations involve the Npr3 gene and provides evidence in vivo that there is a natriuretic-related bone pathway, underscoring the importance of natriuretic peptide clearance by natriuretic peptide type C receptor.

Migration of mesonephric cells into the mammalian gonad depends on Sry.

In mammals, the primary step in male sex determination is the initiation of testis development which depends on the expression of the Y-linked testis determining gene, Sry. The mechanisms by which Sry controls this process are unknown. Studies showed that cell migration from the adjacent mesonephros only occurs into XY gonads; however, it was not known whether this effect depended on Sry, another Y-linked gene, or the presence of one versus two X chromosomes. Here we provide genetic proof that Sry is the only Y-linked gene necessary for cell migration into the gonad. Cell migration from the mesonephros into the differentiating gonad is consistently associated with Sty's presence and with testis cord formation, suggesting that cell migration plays a critical role in the initiation of testis cord development. The induction of cell migration represents the earliest signaling pathway yet assigned to Sry.

Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities.

An RNA-binding motif (RBM) gene family has been identified on the human Y chromosome that maps to the same deletion interval as the 'azoospermia factor' (AZF). We have identified the homologous gene family (Rbm) on the mouse Y with a view to investigating the proposal that this gene family plays a role in spermatogenesis. At least 25 and probably >50 copies of Rbm are present on the mouse Y chromosome short arm located between Sry and the centromere. As in the human, a role in spermatogenesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expression between the two species. Mice carrying the deletion Yd1, that maps to the proximal Y short arm, are female due to a position effect resulting in non-expression of Sry ; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, making this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis. Most of the copies of Rbm map to this deletion interval, and the Yd1males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development. In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm anomalies; however, the different effects of deletion are consistent with the differences in expression between the two species.

Molecular characterization of Mycoplasma arthritidis variable surface protein MAA2.

Earlier studies implied a role for Mycoplasma arthritidis surface protein MAA2 in cytadherence and virulence and showed that it exhibited both size and phase variability. Here we report the further analysis of MAA2 and the cloning and sequencing of the maa2 gene from two M. arthritidis strains, 158p10p9 and H606, expressing two size variants of MAA2. Triton X-114 partitioning and metabolic labeling with [3H]palmitic acid suggested lipid modification of MAA2. Surface exposure of the C terminus was indicated by cleavage of monoclonal antibody-specific epitopes from intact cells by carboxypeptidase Y. The maa2 genes from both strains were highly conserved, consisting largely of six (for 158p10p9) or five (for H606) nearly identical, 264-bp tandem direct repeats. The deduced amino acid sequence predicted a largely hydrophilic, highly basic protein with a 29-amino-acid lipoprotein signal peptide. The maa2 gene was expressed in Escherichia coli from the lacZ promoter of vector pGEM-T. The recombinant product was approximately 3 kDa larger than the native protein, suggesting that the signal peptide was not processed in E. coli. The maa2 gene and upstream DNA sequences were cloned from M. arthritidis clonal variants differing in MAA2 expression state. Expression state correlated with the length of a poly(T) tract just upstream of a putative -10 box. Full-sized recombinant MAA2 was expressed in E. coli from genes derived from both ON and OFF expression variants, indicating that control of expression did not include alterations within the coding region.

Rhenium-188(Sn)HEDP for treatment of osseous metastases.

UNLABELLED: Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. METHODS: It was evaluated by in vitro and in vivo testing in the laboratory, in animals and in humans using 188Re from a variety of sources. It may be produced by a desk-top method developed previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of either enriched 187Re or naturally occurring rhenium targets or the use of a 188W/188Re generator. RESULTS: So long as the mass of rhenium in the 188Re-perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg, satisfactory radiochemical yields and purity may be obtained by all methods. The 188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that are similar to those noted previously for 186Re(Sn)HEDP and appears to result in similar benefits and toxicities in patients with skeletal metastases. External radiation exposure monitoring indicates that, only 4 hr after a therapeutic administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1 meter from the patient would be only 0.5 mR/hr. CONCLUSION: Same-day, on-demand, outpatient therapy of disseminated skeletal metastases appears to be feasible with 188Re(Sn)HEDP.