Todd III Robert Tranquillo Jeffrey Travers Richard Traystman Stephen Tsang Budd Tucker Leo Twiggs Luca Valenti Frank GDC-0980 price Van Buuren Brian Van Tine Nosratola Vaziri Juan Carlos Velez Joseph Verbalis Manilo Vinciguerra Jill Waalen Paul Wade Daniel Wallace Yingqun Wang Xiaosong Wang CR Wang Joel M. Weinberg Neal L. Weintraub Scott Weiss Daniel Weiss Babette B. Weksler Christof Westenfelder Abby R Whittington Trisha

Wise-Draper Julie Wright-Nunes Xiulong Xu Suowen Xu Bruce Yacyshyn Hongna Yang Jerome Yates Sarvari Yellapragada Naoyuki Yokoyama Osamu Yoshino Tomokazu Yoshizaki Xiaojun Yu Lynn Zechiedrich Yingze Zhang Wei-zhen Zhang Jun Zhang Hong Zhang Dan Zhang Weibin Zhou JINXIA ZHU Mike Zile “
“The viral component of the human microbiome is referred to as the “human virome.” The human virome (also referred to as the “viral metagenome”) is the

collection of all viruses that are found in or on humans, including viruses causing acute, persistent, or latent infection, and viruses integrated into the human genome, such as endogenous retroviruses. The human virome includes both eukaryotic and prokaryotic viruses (bacteriophages). Eukaryotic viruses clearly have important effects on human health. Viral infections of humans include acute, self-limited infections; Dasatinib fulminant, uncontrolled acute infections; and chronic infections that may be asymptomatic or associated with serious, even fatal diseases, such as acquired immunodeficiency syndrome.1 Furthermore, many diseases of unknown cause are thought to be of viral origin.2 Human endogenous retroviruses comprise greater than 8% of the human genome.3 They are transcribed ubiquitously Oxymatrine in normal tissues.4 There has been preliminary evidence of their association with diseases, including amyotrophic lateral sclerosis, multiple

sclerosis, and rheumatoid arthritis;5, 6 and 7 however, the association has not been shown to be causal. Bacteriophages may also affect human health because they can influence bacterial population structure or virulence.8 Advances in high-throughput, deep sequencing technology make it possible to characterize virome richness and stability, gene functions, and association with disease phenotypes.9 Thus, we are poised to begin to understand the richness of the virome and the role viruses play within complex microbial communities (Fig 1). The study of the virome is challenging for several reasons. First, viruses do not contain a conserved genomic region that can be used to identify the viruses in a microbial community, such as the 16S rRNA gene that is used to classify bacteria. Instead, the entire viral community must be sampled and viral genomic sequences compared with known viral reference sequences.

This paper has shown that for heavily overfished stocks an MPA may be used to protect stocks and their habitats, to maximize harvest and to increase consumer and producer surplus. It may also cause the number of people employed in the fishery to increase, both as a consequence of increased effort and an increase in landed quantity for processing and distribution. For moderately overfished stocks the

benefits are not as apparent. These findings suggest that applying MPAs as management instruments may be suitable when taking the welfare approach to fisheries management, but not when taking the wealth approach. It is however not unlikely that even if GSK126 molecular weight a country initially may see the welfare approach as the most sensible, a transformation towards a wealth-based management system may be desirable in the long run as the general economy improves and good institutions and systems for redistribution of wealth are developed. In this case the use of MPAs may slow the process simply because more people may be involved in the fishery than would otherwise be the case if it was left in a pure open access state. However, as demonstrated in this paper, when there are other management HKI272 objectives than resource rent maximization, MPAs have a role

to play to enhance resources and marine ecosystem services and to improve economic and social welfare. Comments from an anonymous reviewer is highly appreciated. “
“The question of opening Norway’s northern offshore areas for petroleum production has been a long and heated political debate. The values at stake are considerable. On one hand, petroleum production promises to underpin Norway’s economic wealth and people’s standard of living, both locally and nationally.

On the other hand, petroleum production, and in particular a major oil spill in the area off the Lofoten and Vesterålen islands and Senja (from now on referred to as the ‘Lofoten area’), is feared to have the potential to significantly disturb and alter vulnerable ecosystems and thereby damage fisheries and tourism in the area. Large areas in Norwegian waters have been opened to petroleum exploitation since the first oil field was discovered in this website 1971. Some areas still remain closed, as the northernmost area of the Barents Sea and the Lofoten area. The closure of these areas was a result of political processes where the importance of ecological factors such as biodiversity and biological production played a central role. The Lofoten area holds some of the worlds’ largest fish stocks [1] and bird colonies [2] and [3]. To ‘open’ an area means that the area is earmarked for potential oil exploitation and that petroleum companies can apply for production licenses.

In this study, however, even in the acral lentiginous melanomas selleck showing the highest proportional number of cases of cyclin D1 increase in relation to ROC1 (40%), ROC1/cyclin D1 was not associated with melanoma histological type or Breslow thickness. This shows that ROC1 expression alteration may be an event of melanoma oncogenesis not related to histological type. Even

if a correlation of ROC1/cyclin D1 relationship with Breslow thickness does not occur, the large number of cases with ROC1 expression higher than that of cyclin D1 among melanomas <2 mm in thickness may show a stage during which the host response is still effective in restraining tumor progression. Of the 20 melanoma cases with proportional ROC1 and cyclin D1 expressions (32.3%), amplification of the CCND1 gene was seen in only two. In the melanocytic nevus group, both proteins were proportionally expressed in six cases (10.3%), and none of them showed gene amplification. In the non-amplified melanocytic nevi

with proportional ROC1/cyclin Ku-0059436 in vitro D1, cyclin D1 was expressed in <25% of cells and in most cases. On the other hand, in the melanoma group, only five cases showed cyclin D1 in <25% of cells, while six cases exhibited cyclin D1 expression in >50% of cells associated with ROC1 expression also in >50% of the cells. This finding suggests that, despite a ROC1 expression decrease in some cases, cyclin D1 levels in melanocytic nevi remained unchanged possibly due to a predominating cyclin D1 gene expression control mechanism. In melanomas, not the mechanism regulating cyclin D1 expression may be something other than gene expression increase and ubiquitination failure. It might include the deficiency of other proteins involved in cyclin

ubiquitination, such as cullins proteins. In most melanocytic nevi, ROC1 protein was expressed by >75% of cells. Deficient ROC1 expression was associated with skin melanomas, where ROC1 expression negatively correlated with cyclin D1 expression, demonstrating the leading role of ROC1 in cyclin D1 degradation within these tumors. The ROC1/cyclin D1 expression relationship correlated with neoplasia type. In melanocytic nevi, there was a predominance of increased ROC1 in relation to cyclin D1 expression, whereas in the melanoma group, about one fourth of the cases showed increased cyclin D1 as compared to ROC1 expression. Neither ROC1 levels nor the ROC1/cyclin D1 expression relationship correlated with Breslow thickness or melanoma histological type. However, studies including a larger number of cases with 1.01–2-mm-thick melanomas and acral lentiginous melanomas are necessary to determine whether these parameters actually correlate.

Removal of the oxidized bases by the BER or TCR pathways results in loop formation and expansion. Indeed, loss of OGG1 [ 15••], NEILS 1 [ 46], and XPA [ 47] reduces expansion in mice. Novel mechanisms for enhancing oxidative damage and toxicity are discussed below. Whether RNA–DNA hybrids form at TNRs in other non-coding regions (which generate large expansions) is unknown. In coding regions, the expanded CAG/CTG repeat

BTK inhibitor tracts (n > 35 rpts) overlap in length with those of the FMR-1 ‘normal’ CGG range [ 1, 2••, 3••, 4••, 5•• and 6••] (commonly 30 rpts), which does not form hybrids. Moreover, CAG expansions do not impose transcription silencing of their respective genes [ 1 and 3••]. If a minimum DNA–RNA hybrid causes the transcriptional silencing at a threshold length, then it is unlikely to be a mechanism that is common to all TNR genes. Another consideration in a RNA-dependent hybridization model for threshold is the effect, if any, of bi-directional transcription of the TNR region [48••]. For example, several novel anti-sense FRM1 transcripts exist in the FRM1 locus (ASFMR4-6), and some overlap the CGG repeat region [49]. ASFMR4 transcript selleck inhibitor is spliced, polyadenylated and exported to the cytoplasm [42 and 49]. If a bi-directional transcript overlaps with the sense transcript, double stranded RNA is formed as a Dicer substrate. It is not easy to imagine how short

siRNA hybrids within the TNR tract results directly in expansion. Either multiple siRNA binding creates a RNA–DNA hybrid of similar length to that of an mRNA hybrids [40], and are removed by similar mechanisms, or the shorter RNA–DNA hybrid opens the DNA sufficiently to increase GPCR & G Protein inhibitor exposure to oxidative DNA damage at a preferred threshold length (Figure 2a). New models provide insight on how RNA–protein

complexes of threshold length might provoke chemical lesions in DNA, and lead to expansion. TAR-DNA-binding protein 43 (TDP-43) [50] is poised to bind to a RNA–DNA hybrid. TDP-43 is a dimeric protein with two RNA recognition motif (RRM) domains that bind both DNA and RNA [50, 51•• and 52] (Figure 3a–c), and interact with fragile X mental retardation protein (FMRP) in an (FMRP)/Staufen (STAU1) complex [53]. This complex forms aggregates analogous to those of polyglutamine proteins, which induce cellular stress and oxidative DNA damage. The DNA length at which the encoded RNA forms aberrant protein–RNA complexes may be the threshold for the enhanced stress. The mechanisms of RNA aggregate formation are unknown, but it is likely due to the disruption of complex formation at its C-terminus. TDP-43 interacts at its C-terminus with the hnRNP family of translation factors, as well as the splicing factors muscleblind (MBNL) and CUG-BP1 (CUG binding protein 1) [54]. MBNL and CUG-BP1 impart two opposing effects on splicing, and they occur through binding of distinct regions of the target RNA [55].

The CSG involved placing 2–3 μL whole blood into a receptacle within a plastic cassette,

followed by a few drops of hemolyzing reaction buffer provided with the kit. The cassette was visually read after standing 10 minutes at room temperature. Development of a distinct purple color in the cassette window represented a negative test outcome, whereas development of no color, or color distinctly lighter than most others, constituted evidence of a positive test outcome, that is, positive for G6PD deficiency. Fig 1 illustrates this distinction in color development. The CSG is this website composed of a cellulose strip impregnated with the G6P substrate of G6PD and a colorless tetrazolium compound salt (patent pending). Reduction of that compound yields a purple formazan dye. In the strip containing hemolysate and G6P substrate, the extent of reduction depends on G6PD activity. The package insert for this product specifies that a tested concentration of 0.156 mM

(2.5 mg/dL) CuCl did not impact with the assay system. The highest final concentration of CuCl in the G6PD activity assays did not exceed 0.04 mM (after dilution of RBC suspension in lysates). We thus considered CuCl interference in the assays by direct redox disturbance (as opposed to its known G6PD enzyme inhibitory properties) very unlikely. A total of 9 separate experiments over the course of several months using 2 known G6PD normal blood donors were conducted (see Fig 2). On each occasion a suspension of 0.45 mL whole blood mixed with 0.05 mL water served as the normal (no CuCl) G6PD activity control. In the case of the hemizygote model, 5 other tubes contained Belnacasan the same except with the addition of CuCl to water to provide final whole blood suspension of CuCl concentrations of 0.2, 0.4, 0.6, 0.8, and 1.0 mM. In the case of the heterozygote model, blood was incubated with 1.0 mM CuCl in water or water only.

These were placed in Fludarabine cell line a 37°C water bath and incubated for 24 hours. After gentle mixing, these tubes were immediately treated essentially as whole blood in the conduct of the quantitative and qualitative G6PD assays as outlined previously in accordance with the standard instructions. In case of the hemizygote model, single tubes representing each of the inhibition treatments were aliquoted into 5 tubes. Each of those tubes was then used for all 3 of the G6PD assays that immediately followed: quantitative, FST, and CSG. Each of these 6 experiments thus generated 30 measurements of G6PD activity, 30 FST readings, and 30 CSG readings, or a total of 180 each. In the heterozygote model, each of the 10 distinct CuCl treatments (see Fig 2) were aliquoted into 3 vials, each generating a separate G6PD assessment, or 30 for each of the 3 separate experiments for a total of 90 assessments. In all, 270 separate assessments were conducted for each of the 3 distinct G6PD assays in both models.

O trato digestivo contém 95% do suprimento corpóreo de serotonina, principalmente nas células

enterocromafins9. O restante de 5‐HT é encontrado no sistema nervoso central e nos vasos sanguíneos. A serotonina desempenha várias funções no organismo: controle do humor, da ansiedade, do sono, do apetite, da memória e aprendizado, da hemostasia e do comportamento sexual10. Muitos receptores serotoninérgicos com efeitos diferentes têm sido identificados em várias regiões do organismo11. Estes receptores começaram a ganhar um esquema unificado de classificação com Bradley12. Atualmente, utilizando critérios de biologia molecular, os receptores da serotonina são divididos em 7 classes distintas (5‐HT1, 5‐HT2, 5‐HT3, 5‐HT4, 5‐ht5, 5‐ht6 learn more e 5‐ht7)10 and 13. Os receptores mais estudados são: 5‐HT1, 5‐HT2, 5‐HT3 e 5‐HT4. Os receptores 5‐HT3 localizam‐se na área postrema

(importante região desencadeadora do vómito) e nos terminais nervosos sensitivos. Quando estimulados provocam aumento da motilidade e secreção14 e excitação de neurónios desencadeadores do vómito10. Os 5‐HT4 estão presentes no sistema nervoso central e nas terminações nervosas colinérgicos do tubo digestivo. Foram nomeados e localizados na periferia15, durante estudo de íleo de porcos‐da‐índia16. A ativação desse receptor libera acetilcolina e estimula o peristaltismo intestinal10 and 17. O peristaltismo é um movimento propulsivo básico do trato gastrointestinal ocorrendo em resposta à distensão da musculatura da parede do tubo digestivo ou a estímulos mecânicos ou químicos da mucosa18. A propulsão gastrointestinal é IWR-1 mw dependente de um reflexo entérico local denominado reflexo peristáltico19. O reflexo peristáltico apresenta uma fase oral e outra caudal. A fase

oral é caracterizada pela contração da musculatura circular e relaxamento da musculatura longitudinal. Esta fase é mediada por neurotransmissores excitatórios como acetilcolina e substância P. Na fase caudal, são observados o relaxamento da musculatura circular e a contração da musculatura longitudinal. Os neurotransmissores inibitórios como Adenosine triphosphate o peptídeo intestinal vasoativo (VIP) e o óxido nítrico são exemplos de mediadores da fase caudal20 and 21. Após uma melhor compreensão da fisiologia intestinal, da descoberta dos receptores da serotonina e dos recentes avanços da biologia molecular, pesquisadores criaram novas drogas como a cisaprida, a prucaloprida e o tegaserode, capazes de se ligarem aos receptores 5‐HT4 e promoverem peristalse, consequentemente aumentando a velocidade de trânsito intestinal19. O tegaserode foi desenvolvido no início da década de 90, sendo liberado para uso nos Estados Unidos a partir de 200214, 22 and 23. É um agonista parcial e seletivo dos receptores 5‐HT4, portanto com menor probabilidade de promover dessensibilização no receptor, causando taquifilaxia ou tolerância24.

8–1.0 s/rot; beam pitch: 0.5625–0.9375) and reconstruction parameters were predefined for each type of CT scanner (see Appendix). Beam pitch is defined as the ratio of table feed per rotation to the collimation, where collimation is the product of slice-thickness and the number of slices in each rotation. Beam pitch was kept under 1.0 except for one CT scanner

(Somatom Plus 4 Volume Zoom). Field of View (FOV) was defined as 350 mm to cover both hip regions. In-plane spatial resolution of 0.625–0.652 mm and reconstructed slice thickness of 0.500–0.625 mm was adjusted according to CT scanner type (see Appendix). The CT values were converted to bone mineral scale by using a solid reference phantom, Ku-0059436 B-MAS200 (Fujirebio Inc., Tokyo, Japan), containing hydroxyapatite (HA) at 0, 50, 100, 150, and 200 mg/cm3. For all of the CT data, a constant threshold value of 350 mg/cm3 was used to define the cortical bone. The MDCT scanners used in this study originally included four Asteion 4 scanners, one Aquilion 4 scanner,

and three Aquilion 16 scanners (Toshiba Medical Systems Corporation,Tochigi, Japan); one LightSpeed Ultra_8 scanner, and one LightSpeed Plus_4 scanner (GE-Yokogawa Medical,Tokyo,Japan); and one Somatom Plus 4 Volume Zoom scanner (Siemens, AG, Berlin and Munich, Germany). In two institutions, CT scanners were changed during the trial period (from Aquilion 16 to Aquilion 64, and from LightSpeed Plus_4 to LightSpeed Ultra_16); therefore, the pairs of CT data in 26 patients were obtained Selleckchem Epacadostat using different CT scanners. However, because the results of all patients did not differ from results excluding the 26 patients (data not shown), the results of all patients are presented in this article. Good linear correlations between the

CT values and HA concentrations were demonstrated (r = 0.996–0.999; p < 0.0002–0.05) in all CT scanners. Differences in CT values according to X-ray energy were corrected by using the reference phantom to convert CT values to HA equivalent values. However, it was necessary to confirm the longitudinal stability of the CT values of the threshold value used to define the cortical bone. For the rod containing 200 mg/cm3 HA equivalent, which was used as the threshold value to define the cortical region, there Casein kinase 1 was less than 0.01% difference between the baseline CT value and CT value at 144 weeks. The subjects were scanned in the supine position, with the reference phantom beneath the patient and placed so as to cover a region from the top of the acetabulum to 5 cm below the bottom of the lesser trochanter in each hip joint (average slice number was 298). Bolus bags were placed between the subject and the CT calibration phantom. Both feet were fixed using a custom-made adjuster for hip DXA, which kept the subject’s knees flat and the toes pointed inward.

To determine if this was the case, we carried out tissue extractions using CD3OD, instead of CH3OH, in the extraction solvent. To eliminate variations that may result when comparing tissues extracted from different individuals, the paired eyestalk tissues were removed from one lobster. One eyestalk ganglion was placed in extraction solvent containing CH3OH and the other in extraction solvent containing CD3OD. The samples were homogenized, sonicated, and centrifuged, and the supernatant was separated from the tissue pellet. The samples were dried and reconstituted for analysis by MALDI-FTMS. The MALDI-FT mass spectra for the

two eyestalk tissue extracts show that the Orc[1-11]-OMe-derived peaks at m/z 1270.57, 1253.54, 894.43, 876.42, and 537.28 for the eyestalk extracted with CH3OH ( Fig. 8A and B) have all shifted by 3 Da to m/z 1273.59, 1256.56, 897.45, 879.44, and 540.30, for the eyestalk extracted with CD3OD ( Fig. 8C and D). MALDI-FT mass Bortezomib manufacturer spectra and CID experiments carried out

on the Q-TOF also support our localization of the added methyl group at the C-terminus of the peptide. This localization is supported by the 3 Da mass shifts for the y8, y80, and y5 ion in the MALDI-FT mass spectra of eyestalks extracted with CD3OD (Fig. 8), which localizes the added methyl group to the C-terminal sequence, and by the 3 Da mass shift for y-type (but not b-type) ions produced in the HSP inhibitor clinical trial Q-TOF MS/MS analysis (Fig. 7C and D). The most diagnostic fragment is the y1 peak, which undergoes a 3 Da mass shift (from m/z = 90.06 to 93.07) for the CD3-labeled peptide ( Fig. 7D). This Arachidonate 15-lipoxygenase fragment ion definitively localized the methyl addition to the C-terminus. These results document the incorporation of one CD3 group for Orc[1-11]-OMe

at the C-terminus and demonstrate that the methanolic extraction solvent is the source of the added methyl group. Acid-catalyzed esterifications have been recognized as the source of exogenous protein methylations that occur when methanol and acids are used, for example, in destaining SDS-PAGE gels [5], [17], [24] and [48]. In an early study by Haebel et al. [17], five test peptides were incubated in methanolic trichloroacetic acid (TCA) solutions (12.5:50:37.5, methanol:TCA:water) for 1–24 h to determine the propensity for methylation at different amino acid residues. The authors concluded that glutamate (E) undergoes the most rapid acid-catalyzed esterification, the C-terminus reacts with a rate that is lower by a factor of 2–6, and other groups (D, Q) are less reactive by at least a factor of 10 [17]. When acetic acid replaced TCA, methylation was not observed [17]. A direct chemical modification appeared to be unlikely as an explanation for the production of Orc[1-11]-OMe under our conditions, based upon the following observations and considering the work by Haebel et al. [17]. First, our data clearly show that methylation occurs, with 100% specificity, at the C-terminus.

Prior to embedding in Tissue-Tek, spinal cord samples were photographed with a digital camera (Sony Cyber-Shot DSC-S950, São Paulo—SP, Brazil) on a dark background to provide morphological visualization of the injury site (Fig. 7B). After this, samples were quickly frozen in isopentane (Merck, Germany) cooled in liquid nitrogen and stored at − 80 °C. Primary somatosensory cortex, primary and secondary motor cortex and the entire brainstem were serially sliced (200 μm thick, 150 μm apart) using a cryostat (CM1850, Leica, São Paulo—SP, Brazil) to allow retrograde tracer visualization. These sections were mounted on gelatin-coated glass slides, covered with aqueous mounting medium (FluorSave,

this website Calbiochem, Darmstadt, Germany) and coverslips. The entire spinal cord samples were longitudinally cut (25 μm), in

a series of 5 slides per animal with 7–8 sections per slide. Two slides per animal were used to perform immunohistochemistry by the peroxidase method (Sternberger, 1979). Initially, sections were washed in PBS, followed by a 30 min period with 3% hydrogen peroxide (H2O2). After several washes in PBS, sections were pre-incubated in 1% albumin solution with 0.4% triton X-100 (PBS-Tx). Then, slices were incubated for 48 h at 4 °C in either GFAP (rabbit anti-GFAP, 1:200, DAKO Denmark A/S, Denmark, Z0334) or GAP-43 antibodies (mouse anti-GAP-43, 1:500, Santa Cruz Biotechnology Inc., USA, SC33705). Sections were rinsed in PBS-Tx and re-incubated in goat anti-rabbit IgG (1:100, Sigma-Aldrich, USA, R2004) or goat anti-mouse www.selleckchem.com/products/ABT-263.html IgG (1:100, Sigma-Aldrich, USA, M8642) for 2 h. Following PBS washes, slices were placed in peroxidase anti-peroxidase (1:500, Sigma-Aldrich, USA, P1291) for 1 h and 30 min. The immunohistochemical reaction was developed by incubating the slices in a medium containing 0.06% 3,3 diaminobenzidine (DAB, Sigma-Aldrich, USA, D5637) and then in the same solution containing 1 μM of 3% H2O2 per mL of DAB medium for 10 min each. Finally, slices were rinsed with PBS, dehydrated with ethanol, cleared with xylene and covered

with Carnitine dehydrogenase Permount and coverslips. Control sections were prepared by omitting the primary antibody and replacing it with PBS. In double staining protocols, fibre tracts were stained using the following antibodies: rabbit anti-serotonin (1:5000, Sigma-Aldrich, USA, S5545) for serotonergic axons in the spinal cord coming from raphe nuclei; and rabbit anti-CGRP (1:1500, courtesy of Dr. Rodrigo, Instituto Cajal, Spain) as a marker for ascending sensory neurons. Fibrous scar borders were defined using immunoreactivity to GFAP (mouse anti-GFAP, 1:400, Sigma-Aldrich, USA, G3893). The protocol consisted of washing the sections with PBS, followed by permeabilization with 0.25% PBS-Tx. After this, sections were blocked in 1% albumin for 30 min.

MPAs in the BHS are integrating traditional practices such as sasi into MPA zoning and management, and developing co-management structures that allow communities to actively manage and patrol their MPAs. The majority

of the MPAs in the BHS are in Raja Ampat regency, which has a network of seven MPAs covering 1,185,940 ha of coral reef habitat and associated small islands (Fig. 1; Table 2). Current efforts are underway to institutionalize the Raja Ivacaftor Ampat MPA network under a co-management body (termed ‘Badan Layanan Umum Daerah’ or regency technical unit) and framework that has been successfully applied to hospitals in many parts of Indonesia. This public–private co-management model provides two major benefits compared to traditional Indonesian governance of MPAs. Firstly, it allows the management body to largely manage its own finances, including both governmental budget allocations and grants from aid agencies and private donors, as well as any revenues generated (e.g. tourism entrance fees). PD-0332991 purchase Secondly, it allows non-government

partners to sit on the management board and private individuals to be recruited as MPA staff and paid a professional (i.e., non-civil servant) salary. If successful, this co-management model has the potential to be applied to other MPA networks that are being developed in Indonesia ( Coral Triangle Initiative, 2009). The long term success of MPAs in the BHS will mostly depend on the management of waters outside MPAs and an integrated approach to coastal management across the BHS. Since 2007 and the passing of laws relating to spatial planning (Law 26/2007) and management of coastal areas and small islands (Law 27/2007), the Indonesian Government has provided a legal framework to reform spatial planning processes and achieve more effective and integrated urban and rural planning and sectoral development, and enable greater synergies between spatial plans developed at the regency, province and at the national

level. In the BHS, through the efforts Chloroambucil of international and national NGOs there has been a push for coastal development, fisheries, spatial planning and species management to align with the principles of ‘ecosystem-based management’ and recognize that ecosystems, communities, and economic opportunities are strongly connected. The BHS is currently struggling to keep up with rapid environmental, social and economic change. Local communities and the regional economy rely heavily on natural resources – both terrestrial and marine – for industries such as fishing, mining, forestry, oil and gas, mariculture and tourism. However, certain activities associated with these industries threaten the biodiversity and health of marine and terrestrial ecosystems in the BHS.