Rebuilding relationships on coral reefs: Coral bleaching knowledge-sharing to aid adaptation planning for reef users: Bleaching emergence on reefs demonstrates the need to consider reef scale and accessibility when preparing for, and responding to, coral bleaching.

Coral bleaching has impacted reefs worldwide and the predictions of near-annual bleaching from over two decades ago have now been realized. While technology currently provides the means to predict large-scale bleaching, predicting reef-scale and within-reef patterns in real-time for all reef users is limited. In 2020, heat stress across the Great Barrier Reef underpinned the region's third bleaching event in 5 years. Here we review the heterogeneous emergence of bleaching across Heron Island reef habitats and discuss the oceanographic drivers that underpinned variable bleaching emergence. We do so as a case study to highlight how reef end-user groups who engage with coral reefs in different ways require targeted guidance for how, and when, to alter their use of coral reefs in response to bleaching events. Our case study of coral bleaching emergence demonstrates how within-reef scale nowcasting of coral bleaching could aid the development of accessible and equitable bleaching response strategies on coral reefs. Also see the video abstract here: https://youtu.be/N9Tgb8N-vN0.

Global declines in coral reef calcium carbonate production under ocean acidification and warming.

Ocean warming and acidification threaten the future growth of coral reefs. This is because the calcifying coral reef taxa that construct the calcium carbonate frameworks and cement the reef together are highly sensitive to ocean warming and acidification. However, the global-scale effects of ocean warming and acidification on rates of coral reef net carbonate production remain poorly constrained despite a wealth of studies assessing their effects on the calcification of individual organisms. Here, we present global estimates of projected future changes in coral reef net carbonate production under ocean warming and acidification. We apply a meta-analysis of responses of coral reef taxa calcification and bioerosion rates to predicted changes in coral cover driven by climate change to estimate the net carbonate production rates of 183 reefs worldwide by 2050 and 2100. We forecast mean global reef net carbonate production under representative concentration pathways (RCP) 2.6, 4.5, and 8.5 will decline by 76, 149, and 156%, respectively, by 2100. While 63% of reefs are projected to continue to accrete by 2100 under RCP2.6, 94% will be eroding by 2050 under RCP8.5, and no reefs will continue to accrete at rates matching projected sea level rise under RCP4.5 or 8.5 by 2100. Projected reduced coral cover due to bleaching events predominately drives these declines rather than the direct physiological impacts of ocean warming and acidification on calcification or bioerosion. Presently degraded reefs were also more sensitive in our analysis. These findings highlight the low likelihood that the world's coral reefs will maintain their functional roles without near-term stabilization of atmospheric CO2 emissions.

A longitudinal twin and sibling study of the hopelessness theory of depression in adolescence and young adulthood.

BACKGROUND: Maladaptive cognitive biases such as negative attributional style and hopelessness have been implicated in the development and maintenance of depression. According to the hopelessness theory of depression, hopelessness mediates the association between attributional style and depression. The aetiological processes underpinning this influential theory remain unknown. The current study investigated genetic and environmental influences on hopelessness and its concurrent and longitudinal associations with attributional style and depression across adolescence and emerging adulthood. Furthermore, given high co-morbidity between depression and anxiety, the study investigated whether these maladaptive cognitions constitute transdiagnostic cognitive content common to both internalizing symptoms. METHOD: A total of 2619 twins/siblings reported attributional style (mean age 15 and 17 years), hopelessness (mean age 17 years), and depression and anxiety symptoms (mean age 17 and 20 years). RESULTS: Partial correlations revealed that attributional style and hopelessness were uniquely associated with depression but not anxiety symptoms. Hopelessness partially mediated the relationship between attributional style and depression. Hopelessness was moderately heritable (A = 0.37, 95% confidence interval 0.28-0.47), with remaining variance accounted for by non-shared environmental influences. Independent pathway models indicated that a set of common genetic influences largely accounted for the association between attributional style, hopelessness and depression symptoms, both concurrently and across development. CONCLUSIONS: The results provide novel evidence that associations between attributional style, hopelessness and depression symptoms are largely due to shared genetic liability, suggesting developmentally stable biological pathways underpinning the hopelessness theory of depression. Both attributional style and hopelessness constituted unique cognitive content in depression. The results inform molecular genetics research and cognitive treatment approaches.

Framework of barrier reefs threatened by ocean acidification.

To date, studies of ocean acidification (OA) on coral reefs have focused on organisms rather than communities, and the few community effects that have been addressed have focused on shallow back reef habitats. The effects of OA on outer barrier reefs, which are the most striking of coral reef habitats and are functionally and physically different from back reefs, are unknown. Using 5-m long outdoor flumes to create treatment conditions, we constructed coral reef communities comprised of calcified algae, corals, and reef pavement that were assembled to match the community structure at 17 m depth on the outer barrier reef of Moorea, French Polynesia. Communities were maintained under ambient and 1200 µatm pCO2 for 7 weeks, and net calcification rates were measured at different flow speeds. Community net calcification was significantly affected by OA, especially at night when net calcification was depressed ~78% compared to ambient pCO2 . Flow speed (2-14 cm s(-1) ) enhanced net calcification only at night under elevated pCO2 . Reef pavement also was affected by OA, with dissolution ~86% higher under elevated pCO2 compared to ambient pCO2 . These results suggest that net accretion of outer barrier reef communities will decline under OA conditions predicted within the next 100 years, largely because of increased dissolution of reef pavement. Such extensive dissolution poses a threat to the carbonate foundation of barrier reef communities.

Monoclonal Antibodies in Cancer Therapy: Mechanisms, Successes and Limitations.

Rituximab was the first chemotherapeutic monoclonal antibody (CmAb) approved for clinical use in cancer therapeutics in 1997 and has significantly improved the clinical outcomes in non-Hodgkin's lymphoma. Since then, numerous CmAbs have been developed and approved for the treatment of various haematologic and solid human cancers. In this review, the classification, efficacy and significantly reduced toxicity of CmAbs available for use in the United States of America are presented. Finally, the limitations of CmAbs and future considerations are explored.

Extensive geographic and ontogenetic variation characterizes the trophic ecology of a temperate reef fish on southern California (USA) rocky reefs.

Interactions between predator and prey act to shape the structure of ecological communities, and these interactions can differ across space. California sheephead Semicossyphus pulcher are common predators of benthic invertebrates in kelp beds and rocky reefs in southern California, USA. Through gut content and stable isotope (δ13C and †15N) analyses, we investigated geographic and ontogenetic variation in trophic ecology across 9 populations located at island and mainland sites throughout southern California. We found extensive geographic variation in California sheephead diet composition over small spatial scales. Populations differed in the proportion of sessile filter/suspension feeders or mobile invertebrates in the diet. Spatial variation in diet was highly correlated with other life history and demographic traits (e.g. growth, survivorship, reproductive condition, and energy storage), in addition to proxies of prey availability from community surveys. Multivariate descriptions of the diet from gut contents roughly agreed with the spatial groupings of sites based on stable isotope analysis of both California sheephead and their prey. Ontogenetic changes in diet occurred consistently across populations, despite spatial differences in size structure. As California sheephead increase in size, diets shift from small filter feeders, like bivalves, to larger mobile invertebrates, such as sea urchins. Our results indicate that locations with large California sheephead present, such as many marine reserves, may experience increased predation pressure on sea urchins, which could ultimately affect kelp persistence.

Routine interferon-neutralising antibody testing in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis is a leading cause of disability in young adults, with the Scottish population suffering the highest prevalence in Europe. Disease-modifying therapies, including beta-interferon (IFN-ß), are increasingly used to minimise relapse frequency in the majority of patients who present with a relapsing-remitting disease pattern. Unfortunately, neutralising antibodies (NABs) may develop against IFN-ß and are associated with reduced efficacy. These antibodies may be detected using a serum sample. Despite the importance of this problem, from both a patient's perspective and a wider community and economic standpoint, there is no universally agreed protocol for the use of NAB testing. Authorities variously suggest routine 'screening' testing or, conversely, testing only in specific situations. In Scotland, routine testing is seldom used. We report our experience of routine NAB testing in 105 patients (of whom 35 were NAB-positive) over two years in NHS Tayside and comment on its cost and implications.

Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans.

A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

A functional genomic analysis of cell morphology using RNA interference.

BACKGROUND: The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling specific cell-biological processes, including those required to generate distinct morphologies. RESULTS: We adapted existing RNAi technology in Drosophila cell culture for use in high-throughput screens to enable a comprehensive genetic dissection of cell morphogenesis. To identify genes responsible for the characteristic shape of two morphologically distinct cell lines, we performed RNAi screens in each line with a set of double-stranded RNAs (dsRNAs) targeting 994 predicted cell shape regulators. Using automated fluorescence microscopy to visualize actin filaments, microtubules and DNA, we detected morphological phenotypes for 160 genes, one-third of which have not been previously characterized in vivo. Genes with similar phenotypes corresponded to known components of pathways controlling cytoskeletal organization and cell shape, leading us to propose similar functions for previously uncharacterized genes. Furthermore, we were able to uncover genes acting within a specific pathway using a co-RNAi screen to identify dsRNA suppressors of a cell shape change induced by Pten dsRNA. CONCLUSIONS: Using RNAi, we identified genes that influence cytoskeletal organization and morphology in two distinct cell types. Some genes exhibited similar RNAi phenotypes in both cell types, while others appeared to have cell-type-specific functions, in part reflecting the different mechanisms used to generate a round or a flat cell morphology.

A comparison of the ProSeal and classic laryngeal mask airways for airway management by inexperienced personnel after manikin-only training.

We compared the ProSeal (PLMA) and Classic (LMA) laryngeal mask airway for airway management by inexperienced personnel. Nine nurses from the post-anaesthesia care unit, with no prior experience of LMA or PLMA insertion, were observed inserting the LMA and PLMA in 60 ASA 1 to 2 anaesthetized, paralyzed adults following manikin-only training. The time to achieve an effective airway (2 consecutive expired tidal volumes (6 ml/kg; maximum 2 minutes allowed), the number of insertion attempts and the reasons for failure (inability to insert into pharynx or inadequate ventilation) were determined by analysis of digital video recordings. The first attempt success rate (LMA, 85%; PLMA, 83%), overall success rate (LMA, 88%; PLMA, 90%) and effective airway time (LMA, 39 +/- 13 s; PLMA, 43 +/- 19 s) were similar. Failure was from an inability to insert into the pharynx in five with the LMA and three with the PLMA, and inadequate ventilation with two from the LMA and three from the PLMA. Effective airway time and the number of failures were similar for the first and second device. Failure of both devices occurred in four patients. We conclude that airway management in anaesthetized, paralyzed adults is equally successful for the LMA and PLMA by inexperienced personnel following manikin-only training. The PLMA is worthy of consideration as a tool for emergency airway management by inexperienced personnel.

The axillocoronary bypass. Blood flow and short-term graft histology in a porcine model.

BACKGROUND: Bypass grafts arising from the axillary artery may be indicated for complications during minimally invasive direct coronary artery bypass grafting, for redo operations and for management of a severely atherosclerotic ascending aorta. As basic data research on this technique is scanty, we investigated intraoperative function and postoperative morphology of axillocoronary bypass grafts in a porcine model. METHODS: Thirteen German domestic pigs received an axillocoronary vein graft (Group I, n=7) or an aortocoronary vein graft (Group II, n=6) to the left anterior descending artery. In Group I the proximal anastomosis was performed to the left axillary artery, and after partial rib resection the graft was brought transpleurally to the target vessel. In both groups the coronary anastomosis was carried out on the beating heart without cardiopulmonary bypass. Graft flow was measured using transit time ultrasonic flow probes. RESULTS: Intraoperatively all grafts showed a typical diastolic flow profile. Stable graft flow was lower in axillocoronary bypass grafts: 47 (30-60 mL/min) in Group I and 65 (35-126 mL/min) in Group II (p=0.005). Flow given as percentage of cardiac output, however, did not differ between the two grafts: 0.9 (0.6-1.2%) in Group I and 1.2 (0.8-2.4%) in Group II (p=NS). At day 4 after surgery there was no clear histologic predilection site for microtrauma and early degenerative changes in the axillocoronary graft. CONCLUSIONS: Axillocoronary bypass flow compares well with flow in the aortocoronary graft. Microtrauma after implantation and early degenerative changes in the axillocoronary vein bypass are not particularly impacted by the thoracic entry site.

The lytB gene of Escherichia coli is essential and specifies a product needed for isoprenoid biosynthesis.

LytB and GcpE, because they are codistributed with other pathway enzymes, have been predicted to catalyze unknown steps in the nonmevalonate pathway for isoprenoid biosynthesis. We constructed a conditional Escherichia coli lytB mutant and found that LytB is essential for survival and that depletion of LytB results in cell lysis, which is consistent with a role for this protein in isoprenoid biosynthesis. Alcohols which can be converted to pathway intermediates beyond the hypothesized LytB step(s) support limited growth of E. coli lytB mutants. An informatic analysis of protein structure suggested that GcpE is a globular protein of the TIM barrel class and that LytB is also a globular protein. Possible biochemical roles for LytB and GcpE are suggested.

Risk assessment in genetics: a semi-quantitative approach.

Public awareness of genetic predisposition to diseases such as breast cancer threatens to put severe strain on genetics services. Computer-based decision support for general practitioners (GPs) has the potential to reduce unnecessary referrals, but issues of communicating about levels of risk and uncertainty must be addressed. An argumentation logic formalism can subsume both traditional probability theory and more qualitative, reason-based approaches to communicating uncertainty, and we propose that qualitative, argument-based presentation will make uncertainty information more accessible and comprehensible to both patient and GP. We describe software that uses an argumentation approach to assess genetic risk during a GP consultation and provide referral advice along with detailed qualitative explanations for its advice. The software was evaluated in real-life GP consultations in which actors played patients concerned about genetic risk, and in use by GPs evaluating simulated cases. Significant improvement in accuracy of assessment and appropriateness of referrals was found. GPs viewed the software and the qualitative reporting approach highly favourably.

RAGs: A novel approach to computerized genetic risk assessment and decision support from pedigrees.

OBJECTIVES: To assist general practitioners in evaluating patients' genetic risk of cancer on the basis of family history data. METHODS: A new computer application, RAGs (Risk Assessment in Genetics), has been developed to help doctors create graphical family trees and assess the genetic risk of breast and colorectal cancer. RAGs possesses two features that distinguish it from similar software: (i) a user-centred design, which takes into account the requirements of the doctor-patient encounter; (ii) effective and accessible risk reporting by employing qualitative evidence for or against increased risk, which is more easily understood than numerical probabilities. The system allows any rule-based genetic risk guideline to be implemented, and may be readily modified to cater for the varying degrees of information required by different specialists. RESULTS: RAGs permits fast, accurate data entry, and results in more appropriate management decisions than those made via other techniques. In addition, RAGs enables both the clinician and the patient to understand how it arrives at its conclusions, since the use of qualitative evidence allows the program to provide explanations for its reasoning. CONCLUSIONS: The RAGs system promises to help practitioners be more effective gatekeepers to genetic services. It may empower doctors both to make an informed choice when deciding to refer patients who are at increased genetic risk of breast or colorectal cancer, and to reassure those who are at low risk.

Minimally invasive subclavian/axillary artery to coronary artery bypass (SAXCAB): review and classification.

BACKGROUND AND PURPOSE: Subclavian/axillary artery to coronary artery bypass (SAXCAB) surgery is defined as a minimally (or less) invasive coronary revascularization procedure where one or more grafts are anastomosed to the second or third parts of the subclavian artery or any of the three parts of the axillary artery (inflow source) and attached to one or more coronary arteries, and where there are two separate minimally invasive incisions to expose the target coronary artery and the inflow sources, respectively. The indications and contraindications for SAXCAB surgery are discussed, and the relevant chest wall anatomy and that of the subclavian and axillary arteries are reviewed. The effect of respiration and anatomic variability as they impact the SAXCAB graft are discussed. Three components of the anatomy that are important in SAXCAB surgery are discussed: The relation of the first rib to the clavicle insofar as it affects access to the third part of the subclavian artery, the anatomy of the subclavian and axillary arteries and their branches, and the anatomy of the chest wall and its movement. In addition, the different SAXCAB variations that have been applied clinically are reviewed and classified, and future aspects of SAXCAB research are discussed. SAXCAB surgery is unique among the different types of minimally invasive direct coronary artery bypass (MIDCAB) surgery because of the enormous diversity of the techniques that have been described. Based on these descriptions, a new classification of SAXCAB grafting is proposed depending on whether the graft is inside or outside the rib cage and whether or not the coronary artery is exposed by rib resection or through an intercostal space. The third part of the classification takes into consideration the mode of entry into the chest, whether it is by rib resection or through an intercostal space. METHODS: Inquiries were made by telephone and by mail in the year 2000 to a number of surgeons who had published details of their SAXCAB techniques, and informal information was obtained by a series of personal communications as to the estimated number of operations they had performed and the outcomes. Published data was also used to formulate a rough guide as to the international status of the procedure at this time. RESULTS: The total estimated international experience is about 100 cases and the patency is between 70 and 100 percent in the time frame of about one to two years. CONCLUSIONS: The MIDCAB technique in general has been successful in providing an alternative way to revascularize the coronary arteries, and the SAXCAB has proved to be one of the most interesting classes of MIDCAB surgery. SAXCAB grafts seem to be unique among coronary revascularization procedures and, indeed, probably almost all vascular procedures, in that there is enormous diversity in the route for the graft from the inflow source to the target coronary artery. Being knowledgeable about the different varieties of SAXCAB surgeries will help the surgeon during a rescue operation as the surgery can be tailored to suit a particular patient. The SAXCAB seems to be a very safe operation, and it is striking that so far no one has reported any major complications.

Initial sequencing and analysis of the human genome.

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

RNA-mediated interference as a tool for identifying drug targets.

The nematode Caenorhabditis elegans is the first multicellular organism with a fully sequenced genome. As a model organism, C. elegans is playing a special role in functional genomic analyses because it is experimentally tractable on many levels. Moreover, the lessons learned from C. elegans are often applicable across phyla because many of the key biologic processes involved in development and disease have been well conserved. Many global approaches for analysing gene activity are being pursued in C. elegans. RNA-mediated interference (RNAi) is an efficient high-throughput method to disrupt gene function. The basic technique of RNAi involves introducing sequence-specific double-stranded RNA into C. elegans in order to generate a nonheritable, epigenetic knockout of gene function that phenocopies a null mutation in the targeted gene. This technique drastically reduces the time needed to jump from the identification of an interesting gene sequence to achieving an understanding of its function. Thus, RNAi facilitates the high-throughput functional analysis of gene targets identified during drug discovery. RNAi can also help to identify the biochemical mode of action of a drug or pesticide and to identify other genes encoding products that may respond or interact with specific compounds.

The DNA sequence and comparative analysis of human chromosome 20.

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.