Decadal changes in turbid-water coral communities at Pandora Reef: loss of resilience or too soon to tell?

Coral communities were monitored at Pandora Reef, nearshore Great Barrier Reef from 1981 to 2005 using photography and videography. In the 1980s, regional elevation of land-based nutrients in coastal waters (ca. 2–6 times pre-European levels of early 1800s) did not prevent overall recovery of coral cover and diversity following a sequence of environmental disturbances in the 1970s. However, prospects for a repeat of such resilience following catastrophic mortality from high-temperature bleaching in 1998 and a cyclone in 2000 are not clear. Different coral communities around the reef varied greatly in relation to impacts and recovery. Fore-reef communities dominated by acroporids (fast growing branching and tabular Acropora and foliose Montipora) recovered strongly in the 1980s following apparently severe impacts by cyclone, flood and heat wave disturbances in the 1970s, attaining 60–90% cover by stabilizing rubble and outgrowing macro-algae in <10 years. In the back-reef, by contrast, poritid-dominated communities (massive and finger Porites and columnar Goniopora and Alveopora) had more stable trajectories and smaller impact from recent disturbances: recovery was well underway in 2005. The contrasting trajectories of different parts of the reef reflect differential survival of more persistent versus more ephemeral taxa, notably poritids and acroporids, respectively, both major contributors to framework and cover on reefs globally. A repeat of earlier resilience appears possible in the shallow fore-reef, but unlikely in the deeper fore-reef, which had few viable fragments or recruits in 2005. The main limits on recovery may be (1) reduced supply of coral larvae due to widespread regional losses of coral brood stock and (2) the reduced intervals between disturbances associated with global climate change. The presence of a high abundance of Acroporidae is a major pre-disposing risk factor for climate change impacts.     

Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells

Supernumerary centrosomes promote the assembly of abnormal mitotic spindles in many human tumors. In human cells, overexpression of the cyclin-dependent kinase (Cdk)2 partner cyclin A during a prolonged S phase produces extra centrosomes, called centrosome reduplication. Cdk2 activity protects the Mps1 protein kinase from proteasome-mediated degradation, and we demonstrate here that Mps1 mediates cyclin A-dependent centrosome reduplication. Overexpression of cyclin A or a brief proteasome inhibition increases the centrosomal levels of Mps1, whereas depletion of Cdk2 leads to the proteasome-dependent loss of Mps1 from centrosomes only. When a Cdk2 phosphorylation site within Mps1 (T468) is mutated to alanine, Mps1 cannot accumulate at centrosomes or participate in centrosome duplication. In contrast, phosphomimetic mutations at T468 or deletion of the region surrounding T468 prevent the proteasome-dependent removal of Mps1 from centrosomes in the absence of Cdk2 activity. Moreover, cyclin A-dependent centrosome reduplication requires Mps1, and these stabilizing Mps1 mutations cause centrosome reduplication, bypassing cyclin A. Together, our data demonstrate that the region surrounding T468 contains a motif that regulates the accumulation of Mps1 at centrosomes. We suggest that phosphorylation of T468 attenuates the degradation of Mps1 at centrosomes and that preventing this degradation is necessary and sufficient to cause centrosome reduplication in human cells.     

Rescaling the trophic structure of marine food webs

Measures of trophic position (TP) are critical for understanding food web interactions and human‐mediated ecosystem disturbance. Nitrogen stable isotopes (δ¹⁵N) provide a powerful tool to estimate TP but are limited by a pragmatic assumption that isotope discrimination is constant (change in δ¹⁵N between predator and prey, Δ¹⁵N = 3.4‰), resulting in an additive framework that omits known Δ¹⁵N variation. Through meta‐analysis, we determine narrowing discrimination from an empirical linear relationship between experimental Δ¹⁵N and δ¹⁵N values of prey consumed. The resulting scaled Δ¹⁵N framework estimated reliable TPs of zooplanktivores to tertiary piscivores congruent with known feeding relationships that radically alters the conventional structure of marine food webs. Apex predator TP estimates were markedly higher than currently assumed by whole‐ecosystem models, indicating perceived food webs have been truncated and species‐interactions over simplified. The scaled Δ¹⁵N framework will greatly improve the accuracy of trophic estimates widely used in ecosystem‐based management.     

The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers

The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.     

Papillomavirus E1 protein binds to and stimulates human topoisomerase I

The papillomavirus (PV) E1 helicase plays a direct role in recruiting cellular DNA replication factors, such as replication protein A or polymerase alpha-primase, to replicate PV genomes. Here, E1 is shown to bind to human topoisomerase I and stimulate its relaxation activity up to sevenfold. The interaction between E1 and topoisomerase I was mapped to the E1 DNA binding domain and C terminus. These findings imply a mechanism for the recruitment of topoisomerase I to PV DNA replication forks and for stimulating topoisomerase I to allow for efficient relaxation of the torsional stress induced by replication fork progression.     

A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration

Many human inherited neurodegenerative disorders are characterized by loss of balance due to cerebellar Purkinje cell (PC) degeneration. Although the disease-causing mutations have been identified for a number of these disorders, the normal functions of the proteins involved remain, in many cases, unknown. To gain insight into the function of proteins involved in PC degeneration, we developed an interaction network for 54 proteins involved in 23 inherited ataxias and expanded the network by incorporating literature-curated and evolutionarily conserved interactions. We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen; of 75 pairs tested, 83% of the interactions were verified in mammalian cells. Many ataxia-causing proteins share interacting partners, a subset of which have been found to modify neurodegeneration in animal models. This interactome thus provides a tool for understanding pathogenic mechanisms common for this class of neurodegenerative disorders and for identifying candidate genes for inherited ataxias.     

Diagnosis and treatment of dementia: 4. Approach to management of mild to moderate dementia

Background

The management of mild to moderate dementia presents complex and evolving challenges. Practising physicians are often uncertain about the appropriate approaches to issues such as the disclosure of the diagnosis, driving and caregiver support. In this article, we provide practical guidance on management based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia.

Methods

We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of mild to moderate stages of Alzheimer disease and other forms of dementia. Recommendations based on the literature review were drafted and voted on. Consensus required 80% or more agreement by participants. Subsequent to the conference, we searched for additional articles published from January 2006 to April 2008 using the same major keywords and secondary search terms. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care.

Results

We identified 1615 articles, of which 954 were selected for further study. From a synthesis of the evidence in these studies, we made 48 recommendations for the management of mild to moderate dementia (28) and dementia with a cerebrovascular component (8) as well as recommendations for addressing ethical issues (e.g., disclosure of the diagnosis) (12). The updated literature review did not change these recommendations. In brief, patients and their families should be informed of the diagnosis. Although the specifics of managing comorbid conditions might require modification, standards of care and treatment targets would not change because of a mild dementia. The use of medications with anticholinergic effects should be minimized. There should be proactive planning for driving cessation, since this will be required at some point in the course of progressive dementia. The patient''s ability to drive should be determined primarily on the basis of his or her functional abilities. An important aspect of care is supporting the patient''s primary caregiver.

Interpretation

Much has been learned about the care of patients with mild to moderate dementia and the support of their primary caregivers. There is a pressing need for the development, and dissemination, of collaborative systems of care.

Articles to date in this series

• Chertkow H. Diagnosis and treatment of dementia: Introduction. Introducing a series based on the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. CMAJ 2008;178:316-21.
• Patterson C, Feightner JW, Garcia A, et al. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ 2008;178:548-56.
• Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178:825-36.
• Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008;178: 1273-85.

     

Comparative osteogenic transcription profiling of various fetal and adult mesenchymal stem cell sources

Human mesenchymal stem cells (MSC) from adult and fetal tissues are promising candidates for cell therapy but there is a need to identify the optimal source for bone regeneration. We have previously characterized MSC populations in first trimester fetal blood, liver, and bone marrow and we now evaluate their osteogenic differentiation potential in comparison to adult bone marrow MSC. Using quantitative real-time RT-PCR, we demonstrated that 16 osteogenic-specific genes (OC, ON, BSP, OP, Col1, PCE, Met2A, OPG, PHOS1, SORT, ALP, BMP2, CBFA1, OSX, NOG, IGFII) were expressed in both fetal and adult MSC under basal conditions and were up-regulated under osteogenic conditions both in vivo and during an in vitro 21-day time-course. However, under basal conditions, fetal MSC had higher levels of osteogenic gene expression than adult MSC. Upon osteogenic differentiation, fetal MSC produced more calcium in vitro and reached higher levels of osteogenic gene up-regulation in vivo and in vitro. Second, we observed a hierarchy within fetal samples, with fetal bone marrow MSC having greater osteogenic potential than fetal blood MSC, which in turn had greater osteogenic potential than fetal liver MSC. Finally, we found that the level of gene expression under basal conditions was positively correlated with both calcium secretion and gene expression after 21 days in osteogenic conditions. Our findings suggest that stem cell therapy for bone dysplasias such as osteogenesis imperfecta may benefit from preferentially using first trimester fetal blood or bone marrow MSC over fetal liver or adult bone marrow MSC.     

A field test of the use of pop‐off data storage tags in freshwater fishes

In the present study, pop‐off data storage tags (pDST) without any transmitting capabilities were attached to 118 adult salmonids in a 19 000 km² freshwater system (Lake Ontario). The 9·3 cm long cylindrical tags were externally attached to fishes using a backpack‐style harness, set to record pressure (dBar ≈ depth in m) and temperature every 70 s (and at some key times, every 5 s) and programmed to release from the harness and float to the surface after c. 1 year. Recapture of the bright‐orange tags for data retrieval relied on members of the public finding tags on shore, or on anglers capturing fishes with tags attached and using the contact information displayed on each tag to mail tags to the research team in exchange for a monetary reward. Thirty‐seven tags were found and returned from the 118 released (31%), while 26 of the 118 tags (22%) remained scheduled to pop‐off in summer 2017. Of the 37 tags returned, 23 were from wild‐caught fishes (out of 88 wild‐caught and tagged fishes; 26%) and yielded useful data whereas 14 were from hatchery‐reared fishes that were opportunistically tagged and appear to have been unable to acclimate to life in the wild and died days to weeks after release. The field study described here thus demonstrated that pDSTs can be a viable option for collecting large amounts of high‐resolution depth and temperature data for salmonids in freshwater systems. Technical challenges, limitations and unknowns related to the use of pDSTs with freshwater fishes are discussed. In addition, pDSTs are compared with alternate electronic tagging technologies and assessed for their potential as a more widespread tool in research on freshwater fishes.     

Soil Ca alters processes contributing to C and N retention in the Oa/A horizon of a northern hardwood forest

Recent studies on the effects of calcium (Ca) additions on soil carbon (C) cycling in organic soil horizons present conflicting results, with some studies showing an increase in soil C storage and others a decrease. We tested the legacy effects of soil Ca additions on C and nitrogen (N) retention in a long-term incubation of soils from a plot-scale field experiment at the Hubbard Brook Experimental Forest, NH, USA. Two levels of Ca (850 and 4250 kg Ca/ha) were surface applied to field plots as the mineral wollastonite (CaSiO₃) in summer of 2006. Two years after field Ca additions, Oa/A horizon soils were collected from field plots and incubated in the laboratory for 343 days to test Ca effects on C mineralization, dissolved organic carbon (DOC) export, and net N transformations. To distinguish mineralization of soil organic C (SOC) from that of more recent C inputs to soil, we incubated soils with and without added ¹³C-labeled sugar maple leaf litter. High Ca additions increased exchangeable Ca and pH compared to the control. While low Ca additions had little effect on mineralization of SOC or added litter C, high Ca additions reduced mineralization of SOC and enhanced mineralization of litter C. In litter-free incubations, δ¹³C of respired C was enriched in the high Ca treatment compared to the control, indicating that Ca suppressed mineralization of ¹³C-depleted SOC sources. Leaching of DOC and NH₄ ⁺ were reduced by Ca additions in litter-free and litter-amended soils. Our results suggest that Ca availability in these organic soils influences mineralization of SOC and N primarily by stabilization processes and only secondarily through pH effects on organic matter solubility, and that SOC binding processes become important only with relatively large alterations of Ca status.