Synergistic effects of iron and temperature on Antarctic phytoplankton and microzooplankton assemblages

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution 3.0 License. The definitive version was published in Biogeosciences 6 (2009): 3131-3147, doi: 10.5194/bg-6-3131-2009Iron availability and temperature are important limiting factors for the biota in many areas of the world ocean, and both have been predicted to change in future climate scenarios. However, the impacts of combined changes in these two key factors on microbial trophic dynamics and nutrient cycling are unknown. We examined the relative effects of iron addition (+1 nM) and increased temperature (+4°C) on plankton assemblages of the Ross Sea, Antarctica, a region characterized by annual algal blooms and an active microbial community. Increased iron and temperature individually had consistently significant but relatively minor positive effects on total phytoplankton abundance, phytoplankton and microzooplankton community composition, as well as photosynthetic parameters and nutrient drawdown. Unexpectedly, increased iron had a consistently negative impact on microzooplankton abundance, most likely a secondary response to changes in phytoplankton community composition. When iron and temperature were increased in concert, the resulting interactive effects were greatly magnified. This synergy between iron and temperature increases would not have been predictable by examining the effects of each variable individually. Our results suggest the possibility that if iron availability increases under future climate regimes, the impacts of predicted temperature increases on plankton assemblages in polar regions could be significantly enhanced. Such synergistic and antagonistic interactions between individual climate change variables highlight the importance of multivariate studies for marine global change experiments.This project was supported by US NSF grants ANT 0528715 to JMR, ANT 0741411, ANT 0741428 and OCE 0825319 to DAH, ANT 0338157 to WOS, ANT 0338097 to GRD, and ANT 0338350 to RBD

53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility

Double-strand breaks activate the ataxia telangiectasia mutated (ATM) kinase, which promotes the accumulation of DNA damage factors in the chromatin surrounding the break. The functional significance of the resulting DNA damage foci is poorly understood. Here we show that 53BP1 (also known as TRP53BP1), a component of DNA damage foci, changes the dynamic behaviour of chromatin to promote DNA repair. We used conditional deletion of the shelterin component TRF2 (also known as TERF2) from mouse cells (TRF2fl/-) to deprotect telomeres, which, like double-strand breaks, activate the ATM kinase, accumulate 53BP1 and are processed by non-homologous end joining (NHEJ). Deletion of TRF2 from 53BP1-deficient cells established that NHEJ of dysfunctional telomeres is strongly dependent on the binding of 53BP1 to damaged chromosome ends. To address the mechanism by which 53BP1 promotes NHEJ, we used time-lapse microscopy to measure telomere dynamics before and after their deprotection. Imaging showed that deprotected telomeres are more mobile and sample larger territories within the nucleus. This change in chromatin dynamics was dependent on 53BP1 and ATM but did not require a functional NHEJ pathway. We propose that the binding of 53BP1 near DNA breaks changes the dynamic behaviour of the local chromatin, thereby facilitating NHEJ repair reactions that involve distant sites, including joining of dysfunctional telomeres and AID (also known as AICDA)-induced breaks in immunoglobulin class-switch recombination

Factors associated with knowledge of pre-exposure prophylaxis in pregnant women in Cape Town, South Africa

Pregnant and postpartum women in Southern Africa are at increased risk of HIV infection. Pre-exposure prophylaxis in pregnancy and postpartum periods could significantly reduce the risk of HIV acquisition and transmission in pregnancy. Participants at a community health clinic in Cape Town completed a survey about demographic and sexual risk behaviors, and prior knowledge of pre-exposure prophylaxis. We evaluated factors associated with knowledge of pre-exposure prophylaxis using multivariable logistic regression. We enrolled 50 pregnant and 37 postpartum women, of whom 51% were HIV-uninfected. Twenty-nine (33%) knew about pre-exposure prophylaxis, most from their healthcare provider (69%). Older age (adjusted odds ratio [aOR]/year = 1.09, 95% CI = 1.00–1.19), unintended pregnancy (aOR = 3.36, 95% CI = 1.06–12.12), and more than one sex partner in the last year (aOR = 5.31, 95% CI = 1.12–30.07) were associated with pre-exposure prophylaxis knowledge. Our study identified low levels of pre-exposure prophylaxis knowledge in pregnant and breastfeeding women, but increased knowledge in higher risk women. These results provide guidance to develop interventions to increase pre-exposure prophylaxis knowledge and uptake

Prevalence and correlates of sexually transmitted infections in pregnancy in HIV-infected and- uninfected women in Cape Town, South Africa.

ObjectivesSexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine.MethodsBetween November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy.ResultsIn 242 women (median age 29 years [IQR = 24-34], median gestation 19 weeks [IQR = 14-24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02-3.67), being unmarried or not cohabiting with the fetus' father (aOR = 2.19; 95% CI = 1.16-4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08-20.95) were associated with STI diagnosis.ConclusionWe found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy

Prevalence and correlates of sexually transmitted infections in pregnancy in HIV-infected and- uninfected women in Cape Town, South Africa.

ObjectivesSexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine.MethodsBetween November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy.ResultsIn 242 women (median age 29 years [IQR = 24-34], median gestation 19 weeks [IQR = 14-24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02-3.67), being unmarried or not cohabiting with the fetus' father (aOR = 2.19; 95% CI = 1.16-4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08-20.95) were associated with STI diagnosis.ConclusionWe found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy

White Matter Stroke Induces a Unique Oligo-Astrocyte Niche That Inhibits Recovery

Subcortical white matter stroke is a common stroke subtype. White matter stroke stimulates adjacent oligodendrocyte progenitor cells (OPCs) to divide and migrate to the lesion, but stroke OPCs have only a limited differentiation into mature oligodendrocytes. To understand the molecular systems that are active in OPC responses in white matter stroke, OPCs were virally labeled and laser-captured in the region of partial damage adjacent to the infarct in male mice. RNAseq indicates two distinct OPC transcriptomes associated with the proliferative and limited-regeneration phases of OPCs after stroke. Molecular pathways related to nuclear receptor activation, ECM turnover, and lipid biosynthesis are activated during proliferative OPC phases after stroke; inflammatory and growth factor signaling is activated in the later stage of limited OPC differentiation. Within ECM proteins, Matrilin-2 is induced early after stroke and then rapidly downregulated. Prediction of upstream regulators of the OPC stroke transcriptome identifies several candidate molecules, including Inhibin A-a negative regulator of Matrilin-2. Inhibin A is induced in reactive astrocytes after stroke, including in humans. In functional assays, Matrilin-2 induces OPC differentiation, and Inhibin A inhibits OPC Matrilin-2 expression and inhibits OPC differentiation. In vivo, Matrilin-2 promotes motor recovery after white matter stroke, and promotes OPC differentiation and ultrastructural evidence of remyelination. These studies show that white matter stroke induces an initial proliferative and reparative response in OPCs, but this is blocked by a local cellular niche where reactive astrocytes secrete Inhibin A, downregulating Matrilin-2 and blocking myelin repair and recovery.SIGNIFICANCE STATEMENT Stroke in the cerebral white matter of the brain is common. The biology of damage and recovery in this stroke subtype are not well defined. These studies use cell-specific RNA sequencing and gain-of-function studies to show that white matter stroke induces a glial signaling niche, present in both humans and mice, between reactive astrocytes and oligodendrocyte progenitor cells. Astrocyte secretion of Inhibin A and downregulation of oligodendrocyte precursor production of Matrilin-2 limit OPC differentiation, tissue repair, and recovery in this disease

Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice.

White matter stroke is a distinct stroke subtype, accounting for up to 25% of stroke and constituting the second leading cause of dementia. The biology of possible tissue repair after white matter stroke has not been determined. In a mouse stroke model, white matter ischemia causes focal damage and adjacent areas of axonal myelin disruption and gliosis. In these areas of only partial damage, local white matter progenitors respond to injury, as oligodendrocyte progenitors (OPCs) proliferate. However, OPCs fail to mature into oligodendrocytes (OLs) even in regions of demyelination with intact axons and instead divert into an astrocytic fate. Local axonal sprouting occurs, producing an increase in unmyelinated fibers in the corpus callosum. The OPC maturation block after white matter stroke is in part mediated via Nogo receptor 1 (NgR1) signaling. In both aged and young adult mice, stroke induces NgR1 ligands and down-regulates NgR1 inhibitors during the peak OPC maturation block. Nogo ligands are also induced adjacent to human white matter stroke in humans. A Nogo signaling blockade with an NgR1 antagonist administered after stroke reduces the OPC astrocytic transformation and improves poststroke oligodendrogenesis in mice. Notably, increased white matter repair in aged mice is translated into significant poststroke motor recovery, even when NgR1 blockade is provided during the chronic time points of injury. These data provide a perspective on the role of NgR1 ligand function in OPC fate in the context of a specific and common type of stroke and show that it is amenable to systemic intervention to promote recovery

The Less the Public Knows the Better? The Effects of Increased Knowledge on Celebrity Evaluations

Celebrities are figures that people like a lot but know little about. Two experiments investigated how celebrity evaluations are affected by increased knowledge. In Experiment 1, heightened knowledge of the political orientation, faith, and social attitudes of two prominent actors led to less favorable evaluations and greater differentiation in the evaluations of the actors along political and gender lines. In Experiment 2, increasing participants\u27 cognizance of their limited knowledge of popular entertainers led to less positive evaluations and diminished credibility of the celebrities as spokespersons. The findings suggest that increasing knowledge and meta-knowledge of celebrities may diminish their marketability