Host species vary in infection probability, sub-lethal effects, and costs of immune response when exposed to an amphibian parasite

The amphibian parasite Batrachochytrium dendrobatidis (Bd) is regarded as an extreme generalist, infecting over 500 species, but amongst these hosts there exists a great deal of variation in the susceptibility to and the costs of parasite exposure. We use two infection experiments to determine whether inter-specific variation in the sublethal and lethal effects of parasite exposure exist in two host species. We then tested the relative roles of host density and diversity on infection probability of a focal susceptible host. Our results show significant heterogeneity in host species response to parasite exposure, and that both lethal and sub-lethal costs exist in individuals that are able to resist infection, indicating that successful immune response to infection comes at a cost. Further, we show that increasing host density significantly increased the likelihood of susceptible individuals becoming infected with Bd irrespective of host diversity and variation in host susceptibility. These results suggest that populations of resistant species are likely to suffer ill-effects of exposure to Bd regardless of their infection status, and that at the stage of initial infection there was no support for the dilution of transmission events, in contrast to other studies that focus on subsequent transmission of infection

Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescentlylabelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188-expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.This study is funded by the Cancer Research UK

COVID-19: Analogues and lessons for tackling the extinction and climate crises

As environmental scientists working in countries whose COVID-linked deaths already exceed their military casualties from all campaigns since 1945, we believe there are significant messages from the handling of this horrific disease for efforts addressing the enormous challenges posed by the ongoing extinction and climate emergencies

Childhood maltreatment and the medical morbidity in bipolar disorder: a case-control study.

BACKGROUND: Childhood maltreatment (abuse and neglect) can have long-term deleterious consequences, including increased risk for medical and psychiatric illnesses, such as bipolar disorder in adulthood. Emerging evidence suggests that a history of childhood maltreatment is linked to the comorbidity between medical illnesses and mood disorders. However, existing studies on bipolar disorder have not yet explored the specific influence of child neglect and have not included comparisons with individuals without mood disorders (controls). This study aimed to extend the existing literature by examining the differential influence of child abuse and child neglect on medical morbidity in a sample of bipolar cases and controls. METHODS: The study included 72 participants with bipolar disorder and 354 psychiatrically healthy controls (average age of both groups was 48 years), who completed the Childhood Trauma Questionnaire, and were interviewed regarding various medical disorders. RESULTS: A history of any type of childhood maltreatment was significantly associated with a diagnosis of any medical illness (adjusted OR = 6.28, 95% confidence intervals 1.70-23.12, p = 0.006) and an increased number of medical illnesses (adjusted OR = 3.77, 95% confidence intervals 1.34-10.57, p = 0.012) among adults with bipolar disorder. Exposure to child abuse was more strongly associated with medical disorders than child neglect. No association between childhood maltreatment and medical morbidity was detected among controls. CONCLUSIONS: To summarise, individuals with bipolar disorder who reported experiencing maltreatment during childhood, especially abuse, were at increased risk of suffering from medical illnesses and warrant greater clinical attention.The bipolar case–control genetic association study was funded by an unrestricted grant from GlaxoSmithKline Research and Development. Funding for the depression case–control study was provided by the UK Medical Research Council (MRC; G0701420). The BADGE study was supported by an Interdisciplinary Ph.D. studentship from the UK Economic Social Research Council (ESRC) and MRC to Dr. Hosang. Prof. Uher is supported by the Canada Research Chairs program (http://www.chairs-chaires.gc.ca/him) and Dr. Fisher is supported by an MQ Fellows Award (MQ14F40). The sources of funding had no involvement in the study design, data collection or decision to submit for publication

A coherent middle Pliocene magnetostratigraphy, Wanganui Basin, New Zealand

We document magnetostratigraphies for three river sections (Turakina, Rangitikei, Wanganui) in Wanganui Basin and interpret them as corresponding to the Upper Gilbert, the Gauss and lower Matuyama Chrons of the Geomagnetic Polarity Timescale, in agreement with foraminiferal biostratigraphic datums. The Gauss-Gilbert transition (3.58 Ma) is located in both the Turakina and Wanganui River sections, while the Gauss-Matuyama transition (2.58 Ma) is located in all three sections, as are the lower and upper boundaries of the Mammoth (3.33–3.22 Ma) and Kaena (3.11–3.04 Ma) Subchrons. Our interpretations are based in part on the re-analysis of existing datasets and in part on the acquisition and analysis of new data, particularly for the Wanganui River section. The palaeomagnetic dates of these six horizons provide the only numerical age control for a thick (up to 2000 m) mudstone succession (Tangahoe Mudstone) that accumulated chiefly in upper bathyal and outer neritic palaeoenvironments. In the Wanganui River section the mean sediment accumulation rate is estimated to have been about 1.8 m/k.y., in the Turakina section it was about 1.5 m/k.y., and in the Rangitikei section, the mean rate from the beginning of the Mammoth Subchron to the Hautawa Shellbed was about 1.1 m/k.y. The high rates may be associated with the progradation of slope clinoforms northward through the basin. This new palaeomagnetic timescale allows revised correlations to be made between cyclothems in the Rangitikei River section and the global Oxygen Isotope Stages (OIS) as represented in Ocean Drilling Program (ODP) Site 846. The 16 depositional sequences between the end of the Mammoth Subchron and the Gauss-Matuyama Boundary are correlated with OIS MG2 to 100. The cyclothems average 39 k.y. in duration in our age model, which is close to the 41 k.y. duration of the orbital obliquity cycles. We support the arguments advanced recently in defence of the need for local New Zealand stages as a means of classifying New Zealand sedimentary successions, and strongly oppose the proposal to move stage boundaries to selected geomagnetic polarity transitions. The primary magnetisation of New Zealand mudstone is frequently overprinted with secondary components of diagenetic origin, and hence it is often difficult to obtain reliable magnetostratigraphic records. We suggest specific approaches, analytical methods, and criteria to help ensure robustness and coherency in the palaeomagnetic identification of chron boundaries in typical New Zealand Cenozoic mudstone successions

Childhood maltreatment and adult medical morbidity in mood disorders: comparison of unipolar depression with bipolar disorder.

BACKGROUND: The medical burden in mood disorders is high; various factors are thought to drive this pattern. Little research has examined the role of childhood maltreatment and its effects on medical morbidity in adulthood among people with unipolar depression and bipolar disorder.AimsThis is the first study to explore the association between childhood maltreatment and medical morbidity in bipolar disorder and in unipolar depression, and examine whether the impact of abuse and neglect are distinct or combined. METHOD: The participants consisted of 354 psychiatrically healthy controls, 248 participants with recurrent unipolar depression and 72 with bipolar disorder. Participants completed the Childhood Trauma Questionnaire and received a validated medical history interview. RESULTS: Any type of childhood maltreatment, child abuse and child neglect were significantly associated with the medical burden in bipolar disorder, but not unipolar depression or for controls. These associations worked in a dose-response fashion where participants with bipolar disorder with a history of two or more types of childhood maltreatment had the highest odds of having a medical illness relative to those without such history or those who reported one form. No such significant dose-response patterns were detected for participants with unipolar depression or controls. CONCLUSIONS: These findings suggest that childhood maltreatment may play a stronger role in the development of medical illnesses in individuals with bipolar disorder relative to those with unipolar depression. Individuals who had been maltreated with a mood disorder, especially bipolar disorder may benefit most from prevention and intervention efforts surrounding physical health.Declaration of interestNone.GlaxoSmithKline Research and Development funded BaCCs. The UK Medical Research Council (MRC; G0701420) funded DeCC. The BADGE study was supported by an Interdisciplinary PhD studentship from the UK Economic Social Research Council and MRC to G.M.H. H.L.F. is supported by an MQ Fellows Award (MQ14F40). K.H. is supported by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The sources of funding had no involvement in the study design, data collection or decision to submit for publication

Conditioned stochastic particle systems and integrable quantum spin systems

We consider from a microscopic perspective large deviation properties of several stochastic interacting particle systems, using their mapping to integrable quantum spin systems. A brief review of recent work is given and several new results are presented: (i) For the general disordered symmectric exclusion process (SEP) on some finite lattice conditioned on no jumps into some absorbing sublattice and with initial Bernoulli product measure with density $\rho$ we prove that the probability $S_\rho(t)$ of no absorption event up to microscopic time $t$ can be expressed in terms of the generating function for the particle number of a SEP with particle injection and empty initial lattice. Specifically, for the symmetric simple exclusion process on $\mathbb Z$ conditioned on no jumps into the origin we obtain the explicit first and second order expansion in $\rho$ of $S_\rho(t)$ and also to first order in $\rho$ the optimal microscopic density profile under this conditioning. For the disordered ASEP on the finite torus conditioned on a very large current we show that the effective dynamics that optimally realizes this rare event does not depend on the disorder, except for the time scale. For annihilating and coalescing random walkers we obtain the generating function of the number of annihilated particles up to time $t$, which turns out to exhibit some universal features.Comment: 25 page

Host species vary in infection probability, sub-lethal effects, and costs of immune response when exposed to an amphibian parasite

The amphibian parasite Batrachochytrium dendrobatidis (Bd) is regarded as an extreme generalist, infecting over 500 species, but amongst these hosts there exists a great deal of variation in the susceptibility to and the costs of parasite exposure. We use two infection experiments to determine whether inter-specific variation in the sublethal and lethal effects of parasite exposure exist in two host species. We then tested the relative roles of host density and diversity on infection probability of a focal susceptible host. Our results show significant heterogeneity in host species response to parasite exposure, and that both lethal and sub-lethal costs exist in individuals that are able to resist infection, indicating that successful immune response to infection comes at a cost. Further, we show that increasing host density significantly increased the likelihood of susceptible individuals becoming infected with Bd irrespective of host diversity and variation in host susceptibility. These results suggest that populations of resistant species are likely to suffer ill-effects of exposure to Bd regardless of their infection status, and that at the stage of initial infection there was no support for the dilution of transmission events, in contrast to other studies that focus on subsequent transmission of infection

Targeted ablation and reorganization of the principal preplate neurons and their neuroblasts identified by golli promoter transgene expression in the neocortex of mice

The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11–E13; where E is embryonic day) of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP (τ-enhanced green fluorescent protein) and lacZ (lacZ galactosidase) reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0) and control (HSV-TK0/0) littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and permanently impairs its connectivity