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Natal imprinting to the Earth’s magnetic field in a pelagic seabird
No full textIn migratory animals for whom post-natal care is limited, it is essential that there are inherited mechanisms whereby an individual can navigate—first, to the terminus of their migration, and second, back to a suitable breeding site. In birds, empirical evidence suggests that orientation on first migration is controlled by an inherited navigational vector, a direction and a distance in which to move (the “clock and compass” model) [1, 2, 3, 4, 5]. The mechanism and information that underlie the return to the natal breeding site are, however, almost entirely unknown. A potential solution to this problem would be for an animal to learn the values for spatially and temporally stable gradient cues that specifically indicate the location of the natal site [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. One potential cue for latitude is magnetic inclination. Here, we use ringing recoveries made over the last 80 years to investigate whether magnetic inclination might be used as a navigational cue to control the latitude of recruitment in a trans-global migrant, the Manx shearwater (Puffinus puffinus). We find that small changes in inclination between when a bird fledges and when it returns from first migration correlate with probabilistic changes in latitude at recruitment, in doing so quantitatively fulfilling a priori predictions as to the magnitude and direction of latitudinal shift. This, we believe, suggests that (1) natal magnetic inclination is learnt prior to fledging and (2) is used to provide latitudinal information when making the first return trip from the wintering grounds
Galaxy morphology rules out astrophysically relevant Hu-Sawicki f (R) gravity
No full textf
(
R
)
is a paradigmatic modified gravity theory that typifies extensions to General Relativity with new light degrees of freedom and hence screened fifth forces between masses. These forces produce observable signatures in galaxy morphology, caused by a violation of the weak equivalence principle due to a differential impact of screening among galaxies’ mass components. We compile statistical datasets of two morphological indicators—offsets between stars and gas in galaxies and warping of stellar disks—and use them to constrain the strength and range of a thin-shell-screened fifth force. This is achieved by applying a comprehensive set of upgrades to past work [H. Desmond et al., Phys. Rev. D 98, 064015 (2018); H. Desmond et al., Phys. Rev. D 98, 083010 (2018) ]: we construct a robust galaxy-by-galaxy Bayesian forward model for the morphological signals, including full propagation of uncertainties in the input quantities and marginalization over an empirical model describing astrophysical noise. Employing more stringent data quality cuts than previously we find no evidence for a screened fifth force of any strength
Δ
G
/
G
N
in the Compton wavelength range 0.3–8 Mpc, setting a
1
σ
bound of
Δ
G
/
G
N
<
0.8
at
λ
C
=
0.3
Mpc
that strengthens to
Δ
G
/
G
N
<
3
×
10
−
5
at
λ
C
=
8
Mpc
. These are the tightest bounds to date beyond the Solar System by over an order of magnitude. For the Hu-Sawicki model of
f
(
R
)
with
n
=
1
we require a background scalar field value
f
R
0
<
1.4
×
10
−
8
, forcing practically all astrophysical objects to be screened. We conclude that this model can have no relevance to astrophysics or cosmology
Drug use disorders and violence: associations with individual drug categories
No full textAlthough drug use disorders are among the most important modifiable factors for violence perpetration, previous reviews have not investigated links with individual categories of drug use disorders or explored sources of variation in risk estimates between studies. We conducted a systematic review and meta-analysis of studies that examined the link between individual drug categories and violent outcomes. We searched for primary case-control and cohort investigations that reported risk of violence against others in individuals diagnosed with drug use disorders using validated clinical criteria, and followed PRISMA guidelines. We identified 18 studies published from 1990 to 2019 reporting data from 591,411 individuals with drug use disorders. We reported odds ratios (OR) of the violence risk in different categories of drug use disorders compared with those without. We found ORs ranged from 0.8 to 25.0 for most individual drug categories, with generally higher ORs in individuals with polydrug use disorders. In addition, we explored sources of between-study heterogeneity by subgroup and meta-regression analyses. Cohort investigations reported a lower risk of violence than case-control reports (OR = 2.7 [2.1-3.5] vs 6.6 [5.1-8.6]), and associations were stronger when the outcome was any violence rather than intimate partner violence (OR = 5.7 [3.8-8.6] vs 1.7 [1.4-2.1]), which was consistent with results from the meta-regression. Overall, these findings highlight the potential impact of preventing and treating drug use disorders on reducing violence risk and associated morbidities
Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair
No full textCanonical roles for macrophages in mediating the fibrotic response after a heart attack include extracellular matrix turnover and activation of cardiac fibroblasts to initiate collagen deposition. Here we reveal that macrophages directly contribute collagen to the forming post-injury scar. Unbiased transcriptomics shows an upregulation of collagens in both zebrafish and mouse macrophages following heart injury. Adoptive transfer of macrophages, from either collagen-tagged zebrafish or adult mouse GFPtpz-collagen donors, enhances scar formation via cell autonomous production of collagen. In zebrafish, the majority of tagged collagen localises proximal to the injury, within the overlying epicardial region, suggesting a possible distinction between macrophage-deposited collagen and that predominantly laid-down by myofibroblasts. Macrophage-specific targeting of col4a3bpa and cognate col4a1 in zebrafish significantly reduces scarring in cryoinjured hosts. Our findings contrast with the current model of scarring, whereby collagen deposition is exclusively attributed to myofibroblasts, and implicate macrophages as direct contributors to fibrosis during heart repair
Unveiling the risk period for death after respiratory syncytial virus Illness in young children using a self- controlled case series design
No full textBackground: Respiratory syncytial virus (RSV)–related acute lower respiratory infection is an important cause of death in infants and young children. However, little is known about the risk period for RSV-related deaths after presentation to health services with an RSV illness.
Methods: Using the Scottish national mortality database, we identified deaths from respiratory/circulatory causes (hereafter “respiratory/circulatory deaths”) in young children aged <5 years during 2009–2016, whose medical history and records of laboratory-confirmed RSV infections were obtained by linking the mortality database to the national surveillance data set and the Scottish Morbidity Record. We used a self-controlled case series (SCCS) design to evaluate the relative incidence of deaths with respiratory/circulatory deaths in the first year after an RSV episode. We defined the risk interval as the first year after the RSV episode, and the control interval as the period before and after the risk interval until 5 years after birth. Age-adjusted incidence ratio and attributable fraction were generated using the R software package SCCS.
Results: We included 162 respiratory/circulatory deaths, of which 36 occurred in children with a history of laboratory-confirmed RSV infection. We found that the mortality risk decreased with time after the RSV episode and that the risk was statistically significant for the month after RSV illness. More than 90% of respiratory/circulatory deaths occurring within 1 week after the RSV episode were attributable to RSV (attributable fraction, 93.9%; 95% confidence interval, 77.6%–98.4%), compared with about 80% of those occurring 1 week to 1 month after RSV illness (80.3%; 28.5%–94.6%).
Conclusions: We found an increased risk of death in the first month after an RSV illness episode leading to healthcare attendance. This provides a practical cutoff time window for community-based surveillance studies estimating RSV-related mortality risk. Further studies are warranted to assess the mortality risk beyond the first month after RSV illness episode
Precision non-implantable neuromodulation therapies: a perspective for the depressed brain
No full textCurrent first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more “precision-oriented” practice
Charge interactions modulate the encounter complex ensemble of two differently charged disordered protein partners of KIX
No full textDisordered proteins play important roles in cell signaling and are frequently involved in protein-protein interactions. They also have a larger proportion of charged and polar residues than their folded counterparts. Here we developed a structure-based model and applied molecular dynamics simulations to examine the presence and importance of electrostatic interactions in the binding processes of two differently charged intrinsically disordered ligands of the KIX domain of CBP. We observed non-native opposite-charged contacts in the encounter complexes for both ligands with KIX, and this may be a general feature of coupled folding and binding reactions. The ensemble of successful encounter complexes is a diverse set of structures, and in the case of the highly charged ligand this ensemble was found to be malleable with respect to ionic strength. There are only minor differences between encounter complex ensembles for successful and unsuccessful collisions, with no key interactions that appear to make the process far more productive. The energy landscape at this early stage in the process does not appear highly funneled. Strikingly we observed many native interactions that appear to reduce chances of an encounter complex being productive. Instead it appears that collectively non-native electrostatic interactions in the encounter complex increase the likelihood of productivity by holding the proteins together long enough for folding to take place. This mechanism is more effective for the more highly charged ligand
Identifying the immune interactions underlying HLA class I disease associations
No full textVariation in the risk and severity of many autoimmune diseases, malignancies and infections is strongly associated with polymorphisms at the HLA class I loci. These genetic associations provide a powerful opportunity for understanding the etiology of human disease. HLA class I associations are often interpreted in the light of ‘protective’ or ‘detrimental’ CD8+ T cell responses which are restricted by the host HLA class I allotype. However, given the diverse receptors which are bound by HLA class I molecules, alternative interpretations are possible. As well as binding T cell receptors on CD8+ T cells, HLA class I molecules are important ligands for inhibitory and activating killer immunoglobulin-like receptors (KIRs) which are found on natural killer cells and some T cells; for the CD94:NKG2 family of receptors also expressed mainly by NK cells and for leukocyte immunoglobulin-like receptors (LILRs) on myeloid cells. The aim of this study is to develop an immunogenetic approach for identifying and quantifying the relative contribution of different receptor-ligand interactions to a given HLA class I disease association and then to use this approach to investigate the immune interactions underlying HLA class I disease associations in three viral infections: Human T cell Leukemia Virus type 1, Human Immunodeficiency Virus type 1 and Hepatitis C Virus as well as in the inflammatory condition Crohn’s disease
Efficacy of a spatial repellent for control of malaria in Indonesia: a cluster-randomized controlled trial
No full textA cluster-randomized, double-blinded, placebo-controlled trial was conducted to estimate the protective efficacy (PE) of a spatial repellent (SR) against malaria infection in Sumba, Indonesia. Following radical cure in 1,341 children aged ≥ 6 months to ≤ 5 years in 24 clusters, households were given transfluthrin or placebo passive emanators (devices designed to release vaporized chemical). Monthly blood screening and biweekly human-landing mosquito catches were performed during a 10-month baseline (June 2015–March 2016) and a 24-month intervention period (April 2016–April 2018). Screening detected 164 first-time infections and an accumulative total of 459 infections in 667 subjects in placebo-control households, and 134 first-time and 253 accumulative total infections among 665 subjects in active intervention households. The 24-cluster protective effect of 27.7% and 31.3%, for time to first-event and overall (total new) infections, respectively, was not statistically significant. Purportedly, this was due in part to zero to low incidence in some clusters, undermining the ability to detect a protective effect. Subgroup analysis of 19 clusters where at least one infection occurred during baseline showed 33.3% (P-value = 0.083) and 40.9% (P-value = 0.0236, statistically significant at the one-sided 5% significance level) protective effect to first infection and overall infections, respectively. Among 12 moderate- to high-risk clusters, a statistically significant decrease in infection by intervention was detected (60% PE). Primary entomological analysis of impact was inconclusive. Although this study suggests SRs prevent malaria, additional evidence is required to demonstrate the product class provides an operationally feasible and effective means of reducing malaria transmission