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Sex-Dependent Effects of Prenatal Food and Protein Restriction on Offspring Physiology in Rats and Mice: Systematic Review and Meta-Analyses

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-02-09
Abstract: 

Background:  Males and females may experience different effects of early-life adversity on life-long health. One hypothesis is that male foetuses invest more in foetal growth and relatively less in placental growth, and that this makes them susceptible to poor nutrition in utero, particularly if nutrition is reduced part-way through gestation.

Objectives:  Our objectives were to examine whether (1) food and/ or protein restriction in rats and mice has consistent sex-dependent effects, (2) sex-dependency differs between types of outcomes, and (3) males are more severely affected when restriction starts part-way through gestation.

Data sources:  PubMed and Web of Science were searched to identify eligible studies.

Study eligibility criteria:  Eligible studies described controlled experiments that restricted protein or food during gestation in rats or mice, examined physiological traits in offspring from manipulated pregnancies, and tested whether effects differed between males and females.

Results:  Our search identified 292 articles, of which the full texts of 72 were assessed, and 65 were included for further synthesis. A majority (50) used Wistar or Sprague-Dawley rats and so these were the primary focus. Among studies in which maternal diet was restricted for the duration of gestation, no type of trait was consistently more severely affected in one particular sex, although blood pressure was generally increased in both sexes. Meta-analysis found no difference between sexes in the effect of protein restriction throughout gestation on blood pressure. Among studies restricting food in the latter half of gestation only, there were again few consistent sex-dependent effects, although three studies found blood pressure was increased in males only. Meta-analysis found that food restriction in the second half of gestation increased adult blood pressure in both sexes, with a significantly greater effect in males. Birthweight was consistently reduced in both sexes, a result confirmed by meta-analysis.

Conclusions:  We found little support for the hypotheses that males are more affected by food and protein restriction, or that effects are particularly severe if nutrition is reduced part-way through gestation. However, less than half of the studies tested for sex by maternal diet interactions to identify sex-dependent effects. As a result, many reported sex-specific effects may be false positives.

Document type: 
Article
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Overfishing and Habitat Loss Drives Range Contraction of Iconic Marine Fishes to Near Extinction

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2021-02-10
Abstract: 

Extinctions on land are often inferred from sparse sightings over time, but this technique is ill-suited for wide-ranging species. We develop a space-for-time approach to track the spatial contraction and drivers of decline of sawfishes. These iconic and endangered shark-like rays were once found in warm, coastal waters of 90 nations and are now presumed extinct in more than half (n = 46). Using dynamic geography theory, we predict that sawfishes are gone from at least nine additional nations. Overfishing and habitat loss have reduced spatial occupancy, leading to local extinctions in 55 of the 90 nations, which equates to 58.7% of their historical distribution. Retention bans and habitat protections are urgently necessary to secure a future for sawfishes and similar species.

Document type: 
Article

Spatially Congruent Sites of Importance for Global Shark and Ray Biodiversity

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-07-06
Abstract: 

Many important areas identified for conservation priorities focus on areas of high species richness, however, it is unclear whether these areas change depending on what aspect of richness is considered (e.g. evolutionary distinctiveness, endemicity, or threatened species). Furthermore, little is known of the extent of spatial congruency between biodiversity measures in the marine realm. Here, we used the distribution maps of all known marine sharks, rays, and chimaeras (class Chondrichthyes) to examine the extent of spatial congruency across the hotspots of three measures of species richness: total number of species, evolutionarily distinct species, and endemic species. We assessed the spatial congruency between hotspots considering all species, as well as on the subset of the threatened species only. We consider three definitions of hotspot (2.5%, 5%, and 10% of cells with the highest numbers of species) and three levels of spatial resolution (1°, 4°, and 8° grid cells). Overall, we found low congruency among all three measures of species richness, with the threatened species comprising a smaller subset of the overall species patterns irrespective of hotspot definition. Areas of congruency at 1° and 5% richest cells contain over half (64%) of all sharks and rays and occurred off the coasts of: (1) Northern Mexico Gulf of California, (2) USA Gulf of Mexico, (3) Ecuador, (4) Uruguay and southern Brazil, (5) South Africa, southern Mozambique, and southern Namibia, (6) Japan, Taiwan, and parts of southern China, and (7) eastern and western Australia. Coarsening resolution increases congruency two-fold for all species but remains relatively low for threatened measures, and geographic locations of congruent areas also change. Finally, for pairwise comparisons of biodiversity measures, evolutionarily distinct species richness had the highest overlap with total species richness regardless of resolution or definition of hotspot. We suggest that focusing conservation attention solely on areas of high total species richness will not necessarily contribute efforts towards species that are most at risk, nor will it protect other important dimensions of species richness.

Document type: 
Article
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Gill Slits Provide a Window into the Respiratory Physiology of Sharks

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-12-04
Abstract: 

Metabolically important traits, such as gill surface area and metabolic rate, underpin life histories, population dynamics and extinction risk, as they govern the availability of energy for growth, survival and reproduction. Estimating both gill surface area and metabolic rate can be challenging, especially when working with large-bodied, threatened species. Ideally, these traits, and respiratory physiology in general, could be inferred from external morphology using a faster, non-lethal method. Gill slit height is quick to measure on live organisms and is anatomically connected to the gill arch. Here, we relate gill slit height and gill surface area for five Carcharhiniform sharks. We compared both total and parabranchial gill surface area to mean and individual gill slit height in physical specimens. We also compared empirical measurements of relative gill slit height (i.e. in proportion to total length) to those estimated from field guide illustrations to examine the potential of using anatomical drawings to measure gill slit height. We find strong positive relationships between gill slit height and gill surface area at two scales: (i) for total gill surface area and mean gill slit height across species and (ii) for parabranchial gill surface area and individual gill slit height within and across species. We also find that gill slit height is a consistent proportion of the fork length of physical specimens. Consequently, relative gill slit height measured from field guide illustrations proved to be surprisingly comparable to those measured from physical specimens. While the generality of our findings needs to be evaluated across a wider range of taxonomy and ecological lifestyles, they offer the opportunity that we might only need to go to the library and measure field guide illustrations to yield a non-lethal, first-order approximation of the respiratory physiology of sharks.

Document type: 
Article
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Upholding Science-Based Risk Assessment Under a Weakened Endangered Species Act

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-12-10
Document type: 
Article
File(s): 

Distribution of PDLIM1 at Actin-Rich Structures Generated by Invasive and Adherent Bacterial Pathogens

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-10-06
Abstract: 

The enteric bacterial pathogens Listeria monocytogenes (Listeria) and enteropathogenic Escherichia coli (EPEC) remodel the eukaryotic actin cytoskeleton during their disease processes. Listeria generate slender actin‐rich comet/rocket tails to move intracellularly, and later, finger‐like membrane protrusions to spread amongst host cells. EPEC remain extracellular, but generate similar actin‐rich membranous protrusions (termed pedestals) to move atop the host epithelia. These structures are crucial for disease as diarrheal (and systemic) infections are significantly abrogated during infections with mutant strains that are unable to generate the structures. The current repertoire of host components enriched within these structures is vast and diverse. In this protein catalog, we and others have found that host actin crosslinkers, such as palladin and α‐actinin‐1, are routinely exploited. To expand on this list, we set out to investigate the distribution of PDLIM1, a scaffolding protein and binding partner of palladin and α‐actinin‐1, during bacterial infections. We show that PDLIM1 localizes to the site of initial Listeria entry into cells. Following this, PDLIM1 localizes to actin filament clouds surrounding immotile bacteria, and then colocalizes with actin once the comet/rocket tails are generated. Unlike palladin or α‐actinin‐1, PDLIM1 is maintained within the actin‐rich core of membrane protrusions. Conversely, α‐actinin‐1, but not PDLIM1 (or palladin), is enriched at the membrane invagination that internalizes the Listeria‐containing membrane protrusion. We also show that PDLIM1 is a component of the EPEC pedestal core and that its recruitment is dependent on the bacterial effector Tir. Our findings highlight PDLIM1 as another protein present within pathogen‐induced actin‐rich structures.

Document type: 
Article

Localization of Alpha‐Actinin‐4 During Infections by Actin Remodeling Bacteria

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-10-25
Abstract: 

Bacterial pathogens cause disease by subverting the structure and function of their target host cells. Several foodborne agents such as Listeria monocytogenes (L. monocytogenes), Shigella flexneri (S. flexneri), Salmonella enterica serovar Typhimurium (S. Typhimurium) and enteropathogenic Escherichia coli (EPEC) manipulate the host actin cytoskeleton to cause diarrheal (and systemic) infections. During infections, these invasive and adherent pathogens hijack the actin filaments of their host cells and rearrange them into discrete actin‐rich structures that promote bacterial adhesion (via pedestals), invasion (via membrane ruffles and endocytic cups), intracellular motility (via comet/rocket tails) and/or intercellular dissemination (via membrane protrusions and invaginations). We have previously shown that actin‐rich structures generated by L. monocytogenes contain the host actin cross‐linker α‐actinin‐4. Here we set out to examine α‐actinin‐4 during other key steps of the L. monocytogenes infectious cycle as well as characterize the subcellular distribution of α‐actinin‐4 during infections with other model actin‐hijacking bacterial pathogens (S. flexneri, S. Typhimurium and EPEC). Although α‐actinin‐4 is absent at sites of initial L. monocytogenes invasion, we show that it is a new component of the membrane invaginations formed during secondary infections of neighboring host cells. Importantly, we reveal that α‐actinin‐4 also localizes to the major actin‐rich structures generated during cell culture infections with S. flexneri (comet/rocket tails and membrane protrusions), S. Typhimurium (membrane ruffles) and EPEC (pedestals). Taken together, these findings suggest that α‐actinin‐4 is a host factor that is exploited by an assortment of actin‐hijacking bacterial pathogens.

Document type: 
Article

GSK3β Impairs KIF1A Transport in a Cellular Model of Alzheimer’s Disease but Does Not Regulate Motor Motility at S402

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2020-10-16
Abstract: 

Impairment of axonal transport is an early pathologic event that precedes neurotoxicity in Alzheimer’s disease (AD). Soluble amyloid-β oligomers (AβOs), a causative agent of AD, activate intracellular signaling cascades that trigger phosphorylation of many target proteins, including tau, resulting in microtubule destabilization and transport impairment. Here, we investigated how KIF1A, a kinesin-3 family motor protein required for the transport of neurotrophic factors, is impaired in mouse hippocampal neurons treated with AβOs. By live cell imaging, we observed that AβOs inhibit transport of KIF1A-GFP similarly in wild-type and tau knock-out neurons, indicating that tau is not required for this effect. Pharmacological inhibition of glycogen synthase kinase 3β (GSK3β), a kinase overactivated in AD, prevented the transport defects. By mass spectrometry on KIF1A immunoprecipitated from transgenic AD mouse brain, we detected phosphorylation at S402, which conforms to a highly conserved GSK3β consensus site. We confirmed that this site is phosphorylated by GSK3β in vitro. Finally, we tested whether a phosphomimic of S402 could modulate KIF1A motility in control and AβO-treated mouse neurons and in a Golgi dispersion assay devoid of endogenous KIF1A. In both systems, transport driven by mutant motors was similar to that of WT motors. In conclusion, GSK3β impairs KIF1A transport but does not regulate motor motility at S402. Further studies are required to determine the specific phosphorylation sites on KIF1A that regulate its cargo binding and/or motility in physiological and disease states.

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Article
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Long-Term Continental Changes in Wing Length, but Not Bill Length, of a Long-Distance Migratory Shorebird

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2017-02-20
Abstract: 

We compiled a >50‐year record of morphometrics for semipalmated sandpipers (Calidris pusilla), a shorebird species with a Nearctic breeding distribution and intercontinental migration to South America. Our data included >57,000 individuals captured 1972–2015 at five breeding locations and three major stopover sites, plus 139 museum specimens collected in earlier decades. Wing length increased by ca. 1.5 mm (>1%) prior to 1980, followed by a decrease of 3.85 mm (nearly 4%) over the subsequent 35 years. This can account for previously reported changes in metrics at a migratory stopover site from 1985 to 2006. Wing length decreased at a rate of 1,098 darwins, or 0.176 haldanes, within the ranges of other field studies of phenotypic change. Bill length, in contrast, showed no consistent change over the full period of our study. Decreased body size as a universal response of animal populations to climate warming, and several other potential mechanisms, are unable to account for the increasing and decreasing wing length pattern observed. We propose that the post‐WWII near‐extirpation of falcon populations and their post‐1973 recovery driven by the widespread use and subsequent limitation on DDT in North America selected initially for greater flight efficiency and latterly for greater agility. This predation danger hypothesis accounts for many features of the morphometric data and deserves further investigation in this and other species.

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Article
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Skeletal Muscle Pump Drives Control of Cardiovascular and Postural Systems

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2017-03-27
Abstract: 

The causal interaction between cardio-postural-musculoskeletal systems is critical in maintaining postural stability under orthostatic challenge. The absence or reduction of such interactions could lead to fainting and falls often experienced by elderly individuals. The causal relationship between systolic blood pressure (SBP), calf electromyography (EMG), and resultant center of pressure (COPr) can quantify the behavior of cardio-postural control loop. Convergent cross mapping (CCM) is a non-linear approach to establish causality, thus, expected to decipher nonlinear causal cardio-postural-musculoskeletal interactions. Data were acquired simultaneously from young participants (25 ± 2 years, n = 18) during a 10-minute sit-to-stand test. In the young population, skeletal muscle pump was found to drive blood pressure control (EMG → SBP) as well as control the postural sway (EMG → COPr) through the significantly higher causal drive in the direction towards SBP and COPr. Furthermore, the effect of aging on muscle pump activation associated with blood pressure regulation was explored. Simultaneous EMG and SBP were acquired from elderly group (69 ± 4 years, n = 14). A significant (p = 0.002) decline in EMG → SBP causality was observed in the elderly group, compared to the young group. The results highlight the potential of causality to detect alteration in blood pressure regulation with age, thus, a potential clinical utility towards detection of fall proneness.

Document type: 
Article
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