Toxoplasma ERK7 defends the apical complex from premature degradation

Accurate cellular replication balances the biogenesis and turnover of complex structures. Apicomplexan parasites such as Plasmodium and Toxoplasma replicate by forming daughter cells within an intact mother cell, creating additional challenges to ensuring fidelity of division. Critical to these parasites' infectivity is an intricate cytoskeleton structure called the apical complex. Before the daughter apical complex can be inserted into the plasma membrane, the maternal material must be turned over. We previously identified the kinase ERK7 as required for the maturation of the apical complex in Toxoplasma gondii. Here we define the Toxoplasma ERK7 interactome, and identify a putative E3 ligase, CSAR1, as the downstream effector responsible for the phenotype. Genetic disruption of CSAR1 fully suppresses loss of the apical complex upon ERK7 knockdown. Furthermore, we show that CSAR1 is normally responsible for turnover of maternal cytoskeleton during cytokinesis, and that its aberrant function is driven by a mislocalization from the parasite residual body to the maternal and daughter apical complexes. These data identify a protein homeostasis pathway critical for Toxoplasma replication and fitness and suggest an unappreciated role for the parasite residual body in compartmentalizing processes that threaten the fidelity of parasite development.

How Divergence for Feed Efficiency Traits Affects Body Measurements and Metabolites in Blood and Ruminal Parameters on Pre-Weaning Dairy Heifers

The objectives of this study were: (1) to evaluate feed efficiency indexes and their relationships with body measurements and blood and ruminal metabolites in the pre-weaning period; (2) to determine if such measurements can be used as feed-efficiency markers during the pre-weaning period. Holstein–Gyr heifer calves (n = 36), enrolled between 4 and 12 weeks of age, were classified into two residual feed intake (RFI) and residual body weight gain (RG) groups: high efficiency (HE; RFI, n = 10; and RG, n = 9), and low efficiency (LE; RFI, n = 10; and RG, n = 8). Calves were fed whole milk (6 L/day) and solid feed ad libitum. Body developments were measured weekly and feed intake (milk and solid feed) daily during the whole period. Blood samples were collected at 12 weeks of age and analyzed for glucose, insulin and β-hydroxybutyrate (BHB). Samples of ruminal content were collected on the same day and analyzed for pH, NH3-N, and volatile fatty acids (VFA). Among the growth characteristics, only the initial hip width differed between the RFI groups, and withers height differed between the RG groups. Concentration of BHB was greater and glucose: insulin ratios tended to be greater in LE-RG animals. Butyric acid proportions were similar among RFI groups, but tended to be greater for HE-RG than for LE-RG. Overall, correlation coefficients between RFI or RG and blood, rumen, or morphometric markers were low. Thus, it is unlikely that measurements of metabolic indicators, per se, will be useful in the early identification of more efficient animals. Understanding the underlying physiological basis for improved feed efficiency in dairy heifers requires further investigation.

338 Nitrogen Use Efficiency Is Proportionally More Improved When Young Bulls Are Ranked on Residual Body Gain Rather Than on Residual Feed Intake

Animals with superior feed efficiency (FE) may also have an improved nitrogen use efficiency (NUE), which would be beneficial to economic profitability while reducing environmental impacts. When genetically selecting animals on FE, it is preferable to use residual traits [e.g. residual feed intake (RFI) or residual body gain (RG)] rather than ratios because of their predictable genetic outcomes. We studied the relationship of RFI and RG with NUE, estimated from the validated 15N abundance in plasma, across two contrasted diets based on corn or grass silages. We evaluated FE of 588 (half by diet) Charolais bulls (545 ± 57 kg BW) from 12 experimental cohorts (different farms and periods) over 200 days. Before the end of the FE test, plasma was sampled and analyzed for δ 15N. NUE was related to FE through simple-linear models with variables previously corrected for the cohort and diet effects. The models’ slopes were standardized according to FE deviation in order to compare the response of NUE to FE between indices. Higher NUE was related to higher FE (P < 0.001), showing positive correlations with RG (r=-0.40) and negative with RFI (r=0.29). However, the standardized slope of NUE to RG was significantly higher (+28%; P < 0.05) than that of NUE to RFI. This stronger NUE relation to RG compared to RFI could reflect a higher potential of RG animals to deposit N as compared to a more conservational N metabolism in RFI individuals. Regarding diets, and despite the correction of NUE and FE for this effect, the slopes of NUE to FE were numerically (P > 0.05) higher (-16% and +36%; for RG and RFI) in corn-based diets, which agrees with superior NUE observed in corn-vs-grass diets. Results suggested that superior RG animals may present proportionally higher NUE than superior RFI animals, with even better results in corn-vs-grass diets.

A Therapeutic Matrix: Virtual Reality as a Clinical Tool for Spinal Cord Injury-Induced Neuropathic Pain

Neuropathic pain (NP) is a chronic, debilitating, and resistant form of pain. The onset rate of NP following spinal cord injuries (SCI) is high and may reduce the quality of life more than the sensorimotor loss itself. The long-term ineffectiveness of current treatments in managing symptoms and counteracting maladaptive plasticity highlights the need to find alternative therapeutic approaches. Virtual reality (VR) is possibly the best way to administer the specific illusory or reality-like experience and promote behavioral responses that may be effective in mitigating the effects of long-established NP. This approach aims to promote a more systematic adoption of VR-related techniques in pain research and management procedures, highlighting the encouraging preliminary results in SCI. We suggest that the multisensory modulation of the sense of agency and ownership by residual body signals may produce positive responses in cases of brain-body disconnection. First, we focus on the transversal role embodiment and how multisensory and environmental or artificial stimuli modulate illusory sensations of bodily presence and ownership. Then, we present a brief overview of the use of VR in healthcare and pain management. Finally, we discus research experiences which used VR in patients with SCI to treating NP, including the most recent combinations of VR with further stimulation techniques.

Leptin and Melanocortin Signaling Mediates Hypertension in Offspring From Female Rabbits Fed a High-Fat Diet During Gestation and Lactation

Maternal high-fat diet in rabbits leads to hypertension and elevated renal sympathetic nerve activity (RSNA) in adult offspring but whether this is due to adiposity or maternal programming is unclear. We gave intracerebroventricular (ICV) and ventromedial hypothalamus (VMH) administration of leptin-receptor antagonist, α-melanocyte-stimulating hormone (αMSH), melanocortin-receptor antagonist (SHU9119), or insulin-receptor (InsR) antagonist to conscious adult offspring from mothers fed a high-fat diet (mHFD), control diet (mCD), or mCD offspring fed HFD for 10d (mCD10d, to deposit equivalent fat but not during development). mHFD and mCD10d rabbits had higher mean arterial pressure (MAP, +6.4 mmHg, +12.1 mmHg, p < 0.001) and RSNA (+2.3 nu, +3.2 nu, p < 0.01) than mCD, but all had similar plasma leptin. VMH leptin-receptor antagonist reduced MAP (−8.0 ± 3.0 mmHg, p < 0.001) in mCD10d but not in mHFD or mCD group. Intracerebroventricular leptin-receptor antagonist reduced MAP only in mHFD rabbits (p < 0.05). Intracerebroventricular SHU9119 reduced MAP and RSNA in mHFD but only reduced MAP in the mCD10d group. VMH αMSH increased RSNA (+85%, p < 0.001) in mHFD rabbits but ICV αMSH increased RSNA in both mHFD and mCD10d rabbits (+45%, +51%, respectively, p < 0.001). The InsR antagonist had no effect by either route on MAP or RSNA. Hypothalamic leptin receptor and brain-derived neurotrophic factor (BDNF) mRNA were greater in mHFD compared with mCD rabbits and mCD10d rabbits. In conclusion, the higher MAP in mHFD and mCD10d offspring was likely due to greater central leptin signaling at distinct sites within the hypothalamus while enhanced melanocortin contribution was common to both groups suggesting that residual body fat was mainly responsible. However, the effects of SHU9119 and αMSH on RSNA pathways only in mHFD suggest a maternal HFD may program sympatho-excitatory capacity in these offspring and that this may involve increased leptin receptor and BDNF expression.

The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator of C. elegans spermatogenesis

ABSTRACTIn sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulating C. elegans molting, we discovered that NHR-23/NR1F1 is also constitutively expressed in developing primary spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex-determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm, as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.

Spatially variable larval histories may shape recruitment rates of a temperate reef fish

Several long-standing hypotheses purport variation in recruitment to be positively correlated with pelagic environmental conditions that enhance larval growth, survival, and/or delivery to recruitment sites. However, the relationship between recruitment intensity and larval environmental conditions (or more directly, larval condition) is difficult to evaluate and poorly known for most species. We evaluate this relationship for the reef fish Forsterygion lapillum that commonly inhabits rocky reefs throughout New Zealand. We quantified variation in recruitment of F. lapillum using a nested sampling design, and found that the largest source of variation was between 2 nearby regions (a semi-enclosed harbour and an adjacent open coast system). We estimated 'settler condition' as the composite of residual body mass and 2 measurements of larval growth (reconstructed from otolith microstructure) and found that recruitment intensity was positively correlated with settler condition for sites within the harbour, but negatively correlated with settler condition for sites on the open coast. Mean pelagic larval duration of recruits to the harbour was ̃3 d shorter than recruits to the open coast. These results suggest that larval experience and relationships between recruitment and settler condition are spatially variable. We speculate that (1) larval retention within a productive embayment facilitates a positive relationship between recruitment and settler condition while (2) dispersal through a less productive environment drives a negative relationship for replenishment on the open coast. These putative differences may have important implications for patterns of recruitment, the strength of post-settlement density-dependent interactions, and dynamics of local populations.

Spatially variable larval histories may shape recruitment rates of a temperate reef fish

Several long-standing hypotheses purport variation in recruitment to be positively correlated with pelagic environmental conditions that enhance larval growth, survival, and/or delivery to recruitment sites. However, the relationship between recruitment intensity and larval environmental conditions (or more directly, larval condition) is difficult to evaluate and poorly known for most species. We evaluate this relationship for the reef fish Forsterygion lapillum that commonly inhabits rocky reefs throughout New Zealand. We quantified variation in recruitment of F. lapillum using a nested sampling design, and found that the largest source of variation was between 2 nearby regions (a semi-enclosed harbour and an adjacent open coast system). We estimated 'settler condition' as the composite of residual body mass and 2 measurements of larval growth (reconstructed from otolith microstructure) and found that recruitment intensity was positively correlated with settler condition for sites within the harbour, but negatively correlated with settler condition for sites on the open coast. Mean pelagic larval duration of recruits to the harbour was ̃3 d shorter than recruits to the open coast. These results suggest that larval experience and relationships between recruitment and settler condition are spatially variable. We speculate that (1) larval retention within a productive embayment facilitates a positive relationship between recruitment and settler condition while (2) dispersal through a less productive environment drives a negative relationship for replenishment on the open coast. These putative differences may have important implications for patterns of recruitment, the strength of post-settlement density-dependent interactions, and dynamics of local populations.

Effects of bird feeder density on the foraging behaviors of a backyard songbird (the House Finch, Haemorhous mexicanus) subject to seasonal disease outbreaks

Provisioning of wildlife, such as backyard bird feeding, can alter animal behavior and ecology in diverse ways. For species that are highly dependent on supplemental resources, it is critical to understand how variation in the degree of provisioning, as occurs naturally across backyards, alters wildlife behavior and ecology in ways potentially relevant to disease spread. We experimentally manipulated feeder density at suburban sites and tracked local abundance, foraging behaviors, body mass, and movement in House Finches (Haemorhous mexicanus (P.L. Statius Müller, 1776)), the primary host of a pathogen commonly spread at feeders. Sites with high feeder density harbored higher local House Finch abundance, and birds at these sites had longer feeding bouts and total time on feeders relative to sites with low feeder density. House Finches at high-density feeder sites had lower residual body mass despite greater apparent feeder access. Finally, birds first recorded at low-density feeder sites were more likely to move to neighboring high-density feeder sites than vice versa. Because local abundance and time spent on feeders have both been linked with disease risk in this species, the effects of heterogeneity in bird feeder density on these traits may have important consequences for disease dynamics in this system and more broadly.