Parental effects on offspring sex ratio in the Numbat (Myrmecobius fasciatus): does captivity influence paternal sex allocation?

Sex allocation theories predict that under different ecological conditions the production of sons and daughters will affect parental fitness differently. Skewed offspring sex ratios often occur under captive conditions where individuals are exposed to nutritional and social conditions that differ from nature. Here, we analyzed 29 years of offspring sex ratio data from a captive population of an endangered marsupial, the Numbat (Myrmecobius fasciatus). We partitioned variation in offspring sex ratio based on parental origin (captive- vs. wild-bred), parental weight, maternal age, and maternal reproductive history. Our analyses revealed no effect of parental weight or maternal origin on offspring sex ratio-however, there was a significant effect of paternal origin. Data visualization indicated that captive-bred males tended to produce male-biased litters. We discuss the result in relation to recent studies that have shown that male mammals have the capacity to be arbiters of sex allocation and highlight candidate mechanisms, but consider it with caution due to the small sample size from which the result was derived. We performed a population viability analysis (PVA) to explore the potential impact of a sex ratio skew on the sustainability of the captive Numbat population under hypothetical scenarios. Our PVA revealed that supplementation with wild individuals is critical to the persistence of the captive Numbat population and that a biased sex ratio will lead to extinction of the captive colony under certain conditions. Overall, our study demonstrates that covert sex ratio skews can persist undetected in captive populations, which have the potential to become impactful and compromise population sustainability under changed management processes.

The use of metronidazole in acute diarrhea in dogs: a narrative review.

Acute diarrhea is a common reason for non-wellness veterinary visits in dogs. Treatment for acute diarrhea usually consists of supportive care with nutritional intervention, fluid therapy, anthelmintics, and often an antibiotic - commonly metronidazole in North America. The empirical use of metronidazole for acute diarrhea in dogs has been a common practice in veterinary medicine for many decades; however, recent studies evaluating its use suggest it may be inappropriately utilized in many cases. Herein, we review the evidence evaluating the use of metronidazole and other antibiotics in acute diarrhea in the human and veterinary literature. Recommendations on the use of metronidazole and other antibiotics as well as other therapeutic considerations in the treatment of acute diarrhea are also provided.

Ultrahigh magnetic resonance contrast switching with water gated polymer-silica nanoparticles.

Very high T1 magnetic resonance imaging (MRI) switches can be obtained with pH-responsive polymer-coated paramagnetic mesoporous silica nanoparticles (MSNs), as the local environment traverses the pKa of the polymer coat (Δr1 ∼ 50 mM-1 s-1 at 1.5 T and Δr1 ∼ 22 mM-1 s-1 at 3 T). We assign these characteristics to a strong peripheral hydration capping at the mesopores, impacting channel-confined water mobility such that outer sphere contributions to contrast are greatly enhanced.

Reversible pH-responsive MRI contrast with paramagnetic polymer micelles.

Paramagnetically-doped polymer micelles, containing an ionizable poly(acrylic acid) (PAA) block, support high-contrast MR imaging at clinically relevant field strengths in a manner that is strongly pH responsive. A reversible switch in polymer strand charge specifically has a direct impact on local rigidity, and rotational correlation time characteristics, of the integrated Gd-chelate, driving a ∼50% amplitude switch in positive contrast.

Promoting high T2 contrast in Dy-doped MSNs through Curie effects.

Contrast agents retaining high relaxivities at ultrahigh magnetic fields underpin an enhanced image sensitivity within derived MRI scans. By varying the Dy3+ loading density inside a mesoporous silica architecture the dominant Curie effect can be effectively tuned so as to optimise T2 contrast at magnetic fields as high as 11.7 T.

Mesoporous Silica Nanoparticles in Bioimaging.

A biomedical contrast agent serves to enhance the visualisation of a specific (potentially targeted) physiological region. In recent years, mesoporous silica nanoparticles (MSNs) have developed as a flexible imaging platform of tuneable size/morphology, abundant surface chemistry, biocompatibility and otherwise useful physiochemical properties. This review discusses MSN structural types and synthetic strategies, as well as methods for surface functionalisation. Recent applications in biomedical imaging are then discussed, with a specific emphasis on magnetic resonance and optical modes together with utility in multimodal imaging.

Magnetic Nanoparticles Supporting Bio-responsive T1/T2 Magnetic Resonance Imaging.

: The use of nanoparticulate systems as contrast agents for magnetic resonance imaging (MRI) is well-established and known to facilitate an enhanced image sensitivity within scans of a particular pathological region of interest. Such a capability can enable both a non-invasive diagnosis and the monitoring of disease progression/response to treatment. In this review, magnetic nanoparticles that exhibit a bio-responsive MR relaxivity are discussed, with pH-, enzyme-, biomolecular-, and protein-responsive systems considered. The ability of a contrast agent to respond to a biological stimulus provides not only enriched diagnostic capabilities over corresponding non-responsive analogues, but also an improved longitudinal monitoring of specific physiological conditions.

Water gated contrast switching with polymer-silica hybrid nanoparticles.

Bioresponsive contrast agents can provide smart signaling in MRI. In wrapping pore functionalised Gd-DOTA mesoporous silica nanoparticles with pH-responsive poly(acrylic acid), exchange between pore and bulk water can be reversibly switched by local pH. The generated high contrast then exhibits a large amplitude switch in a manner relevant to environmentally responsive imaging.

Nanoparticle-Based Paramagnetic Contrast Agents for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is a noninvasive medical imaging modality that is routinely used in clinics, providing anatomical information with micron resolution, soft tissue contrast, and deep penetration. Exogenous contrast agents increase image contrast by shortening longitudinal (T 1) and transversal (T 2) relaxation times. Most of the T 1 agents used in clinical MRI are based on paramagnetic lanthanide complexes (largely Gd-based). In moving to translatable formats of reduced toxicity, greater chemical stability, longer circulation times, higher contrast, more controlled functionalisation and additional imaging modalities, considerable effort has been applied to the development of nanoparticles bearing paramagnetic ions. This review summarises the most relevant examples in the synthesis and biomedical applications of paramagnetic nanoparticles as contrast agents for MRI and multimodal imaging. It includes the most recent developments in the field of production of agents with high relaxivities, which are key for effective contrast enhancement, exemplified through clinically relevant examples.

Malignant canine mammary epithelial cells shed exosomes containing differentially expressed microRNA that regulate oncogenic networks.

BACKGROUND: Breast (mammary) cancers in human (BC) and canine (CMT) patients share clinical, pathological, and molecular similarities that suggest dogs may be a useful translational model. Many cancers, including BC, shed exosomes that contain microRNAs (miRs) into the microenvironment and circulation, and these may represent biomarkers of metastasis and tumor phenotype. METHODS: Three normal canine mammary epithelial cell (CMEC) cultures and 5 CMT cell lines were grown in serum-free media. Exosomes were isolated from culture media by ultracentrifugation then profiled by transmission electron microscopy, dynamic light scattering, and Western blot. Exosomal small RNA was deep-sequenced on an Illumina HiSeq2500 sequencer and validated by qRT-PCR. In silico bioinformatic analysis was carried out to determine microRNA gene and pathway targets. RESULTS: CMEC and CMT cell lines shed round, "cup-shaped" exosomes approximately 150-200 nm, and were immunopositive for exosomal marker CD9. Deep-sequencing averaged ~ 15 million reads/sample. Three hundred thirty-eight unique miRs were detected, with 145 having > ±1.5-fold difference between one or more CMT and CMEC samples. Gene ontology analysis revealed that the upregulated miRs in this exosomal population regulate a number of relevant oncogenic networks. Several miRNAs including miR-18a, miR-19a and miR-181a were predicted in silico to target the canine estrogen receptor (ESR1α). CONCLUSIONS: CMEC and CMT cells shed exosomes in vitro that contain differentially expressed miRs. CMT exosomal RNA expresses a limited number of miRs that are up-regulated relative to CMEC, and these are predicted to target biologically relevant hormone receptors and oncogenic pathways. These results may inform future studies of circulating exosomes and the utility of miRs as biomarkers of breast cancer in women and dogs.