Tooth and consequences: Heterodonty and dental replacement in piranhas and pacus (Serrasalmidae)

Tooth replacement in piranhas is unusual: all teeth on one side of the head are lost as a unit, then replaced simultaneously. We used histology and microCT to examine tooth‐replacement modes across carnivorous piranhas and their herbivorous pacu cousins (Serrasalmidae) and then mapped replacement patterns onto a molecular phylogeny. Pacu teeth develop and are replaced in a manner like piranhas. For serrasalmids, unilateral tooth replacement is not an “all or nothing” phenomenon; we demonstrate that both sides of the jaws have developing tooth rows within them, albeit with one side more mineralized than the other. All serrasalmids (except one) share unilateral tooth replacement, so this is not an adaptation for carnivory. All serrasalmids have interlocking teeth; piranhas interdigitate lateral tooth cusps with adjacent teeth, forming a singular saw‐like blade, whereas lateral cusps in pacus clasp together. For serrasalmids to have an interlocking dentition, their teeth need to develop and erupt at the same time. We propose that interlocking mechanisms prevent tooth loss and ensure continued functionality of the feeding apparatus. Serrasalmid dentitions are ubiquitously heterodont, having incisiform and molariform dentitions reminiscent of mammals. Finally, we propose that simultaneous tooth replacement be considered as a synapomorphy for the family.     

Estimating site occupancy and detectability of the threatened partridge pigeon (Geophaps smithii) using camera traps

Since European settlement, many granivorous birds of northern Australia's savanna landscapes have declined. One such example, the partridge pigeon (Geophaps smithii), has suffered a significant range contraction, disappearing from at least half of its pre‐European range. Multiple factors have been implicated in this decline, including the loss of traditional Aboriginal burning practices, grazing by large exotic herbivores and predation by feral cats (Felis catus). While populations of partridge pigeon on the Tiwi Islands may be particularly important for the long‐term persistence of this species, they too may be at risk of decline. However, as a reliable method to detect this species has not yet been developed and tested, we lack the ability to identify, at an early stage, the species' decline in a given location or region. This severely limits our capacity to make informed management decisions. Here, we demonstrate that the standard camera trapping approach for native mammal monitoring in northern Australia attained an overall probability of detecting partridge pigeon greater than 0.98. We thus provide a robust estimate of partridge pigeon site occupancy (0.30) on Melville Island, the larger of the two main Tiwi Islands. The information presented here for the partridge pigeon represents a critical first step towards the development of optimal monitoring programmes with which to gauge population trajectories, as well as the response to remedial management actions. In the face of ongoing biodiversity loss, such baseline information is vital for management agencies to make informed decisions and should therefore be sought for as many species as possible.     

Diffuse and nonlinear imaging of multiscale vascular parameters for in vivo monitoring of preclinical mammary tumors

Diffuse optical imaging (DOI) techniques provide a wide‐field or macro assessment of the functional tumor state and have shown substantial promise for monitoring treatment efficacy in cancer. Conversely, intravital microscopy provides a high‐resolution view of the tumor state and has played a key role in characterizing treatment response in the preclinical setting. There has been little prior work in investigating how the macro and micro spatial scales can be combined to develop a more comprehensive and translational view of treatment response. To address this, a new multiscale preclinical imaging technique called diffuse and nonlinear imaging (DNI) was developed. DNI combines multiphoton microscopy with spatial frequency domain imaging (SFDI) to provide multiscale data sets of tumor microvascular architecture coregistered within wide‐field hemodynamic maps. A novel method was developed to match the imaging depths of both modalities by utilizing informed SFDI spatial frequency selection. An in vivo DNI study of murine mammary tumors revealed multiscale relationships between tumor oxygen saturation and microvessel diameter, and tumor oxygen saturation and microvessel length (|Pearson's ρ| ≥ 0.5, P < 0.05). Going forward, DNI will be uniquely enabling for the investigation of multiscale relationships in tumors during treatment.      

The effects of different cold‐temperature regimes on development,growth, and susceptibility to an abiotic and biotic stressor

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The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma

Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1-associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM. Here, we found that phosphorylation of AMP-dependent kinase (AMPK) was elevated in BAP1-altered (or mutant) compared to BAP1-unaltered (or wild-type [WT]) UM tumors. As a readout of AMPK pathway activation, phosphorylation of an AMPK downstream effector, acetyl-CoA-carboxylase (ACC), was also elevated. BAP1 re-expression in BAP1-null UM cell lines decreased phospho-AMPK (pAMPK) and phospho-ACC (pACC) levels. AMPK phosphorylation is mediated by calcium/calmodulin dependent protein kinase kinase 2 (CaMKK2) and potentially liver kinase B1 (LKB1) in BAP1 mutant UM cells. Knockdown of AMPKα1/2 reduced the viability of BAP1 mutant UM cells, indicating a survival function of AMPK in BAP1 mutant UM. Our data suggest that the AMPK pathway is an important mechanism mediating the survival of BAP1 mutant UM. Targeting the AMPK pathway may be a novel therapeutic strategy for metastatic UM.     

PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex

Signaling through the mammalian target of rapamycin complex 1 (mTORC1) is positively regulated by amino acids and insulin. PRAS40 associates with mTORC1 (which contains raptor) but not mTORC2. PRAS40 interacts with raptor, and this requires an intact TOR-signaling (TOS) motif in PRAS40. Like TOS motif-containing proteins such as eIF4E-binding protein 1 (4E-BP1), PRAS40 is a substrate for phosphorylation by mTORC1. Consistent with this, starvation of cells of amino acids or treatment with rapamycin alters the phosphorylation of PRAS40. PRAS40 binds 14-3-3 proteins, and this requires both amino acids and insulin. Binding of PRAS40 to 14-3-3 proteins is inhibited by TSC1/2 (negative regulators of mTORC1) and stimulated by Rheb in a rapamycin-sensitive manner. This confirms that PRAS40 is a target for regulation by mTORC1. Small interfering RNA-mediated knockdown of PRAS40 impairs both the amino acid- and insulin-stimulated phosphorylation of 4E-BP1 and the phosphorylation of S6. However, this has no effect on the phosphorylation of Akt or TSC2 (an Akt substrate). These data place PRAS40 downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1.     

Rapid intraoperative insulin assay: a novel method to differentiate insulinoma from nesidioblastosis in the pediatric patient

Background

The essential objectives for thyroidectomy are: avoidance of injury to the recurrent laryngeal nerves, conservation of the parathyroid glands, an accurate haemostasis and an excellent cosmesis. In the last 10 years major improvements and new technologies have been proposed and applied in thyroid surgery; among these mini-invasive thyroidectomy, regional anaesthesia and intraoperative neuromonitoring, and new devices for achieving dissection and haemostasis. Minor bleeding from small vessels could be a major complication in thyroid surgery. The purpose of ligating vessels is to maintain the surgical site free from an excess of blood and reduce blood loss in the patient.

Materials and methods

Hydroxylated polyvinyl acetal tampons (HPA) are made by a synthetic, open cell foam structure able to absorb fluids up to 25 times the initial weight. We tested their efficacy for small bleeding control and tissue dissection during several thyroid procedures.

Results

HPA tampons have been found extremely useful to absorb blood coming from minor and diffuse loss, helping to control bleeding by a combined action of fluid absorption and local compression. The porous design of the tampon allows the use of the suction device right through the tampon itself. Thanks to the initial mildly hard consistency, we also used HPA tampons as dissecting instruments.

Conclusion

In our experience the use of HPA tampons resulted extremely efficient for minor bleeding control, fluids removal and tissue dissection during thyroid surgery.