Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria.

Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260-330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics.

Case Report: Watching and Waiting? A Case of Incomplete Glenosphere Seating With Spontaneous Reversal in Reverse Shoulder Arthroplasty.

Introduction: Reverse shoulder arthroplasty is a useful procedure with broadening applications, but it has the best outcomes when used for rotator cuff tear arthropathy. However, this procedure is not without complications. While scapular notching and aseptic loosening are more common complications that have been extensively studied in the literature, dissociation of the glenoid component and incomplete glenosphere seating has not received much attention. Specifically, little research has explored appropriate management of incomplete seating of the glenosphere component, and no gold standard for treatment of this complication has emerged. Methods: In the case described here, an elderly patient with an incompletely seated glenosphere component post-operatively opted to pursue conservative management in order to avoid revision surgery if possible. Results: The partially engaged, superiorly directed components in this case exhibited spontaneous complete and symmetric seating of the glenosphere between six and twelve months post-operatively, indicating that conservative management of this complication in low-demand patients may be a viable option to avoid the risks associated with revision surgery. Conclusion: Further research should be pursued to explore what patient and prosthesis design factors may be suited to observation with serial radiographs when incomplete seating of the glenosphere component occurs.

Nuclear transport of parathyroid hormone (PTH)-related protein is dependent on microtubules.

PTH-related protein (PTHrP) was first discovered as a circulating factor secreted by certain cancers and is responsible for the syndrome of humoral hypercalcemia of malignancy induced by various tumors. The similarity of its N terminus to that of PTH enables PTHrP to share the signaling properties of PTH, but the rest of the molecule possesses distinct functions, including a role in the nucleus/nucleolus in reducing apoptosis and enhancing cell proliferation. PTHrP nuclear import is mediated by importin beta1. In this study we use the technique of fluorescence recovery after photobleaching to demonstrate the ability of PTHrP to shuttle between cytoplasm and nucleus and to visualize directly the transport of PTHrP into the nucleus in living cells. Endogenous and transfected PTHrP was demonstrated to colocalize with microtubule structures in situ using various high-resolution microscopic approaches, as well as in in vitro binding studies, where importin beta1, but not importin alpha, enhanced the microtubular association of PTHrP with microtubules. Significantly, the dependence of PTHrP nuclear import on microtubules was shown by the inhibitory effect of pretreatment with the microtubule-disrupting agent nocodazole on nuclear-cytoplasmic flux. These results indicate that PTHrP nuclear/nucleolar import is dependent on microtubule integrity and are consistent with a direct role for the cytoskeleton in protein transport to the nucleus.

Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling protein with distinct paracrine and intracrine roles.

Parathyroid hormone-related protein (PTHrP) was first discovered as a circulating factor secreted by certain cancers responsible for the syndrome of humoral hypercalcemia of malignancy. PTHrP possesses distinct paracrine and intracrine signaling roles. The similarity of its N-terminus to that of parathyroid hormone (PTH) enables it to share PTH's paracrine signaling properties, whereas the rest of the molecule possesses other functions, largely relating to an intracrine signaling role in the nucleus/nucleolus in regulating apoptosis and cell proliferation. Recent advances have shown that intracellularly expressed PTHrP is able to shuttle in cell-cycle- and signal-dependent fashion between nucleus and cytoplasm through the action of the distinct intracellular transport receptors importin beta 1 and exportin 1 (Crm1) mediating nuclear import and export of PTHrP, respectively. Together, the import and export pathways constitute an integrated system for PTHrP subcellular localization. Intriguingly, PTHrP nuclear/nucleolar import is dependent on microtubule integrity, transport to the nucleus appearing to occur in vectorial fashion along microtubules, mediated in part by the action of importin beta 1. PTHrP has recently been shown to be able to bind to RNA, meaning that PTHrP's nucleocytoplasmic shuttling ability may relate to a specific role within the nucleus/nucleolus to regulate RNA synthesis and/or transport.