SummaryCdc42-interacting protein 4 (CIP4), a member of the F-BAR family of proteins, plays important roles in a variety of cellular events by regulating both membrane and actin dynamics. In many cell types, CIP4 functions in vesicle formation, endocytosis and membrane tubulation. However, recent data indicate that CIP4 is also involved in protrusion in some cell types, including cancer cells (lamellipodia and invadopodia) and neurons (ribbed lamellipodia and veils). In neurons, CIP4 localizes specifically to extending protrusions and functions to limit neurite outgrowth early in development. The mechanism by which CIP4 localizes to the protruding edge membrane and induces lamellipodial/veil protrusion and actin rib formation is not known. Here, we show that CIP4 localization to the protruding edge of neurons is dependent on both the phospholipid content of the plasma membrane and the underlying organization of actin filaments. Inhibiting phosphatidylinositol (3,4,5)-trisphosphate (PIP 3 ) production decreases CIP4 at the membrane. CIP4 localization to the protruding edge is also dependent on Rac1/WAVE1, rather than Cdc42/N-WASP. Capping actin filaments with low concentrations of cytochalasin D or by overexpressing capping protein dramatically decreases CIP4 at the protruding edge, whereas inactivating Arp2/3 drives CIP4 to the protruding edge. We also demonstrate that CIP4 dynamically colocalizes with Ena/VASP and DAAM1, two proteins known to induce unbranched actin filament arrays and play important roles in neuronal development. Together, this is the first study to show that the localization of an F-BAR protein depends on both actin filament architecture and phospholipids at the protruding edge of developing neurons.

We demonstrate embedded growth of cortical mouse neurons in dense arrays of semiconductor microtubes. The microtubes, fabricated from a strained GaAs/InGaAs heterostructure, guide axon growth through them and enable electrical and optical probing of propagating action potentials. The coaxial nature of the microtubes -similar to myelin -is expected to enhance the signal transduction along the axon. We present a technique of suppressing arsenic toxicity and prove the success of this technique by overgrowing neuronal mouse cells.

Background The optimal extent of surgery for patients with papillary thyroid microcarcinoma (PTMC), tumors ≤1 cm, is controversial, because survival is excellent regardless of approach. The objective of this study was to investigate patient and surgeon decision making about the extent of surgery for PTMC. Materials and Methods We conducted a retrospective review of thyroid cancer patients operated on at a single institution from 2008–2016. To examine decision-making about the extent of surgery, we performed a discourse analysis on all available documentation looking for patient or surgeon reasons. Results Of the 853 thyroid cancer patients, 125 (14.7%) had a PTMC as their largest tumor. Overall, 27.2% of the PTMC patients underwent a thyroid lobectomy (TL), while 72.8% had a total thyroidectomy (TT). Of those patients diagnosed with PTMC preoperatively (19/125), a significantly higher proportion underwent a TT (94.7% vs. 68.9%, p=0.02). In all cases, documentation indicated that these preoperatively diagnosed patients followed the surgeon’s recommendation regarding the extent of surgery. Reasons surgeons cited for recommending a TT included patient and disease factors (34.6%), belief that TT was the standard treatment (21.7%), ease of follow-up (8.7%), and referring provider preference (4.3%). Of the 19 patients diagnosed preoperatively, 4 (21.1%) patients had a complication, one (5.3%) of which was permanent and potentially avoidable with less extensive surgery. Conclusions These data suggest that surgeons drive decision making about the extent of thyroidectomy in patients with preoperatively diagnosed PTMC. With recent guidelines recommending TL, closer examination of decision-making is needed to ensure that patients make well-informed, preference-based decisions.

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