Embryonically Active Piriform Cortex Neurons Promote Intracortical Recurrent Connectivity during Development.

Neuronal activity plays a critical role in the maturation of circuits that propagate sensory information into the brain. How widely does early activity regulate circuit maturation across the developing brain? Here, we used Targeted Recombination in Active Populations (TRAP) to perform a brain-wide survey for prenatally active neurons in mice and identified the piriform cortex as an abundantly TRAPed region. Whole-cell recordings in neonatal slices revealed preferential interconnectivity within embryonically TRAPed piriform neurons and their enhanced synaptic connectivity with other piriform neurons. In vivo Neuropixels recordings in neonates demonstrated that embryonically TRAPed piriform neurons exhibit broad functional connectivity within piriform and lead spontaneous synchronized population activity during a transient neonatal period, when recurrent connectivity is strengthening. Selectively activating or silencing of these neurons in neonates enhanced or suppressed recurrent synaptic strength, respectively. Thus, embryonically TRAPed piriform neurons represent an interconnected hub-like population whose activity promotes recurrent connectivity in early development.

Exogenous protease supplementation to the diet enhances growth performance, improves nitrogen utilization, and reduces stress in finishing pigs.

We have conducted this experiment to evaluate a new exogenous protease in finishing pigs' growth performance, nutrient digestibility, gas emission, blood profiles, and meat quality. A total of 200 pigs of 52.15 ± 2.31 kg average body weight (BW) were divided into four dietary treatments named as: CON, basal diet; TRT1, basal diet + 0.05% protease; TRT2, basal diet + 0.1% protease; TRT3, basal diet + 1.5% protease. Each treatment consisted of 10 pens, where five pigs were allotted to each pen according to their body weight and sex. The dietary treatments were allotted to the pens in a randomized block design. During this 10-week-long experiment, BW, average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) were calculated for Week 0-5, Week 6-10, and the overall period. During Week 6-10, ADG was higher in TRT2 and TRT3 than in the CON and TRT1 groups. At the same time, a linear increase was observed in ADG and G:F of the pigs. In addition, the final BW of pigs' was linearly increased by protease supplementation. On Week 10, there was a linear trend of increase (p = 0.0575) in crude protein digestibility and a trend of linear reduction (p = 0.0651) in NH3 gas emission. In blood profile, cortisol presented a linear decrease in both Week 5 (p = 0.251) and Week 10 (p = 0.0585). In addition, increasing doses of protease showed a trend of linear increase (p = 0.0592) in creatinine, whereas linear reduction was observed in the concentration of epinephrine (p = 0.0636) and norepinephrine (p = 0.0167) during Week 10. In conclusion, protease supplementation helped in improving daily gain in finishing pigs through protein digestibility with associated reduction of ammonia emission and blood stress hormones.

IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers.

Myc activation is a primary oncogenic event in many human cancers; however, these transcription factors are difficult to inhibit pharmacologically, suggesting that Myc-dependent downstream effectors may be more tractable therapeutic targets. Here, we show that Myc overexpression induces endoplasmic reticulum (ER) stress and engages the inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 (XBP1) pathway through multiple molecular mechanisms in a variety of c-Myc- and N-Myc-dependent cancers. In particular, Myc-overexpressing cells require IRE1α/XBP1 signaling for sustained growth and survival in vitro and in vivo, dependent on elevated stearoyl-CoA-desaturase 1 (SCD1) activity. Pharmacological and genetic XBP1 inhibition induces Myc-dependent apoptosis, which is alleviated by exogenous unsaturated fatty acids. Of note, SCD1 inhibition phenocopies IRE1α RNase activity suppression in vivo. Furthermore, IRE1α inhibition enhances the cytotoxic effects of standard chemotherapy drugs used to treat c-Myc-overexpressing Burkitt's lymphoma, suggesting that inhibiting the IRE1α/XBP1 pathway is a useful general strategy for treatment of Myc-driven cancers.

Obturator Compartment Syndrome Secondary to Pelvic Hematoma After Robot-Assisted Laparoscopic Radical Prostatectomy.

Obturator nerve injury is a known injury after robot-assisted laparoscopic radical prostatectomy (RALP) and patients often present with motor and sensory deficits in the immediate postoperative period. We describe a 65-year-old male who presented with motor deficits, indicative of obturator neurapraxia after RALP upon waking from anesthesia. Work-up revealed an expansile hematoma possibly compressing the obturator nerve. After evacuation of the hematoma, the patient had immediate improvement of his neurologic deficits. Our patient's clinical vignette illustrates the importance of considering postsurgical hematoma in the differential diagnosis when patients present with signs and symptoms of obturator neurapraxia after RALP.