MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a p53-R270H Mouse Model.

Unlabelled: Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment are understood. MYC, an oncogene, is amongst the most amplified genes in high-grade serous ovarian cancer (HGSOC), but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant-negative mutant p53-R270H with a fallopian tube epithelium (FTE)-specific promoter Ovgp1 to generate a new GEMM of HGSOC.

Effects of parenteral nutrition + best supportive nutritional care vs. best supportive nutritional care alone on quality of life in patients with pancreatic cancer-a secondary analysis of PANUSCO.

Purpose: Parenteral nutrition (PN) can be an effective treatment to improve the nutritional status of patients with pancreatic cancer, but the effects of PN on quality of life (QoL) are still understudied. Therefore, we aimed at investigating whether the best supportive nutritional care (BSNC) in combination with PN at home compared to BSNC alone changed QoL in patients with advanced pancreatic cancer undergoing chemotherapy over a period of 7 weeks.

Methods: n = 12 patients in the PANUSCO study received nutritional counseling only (control group (CG)) and n = 9 patients were also given supportive PN (intervention group (IG)).

Spiking networks that efficiently process dynamic sensory features explain receptor information mixing in somatosensory cortex.

How do biological neural systems efficiently encode, transform and propagate information between the sensory periphery and the sensory cortex about sensory features evolving at different time scales? Are these computations efficient in normative information processing terms? While previous work has suggested that biologically plausible models of of such neural information processing may be implemented efficiently within a single processing layer, how such computations extend across several processing layers is less clear. Here, we model propagation of multiple time-varying sensory features across a sensory pathway, by extending the theory of efficient coding with spikes to efficient encoding, transformation and transmission of sensory signals. These computations are optimally realized by a multilayer spiking network with feedforward networks of spiking neurons (receptor layer) and recurrent excitatory-inhibitory networks of generalized leaky integrate-and-fire neurons (recurrent layers).

The impact of task (un)certainty on repeated grip force production.

Many studies found that in physical tasks, reducing certainty regarding their endpoints hinders performance. However, the impact of reducing certainty regarding other aspects of physical tasks is unknown. Here we manipulated the certainty of the required effort on an unrelated, parallel task (i.

MYC is sufficient to generate mid-life high-grade serous ovarian and uterine serous carcinomas in a p53-R270H mouse model.

Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. , an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs.

Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV interneurons.

How mechanical allodynia following nerve injury is encoded in patterns of neural activity in the spinal cord dorsal horn (DH) remains incompletely understood. We address this in mice using the spared nerve injury model of neuropathic pain and in vivo electrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to mechanical stimuli following nerve injury, an overall increase in sensitivity or reactivity of DH neurons is not observed.

The Multistable Melanopsins of Mammals.

Melanopsin is a light-activated G protein coupled receptor that is expressed widely across phylogeny. In mammals, melanopsin is found in intrinsically photosensitive retinal ganglion cells (ipRGCs), which are especially important for "non-image" visual functions that include the regulation of circadian rhythms, sleep, and mood. Photochemical and electrophysiological experiments have provided evidence that melanopsin has at least two stable conformations and is thus multistable, unlike the monostable photopigments of the classic rod and cone photoreceptors.

Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV interneurons.

How mechanical allodynia following nerve injury is encoded in patterns of neural activity in the spinal cord dorsal horn (DH) is not known. We addressed this using the spared nerve injury model of neuropathic pain and electrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to mechanical stimuli following nerve injury, an overall increase in sensitivity or reactivity of DH neurons was not observed.

Encoding of environmental illumination by primate melanopsin neurons.

Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina.

Emotions as computations.

Emotions ubiquitously impact action, learning, and perception, yet their essence and role remain widely debated. Computational accounts of emotion aspire to answer these questions with greater conceptual precision informed by normative principles and neurobiological data. We examine recent progress in this regard and find that emotions may implement three classes of computations, which serve to evaluate states, actions, and uncertain prospects.

Return to Learn ECHO: Telementoring for School Personnel to Help Children Return to School and Learning After Mild Traumatic Brain Injury.

Background: Return to learn (RTL) after mild traumatic brain injury (mTBI) presents unique challenges for school professionals. A multidisciplinary team approach is necessary yet training school professionals is logistically difficult. This paper describes an innovative pilot RTL program and its evaluation.

Mechanoreceptor signal convergence and transformation in the dorsal horn flexibly shape a diversity of outputs to the brain.

The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical stimuli applied to the skin, large-scale in vivo electrophysiological recordings, and genetic manipulations, here we show that neurons in the mouse spinal cord DH receive convergent inputs from both low- and high-threshold mechanoreceptor subtypes and exhibit one of six functionally distinct mechanical response profiles. Genetic disruption of DH feedforward or feedback inhibitory motifs, comprised of interneurons with distinct mechanical response profiles, revealed an extensively interconnected DH network that enables dynamic, flexible tuning of postsynaptic dorsal column (PSDC) output neurons and dictates how neurons in the primary somatosensory cortex respond to touch.

Seeing Effort: Assessing Coaches' Prediction of the Number of Repetitions in Reserve Before Task-Failure.

Background: A key role of resistance training (RT) coaches is to personalize programs based on their trainees' abilities and goals. Specifically, coaches often assess how many repetitions in reserve (RIR) their trainees have until task-failure. Coaches can then modify the number of repetitions assigned per set accordingly.

A Perspective on Plant Phenomics: Coupling Deep Learning and Near-Infrared Spectroscopy.

The trait-based approach in plant ecology aims at understanding and classifying the diversity of ecological strategies by comparing plant morphology and physiology across organisms. The major drawback of the approach is that the time and financial cost of measuring the traits on many individuals and environments can be prohibitive. We show that combining near-infrared spectroscopy (NIRS) with deep learning resolves this limitation by quickly, non-destructively, and accurately measuring a suite of traits, including plant morphology, chemistry, and metabolism.

Why do people increase effort near a deadline? An opportunity-cost model of goal gradients.

People tend to gradually reduce effort when performing lengthy tasks, experiencing physical or mental fatigue. Yet, they often increase their effort near deadlines. How can both phenomena co-occur? If fatigue causes the level of effort to decline, why does effort rise again near a deadline? The present article proposes a model to explain this pattern of behavior and tests three predictions that follow from it.

Cortical responses to touch reflect subcortical integration of LTMR signals.

Current models to explain how signals emanating from cutaneous mechanoreceptors generate representations of touch are based on comparisons of the tactile responses of mechanoreceptor subtypes and neurons in somatosensory cortex. Here we used mouse genetic manipulations to investigate the contributions of peripheral mechanoreceptor subtypes to cortical responses to touch. Cortical neurons exhibited remarkably homogeneous and transient responses to skin indentation that resembled rapidly adapting (RA) low-threshold mechanoreceptor (LTMR) responses.

Mechanoreceptor synapses in the brainstem shape the central representation of touch.

Mammals use glabrous (hairless) skin of their hands and feet to navigate and manipulate their environment. Cortical maps of the body surface across species contain disproportionately large numbers of neurons dedicated to glabrous skin sensation, in part reflecting a higher density of mechanoreceptors that innervate these skin regions. Here, we find that disproportionate representation of glabrous skin emerges over postnatal development at the first synapse between peripheral mechanoreceptors and their central targets in the brainstem.

Exploring the acute affective responses to resistance training: A comparison of the predetermined and the estimated repetitions to failure approaches.

Background: In resistance-training (RT), the number of repetitions is traditionally prescribed using a predetermined approach (e.g., three sets of 10 repetitions).

[How to manage acute urine retention?].

Acute urinary retention is a common problem, mainly among elderly men. The first step in the treatment is the placement of an indwelling urinary catheter. It's common practice to remove the catheter after a short period of time to observe if spontaneous micturition returns.

3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration.

The retinal pigment epithelium (RPE)-choriocapillaris (CC) complex in the eye is compromised in age-related macular degeneration (AMD) and related macular dystrophies (MDs), yet in vitro models of RPE-CC complex that enable investigation of AMD/MD pathophysiology are lacking. By incorporating iPSC-derived cells into a hydrogel-based extracellular matrix, we developed a 3D RPE-CC model that recapitulates key features of both healthy and AMD/MD eyes and provides modular control over RPE and CC layers. Using this 3D RPE-CC model, we demonstrated that both RPE- and mesenchyme-secreted factors are necessary for the formation of fenestrated CC-like vasculature.

Alveolar soft part sarcoma presenting in an unusual laryngeal location.

Alveolar soft part sarcoma (ASPS) is a rare malignant neoplasm that tends to occur in the deep soft tissues of both adults and children. ASPS has a progressive clinical course that is unfortunately characterised by late metastases and an overall poor prognosis. Although the tumour has been reported in a wide range of anatomic sites, few cases of primary laryngeal ASPS are reported in the literature.

Inhibition of the supplementary motor area affects distribution of effort over time.

In tasks that extend over time, people tend to exert much effort at the beginning and the end, but not in the middle, exhibiting the stuck-in-the-middle pattern (STIM). To date, little is known about the neural mechanisms underlying this effect. As the supplementary motor area (SMA) was previously implicated in coding prospective task-demands, we tested its role in producing the STIM pattern.