mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR-dependent regulatory network for nutrient transport in renal proximal tubular cells.

Recovery of movement-related potentials in the temporal course after prefrontal traumatic brain injury: a follow-up study.

OBJECTIVE: The movement-related potential (MRP) is an EEG measure related to self-initiated movements, consisting of the Bereitschaftspotential (BP), the negative slope, and the motor potential. Since in a former study the BP was reduced in acute prefrontal traumatic brain injury (TBI) patients, the present study examined the MRPs' course in follow-up examinations. METHODS: Right index finger MRPs of 22 patients with contusions of the prefrontal cortex were recorded 12, 26, and 52 weeks after TBI and compared to controls. RESULTS: Within the patient group, a significant increase of the BP in the temporal course after TBI was observed. MRPs 12 and 26 weeks after TBI did not differ significantly from the control group. One year after TBI, significantly enhanced BPs were found. CONCLUSIONS: In the temporal course after prefrontal TBI, a recovery of the initially reduced BP was observed. The enhanced BP areas 1 year after TBI might represent the need for increased cognitive resources during movement preparation, supporting a recovered, but less effective neuronal network. SIGNIFICANCE: The present study represents the first longitudinal follow-up study of MRPs after prefrontal brain lesion. The observed changes reflect the plastic capacity of the brain, reorganizing the neuronal network function.

Impaired movement-related potentials in acute frontal traumatic brain injury.

OBJECTIVE: Focal brain lesions due to traumatic brain injury (TBI) do not only lead to functional deficits in the lesion area, but also disturb the structurally intact neuronal network connected to the lesion site. Therefore we hypothesized dysfunctions of the cortical motor network after frontal TBI. The movement related potential (MRP) is an EEG component related to voluntary movement consisting of the Bereitschaftspotential (BP), the negative slope (NS), and the motor potential (MP). The aim of our study was to demonstrate alterations in the movement related cortical network in the acute stage after TBI by comparing our patients' MRPs to those of a healthy control group. METHODS: EEGs of 22 patients with magnetic resonance imaging defined contusions of the prefrontal cortex were recorded within 8 weeks after TBI. We further recruited a healthy control group. The paradigm consisted of self-paced abductions of the right index finger. RESULTS: Compared to healthy controls, the BP in the patient group was significantly reduced and its onset delayed. Moreover, an enhanced contribution of the postrolandic hemisphere ipsilateral to the movement and a reduced contribution of the left frontal cortex, ipsilateral to the lesion in the majority of the patients, were observed during motor execution (MP). CONCLUSIONS: Anatomical connections between the prefrontal cortex and the supplementary motor area (SMA) are known to exist. We suggest that prefrontal lesions lead to reduced neuronal input into the SMA. This deficit in the preparatory motor network may cause the reduced BPs in our patients. Moreover, an increased need for attentional resources might explain the enhanced motor potentials during movement execution. In conclusion, we demonstrated altered MRPs in the acute stage after frontal TBI, which are a consequence of disturbed neuronal networks involved in the preparation and execution of voluntary movements.

The aimed or feared professional future of medical students at the Univesity of Witten/Herdecke.

The current challenges of educational policy seem to be associated to changes of the health care system, to counteract concerns regarding the lack of physicians, supply shortage and migration of specialists. Therefore, expectations, wishes and concerns relevant to the anticipated everyday life as a physician of medical students at the Witten/Herdecke University (UWH) were acquired with an online questionnaire. Useful for a direct comparison the results of the online survey 'Medical Study and Future' throughout Germany have been used. Findings from this survey are common characteristics regarding the choice of the profession and planning of an establishment as a general practitioner and clear differences in reflecting on future issues in the occupational field.

[Reduced contralateral preponderance of the movement-related potential during execution of self-initiated movements in acute prefrontal traumatic brain injury]. / Reduktion kontralateraler Präponderanz bewegungsbezogener Potenziale bei selbstinitiierten Fingerbewegungen nach präfrontaler Kontusion.

OBJECTIVES: An enhanced ipsilateral motor potential after prefrontal TBI is known. Our aim was to examine, whether this contributes to movement initiation or execution. METHODS: EEGs of 22 patients and 28 healthy controls were recorded. Subjects performed self-initiated movements of their right index finger. From the resulting movement-related potentials difference curves of corresponding left and right hemispheric electrodes were calculated. RESULTS: We observed significantly reduced difference curves at parietal electrodes P3 - P4 in the patient group during movement execution, but not at movement initiation. CONCLUSIONS: Our results point to compensatorily enhanced monitoring processes during movement execution following TBI. This is provided by enhanced activity of the ipsilateral postrolandic cortex, leading to the reduced preponderance observed in the present study.