Background: Preliminary evidence suggests that diet manipulation may influence motor and nonmotor symptoms in PD, but conflict exists regarding the ideal fat to carbohydrate ratio. Objectives: We designed a pilot randomized, controlled trial to compare the plausibility, safety, and efficacy of a low‐fat, high‐carbohydrate diet versus a ketogenic diet in a hospital clinic of PD patients. Methods: We developed a protocol to support PD patients in a diet study and randomly assigned patients to a low‐fat or ketogenic diet. Primary outcomes were within‐ and between‐group changes in MDS‐UPDRS Parts 1 to 4 over 8 weeks. Results: We randomized 47 patients, of which 44 commenced the diets and 38 completed the study (86% completion rate for patients commencing the diets). The ketogenic diet group maintained physiological ketosis. Both groups significantly decreased their MDS‐UPDRS scores, but the ketogenic group decreased more in Part 1 (−4.58 ± 2.17 points, representing a 41% improvement in baseline Part 1 scores) compared to the low‐fat group (−0.99 ± 3.63 points, representing an 11% improvement) (P < 0.001), with the largest between‐group decreases observed for urinary problems, pain and other sensations, fatigue, daytime sleepiness, and cognitive impairment. There were no between‐group differences in the magnitude of decrease for Parts 2 to 4. The most common adverse effects were excessive hunger in the low‐fat group and intermittent exacerbation of the PD tremor and/or rigidity in the ketogenic group. Conclusions: It is plausible and safe for PD patients to maintain a low‐fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in motor and nonmotor symptoms; however, the ketogenic group showed greater improvements in nonmotor symptoms. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Metastasis to a variety of distant organs, such as lung, brain, bone, and liver, is a leading cause of mortality in the breast cancer patients. The tissue tropism of breast cancer metastasis has been recognized and studied extensively, but the cellular processes underlying this phenomenon, remain elusive. Modern technologies have enabled the discovery of a number of the genetic factors determining tissue tropism of malignant cells. However, the effect of these genetic differences on the cell motility and invasiveness is poorly understood. Here, we report that cellular responses to the mechanical rigidity of the extracellular matrix correlate with the rigidity of the target tissue. We tested a series of single cell populations isolated from MDA-MB-231 breast cancer cell line in a variety of assays where the extracellular matrix rigidity was varied to mimic the environment that these cells might encounter in vivo. There was increased proliferation and migration through the matrices of rigidities corresponding to the native rigidities of the organs where metastasis was observed. We were able to abolish the differential matrix rigidity response by knocking down Fyn kinase, which was previously identified as a critical component of the FN rigidity response pathway in healthy cells. This result suggests possible molecular mechanisms of the rigidity response in the malignant cells, indicating potential candidates for therapeutic interventions.

The mechanism by which extracellular cues influence intracellular biochemical cascades that guide axons is important, yet poorly understood. Because of the mechanical nature of axon extension, we explored whether the physical interactions of growth cones with their guidance cues might be involved. In the context of mouse spinal commissural neuron axon attraction to netrin-1, we found that mechanical attachment of netrin-1 to the substrate was required for axon outgrowth, growth cone expansion, axon attraction and phosphorylation of focal adhesion kinase (FAK) and Crk-associated substrate (CAS). Myosin II activity was necessary for traction forces >30 pN on netrin-1. Interestingly, while these myosin II-dependent forces on netrin-1 substrates or beads were needed to increase the kinase activity and phosphorylation of FAK, they were not necessary for netrin-1 to increase CAS phosphorylation. When FAK kinase activity was inhibited, the growth cone’s ability to recruit additional adhesions and to generate forces >60 pN on netrin-1 was disrupted. Together, these findings demonstrate an important role for mechanotransduction during chemoattraction to netrin-1 and that mechanical activation of FAK reinforces interactions with netrin-1 allowing greater forces to be exerted.

No abstract

Cells severely depleted of filamins were observed to have numerous motility-related defects, including a defect in endoplasmic spreading; smaller, more dynamic focal adhesions; and an inability to sustain high levels of traction force. The endoplasm as a separate mechanical unit spread by pulling forces is also discussed.