Movement persistency, reflected in systematic cycle to cycle fluctuations of a rhythmical task such as walking or voluntary sway, is compromised with increasing age, making older adults more susceptible to falls. In the present study, we tested whether it is possible to improve rhythmic voluntary sway persistency in old age by actively tracking the complex (i.e. persistent) motion of a visual target. Twenty healthy young and 20 older adults performed 132 cycles of anterior-posterior sway under two conditions a) self-paced sway and b) sway while tracking the vertical motion of a complex visual target. The persistency of sway cycle amplitude and duration, detected from the center of pressure displacement, was quantified using the Fractal exponent α. We also recorded body kinematics in order to assess the intersegmental coordination that was quantified in the Mean Absolute Relative Phase (MARP) and the Deviation Phase (DPh) between the trunk and the lower limbs. In self-paced sway, older adults showed a lower persistency of cycle duration and a higher MARP and DPh between the trunk and the lower limbs compared to young adults. Tracking the complex visual target motion increased the persistency of cycle amplitude, in young but not in older adults, when compared to the self-paced sway while it decreased the persistency of cycle duration in both groups. The relative phase measures showed a moderate to strong relationship with the persistency of cycle amplitude and duration when older adults swayed in their self-pace.  https://www.selleckchem.com/products/cilofexor-gs-9674.html  These findings suggest older adults cannot exploit active tracking of the complex visual motion cue to improve voluntary sway persistency. This could be related to the less stable and out of phase intersegmental coordination characterizing rhythmic voluntary sway in old age.Iron oxides are Group 3 (not classifiable as to its carcinogenicity to humans) according to the International Agency for Research on Cancer (IARC). Occupational exposures during iron and steel founding and hematite underground mining as well as other iron predominant exposures such as welding are Group 1 (carcinogenic to humans). The objective of this study was to investigate the potential of iron as iron (III) oxide (Fe2O3) to initiate lung tumors in A/J mice, a lung tumor susceptible strain. Male A/J mice were exposed by oropharyngeal aspiration to suspensions of Fe2O3 (1 mg) or calcium chromate (CaCrO4; 100 μg; positive control) for 26 weeks (once per week). Shams were exposed to 50 μL phosphate buffered saline (PBS; vehicle). Mice were euthanized 70 weeks after the first exposure and lung nodules were enumerated. Both CaCrO4 and Fe2O3 significantly increased gross-observed lung tumor multiplicity in A/J mice (9.63 ± 0.55 and 3.35 ± 0.30, respectively) compared to sham (2.31 ± 0.19). Histopathological analysis showed that bronchiolo-alveolar adenomas (BAA) and carcinomas (BAC) were the primary lung tumor types in all groups and were increased in the exposed groups compared to sham. BAC were significantly increased (146 %) in the CaCrO4 group and neared significance in the Fe2O3 group (100 % increase; p = 0.085). BAA and other histopathological indices of toxicity followed the same pattern with exposed groups increased compared to sham control. In conclusion, evidence from this study, in combination with our previous studies, demonstrate that exposure to iron alone may be a potential risk factor for lung carcinogenesis.Microtubule Associated Protein Tau (MAPT) forms proteopathic aggregates in several diseases. The G273R tau mutation, located in the first repeat region, was found by exome sequencing in a patient who presented with dementia and parkinsonism. We herein return to pathological examination which demonstrated tau immunoreactivity in neurons and glia consistent of mixed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) features. To rationalize the pathological findings, we used molecular biophysics to characterize the mutation in more detail in vitro and in Drosophila. The G273R mutation increases the aggregation propensity of 4-repeat (4R) tau and alters the tau binding affinity towards microtubules (MTs) and F-actin. Tau aggregates in PSP and CBD are predominantly 4R tau. Our data suggest that the G273R mutation induces a shift in pool of 4R tau by lower F-actin affinity, alters the conformation of MT bound 4R tau, while increasing chaperoning of 3R tau by binding stronger to F-actin. The mutation augmented fibrillation of 4R tau initiation in vitro and in glial cells in Drosophila and showed preferential seeding of 4R tau in vitro suggestively causing a late onset 4R tauopathy reminiscent of PSP and CBD.
  Inflammasome-mediated neuroinflammation plays an important role in the pathogenesis of early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of the TGR5 receptor has been shown to be neuroprotective in a variety of neurological diseases. This study aimed to investigate the effects of the specific synthetic TGR5 agonist, INT-777, in attenuating NLRP3-ASC inflammasome activation and reducing neuroinflammation after SAH.
 
  One hundred and eighty-four male Sprague Dawley rats were used. SAH was induced by the endovascular perforation. INT-777 was administered intranasally at 1h after SAH induction. To elucidate the signaling pathway involved in the effect of INT-777 on inflammasome activation during EBI, TGR5 knockout CRISPR and PKA inhibitor H89 were administered intracerebroventricularly and intraperitoneally at 48h and 1h before SAH. The SAH grade, short- and long-term neurobehavioral assessments, brain water content, western blot, immunofluorescence staining, and Nissl staining wertially via TGR5/cAMP/PKA signaling pathway. Early administration of INT-777 may serve as a potential therapeutic strategy for EBI management in the setting of SAH.Since the first descriptions of hepatocyte-released exosome-like vesicles in 2008, the number of publications describing Extracellular Vesicles (EVs) released by liver cells in the context of hepatic physiology and pathology has grown exponentially. This growing interest highlights both the importance that cell-to-cell communication has in the organization of multicellular organisms from a physiological point of view, as well as the opportunity that these circulating organelles offer in diagnostics and therapeutics. In the present review, we summarize systematically and comprehensively the myriad of works that appeared in the last decade and lighted the discussion about the best opportunities for using EVs in liver disease therapeutics.