A direct reconstruction algorithm for the anisotropic inverse conductivity problem based on Calderon's method in the plane

A direct reconstruction algorithm based on Calderon's linearization method for the reconstruction of isotropic conductivities is proposed for anisotropic conductivities in two-dimensions. To overcome the non-uniqueness of the anisotropic inverse conductivity problem, the entries of the unperturbed anisotropic tensors are assumed known a priori, and it remains to reconstruct the multiplicative scalar field. The quasi-conformal map in the plane facilitates the Calderon-based approach for anisotropic conductivities. The method is demonstrated on discontinuous radially symmetric conductivities of high and low contrast.Peer reviewe

LSF small molecule inhibitors phenocopy LSF-targeted siRNAs causing mitotic defects and senescence in cancer cells

The oncogene LSF has been proposed as a novel target with therapeutic potential for multiple cancers. LSF overexpression correlates with poor prognosis for both liver and colorectal cancers, for which there are currently limited therapeutic treatment options. In particular, molecularly targeted therapies for hepatocellular carcinoma targeting cellular receptors and kinases have yielded disappointing clinical results, providing an urgency for targeting distinct mechanisms. LSF small molecule inhibitors, Factor Quinolinone Inhibitors (FQIs), have exhibited robust anti-tumor activity in multiple pre-clinical models of hepatocellular carcinoma, with no observable toxicity. To understand how the inhibitors impact cancer cell proliferation, we characterized the cellular phenotypes that result from loss of LSF activity. Phenotypically, inhibition of LSF activity induced a mitotic delay with condensed, but unaligned, chromosomes. This mitotic disruption resulted in improper cellular division leading to multiple outcomes: multi-nucleation, apoptosis, and cellular senescence. The cellular phenotypes observed upon FQI1 treatment were due specifically to the loss of LSF activity, as siRNA specifically targeting LSF produced nearly identical phenotypes. Taken together, these findings confirm that LSF is a promising therapeutic target for cancer treatment.First author draf

Stored elastic energy powers the 60-μm extension of the Limulus polyphemus sperm actin bundle

During the 5 s of the acrosome reaction of Limulus polyphemus sperm, a 60-μm-long bundle of scruin-decorated actin filaments straightens from a coiled conformation and extends from the cell. To identify the motive force for this movement, we examined the possible sources of chemical and mechanical energy and show that the coil releases ∼10−13 J of stored mechanical strain energy, whereas chemical energy derived from calcium binding is ∼10−15 J. These measurements indicate that the coiled actin bundle extends by a spring-based mechanism, which is distinctly different from the better known polymerization or myosin-driven processes, and that calcium initiates but does not power the reaction

Amygdala and fusiform gyrus temporal dynamics: Responses to negative facial expressions

<p>Abstract</p> <p>Background</p> <p>The amygdala habituates in response to repeated human facial expressions; however, it is unclear whether this brain region habituates to schematic faces (i.e., simple line drawings or caricatures of faces). Using an fMRI block design, 16 healthy participants passively viewed repeated presentations of schematic and human neutral and negative facial expressions. Percent signal changes within anatomic regions-of-interest (amygdala and fusiform gyrus) were calculated to examine the temporal dynamics of neural response and any response differences based on face type.</p> <p>Results</p> <p>The amygdala and fusiform gyrus had a within-run "U" response pattern of activity to facial expression blocks. The initial block within each run elicited the greatest activation (relative to baseline) and the final block elicited greater activation than the preceding block. No significant differences between schematic and human faces were detected in the amygdala or fusiform gyrus.</p> <p>Conclusion</p> <p>The "U" pattern of response in the amygdala and fusiform gyrus to facial expressions suggests an initial orienting, habituation, and activation recovery in these regions. Furthermore, this study is the first to directly compare brain responses to schematic and human facial expressions, and the similarity in brain responses suggest that schematic faces may be useful in studying amygdala activation.</p

Comparison of Quarterly and Yearly Calibration Data for Propensity Score Adjusted Web Survey Estimates

While web surveys have become increasingly popular as a method of data collection, there is concern that estimates obtained from web surveys may not reflect the target population of interest. Web survey estimates can be calibrated to existing national surveys using a propensity score adjustment, although requirements for the size and collection timeline of the reference data set have not been investigated. We evaluate health outcomes estimates from the National Center for Health Statistics’ Research and Development web survey. In our study, the 2016 National Health Interview Survey as well as its quarterly subsets are considered as reference datasets for the web data. It is demonstrated that the calibrated health estimates overall vary little when using the quarterly or yearly data, suggesting that there is flexibility in selecting the reference dataset. This finding has many practical implications for constructing reference data, including the reduced cost and burden of a smaller sample size and a more flexible timeline

The catalytic core of DEMETER guides active DNA demethylation in Arabidopsis.

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing dme developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets

Knockout of TSC2 in Nav1.8+ neurons predisposes to the onset of normal weight obesity

OBJECTIVE: Obesity and nutrient oversupply increase mammalian target of rapamycin (mTOR) signaling in multiple cell types and organs, contributing to the onset of insulin resistance and complications of metabolic disease. However, it remains unclear when and where mTOR activation mediates these effects, limiting options for therapeutic intervention. The objective of this study was to isolate the role of constitutive mTOR activation in Nav1.8-expressing peripheral neurons in the onset of diet-induced obesity, bone loss, and metabolic disease. METHODS: In humans, loss of function mutations in tuberous sclerosis complex 2 (TSC2) lead to maximal constitutive activation of mTOR. To mirror this in mice, we bred Nav1.8-Cre with TSC2 RESULTS: By lineage tracing, Nav1.8-Cre targeted peripheral sensory neurons, a subpopulation of postganglionic sympathetics, and several regions of the brain. Conditional knockout of TSC2 in Nav1.8-expressing neurons (Nav1.8-TSC2 CONCLUSIONS: Knockout of TSC2 in Nav1.8+ neurons increases itch- and anxiety-like behaviors and substantially modifies fat storage and metabolic responses to HFD. Though this prevents HFD-induced weight gain, it masks depot-specific fat expansion and persistent detrimental effects on metabolic health and peripheral organs such as bone, mimicking the \u27normal weight obesity\u27 phenotype that is of growing concern. This supports a mechanism by which increased neuronal mTOR signaling can predispose to altered adipose tissue distribution, adipose tissue expansion, impaired peripheral metabolism, and detrimental changes to skeletal health with HFD - despite resistance to weight gain

Pancreatic polypeptide inhibits somatostatin secretion

AbstractPancreatic polypeptide (PP) is a major agonist for neuropeptide Y4 receptors (NPY4R). While NPY4R has been identified in various tissues, the cells on which it is expressed and its function in those cells has not been clearly delineated. Here we report that NPY4R is present in all somatostatin-containing cells of tissues that we tested, including pancreatic islets, duodenum, hippocampus, and hypothalamus. Its agonism by PP decreases somatostatin secretion from human islets. Mouse embryonic hippocampal (mHippo E18) cells expressed NPY4Rs and their activation by PP consistently decreased somatostatin secretion. Furthermore, central injection of PP in mice induced c-Fos immunoreactivity in somatostatin-containing cells in the hippocampus compared with PBS-injected mice. In sum, our results identify PP as a pivotal modulator of somatostatin secretion

Music-based multicomponent exercise training for community-dwelling older adults with mild-to-moderate cognitive decline: a feasibility study

IntroductionThis study explored the feasibility and preliminary efficacy of a music-based, multicomponent exercise intervention among community-dwelling older adults with mild-to-moderate cognitive impairment.Methods16 older adults aged 85±9 years with mild-to-moderate cognitive impairment received music-based multicomponent exercise training for 20 weeks at an independent living facility. Participants received aerobic, resistance, and balance training paired with beat-accentuated music stimulation. Participants’ adherence to the training was tracked down and their cognitive and physical functioning and health-related quality of life were assessed at pre- and post-test.Results3 participants withdrew due to unexpected issues unrelated to the intervention and thus 13 participants (7 females) attended an average of 4.6 days/week over 20 weeks and reported high satisfaction with the intervention (90.6%). Participants showed significant improvement in global cognition, cognitive processing speed, and walking endurance/aerobic fitness at post-test.DiscussionThese findings support the feasibility of music-based, multicomponent exercise training for older adults in an independent living facility and set the stage for future studies to test the efficacy of music on physical activity and ensuing health outcomes. We conclude that music-based, multicomponent exercise training can be beneficial for community-dwelling older adults with mild-to-moderate cognitive decline. As a form of rhythmic auditory stimulation, beat-accentuated music can be combined with exercise training to manipulate exercise tempo and may provide a source of motivation to help older adults adhere to exercise