History information emerges in the cortex during learning.

We learn from our experience but the underlying neuronal mechanisms incorporating past information to facilitate learning is relatively unknown. Specifically, which cortical areas encode history-related information and how is this information modulated across learning? To study the relationship between history and learning, we continuously imaged cortex-wide calcium dynamics as mice learn to use their whiskers to discriminate between two different textures. We mainly focused on comparing the same trial type with different trial history, that is, a different preceding trial. We found trial history information in barrel cortex (BC) during stimulus presentation. Importantly, trial history in BC emerged only as the mouse learned the task. Next, we also found learning-dependent trial history information in rostrolateral (RL) association cortex that emerges before stimulus presentation, preceding activity in BC. Trial history was also encoded in other cortical areas and was not related to differences in body movements. Interestingly, a binary classifier could discriminate trial history at the single trial level just as well as current information both in BC and RL. These findings suggest that past experience emerges in the cortex around the time of learning, starting from higher-order association area RL and propagating down (i.e., top-down projection) to lower-order BC where it can be integrated with incoming sensory information. This integration between the past and present may facilitate learning.

Spin-Controlled Helical Quantum Sieve Chiral Spectrometer.

This article reports on a molecular-spin-sensitive-antenna (MSSA) that is based on stacked layers of organically functionalized graphene on a fibrous helical cellulose network for carrying out spatiotemporal identification of chiral enantiomers. The MSSA structures combine three complementary features: (i) chiral separation via a helical quantum sieve for chiral trapping, (ii) chiral recognition by a synthetically implanted spin-sensitive center in a graphitic lattice; and (iii) chiral selectivity by a chirality-induced-spin mechanism that polarizes the local electronic band-structure in graphene through chiral-activated Rashba spin-orbit interaction field. Combining the MSSA structures with decision-making principles based on neuromorphic artificial intelligence shows fast, portable, and wearable spectrometry for the detection and classification of pure and a mixture of chiral molecules, such as butanol (S and R), limonene (S and R), and xylene isomers, with 95-98% accuracy. These results can have a broad impact where the MSSA approach is central as a precautionary risk assessment against potential hazards impacting human health and the environment due to chiral molecules; furthermore, it acts as a dynamic monitoring tool of all parts of the chiral molecule life cycles.

Ultra-Fast Portable and Wearable Sensing Design for Continuous and Wide-Spectrum Molecular Analysis and Diagnostics.

The design and characterization of spatiotemporal nano-/micro-structural arrangement that enable real-time and wide-spectrum molecular analysis is reported and demonestrated in new horizons of biomedical applications, such as wearable-spectrometry, ultra-fast and onsite biopsy-decision-making for intraoperative surgical oncology, chiral-drug identification, etc. The spatiotemporal sesning arrangement is achieved by scalable, binder-free, functionalized hybrid spin-sensitive (<↑| or <↓|) graphene-ink printed sensing layers on free-standing films made of porous, fibrous, and naturally helical cellulose networks in hierarchically stacked geometrical configuration (HSGC). The HSGC operates according to a time-space-resolved architecture that modulate the mass-transfer rate for separation, eluation and detection of each individual compound within a mixture of the like, hereby providing a mass spectrogram. The HSGC could be used for a wide range of applictions, including fast and real-time spectrogram generator of volatile organic compounds during liquid-biopsy, without the need of any immunochemistry-staining and complex power-hungry cryogenic machines; and wearable spectrometry that provide spectral signature of molecular profiles emiited from skin in the course of various dietry conditions.

Kidney Failure Alters Parathyroid Pin1 Phosphorylation and Parathyroid Hormone mRNA-Binding Proteins, Leading to Secondary Hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHP) is a common complication of CKD that increases morbidity and mortality. In experimental SHP, increased parathyroid hormone (PTH) expression is due to enhanced PTH mRNA stability, mediated by changes in its interaction with stabilizing AUF1 and destabilizing KSRP. The isomerase Pin1 leads to KSRP dephosphorylation, but in SHP parathyroid Pin1 activity is decreased and hence phosphorylated KSRP fails to bind PTH mRNA, resulting in high PTH mRNA stability and levels. The up- and downstream mechanisms by which CKD stimulates the parathyroid glands remain elusive. METHODS: Adenine-rich high-phosphate diets induced CKD in rats and mice. Parathyroid organ cultures and transfected cells were incubated with Pin1 inhibitors for their effect on PTH expression. Mass spectrometry was performed on both parathyroid and PTH mRNA pulled-down proteins. RESULTS: CKD led to changes in rat parathyroid proteome and phosphoproteome profiles, including KSRP phosphorylation at Pin1 target sites. Furthermore, both acute and chronic kidney failure led to parathyroid-specific Pin1 Ser16 and Ser71 phosphorylation, which disrupts Pin1 activity. Pharmacologic Pin1 inhibition, which mimics the decreased Pin1 activity in SHP, increased PTH expression ex vivo in parathyroid glands in culture and in transfected cells through the PTH mRNA-protein interaction element and KSRP phosphorylation. CONCLUSIONS: Kidney failure leads to loss of parathyroid Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through impaired PTH mRNA decay that is dependent on KSRP phosphorylation at Pin1-target motifs. Pin1 and KSRP phosphorylation and the Pin1-KSRP-PTH mRNA axis thus drive SHP.

Non-Invasive Staging of In Vitro Mice Embryos by Means of Volatolomics.

Current methods for embryo selection are limited. This study assessed a novel method for the prediction of embryo developmental potential based on the analysis of volatile organic compounds (VOCs) emitted by embryo samples. The study included mice embryos monitored during the pre-implantation period. Four developmental stages of the embryos were tested, covering the period from 1 to 4 days after fecundation. In each stage, the VOCs released by the embryos were collected and examined by employing two different volatolomic techniques, gas-chromatography coupled to mass-spectrometry (GC-MS) and a nanoarray of chemical gas sensors. The GC-MS study revealed that the VOC patterns emanating from embryo samples had statistically different values at different stages of embryo development. The sensor nanoarray was capable of classifying the developmental stages of the embryos. The proposed volatolomics analysis approach for embryos presents a promising potential for predicting their developmental stage. In combination with conventional morphokinetic parameters, it could be effective as a predictive model for detecting metabolic shifts that affect embryo quality before preimplantation.

Color-flow doppler sonography in patients with subclinical thyroid dysfunction.

OBJECTIVE: To assess the value of color-flow Doppler sonography (CFDS) in evaluating intrathyroidal blood flow and velocity in patients with subclinical thyroid dysfunction. METHODS: In this prospective study, patients with subclinical hypothyroidism, patients with subclinical hyperthyroidism, and euthyroid patients without known thyroid autoimmune disease who served as controls were included. Subclinical thyroid dysfunction was defined as normal se-rum free thyroxine (FT4) and free triiodothyronine (FT3) in the presence of high (subclinical hypothyroidism), or low-suppressed (subclinical hyperthyroidism) serum thyrotropin (TSH) levels. Serum FT4, FT3, TSH, and antibodies to thyroid peroxidase and thyroglobulin were measured in all participants. In addition, TSH receptor antibody levels were determined in patients with subclinical hyperthyroid-ism. All participants underwent conventional sonography and CFDS. Mean peak systolic velocity (PSV) and resistive index were obtained from multiple extranodular thyroid parenchyma samplings and inferior thyroid artery measurements. RESULTS: The study population included 27 patients with subclinical hypothyroidism, 15 patients with subclinical hyperthyroidism, and 20 euthyroid patients. Patients with subclinical hypothyroidism had significantly higher mean intrathyroidal PSV values than control patients (19.9 +/- 5.6 cm/s vs 15.7 +/- 4.4 cm/s; P = .008), whereas patients with subclinical hyperthyroidism had significantly higher mean PSV values than control patients at the inferior thyroid artery level (29.7 +/- 10.7 cm/s vs 21.9 +/- 6.8 cm/s; P = .014). Compared with control patients, a greater proportion of patients with subclinical hypothyroidism and patients with subclinical hyperthyroidism had marked CFDS patterns (78% vs 15% [P<.001] and 53% vs 15%; [P<.001], respectively). A significant association was found between positivity for thyroid autoantibodies and intense CFDS patterns. No correlation was found between TSH or thyroid hormone levels and CFDS pattern or blood flow velocity. CONCLUSION: We have demonstrated that significantly increased thyroid blood flow velocity and vascularity are already present in patients with mild thyroid dysfunction.