Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation

After a brief period of antigenic stimulation, T cells become committed to a program of autonomous expansion and differentiation. We investigated the role of antigen-specific T cell precursor frequency as a possible cell-extrinsic factor impacting T cell programming in a model of allogeneic tissue transplantation. Using an adoptive transfer system to incrementally raise the precursor frequency of antigen-specific CD8+ T cells, we found that donor-reactive T cells primed at low frequency exhibited increased cellular division, decreased development of multifunctional effector activity, and an increased requirement for CD28- and CD154-mediated costimulation relative to those primed at high frequency. The results demonstrated that recipients with low CD4+ and CD8+ donor-reactive T cell frequencies exhibited long-term skin graft survival upon CD28/CD154 blockade, whereas simultaneously raising the frequency of CD4+ T cells to ∼0.5% and CD8+ T cells to ∼5% precipitated graft rejection despite CD28/CD154 blockade. Antigenic rechallenge of equal numbers of cells stimulated at high or low frequency revealed that cells retained an imprint of the frequency at which they were primed. These results demonstrate a critical role for initial precursor frequency in determining the CD8+ T cell requirement for CD28- and CD154-mediated costimulatory signals during graft rejection

Nicotine Regulates Activity Of Lateral Habenula Neurons Via Presynaptic And Postsynaptic Mechanisms

There is much interest in brain regions that drive nicotine intake in smokers. Interestingly, both the rewarding and aversive effects of nicotine are probably critical for sustaining nicotine addiction. The medial and lateral habenular (LHb) nuclei play important roles in processing aversion, and recent work has focused on the critical involvement of the LHb in encoding and responding to aversive stimuli. Several neurotransmitter systems are implicated in nicotine\u27s actions, but very little is known about how nicotinic acetylcholine receptors (nAChRs) regulate LHb activity. Here we report in brain slices that activation of nAChRs depolarizes LHb cells and robustly increases firing, and also potentiates glutamate release in LHb. These effects were blocked by selective antagonists of α6-containing (α6∗) nAChRs, and were absent in α6∗-nAChR knockout mice. In addition, nicotine activates GABAergic inputs to LHb via α4β2-nAChRs, at lower concentrations but with more rapid desensitization relative to α6∗-nAChRs. These results demonstrate the existence of diverse functional nAChR subtypes at presynaptic and postsynaptic sites in LHb, through which nicotine could facilitate or inhibit LHb neuronal activity and thus contribute to nicotine aversion or reward

Modification of TiO_2 Nanoparticles with Organodiboron Molecules Inducing Stable Surface Ti^(3+) Complex

As one of the most promising semiconductor oxide materials, titanium dioxide (TiO_2) absorbs ultraviolet (UV) light but not visible light. To address this limitation, the introduction of Ti^(3+) defects represents a common strategy to render TiO_2 visible-light-responsive. Unfortunately, current hurdles in Ti^(3+) generation technologies impeded the widespread application of Ti^(3+) modified materials. Herein, we demonstrate a simple and mechanistically distinct approach to generating abundant surface-Ti^(3+) sites without leaving behind oxygen vacancy and sacrificing one-off electron donors. In particular, upon adsorption of organodiboron reagents onto TiO_2 nanoparticles, spontaneous electron injection from the dibron-bound O^(2-) site to adjacent Ti^(4+) site leads to an extremely stable blue surface Ti^(3+)‒O^(-•) complex. Notably, this defect generation protocol is also applicable to other semiconductor oxides including ZnO, SnO_2, Nb_2O_5 and In_2O_3. Furthermore, the as-prepared photoelectronic device using this strategy affords 10^3 fold higher visible light response, and the fabricated perovskite solar cell shows an enhanced performance

The impact of metabolic overweight/obesity phenotypes on unplanned readmission risk in patients with COPD: a retrospective cohort study

Background: There is an inconsistent association between overweight/obesity and chronic obstructive pulmonary disease (COPD). Considering that different metabolic characteristics exist among individuals in the same body mass index (BMI) category, the classification of overweight/obesity based on metabolic status may facilitate the risk assessment of COPD. Our study aimed to explore the relationship between metabolic overweight/obesity phenotypes and unplanned readmission in patients with COPD.Methods: We conducted a retrospective cohort study using the Nationwide Readmissions Database (NRD). According to metabolic overweight/obesity phenotypes, patients were classified into four groups: metabolically healthy non-overweight/obesity (MHNO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically healthy with overweight/obesity (MHO), and metabolically unhealthy with overweight/obesity (MUO). The primary outcome was unplanned readmission to hospital within 30 days of discharge from index hospitalization. Secondary outcomes included in-hospital mortality, length of stay (LOS) and total charges of readmission within 30 days.Results: Among 1,445,890 patients admitted with COPD, 167,156 individuals were unplanned readmitted within 30 days. Patients with the phenotype MUNO [hazard ratio (HR), 1.049; 95%CI, 1.038–1.061; p < 0.001] and MUO (HR, 1.061; 95%CI, 1.045–1.077; p < 0.001) had a higher readmission risk compared with patients with MHNO. But in elders (≥65yr), MHO also had a higher readmission risk (HR, 1.032; 95%CI, 1.002–1.063; p = 0.039). Besides, the readmission risk of COPD patients with hyperglycemia or hypertension regardless of overweight/obesity increased (p < 0.001).Conclusion: In patients with COPD, overweight/obesity alone had little effect on unplanned readmission, whereas metabolic abnormalities regardless of overweight/obesity were associated with an increased risk of unplanned readmission. Among the metabolic abnormalities, particular attention should be paid to hyperglycemia and hypertension. But in elders (≥65yr) overweight/obesity and metabolic abnormalities independently exacerbated the adverse outcomes

Modification of TiO_2 Nanoparticles with Organodiboron Molecules Inducing Stable Surface Ti^(3+) Complex

As one of the most promising semiconductor oxide materials, titanium dioxide (TiO_2) absorbs ultraviolet (UV) light but not visible light. To address this limitation, the introduction of Ti^(3+) defects represents a common strategy to render TiO_2 visible-light-responsive. Unfortunately, current hurdles in Ti^(3+) generation technologies impeded the widespread application of Ti^(3+) modified materials. Herein, we demonstrate a simple and mechanistically distinct approach to generating abundant surface-Ti^(3+) sites without leaving behind oxygen vacancy and sacrificing one-off electron donors. In particular, upon adsorption of organodiboron reagents onto TiO_2 nanoparticles, spontaneous electron injection from the dibron-bound O^(2-) site to adjacent Ti^(4+) site leads to an extremely stable blue surface Ti^(3+)‒O^(-•) complex. Notably, this defect generation protocol is also applicable to other semiconductor oxides including ZnO, SnO_2, Nb_2O_5 and In_2O_3. Furthermore, the as-prepared photoelectronic device using this strategy affords 10^3 fold higher visible light response, and the fabricated perovskite solar cell shows an enhanced performance

Interaction between CRHR1 and BDNF Genes Increases the Risk of Recurrent Major Depressive Disorder in Chinese Population

BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH) regulates brain-derived neurotrophic factor (BDNF) expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1) and BDNF genes in recurrent major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). CRHR1 gene (rs1876828, rs242939 and rs242941) and BDNF gene (rs6265) were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022) with an Odds Ratio 0.454 (95% CI 0.266-0.775). A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05) using a generalized multifactor dimensionality reduction (GMDR) method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD

Contactless hand recognition

Because of the increased hygiene concern in biometric systems and the difficulty in recognizing fingerprints of manual laborers and elderly people, hand geometry has been currentl

Pathophysiology and Neuroimmune Interactions Underlying Parkinson’s Disease and Traumatic Brain Injury

Parkinson’s disease (PD) is a progressive neurodegenerative disorder clinically defined by motor instability, bradykinesia, and resting tremors. The clinical symptomatology is seen alongside pathologic changes, most notably the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of α-synuclein and neuromelanin aggregates throughout numerous neural circuits. Traumatic brain injury (TBI) has been implicated as a risk factor for developing various neurodegenerative diseases, with the most compelling argument for the development of PD. Dopaminergic abnormalities, the accumulation of α-synuclein, and disruptions in neural homeostatic mechanisms, including but not limited to the release of pro-inflammatory mediators and the production of reactive oxygen species (ROS), are all present following TBI and are closely related to the pathologic changes seen in PD. Neuronal iron accumulation is discernable in degenerative and injured brain states, as is aquaporin-4 (APQ4). APQ4 is an essential mediator of synaptic plasticity in PD and regulates edematous states in the brain after TBI. Whether the cellular and parenchymal changes seen post-TBI directly cause neurodegenerative diseases such as PD is a point of considerable interest and debate; this review explores the vast array of neuroimmunological interactions and subsequent analogous changes that occur in TBI and PD. There is significant interest in exploring the validity of the relationship between TBI and PD, which is a focus of this review

Robust Hand Geometry Measurements for Person Identification using Active Appearance Models

Abstract—The increased demand for tighter border and building security has renewed public interest in biometric iden-tification and verification systems. With fingerprint recognition being socially stigmatized, hand geometry-based recognizers have emerged as niche solutions. However, systems currently available in the marketplace require direct contact with the device, raising, among others, significant hygiene concerns. In this paper we introduce a novel approach to hand geometry-based identification. The proposed method employs Active Appearance Models to track the hand inside the capture device and to extract geometry features for identification. The AAM fitting algorithm runs faster than real-time, enabling robust system performance. In experiments on a small-scale database of hand images, the accuracy of our system exceeds 90 % using as little as five features. I