Single-molecule localization microscopy at 2.4-fold resolution improvement with optical lattice pattern illumination.

Traditional camera-based single-molecule localization microscopy (SMLM), with its high imaging resolution and localization throughput, has made significant advancements in biological and chemical researches. However, due to the limitation of the fluorescence signal-to-noise ratio (SNR) of a single molecule, its resolution is difficult to reach to 5 nm. Optical lattice produces a nondiffracting beam pattern that holds the potential to enhance microscope performance through its high contrast and penetration depth. Here, we propose a new method named LatticeFLUX which utilizes the wide-field optical lattice pattern illumination for individual molecule excitation and localization. We calculated the Cramér-Rao lower bound of LatticeFLUX resolution and proved that our method can improve the single molecule localization precision by 2.4 times compared with the traditional SMLM. We propose a scheme using 9-frame localization, which solves the problem of uneven lattice light illumination. Based on the experimental single-molecule fluorescence SNR, we coded the image reconstruction software to further verify the resolution enhancement capability of LatticeFLUX on simulated punctate DNA origami, line pairs, and cytoskeleton. LatticeFLUX confirms the feasibility of using 2D structured light illumination to obtain high single-molecule localization precision under high localization throughput. It paves the way for further implementation of ultra-high resolution full 3D structured-light-illuminated SMLM.

Light-Sheet Microscopic Imaging of Whole-Mouse Vascular Network with Fluorescent Microsphere Perfusion.

Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 µm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.

Charge-Assisted Ionic Hydrogen-Bonded Organic Frameworks: Designable and Stabilized Multifunctional Materials.

Hydrogen-bonded organic frameworks (HOFs) are a class of crystalline framework materials assembled by hydrogen bonds. HOFs have the advantages of high crystallinity, mild reaction conditions, good solution processability, and reproducibility. Coupled with the reversibility and flexibility of hydrogen bonds, HOFs can be assembled into a wide diversity of crystalline structures. Since the bonding energy of hydrogen bonds is lower than that of ligand and covalent bonds, the framework of HOFs is prone to collapse after desolventisation and the stability is not high, which limits the development and application of HOFs. In recent years, numerous stable and functional HOFs have been developed by π-π stacking, highly interpenetrated networks, charge-assisted, ligand-bond-assisted, molecular weaving, and covalent cross-linking. Charge-assisted ionic HOFs introduce electrostatic attraction into HOFs to improve stability while enriching structural diversity and functionality. In this paper, we review the development, the principles of rational design and assembly of charge-assisted ionic HOFs, and introduces the different building block construction modes of charge-assisted ionic HOFs. Highlight the applications of charge-assisted ionic HOFs in gas adsorption and separation, proton conduction, biological applications, etc., and prospects for the diverse design of charge-assisted ionic HOFs structures and multifunctional applications.

Understanding the Role of Parent‒Child Relationships in Conscientiousness and Neuroticism Development among Chinese Middle School Students: A Cross-Lagged Model.

The parent‒child relationship is a crucial factor in promoting adolescent mental health. However, the current evidence on the relationship between parent‒child relationships and adolescent conscientiousness and neuroticism, as well as the directionality of these relationships, remains limited. In particular, there is a lack of analysis focusing on Chinese middle school students. Based on a sample of 8437 students from the China Education Panel Survey (CEPS) database, this study empirically examined the bidirectional relationships between parent‒child relationships, conscientiousness and neuroticism among Chinese middle school students, with specific emphasis on the significant role of parent‒child relationships in the development of conscientiousness and neuroticism. Descriptive statistical results indicated that during the seventh and eighth grades of Chinese middle school students, the closeness of their parent‒child relationships with both parents decreased, while the level of conscientiousness showed a slight decrease, and neuroticism showed an increasing trend. Correlational results demonstrated a significant positive correlation between parent‒child relationships and conscientiousness and a significant negative correlation between parent‒child relationships and neuroticism. Further analysis using cross-lagged models revealed that parent‒child relationships significantly positively predicted subsequent conscientiousness development, and conscientiousness significantly positively predicted subsequent parent‒child relationships. Parent‒child relationships significantly negatively predicted subsequent neuroticism development, and neuroticism levels also significantly negatively predicted subsequent parent‒child relationships. Based on these findings, we believe that there is a need to strengthen parent‒child relationships and to recognize the important role that both mothers and fathers play in the healthy development of their children. Both parents should actively contribute to their children's upbringing and take responsibility for their family education.

A female case report of LGMD2B with compound heterozygous mutations of the DYSF gene and asymptomatic mutation of the X-linked DMD gene.

We report the case of a 31-year-old Chinese woman with a chief complaint of weakness in the lower limbs, which was diagnosed as limb-girdle muscular dystrophy 2B (LGMD2B) with compound heterozygous mutations of the DYSF gene. Meanwhile, this woman is an asymptomatic carrier with the mutation of the X-linked DMD gene. The electromyography, muscle MRI, and muscle biopsy indicated a chronic myogenic injury with dysferlin deletion. As a result of genetic testing, compound heterozygous G-to-T base substitution at position 5,497 in exon 49 of the DYSF gene, leading to a codon change from glutamic acid to termination codon at position 1,833, and a heterozygous C-to-G base change at position 4,638 + 8 in intron 42 of the DYSF gene with a consequence of splice, which has never been reported, were identified as candidate causative mutations. Unfortunately, DMD gene mutation c.3921+12A>G of the DMD gene on the X chromosome was also found in this patient. Finally, the patient was diagnosed as LGMD2B clinically and genetically. In the previous 2 years, the patient's lower limb weakness became slightly worse, resulting in even the total distance walked than before. Fortunately, during the follow-up, her son had not shown slowness or limitation of movement. Genetic testing by next-generation sequencing confirmed the final diagnosis of LGMD2B, and we identified the novel compound heterozygous variants in the DYSF gene, which is of great significance to the accurate diagnosis of genetically coded diseases. Much attention needs to be paid in clinics toward hereditary neuromuscular diseases with multiple pathogenic gene mutations. Genetic counseling and clinical follow-up should be the priorities in future, and promising treatments are also worth exploring.

Time Use and Cognitive Achievement among Adolescents in China: Depression Symptoms as Mediators.

Everyone's time is limited, and there is competition between different aspects of time use; this requires comprehensive consideration of the effects of different aspects of time use on cognitive achievement in adolescents. This study uses a dataset of 11,717 students from a nationally representative large-scale survey project conducted in 2013 to 2014 to clarify the relationship between time use (including working on homework, playing sports, surfing the Internet, watching TV, and sleeping) and cognitive achievement among Chinese adolescents, and explores the mediating role of depression symptoms in the relationship between time use and cognitive achievement. The results of the correlation analysis show that the average daily time spent on homework, playing sports, and sleeping is significantly positively correlated with cognitive achievement (p < 0.01), while time spent surfing the Internet and watching TV are significantly negatively correlated with cognitive achievement (p < 0.01). The results of the mediating effect model show that depression symptoms play a mediating role in the relationship between time use and cognitive achievement among Chinese adolescents. Specifically, time spent playing sports (indirect effect = 0.008, p < 0.001) and sleeping (indirect effect = 0.015, p < 0.001) have a positive effect on cognitive achievement when using depression symptoms as mediators; time spent on homework (indirect effect = -0.004, p < 0.001), surfing the Internet (indirect effect = -0.002, p = 0.046), and watching TV (indirect effect = -0.005, p < 0.001) have a negative effect on cognitive achievement when using depression symptoms as mediators. This study contributes to the understanding of the relationship between time use and cognitive achievement among Chinese adolescents.

Sleep Time and Depression Symptoms as Predictors of Cognitive Development Among Adolescents: A Cross-Lagged Study From China.

Sleep time and depression symptoms are important factors affecting cognitive development in adolescents. Based on the China Education Panel Survey (CEPS) database, this study used a two-wave cross-lagged model to examine the bidirectional relationship between sleep time, depression symptoms, and cognitive development. Descriptive statistics showed that Chinese adolescents' cognitive development increased significantly from 7th to 8th grade in junior high school, but unfortunately, their depression level and average sleep time per night demonstrated a slightly deteriorating trend. Correlation analysis showed that there was a relatively stable negative correlation between cognitive development, sleep time, and depression symptoms. Moreover, the cross-lagged model revealed that there was a bidirectional relationship between cognitive development and sleep time, a bidirectional relationship between depression symptoms and sleep time, and a unidirectional relationship between depression symptoms and cognitive development. Male adolescents in the subgroup were consistent with the total sample. Among female adolescents, only cognitive development and sleep time have a bidirectional relationship, while depression symptoms and cognitive development, and depression symptoms and sleep time have a unidirectional relationship. Therefore, it is of significance to take targeted action to promote cognitive development and healthy growth in adolescents worldwide.

Water-Induced Single-Crystal to Single-Crystal Transformation of Ionic Hydrogen-Bonded Organic Frameworks with Enhanced Proton Conductivity.

Two ionic hydrogen-bonded organic frameworks (iHOF-10, iHOF-11) were prepared using 1,1'-diamino-4,4'-bipyridine diiodide (Dbpy ⋅ 2I) and tetrakis(4-sulfophenyl)ethylene (H4 TPE). With increasing RH and temperature, water molecules induce single crystal to single crystal (SCSC) transformation of iHOF-10, resulting in the formation of iHOF-11. At 90 °C, 98 % RH, the proton conductivity of iHOF-11 (7.03×10-3  S cm-1 ) is 2.09 times higher than iHOF-10 (3.37×10-3  S cm-1 ). At 50 °C, 98 % RH, iHOF-11 (9.49×10-4  S cm-1 ) is 19.06 times higher than iHOF-10 (4.98×10-5  S cm-1 ). The proton conductivity shows water molecules enter the crystal and induce crystal transformation and reorganization of the hydrogen bonding structure, thus increasing the proton conductivity and stability.

Imaging Voltage Globally and in Isofrequency Lamina in Slices of Mouse Ventral Cochlear Nucleus.

The cochlear nuclei (CNs) receive sensory information from the ear and perform fundamental computations before relaying this information to higher processing centers. These computations are performed by distinct types of neurons interconnected in circuits dedicated to the specialized roles of the auditory system. In the present study, we explored the use of voltage imaging to investigate CN circuitry. We tested two approaches based on fundamentally different voltage sensing technologies. Using a voltage-sensitive dye we recorded glutamate receptor-independent signals arising predominantly from axons. The mean conduction velocity of these fibers of 0.27 m/s was rapid but in range with other unmyelinated axons. We then used a genetically-encoded hybrid voltage sensor (hVOS) to image voltage from a specific population of neurons. Probe expression was controlled using Cre recombinase linked to c-fos activation. This activity-induced gene enabled targeting of neurons that are activated when a mouse hears a pure 15-kHz tone. In CN slices from these animals auditory nerve fiber stimulation elicited a glutamate receptor-dependent depolarization in hVOS probe-labeled neurons. These cells resided within a band corresponding to an isofrequency lamina, and responded with a high degree of synchrony. In contrast to the axonal origin of voltage-sensitive dye signals, hVOS signals represent predominantly postsynaptic responses. The introduction of voltage imaging to the CN creates the opportunity to investigate auditory processing circuitry in populations of neurons targeted on the basis of their genetic identity and their roles in sensory processing.

Integrated Metabolomic and Transcriptomic Analysis Reveals That Amino Acid Biosynthesis May Determine Differences in Cold-Tolerant and Cold-Sensitive Tea Cultivars.

Cold stress is one of the major abiotic stresses limiting tea production. The planting of cold-resistant tea cultivars is one of the most effective measures to prevent chilling injury. However, the differences in cold resistance between tea cultivars remain unclear. In the present study, we perform a transcriptomic and metabolomic profiling of Camellia sinensis var. "Shuchazao" (cold-tolerant, SCZ) and C. sinensis var. assamica "Yinghong 9" (cold-sensitive, YH9) during cold acclimation and analyze the correlation between gene expression and metabolite biosynthesis. Our results show that there were 51 differentially accumulated metabolites only up-regulated in SCZ in cold-acclimation (CA) and de-acclimation (DA) stages, of which amino acids accounted for 18%. The accumulation of L-arginine and lysine in SCZ in the CA stage was higher than that in YH9. A comparative transcriptomic analysis showed an enrichment of the amino acid biosynthesis pathway in SCZ in the CA stage, especially "arginine biosynthesis" pathways. In combining transcriptomic and metabolomic analyses, it was found that genes and metabolites associated with amino acid biosynthesis were significantly enriched in the CA stage of SCZ compared to CA stage of YH9. Under cold stress, arginine may improve the cold resistance of tea plants by activating the polyamine synthesis pathway and CBF (C-repeat-binding factor)-COR (cold-regulated genes) regulation pathway. Our results show that amino acid biosynthesis may play a positive regulatory role in the cold resistance of tea plants and assist in understanding the cold resistance mechanism differences among tea varieties.

Production of iturin A by Bacillus velezensis ND and its biological control characteristics.

Bacillus subtilis, as a biocontrol bacterium, possess a variety of biological functions and the capacity to control plant pathogens. Iturin A is a biosurfactant with broad-spectrum antifungal activity produced by fermentation of B. subtilis. In this study, the dynamic parameters of solid-state fermentation (SSF) and submerged fermentation (SMF) of Bacillus velezensis ND were compared, and a method for producing iturin A with a yield of 12.46 g/kg utilizing SSF was proposed. It has significant advantages over SMF and has the highest yield of all previously reported studies. B. velezensis ND also contains protease activity, cellulase activity, iron-carrying activity, the ability to synthesis 3-indoleacetic acid (IAA), fixation nitrogen, and degrade phosphorus. In cotton pot experiments, it can effectively increase cotton growth and minimize Verticillium wilt. This strain's superior fermentation efficiency, biological function, and biocontrol ability are sufficient to demonstrate its promise for the development and use of biocontrol agents.

Artificial intelligence-assisted psychosis risk screening in adolescents: Practices and challenges.

Artificial intelligence-based technologies are gradually being applied to psych-iatric research and practice. This paper reviews the primary literature concerning artificial intelligence-assisted psychosis risk screening in adolescents. In terms of the practice of psychosis risk screening, the application of two artificial intelligence-assisted screening methods, chatbot and large-scale social media data analysis, is summarized in detail. Regarding the challenges of psychiatric risk screening, ethical issues constitute the first challenge of psychiatric risk screening through artificial intelligence, which must comply with the four biomedical ethical principles of respect for autonomy, nonmaleficence, beneficence and impartiality such that the development of artificial intelligence can meet the moral and ethical requirements of human beings. By reviewing the pertinent literature concerning current artificial intelligence-assisted adolescent psychosis risk screens, we propose that assuming they meet ethical requirements, there are three directions worth considering in the future development of artificial intelligence-assisted psychosis risk screening in adolescents as follows: nonperceptual real-time artificial intelligence-assisted screening, further reducing the cost of artificial intelligence-assisted screening, and improving the ease of use of artificial intelligence-assisted screening techniques and tools.

CsCBF5 depletion impairs cold tolerance in tea plants.

CBFs play important roles in tea plant cold tolerance. In our study, 16 tea varieties were used to investigate the relationship between the expression level of CsCBFs and cold tolerance in field experiments. A strong and positive correlation was found between cold stress-regulated CsCBF1, CsCBF3 and CsCBF5 expression levels (R2 > 0.8) in tea mesophyll cells and cold tolerance in 16 tea varieties. A previous study reported that CsCBF1 and CsCBF3 were important components associated with cold tolerance in tea plants; thus, the function of CsCBF5 in the CsCBF family was targeted. Our previous study reported that CsCBF5 was localized in the nucleus and exhibited transcriptional activity. In the current study, MDA content in leaves was significantly increased in CsCBF5-silenced leaves, which exhibited poor cold tolerance, compared with WT plants under cold stress. In contrast, increased germination rates and antioxidant enzyme activities under cold conditions compared with WT plants. Furthermore, CsCBF5 overexpression in Arabidopsis promoted the expression levels of the cold-regulated genes AtCOR15a, AtCOR78, AtERD4 and AtRD29B; however, the expression levels of downstream genes, including CsCOR47, CsCOR413, CsERD4 and CsRD29B, were significantly reduced in CsCBF5-silenced tea leaves. Taken together, our results indicated that CsCBF5 could function as a positive regulator in the cold stress response.

Does Low Self-Esteem Predict Anxiety Among Chinese College Students?

Purpose: This study aimed to investigate the longitudinal relationship between anxiety and self-esteem among college students. Participants and methods: A total of 2473 Chinese college students were tracked, with their anxiety and self-esteem levels collected annually over the four academic years. The study employed a four-wave random intercept cross-lagged panel model to examine the prospective relationship between anxiety and self-esteem. Results: The anxiety levels were negatively associated with self-esteem over campus life. Results of the four-wave cross-lagged panel model revealed that low self-esteem maintained having subsequent negative impacts on students' anxiety levels, while the effects became progressively stronger over the four academic years. Meanwhile, no significant prospective effects were identified of anxiety levels on self-esteem. Conclusion: The study confirmed self-esteem as one of the leading contributors to anxiety for college students and emphasized the importance of nourishing the self-esteem of students to alleviate their anxiety issues and improve their mental health at college.

Comparative genomics and analysis of the mechanism of PQQ overproduction in Methylobacterium.

Methylobacterium sp. CLZ was isolated from soil contaminated with chemical wastewater. This strain simultaneously synthesizes Pyrroloquinoline quinone (PQQ), Coenzyme Q10 (CoQ10), and carotenoids by utilizing methanol as a carbon source. Comparative genomic analysis was performed for five Methylobacterium strains. As per the outcomes, the Methylobacterium CLZ strain showed the smallest genome size and the lowest number of proteins. Thus, it can serve as an ideal cell model for investigating the biological process of Methylobacterium and constructing genetically engineered Methylobacterium. The Methylobacterium CLZ strain's pqqL gene, which does not occur in other Methylobacterium strains but plays a crucial role in PQQ synthesis. This was a surprising finding for the study of PQQ biosynthesis in Methylobacterium. Methylobacterium sp. NI91 strain was generated by random mutagenesis of CLZ strain, and NI91 strain showed a 72.44% increase in PQQ yield. The mutation in the mxaJ gene involved in the methanol dehydrogenase (MDH) synthesis was identified through comparative genomic analysis of the whole genome of mutant strain NI91 and wild-type strain CLZ. The mxaJ gene was found to be upregulated in the NI91 strain. Thus, the up-regulation of the mxaJ gene could be correlated with the high yield of PQQ, and it could provide valuable clues for strain engineering to improve PQQ production.

Multiple neurological manifestations in a patient with systemic lupus erythematosus and anti-NXP2-positive myositis: A case report.

RATIONALE: Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease that frequently affects various organs. Neuropsychiatric manifestations in SLE patients, known as neuropsychiatric SLE, are clinically common. However, the principal manifestation of cranial neuropathy in patients with SLE and comorbidities is relatively rare. PATIENT CONCERNS: In this report, we describe a 51-year-old Chinese woman who was admitted with a chief complaint of chronic-onset facial paresthesia, dysphagia, and choking cough when drinking water, accompanied by slurred speech, salivation, and limb weakness. The blood autoantibody test results showed that many SLE-associated antibodies were positive. Meanwhile, anti-nuclear matrix protein 2 (NXP2) antibody was strongly positive in the idiopathic inflammatory myopathy (IIM) spectrum test from the serum. Muscle biopsy indicated inflammatory infiltration of the muscle fiber stroma. DIAGNOSES: Taking into account the clinical manifestations and laboratory tests of the present case, the diagnosis of SLE and probable IIM was established. INTERVENTIONS: Corticosteroids and additional gamma globulin were administered and the clinical symptoms were relieved during the treatment process. OUTCOMES: Unfortunately, the patient experienced sudden cardiac and respiratory arrest. Multiple system dysfunctions exacerbated disease progression, but in the present case, we speculated that myocardial damage resulting from SLE could explain why she suddenly died. LESSONS: To our knowledge, multiple neurological manifestations in patients with SLE and anti-NXP2-positive myositis are rare. Note that SLE is still a life-threatening disease that causes multiple system dysfunctions, which requires increasing attention.

Corynebacterium striatum meningitis combined with suspected brain and lung abscesses: a case report and review.

BACKGROUND: Intracranial infections with Corynebacterium striatum (C. striatum) have been described sporadically in the literature over the last two decades. However, C. striatum meningitis combined with multiple abscesses has not been published before. CASE PRESENTATION: In this report, we describe the clinical and imaging findings in a 54-year-old woman with meningitis caused by C. striatum and combined with suspected brain and lung abscesses. This patient who underwent multiple fractures and a recent cut presented with headache and paraphasia. C. striatum was isolated in cerebrospinal fluid and supposedly transmitted from the skin purulent wound through blood. The patient was treated with intravenous vancomycin and had a transient improvement, but died finally. Multiple abscesses, especially in the brain, could be a reason to explain her conditions were deteriorating rapidly. CONCLUSIONS: Note that C. striatum can cause life-threatening infections. Early identification and diagnosis, early administration of antibiotics to which the bacterium is susceptible, and treatment of complications will be beneficial in patients with C. striatum-related infection.

Nitric Oxide-Mediated Plasticity of Interconnections Between T-Stellate cells of the Ventral Cochlear Nucleus Generate Positive Feedback and Constitute a Central Gain Control in the Auditory System.

T-stellate cells in the ventral cochlear nucleus (VCN) form an ascending pathway that conveys spectral information from the cochlea to brainstem nuclei, the inferior colliculi, and the thalamus. The tonotopic array of T-stellate cells enhances the encoding of spectral peaks relative to their auditory nerve fiber inputs. The alignment of local collaterals and T-stellate cell dendrites within the isofrequency lamina suggests that the cells make connections within the isofrequency lamina in which they reside. Recordings from pairs of T-stellate cells in mice of both sexes revealed that firing in the presynaptic cell evoked responses in the postsynaptic cell when presynaptic firing was paired with depolarization of the postsynaptic cell. After such experimental coactivation, presynaptic firing evoked EPSCs of uniform amplitude whose frequency depended on the duration of depolarization and diminished over minutes. Nitric oxide (NO) donors evoked EPSCs in T-stellate cells but not in the other types of principal cells. Blockers of neuronal nitric oxide synthase (nNOS) and of NMDA receptors blocked potentiation, indicating that NO mediates potentiation. nNOS and its receptor, guanylate cyclase (NO-GC), are expressed in somata of T-stellate cells. Excitatory interconnections were bidirectional and polysynaptic, indicating that T-stellate cells connect in networks. Positive feedback provided by temporarily potentiated interconnections between T-stellate cells could enhance the gain of auditory nerve excitation in proportion to the excitation, generating a form of short-term central gain control that could account for the ability of T-stellate cells to enhance the encoding of spectral peaks.SIGNIFICANCE STATEMENT T-stellate cells are interconnected through synapses that have a previously undescribed form of temporary, nitric oxide-mediated plasticity. Coactivation of neighboring cells enhances the activation of an excitatory network that feeds back on itself by enhancing the probability of EPSCs. Although there remain gaps in our understanding of how the interconnections revealed in slices contribute to hearing, our findings have interesting implications. Positive feedback through a network of interconnections could account for how T-stellate cells are able to encode spectral peaks over a wider range of intensities than many of their auditory nerve inputs (Blackburn and Sachs, 1990; May et al., 1998). The magnitude of the gain may itself be plastic because neuronal nitric oxide synthase increases when animals have tinnitus (Coomber et al., 2015).

TLR4 mediates high-fat diet induced physiological changes in mice via attenuating PPARγ/ABCG1 signaling pathway.

High-fat diet (HFD) is known to promote atherosclerosis which accelerates the development of atherosclerotic cardiovascular diseases. Vascular dysfunction characterized by inflammation and lipid accumulation is common in atherosclerosis caused by HFD. The specific effects of HFD on blood vessels and the underlying mechanisms need to be further clarified. Toll-like receptor 4 (TLR4) is a key contributing factor in atherosclerosis and TLR4 deficiency protects vascular smooth muscle cells against inflammatory responses and lipid accumulation in vitro. However, the physiological significance of TLR4 signaling in HFD-induced changes is unknown. In this study, we observed that HFD feeding increased body weight, circulating inflammatory cytokines and lipid accumulation in the aorta of wild-type mice but apart from increasing body weight, did not affect the TLR4 knockout mice. TLR4 expression increased significantly in the arterial walls after receiving HFD treatment, while that of the co-localizing PPARγ and ABCG1 markedly decreased. TLR4 deficiency reversed the HFD-induced attenuation of PPARγ and ABCG1. In conclusion, TLR4 mediates HFD induced increase in body weight, inflammation and aortic lipid accumulation through, at least partly, the PPARγ/ABCG1 signaling pathway. Therefore, interfering with TLR4 signaling is a viable therapeutic option in diet induced atherosclerosis.

Cellular Computations Underlying Detection of Gaps in Sounds and Lateralizing Sound Sources.

In mammals, acoustic information arises in the cochlea and is transmitted to the ventral cochlear nuclei (VCN). Three groups of VCN neurons extract different features from the firing of auditory nerve fibers and convey that information along separate pathways through the brainstem. Two of these pathways process temporal information: octopus cells detect coincident firing among auditory nerve fibers and transmit signals along monaural pathways, and bushy cells sharpen the encoding of fine structure and feed binaural pathways. The ability of these cells to signal with temporal precision depends on a low-voltage-activated K+ conductance (gKL) and a hyperpolarization-activated conductance (gh). This 'tale of two conductances' traces gap detection and sound lateralization to their cellular and biophysical origins.