EndoQuad: a comprehensive genome-wide experimentally validated endogenous G-quadruplex database.

G-quadruplexes (G4s) are non-canonical four-stranded structures and are emerging as novel genetic regulatory elements. However, a comprehensive genomic annotation of endogenous G4s (eG4s) and systematic characterization of their regulatory network are still lacking, posing major challenges for eG4 research. Here, we present EndoQuad (https://EndoQuad.chenzxlab.cn/) to address these pressing issues by integrating high-throughput experimental data. First, based on high-quality genome-wide eG4s mapping datasets (human: 1181; mouse: 24; chicken: 2) generated by G4 ChIP-seq/CUT&Tag, we generate a reference set of genome-wide eG4s. Our multi-omics analyses show that most eG4s are identified in one or a few cell types. The eG4s with higher occurrences across samples are more structurally stable, evolutionarily conserved, enriched in promoter regions, mark highly expressed genes and associate with complex regulatory programs, demonstrating higher confidence level for further experiments. Finally, we integrate millions of functional genomic variants and prioritize eG4s with regulatory functions in disease and cancer contexts. These efforts have culminated in the comprehensive and interactive database of experimentally validated DNA eG4s. As such, EndoQuad enables users to easily access, download and repurpose these data for their own research. EndoQuad will become a one-stop resource for eG4 research and lay the foundation for future functional studies.

From Molecular to Behavior: Higher Order Occipital Cortex in Major Depressive Disorder.

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.

Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder.

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

Focal Electrical Stimulation of Cortical Functional Networks.

Traditional electrical stimulation of brain tissue typically affects relatively large volumes of tissue spanning multiple millimeters. This low spatial resolution stimulation results in nonspecific functional effects. In addition, a primary shortcoming of these designs was the failure to take advantage of inherent functional organization in the cerebral cortex. Here, we describe a new method to electrically stimulate the brain which achieves selective targeting of single feature-specific domains in visual cortex. We provide evidence that this paradigm achieves mesoscale, functional network-specificity, and intensity dependence in a way that mimics visual stimulation. Application of this approach to known feature domains (such as color, orientation, motion, and depth) in visual cortex may lead to important functional improvements in the specificity and sophistication of brain stimulation methods and has implications for visual cortical prosthetic design.

Contrast-dependent variations in the excitatory classical receptive field and suppressive nonclassical receptive field of cat primary visual cortex.

In area V1 of cat and monkey, there is a surround region beyond the classical receptive field (CRF) which alone is unresponsive but may modulate the cell's response. This field is referred to as the "nonclassical receptive field" (nCRF). It has been reported in monkey that the extent of CRF and/or nCRF of V1 neurons is not fixed but varies with stimulus contrast. We reexamined the contrast dependence of V1 neurons in cat to determine whether this differs from previous studies in macaque. By fitting the spatial summation curves obtained at different contrasts with a difference of Gaussians model, we estimated quantitatively the effect of contrast on the spatial extent of the CRF and nCRF as well as the strength of surround suppression. Our results showed that both the CRF and nCRF expanded at low contrast, but the expansion is more marked for the CRF than for the nCRF. Although the effect of contrast on surround suppression was varied, the overall suppression increased significantly at high contrast. Moreover, the contrast-dependent change in the extent of CRF is independent of the change in suppression strength. Overall, our results in cat are in agreement with those obtained in macaque money.

Abnormal activation patterns in MT+ during visual motion perception in major depressive disorder.

Objective: Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC). Methods: Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC. Results: Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus. Conclusion: Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.

Irregularity of visual motion perception and negative symptoms in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Motor versus Psychomotor? Deciphering the Neural Source of Psychomotor Retardation in Depression.

Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local-to-global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local-to-local BA4 - MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local-to-global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

GABAergic inhibition in human hMT+ predicts visuo-spatial intelligence mediated through the frontal cortex.

The prevailing opinion emphasizes fronto-parietal network (FPN) is key in mediating general fluid intelligence (gF). Meanwhile, recent studies show that human MT complex (hMT+), located at the occipito-temporal border and involved in 3D perception processing, also plays a key role in gF. However, the underlying mechanism is not clear, yet. To investigate this issue, our study targets visuo-spatial intelligence, which is considered to have high loading on gF. We use ultra-high field magnetic resonance spectroscopy (MRS) to measure GABA/Glu concentrations in hMT+ combining resting-state fMRI functional connectivity (FC), behavioral examinations including hMT+ perception suppression test and gF subtest in visuo-spatial component. Our findings show that both GABA in hMT+ and frontal-hMT+ functional connectivity significantly correlate with the performance of visuo-spatial intelligence. Further, serial mediation model demonstrates that the effect of hMT+ GABA on visuo-spatial gF is fully mediated by the hMT+ frontal FC. Together our findings highlight the importance in integrating sensory and frontal cortices in mediating the visuo-spatial component of general fluid intelligence.

[Progress on miRNA in mammal breast milk].

As an important regulator in eukaryote, miRNAs could be in the animal body fluids, including serum, blood plasma, saliva, urine and so on. More recently, it was reported that miRNAs were also in the breast milk of human or cow, which indicates that miRNAs could probably be transferred into the body of the next generation by lactation and play their key roles. This might be the prelude of studies on the regulation function of miRNAs in generations. Here, we introduced the process of finding miRNAs in mammal milk, the format of miRNAs in milk and the method for isolating miRNAs, and reviewed the main functions of several miRNAs in milk. We also discussed the research task and challenge associated with miRNAs in milk at the next.

[Monitoring the flux of carbon dioxide gas with tunable diode laser absorption spectroscopy].

The greenhouse effect exacerbated by the increase of Carbon-containing gases is the more important causes of the climate change, It is very meaningful to the large-scale flux of carbon dioxide detection for the estimate the contributions of the main greenhouse gases in the atmosphere of various errestrial eco-systems. Tunable diode laser absorption spectroscopy (TDLAS) is a highly sensitive, highly selective and fast time response trace gas detection technique. In the present paper, the authors used a DFB laser was used as the light source, and by employing wavelength modulation method, and measuring the second harmonic signal of one absorption line near 1.573 microm of carbon dioxide molecule, the authors built a system for online monitoring of carbon dioxide concentration within the optical path of more than 700 meters at different heights. Combined with Alonzo Mourning -Obukhov length and characteristic velocity detected by large aperture scintillometer, the flux of carbon dioxide gas within one day calculated by the formula is within--1.5-2.5, breaking through the phenomenon of only providing the flux of trace gases near the ground at present, makking the measurement of trace gas fluxes within a large area possible.

[Study of remote sensing the flux of carbon dioxide gas with tunable diode laser absorption spectroscopy].

Tunable diode laser absorption spectroscopy (TDLAS) technique is a new method to detect trace gas qualitatively or quantificationally based on the scan characteristic of the diode laser to obtain the absorption spectra in the characteristic absorption region. TDLAS is a highly sensitive, highly selective and fast time response trace gas detection technique. In the present paper, a DFB laser at room temperature was used as the light source, wavelength modulation method was employed, and the second harmonic signal of one absorption line near 1.578 microm of carbon dioxide molecule was measured. A system was built for online monitoring of carbon dioxide concentration within the optical path of more than 700 meters at different heights. Combined with Alonzo Mourning-Obukhov length and characteristic velocity detected by large aperture scintillometer, the flux of carbon dioxide gas calculated by the experiential formula is within -60-60 mg x m(-2) x s(-1). The comparison of the datea detected by TDLAS system and the eddy covariance showed that the change of the data detected by TDLAS had a similar trend to that detected by the eddy covariance, and the best results can be produced by this method, breaking through the phenomenon of only providing the flux of trace gases near the ground at present, and making the measurement of trace gas fluxes within a large area possible.

Spatial suppression of chromatic motion.

Center-surround antagonism, as a ubiquitous feature in visual processing, usually leads to inferior perception for a large stimulus compared to a small one. For example, it is more difficult to judge the motion direction of a large high-contrast pattern than that of a small one. However, this spatial suppression in the motion dimension was only reported for luminance motion, and was not found for chromatic motion. Given that center-surround suppression only occurs for strong visual inputs, we hypothesized that previous failure in finding spatial suppression of chromatic motion might be due to weak chromatic motion being induced with stimuli of limited parameters. In this study, we used phase-shift discrimination and motion-direction discrimination tasks to measure motion spatial suppression induced by stimuli of two spatial frequencies (0.5 and 2 cpd) and two contrasts (low and high). We found that spatial suppression of the chromatic motion was stably observed for stimuli of high spatial frequency (2 cpd) and high contrast and spatial summation occurred for stimuli of low spatial frequency (0.5 cpd). Intriguingly, there was no correlations between the motion spatial suppressions of luminance motion and chromatic motion, implying that the two types of spatial suppression are not originated from the same neural processing. Our findings indicate that spatial suppression also exists for chromatic motion, and the mechanisms underlying the spatial suppression of chromatic motion is different from that of luminance motion.

Curvature domains in V4 of macaque monkey.

An important aspect of visual object recognition is the ability to perceive object shape. Two basic components of complex shapes are straight and curved contours. A large body of evidence suggests a modular hierarchy for shape representation progressing from simple and complex orientation in early areas V1 and V2, to increasingly complex stages of curvature representation in V4, TEO, and TE. Here, we reinforce and extend the concept of modular representation. Using intrinsic signal optical imaging in Macaque area V4, we find sub-millimeter sized modules for curvature representation that are organized from low to high curvatures as well as domains with complex curvature preference. We propose a possible 'curvature hypercolumn' within V4. In combination with previous studies, we suggest that the key emergent functions at each stage of cortical processing are represented in systematic, modular maps.

Precise Targeting of Single Microelectrodes to Orientation Pinwheel Centers.

In the mammalian visual system, early stages of visual form perception begin with orientation selective neurons in primary visual cortex (V1). In many species (including humans, monkeys, tree shrews, cats, and ferrets), these neurons are organized in pinwheel-like orientation columns. To study the functional organization within orientation pinwheels, it is important to target pinwheel subdomains precisely. We therefore developed a technique to provide a quantitative determination of the location of pinwheel centers (PCs). Previous studies relied solely on blood vessel images of the cortical surface to guide electrode penetrations to PCs in orientation maps. However, considerable spatial error remained using this method. In the present study, we improved the accuracy of targeting PCs by ensuring perpendicularity of electrodes and by utilizing the orientation tuning of local field potentials (LFP) recorded at or near the optically determined positions.

Contrast-dependent and contrast-independent spatial summation of primary visual cortical neurons of the cat.

Recent studies have reported that the size of the classical receptive field (CRF) and the extent of spatial summation of V1 neurons depend on stimulus contrast. We reexamined these properties for 48 V1 neurons in the cat and found that all the cells had a constant CRF size, whereas their spatial summation properties can be contrast dependent (CD) or contrast independent (CID). Of the 29 CD cells, 17 showed facilitatory summation at low contrast (10%), but suppressive summation at high contrast (80%); the other 12 showed weak suppressive summation at low contrast, whereas the strength of suppression increased significantly at high contrast. The 19 CID cells showed similar facilitative (CIDf) or suppressive (CIDs) summation at low and high contrast, without changes in shape and/or peak location. We successfully labeled 11 CD cells and 10 CID cells with biocytin. The morphological results demonstrated that all the labeled CD cells were pyramidal cells, whereas all labeled CID cells were nonpyramidal cells, in which the CIDf cells were spiny stellates and the CIDs cells, smooth interneurons. There is thus a global distinction between summation properties of pyramidal and nonpyramidal cells, and between the smooth and spiny nonpyramidal cells as well.

Subdomains within orientation columns of primary visual cortex.

In the mammalian visual system, early stages of visual form processing begin with orientation-selective neurons in primary visual cortex (V1). In many species (including humans, monkeys, tree shrews, cats, and ferrets), these neurons are organized in a beautifully arrayed pinwheel-like orientation columns, which shift in orientation preference across V1. However, to date, the relationship of orientation architecture to the encoding of multiple elemental aspects of visual contours is still unknown. Here, using a novel, highly accurate method of targeting electrode position, we report for the first time the presence of three subdomains within single orientation domains. We suggest that these zones subserve computation of distinct aspects of visual contours and propose a novel tripartite pinwheel-centered view of an orientation hypercolumn.

Type-dependent differential expression of neuropeptide Y in chicken hypothalamus (Gallus domesticus).

Neuropeptide Y (NPY) is one of the most important orexigenic agents in central regulation of feeding behavior, body weight and energy homeostasis in domestic chickens. To examine differences in the hypothalamic NPY between layer-type and meat-type of chickens, which are two divergent kinds of the domestic chickens in feeding behavior and body weight, we detected mRNA levels of NPY in hypothalamic infundibular nucleus (IN), paraventricular nucleus (PVN) and lateral hypothalamic area (LHA) of these two types of chickens using one-step real time RT-PCR. The meat-type chicken had more food daily (about 1.7 folds) and greater body weights (about 1.5 folds) and brain weights than the layer-type chicken at the age of 14 d. In the meat-type of chicken, NPY mRNA levels of the IN and PVN were significantly greater than those of the LHA, and were not significantly different between the IN and PVN. However, in the layer-type of chicken, NPY mRNA levels were significantly greater in the IN than those in the LHA and PVN, and were not significantly different between the PVN and LHA. In all these hypothalamic regions, the layer-type of chicken had significantly higher NPY mRNA levels than the meat-type chicken did. These results suggest the expression of NPY in the hypothalamus has a type-dependent pattern in domestic chickens.

[Components and assembly of RNA-induced silencing complex].

Degradation of homologous RNA in RNA interference is carried out by functional RNA-induced silencing complex (RISC). RISC contains Dicer, Argonaute proein, siRNA and other components. Researching structures and functions of these components is primary important for understanding assembly and functional mechanism of RISC, as well as the whole RNAi pathway. Recent research works showed that Dicer, containing RNaseIII domain, is responsible for production of siRNA at the beginning of RNAi, and guarantees the stability of RISC intermediate in assembly process. As the core component of RISC, Argonaute protein functions as slicer to cleave target RNA and offers the binding site of siRNA in RISC assembly, which are depended on PIWI domain and PAZ domain separately. Although there is only one strand of siRNA that is the guider of RISC, the double stranded structural character of siRNA is determinant of RNAi. Except those, there are still other components with unknown functions in RISC. The knowledge about RISC components and assembly now, is basis of a presumed RISC assembly model.

Orientation selectivity in cat primary visual cortex: local and global measurement.

In this study, we investigated orientation selectivity in cat primary visual cortex (V1) and its relationship with various parameters. We found a strong correlation between circular variance (CV) and orthogonal-topreferred response ratio (O/P ratio), and a moderate correlation between tuning width and O/P ratio. Moreover, the suppression far from the peak that accounted for the lower CV in cat V1 cells also contributed to the narrowing of the tuning width of cells. We also studied the dependence of orientation selectivity on the modulation ratio for each cell, which is consistent with robust entrainment of the neuronal response to the phase of the drifting grating stimulus. In conclusion, the CV (global measure) and tuning width (local measure) are signifi cantly correlated with the modulation ratio.