Comparison of the Effect of and Compliance With Cyclosporine 0.1% After Various Pretreatments in Dry Eye Disease.

We sought to compare the effect of cyclosporine 0.1% after various pretreatments in patients with dry eye disease. Two hundred seventy-four eyes of 137 patients diagnosed with dry eye disease were retrospectively enrolled.

Multi-dimensional oscillatory activity of mouse GnRH neurons in vivo.

The gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt ~8 min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH).

Shifting GnRH Neuron Ensembles Underlie Successive Preovulatory Luteinizing Hormone Surges.

The gonadotropin-releasing hormone (GnRH) neurons operate as a neuronal ensemble exhibiting coordinated activity once every reproductive cycle to generate the preovulatory GnRH surge. Using GCaMP fiber photometry at the GnRH neuron distal dendrons to measure the output of this widely scattered population in female mice, we find that the onset, amplitude, and profile of GnRH neuron surge activity exhibits substantial variability from cycle to cycle both between and within individual mice. This was also evident when measuring successive proestrous luteinizing hormone surges.

Long-term Recordings of Arcuate Nucleus Kisspeptin Neurons Across the Mouse Estrous Cycle.

The arcuate nucleus kisspeptin (ARNKISS) neurons represent the GnRH pulse generator that likely drives pulsatile gonadotropin secretion in all mammals. Using an improved GCaMP fiber photometry system enabling long-term continuous recordings, we aimed to establish a definitive profile of ARNKISS neuronal activity across the murine estrous cycle. As noted previously, a substantial reduction in the frequency of ARNKISS neuron synchronization events (SEs) occurs on late proestrus and extends into estrus.

Daily changes in spatial accessibility to ICU beds and their relationship with the case-fatality ratio of COVID-19 in the state of Texas, USA.

During the COVID-19 pandemic, many patients could not receive timely healthcare services due to limited availability and access to healthcare resources and services. Previous studies found that access to intensive care unit (ICU) beds saves lives, but they overlooked the temporal dynamics in the availability of healthcare resources and COVID-19 cases. To fill this gap, our study investigated daily changes in ICU bed accessibility with an enhanced two-step floating catchment area (E2SFCA) method in the state of Texas.

QUANTITATIVE ANALYSIS OF CHOROIDAL MORPHOLOGY USING MULTIMODAL IMAGING IN ACUTE AND PERSISTENT CENTRAL SEROUS CHORIORETINOPATHY.

Purpose: To analyze quantitative differences in choroidal morphology between acute and persistent central serous chorioretinopathy using multimodal images.

Methods: Ultra-widefield indocyanine green angiography (UWICGA) and optical coherence tomography images of 72 eyes of 72 patients with acute (32 eyes) and persistent (40 eyes) central serous chorioretinopathy were collected. Choroidal thickness, area, vessel density, symmetry, and intervortex anastomosis were assessed.

Choroidal Morphology on Ultra-Widefield Indocyanine Green Angiography and Response to Aflibercept in Pachychoroid Neovasculopathy.

Purpose: This study assessed the relationship between the choroidal morphology and short-term response to aflibercept treatment in pachychoroid neovasculopathy (PNV). Methods: This was a retrospective case-control study. Ultra-widefield indocyanine green angiography (UWICGA) and optical coherence tomography (OCT) images of 90 PNV eyes of 90 patients treated with aflibercept were enrolled.

Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge.

Recurrent spillovers of α- and β-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and β-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown.

Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice.

The mechanism by which arcuate nucleus kisspeptin (ARN) neurons co-expressing glutamate, neurokinin B, and dynorphin intermittently synchronize their activity to generate pulsatile hormone secretion remains unknown. An acute brain slice preparation maintaining synchronized ARN neuron burst firing was used alongside in vivo GCaMP GRIN lens microendoscope and fiber photometry imaging coupled with intra-ARN microinfusion. Studies in intact and gonadectomized male mice revealed that ARN neuron synchronizations result from near-random emergent network activity within the population and that this was critically dependent on local glutamate-AMPA signaling.

Sympathetic and vagal interaction in the control of cardiac pacemaker rhythm in the guinea-pig heart: Importance of expressing heart rhythm using an appropriate metric.

There are many reports that, through pre- and post-junctional mechanisms, sympathetic and parasympathetic (vagal) nerves can interact in the control of heart rate. The predominant interaction is accentuated antagonism (AA), where the bradycardia produced by vagal stimulation (VNS) is amplified when heart rate has been increased by sympathetic stimulation (SNS) or beta-adrenergic agonists. The acetylcholine-activated potassium current (I), is the primary driver of vagal bradycardia.

An integrated cyberGIS and machine learning framework for fine-scale prediction of Urban Heat Island using satellite remote sensing and urban sensor network data.

Due to climate change and rapid urbanization, Urban Heat Island (UHI), featuring significantly higher temperature in metropolitan areas than surrounding areas, has caused negative impacts on urban communities. Temporal granularity is often limited in UHI studies based on satellite remote sensing data that typically has multi-day frequency coverage of a particular urban area. This low temporal frequency has restricted the development of models for predicting UHI.

MMTR/Dmap1 Sets the Stage for Early Lineage Commitment of Embryonic Stem Cells by Crosstalk with PcG Proteins.

Chromatin remodeling, including histone modification, chromatin (un)folding, and nucleosome remodeling, is a significant transcriptional regulation mechanism. By these epigenetic modifications, transcription factors and their regulators are recruited to the promoters of target genes, and thus gene expression is controlled through either transcriptional activation or repression. The -mediated transcriptional repressor (MMTR)/DNA methyltransferase 1 (DNMT1)-associated protein (Dmap1) is a transcription corepressor involved in chromatin remodeling, cell cycle regulation, DNA double-strand break repair, and tumor suppression.

Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice.

The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice.

Stress experience and hormone feedback tune distinct components of hypothalamic CRH neuron activity.

Stress leaves a lasting impression on an organism and reshapes future responses. However, the influence of past experience and stress hormones on the activity of neural stress circuits remains unclear. Hypothalamic corticotropin-releasing hormone (CRH) neurons orchestrate behavioral and endocrine responses to stress and are themselves highly sensitive to corticosteroid (CORT) stress hormones.

GnRH Pulse Generator Activity Across the Estrous Cycle of Female Mice.

A subpopulation of kisspeptin neurons located in the arcuate nucleus (ARN) operate as the GnRH pulse generator. The activity of this population of neurons can be monitored in real-time for long periods using kisspeptin neuron-selective GCaMP6 fiber photometry. Using this approach, we find that ARN kisspeptin neurons exhibit brief (∼50 seconds) periods of synchronized activity that precede pulses of LH in intact female mice.

Characterization of GnRH Pulse Generator Activity in Male Mice Using GCaMP Fiber Photometry.

Kisspeptin neurons located in the hypothalamic arcuate nucleus are thought to represent the GnRH pulse generator responsible for driving pulsatile LH secretion. The recent development of GCaMP6 fiber photometry technology has made it possible to perform long-term recordings of the population activity of the arcuate nucleus kisspeptin (ARNKISS) neurons in conscious-behaving mice. Using this approach, we show that ARNKISS neurons in intact male mice exhibit episodes of synchronized activity that last ∼2 minutes and have a mean inter-episode interval of 166 minutes, with a very wide range (43 to 347 minutes).

Multifaceted C-terminus of HSP70-interacting protein regulates tumorigenesis via protein quality control.

C-terminus of heat shock protein 70 (HSP70)-interacting protein (CHIP) is an E3 ligase involved in a variety of protein homeostasis events implicated in diverse signaling pathways. Its involvement in varied and even opposite signaling circuits might be due to its hallmark signature of associating with molecular chaperones, including HSP90 and HSP70. Together, these proteins may be pivotal in implementing protein quality control.

[Effects of straw returning on maize yield and root system spatial distribution under water stress].

To investigate the effects of straw amendments on the yield and root spatial distribution of maize under water stress, an experiment with rainproof shelter was conducted in the field experimental station of Shenyang Agricultural University in 2016 and 2017. The drip irrigation facilities were used to perform water stress treatments. Straw burying (T) and straw incorporation (T) as two approaches of straw amendments were conducted combined with three depths of 15 cm (D), 30 cm (D), and 45 cm (D) for straw returning, ploughing tillage at above three depths without straw presence as control in this study.

Optical Approaches for Interrogating Neural Circuits Controlling Hormone Secretion.

Developments in optical imaging and optogenetics are transforming the functional investigation of neuronal networks throughout the brain. Recent studies in the neuroendocrine field have used genetic mouse models combined with a variety of light-activated optical tools as well as GCaMP calcium imaging to interrogate the neural circuitry controlling hormone secretion. The present review highlights the benefits and caveats of these approaches for undertaking both acute brain slice and functional studies in vivo.

Loss of the E3 ubiquitin ligase MKRN1 represses diet-induced metabolic syndrome through AMPK activation.

AMP-activated protein kinase (AMPK) plays a key role in controlling energy metabolism in response to physiological and nutritional status. Although AMPK activation has been proposed as a promising molecular target for treating obesity and its related comorbidities, the use of pharmacological AMPK activators has been met with contradictory therapeutic challenges. Here we show a regulatory mechanism for AMPK through its ubiquitination and degradation by the E3 ubiquitin ligase makorin ring finger protein 1 (MKRN1).

Regulatory Network of ARF in Cancer Development.

ARF is a tumor suppressor protein that has a pivotal role in the prevention of cancer development through regulating cell proliferation, senescence, and apoptosis. As a factor that induces senescence, the role of ARF as a tumor suppressor is closely linked to the p53-MDM2 axis, which is a key process that restrains tumor formation. Thus, many cancer cells either lack a functional ARF or p53, which enables them to evade cell oncogenic stress-mediated cycle arrest, senescence, or apoptosis.

Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF.

Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated.