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AIM: To describe the characteristics of peripapillary hyperreflective ovoid mass-like structure (PHOMS) in myopic children and to investigate factors associated with PHOMS. METHODS: This retrospective observational study included 101 eyes of 101 children (age ≤17y) with myopia. All included patients underwent comprehensive clinical examination. Optic nerve canal parameters, including disc diameter, optic nerve head (ONH) tilt angle, and border tissue angle were measured using serial enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Based on the optic disc drusen consortium's definition of PHOMS, eyes were classified as PHOMS group and non-PHOMS group. PHOMS was categorized according to height. RESULTS: Sixty-seven (66.3%) eyes were found with PHOMS. Small PHOMS could only be detected by optical coherence tomography (OCT). Medium PHOMS could be seen with blurred optic disc borders corresponding to OCT. The most frequent location of PHOMS was at the nasosuperior (91%, 61 of 67 eyes) to ONH disc. The axial length and spherical equivalent were more myopic in the PHOMS group than in the non-PHOMS group (both P

Retinal vascular bed area(RVBA)is the total area of retinal vasculature segmented by ultra-widefield fluorescein angiography(UWFA)images, and is an objective absolute value in square millimeter. RVBA is mainly affected by the diameter and length of retinal vessels, and whether RVBA increases or decreases depends on the “competition” between ischemia and angiogenesis, indicating subtle changes in retinal vascular morphology. As a new indicator for the study of retinal vascular diseases, RVBA may have higher stability and accuracy than the ischemia index(ISI)and non-perfusion area(NPA). RVBA is currently mainly used to evaluate the progression and prognosis of diabetic retinopathy(DR). It was found that retinal total RVBA in DR eyes was greater than the normal eyes and it decreased in DR eyes after anti-vascular endothelial growth factor(VEGF)treatment. These findings provide favorable support for the study of microvascular lesions in DR. In this article, the application of RVBA in DR was reviewed to provide a reference for the clinical study of RVBA in other retinal vascular diseases such as retinal vein occlusion(RVO).

AIM: To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy (LHON) using full-field electroretinography (FERG) and optical coherence tomography (OCT). METHODS: Individuals diagnosed with LHON at the Renmin Hospital of Wuhan University and their family members were included in this cross-sectional observational study. The FERG a-wave amplitude of affected patients and asymptomatic carriers was analyzed. The thickness of the outer nuclear layer (ONL), inner and outer segment (IS/OS) and total photoreceptors in the macular fovea and parafovea were measured. RESULTS: This study included 14 LHON patients (mean age: 20.00±9.37y), 12 asymptomatic carriers (mean age: 39.83±6.48y), and 14 normal subjects (mean age: 24.20±1.52y). The FERG results showed that the dark-adapted 3.0 electroretinography and light-adapted 3.0 electroretinography a-wave amplitudes of patients and carriers were significantly decreased (P0.05). CONCLUSION: Photoreceptors function is significantly impaired in LHON-affected patients and asymptomatic carriers. Meanwhile, photoreceptors morphology is slightly altered, mainly manifesting as a change in ONL thickness.

Peripapillary hyper-reflective ovoid mass-like structure(PHOMS)is a new finding in 2018, which is based on the enhanced-depth imaging optical coherence tomography(EDI-OCT). A PHOMS is peripapillary in location, situated just above the lip of Bruch membrane open(BMO), and it is an ovoid, mass-like homogeneous structure similar to the hyper-reflectiveretinal nerve fiber layer. Although previously assumed to represent a form of buried optic disc drusen(ODD), the prevailing view is that PHOMS is the bulge of the axons of optic nerve fibers and a marker of axoplasmic stasis in the optic nerve fibers. This article describes the reasons for the concept of PHOMS, identifies its relationship with ODD, and discusses the possible histopathological mechanisms. In addition, we detail the differences between PHOMS on fundus multimodal images and other imaging features and explore the clinical manifestations and possible pathophysiological mechanisms of PHOMS in different diseases, which are important for a better understanding of neuro-ophthalmic related diseases such as myopic optic neuropathy and optic neuritis. Furthermore, we propose possible future research directions for PHOMS to gain new insights into PHOMS and its related diseases.

Targeted retinal photocoagulation(TRP)refers to targeted photocoagulation of the non-perfusion areas(NPA)of the retina, which can greatly reduce the risk of complications of panretinal photocoagulation(PRP). Ultra-wide field fluorescein angiography(UWFFA)can clearly show NPA of the far peripheral retina, which is conducive to precise positioning and implementation of TRP therapy. At present, the safety of short-term TRP treatment programs for proliferative diabetic retinopathy(PDR)is reasonable, but the long-term efficacy is still uncertain. In the future, TRP may become an early treatment option for some PDR patients, by delaying PRP to maintain the visual acuity and central field of vision. Anti-vascular endothelial growth factor(VEGF)drugs are currently the first-line drugs for diabetic macular edema(DME), for which with retinal neovascularization(NV)or poor compliance, combined TRP therapy may be considered. The ischemic index(ISI)is used to quantitatively analyze NPA of the retina under the vision of UWFFA, which is expected to become an important index in the future to guide the selection of clinical TRP treatment options.

AIM: To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). METHODS: In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. RESULTS: Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P

Background Previous studies recruited unrepresentative samples of Chinese patients with cataract and reported a wide range of prevalence of depressive symptoms in this patient population (18.0–89.7%). The present study determined the prevalence and correlates of depressive symptoms among a consecutive sample of Chinese patients with cataract treated in tertiary general hospitals. Methods A total of 339 patients with cataract were consecutively selected from ophthalmology departments of two large general hospitals in Wuhan, China. Depressive symptoms were assessed with the Chinese Hospital Anxiety and Depression Scale. Logistic regression was used to identify factors that were associated with depression. Results The prevalence of depressive symptoms was 23.9% (95% CI [19.4–28.4]%) among patients with cataract. Correlates for depressive symptoms include an education level of primary school and below (OR = 1.93, P = 0.038), marital status of “others” (OR =3.15, P

AIM:To observe the clinical efficacy and safety of vincamine sustained release capsules on non-arteritic anterior ischemic optic neuropathy(NAION).METHODS:Patients who were diagnosed with monocular onset NAION in acute stage from January to September 2015 were divided into two groups. Routine treatment such as steroid pulse therapy and neurotrophic treatment were given to all the patients. Vincamine was added to the treatment group patients with 30mg twice a day for 3mo. The best corrected visual acuity(BCVA), mean deviation(MD)of visual field, retinal nerve fiber layer(RNFL), ganglion cell complex(GCC), pattern visual evoked potential(PVEP)and OCT results were analyzed before and after the treatment.RESULTS: Totally 42 eyes of 42 patients were enrolled in our study. There were 27 patients in the treatment group, aged from 33 to 79 years old, the average value was 55.55±11.83 years old. The control group has 15 patients, aged from 40 to 70 years old, the average value was 55.71±10.06 years old. There were no statistical differences between the two groups in the baseline. After 3mo of the treatment, MD value of the two groups were lower compared with the baseline, the difference was statistically significant in the treatment and control group respectively(t=2.342, 2.692; P=0.027, 0.041). The difference of PVEP amplitude and potential of the two groups before and after the treatment were not statistically significant. The thickness of retinal nerve fiber layer and the ganglion cell complex were all lower than the baseline, and the difference was statistically significant(PCONCLUSION: Vincamine is helpful in the treatment of non-arteritic anterior ischemic optic neuropathy.

AIM: To evaluate the repeatability and reproducibility of thickness profile measurement of intra-retinal layers determined by an automated algorithm applied to OCT images from Cirrus optical coherence tomography(OCT)instrument.METHODS: In this prospective cross-sectional study, retinal thickness images at 6mm×6mm around fovea were obtained from 86 eyes of 43 normal subjects with Cirrus HD- OCT instrument. The retinal images from patients were analysis by Cirrus automated algorithm GCA software, including ganglion cell layer and inner plexiform layer(GCIPL). During this study, operator A would make 2 times measurements to all patients, after that operator B would make another 2 times measurements by Repeat scan model. All the data, including GCL average thickness, min thickness, 12 clock average thickness, 2 clock average thickness, 4 clock average thickness,6 clock average thickness, 8 clock average thickness and 10 clock average thickness were measured by SPSS 15.0 software. Standard deviation(SD), coefficient of variation(CV)and interclass correlation coefficient(ICC)were calculated from the results of three-times tests by different examiner to evaluate the repeatability and from the results of two different examiners to assess the reproducibility. Written informed consent was obtained from each subject prior to any medical procedure. RESULTS: The average GCIPL thickness of OD was 85.12±3.95μm; the minimum average GCIPL thickness was 83.21±4.41μm; the standard deviation of OD in clock map was from 3.79μm to 4.84μm; CV(95%CI)was between 0.26 and 0.93; ICC was from 0.939 to 0.989. The average GCL+IPL thickness of OS was 84.65±8.73μm; the minimum average GCPL thickness was 81±13.08μm; the standard deviation of OS in clock map was from 8.24μm to 10.56μm; CV(95%CI)was between 0.92 and 4.94; ICC was from 0.264 to 0.968. CONCLUSION: Cirrus HD-OCT GCA software with automated algorithm can offer accurate and repeatable thickness profile of OCT retinal image. GCA is a useful and reliable approach to the measurement of intra-retinal layer thickness, which may improve the diagnosis and monitoring of retinal diseases.

AIM: To investigate the effect of HtrA1 on the proliferation, migration and apoptosis of human retinal pigment epithelium (RPE) cells in the light injured model, as well as the expression of the apoptosis related molecules. METHODS: The human RPE cell line ARPE-19 was exposed to blue light to establish the light injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1 expression. Subsequent expression of HtrA1 was determined by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Changes in cell proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK-8), Transwell assay and flow cytometry respectively, as well as changes in the mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1 was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue-light-irradiated ARPE-19 cells (P

Protocol Summary Here, we describe targeted gene deletion and replacement in human cells via the CRISPR/Cas9 system using two guide RNAs. The system effectively generated targeted deletions of varied length, regardless of the transcriptional status of the target gene. It is notable that targeted gene deletions generated via CRISPR/Cas9 and two guide RNAs resulted in the formation of correct junctions at high efficiency. Moreover, in the presence of a homology repair donor, the CRISPR/Cas9 system could guide precise gene replacement. Our results illustrate that the CRISPR/Cas9 system can be used to precisely and effectively generate targeted deletions or gene replacement in human cells, which will facilitate characterization of functional domains in protein-coding genes as well as noncoding regulatory sequences in animal genomes.

In the actual measurements, vibration and noise spectrum of gear pair often exhibits sidebands around the gear mesh harmonic orders. In this study, a nonlinear time-varying dynamic model of spur gear pair was established to predict the modulation sidebands caused by the AM-FM modulation internal excitation. Here, backlash, modulation time-varying mesh stiffness, and modulation transmission error are considered. Then the undamped natural mode was studied. Numerical simulation was made to reveal the dynamic characteristic of a spur gear under modulation condition. The internal excitation was shown to exhibit obvious modulation sideband because of the modulation time-varying mesh stiffness and modulation transmission error. The Runge-Kutta method was used to solve the equations for analyzing the dynamic characteristics with the effect of modulation internal excitation. The result revealed that the response under modulation excitation exhibited obvious modulation sideband. The response under nonmodulation condition was also calculated for comparison. In addition, an experiment was done to verify the prediction of the modulation sidebands. The calculated result was consistent with the experimental result.

The prokaryotic type II CRISPR/Cas9 system has been adapted to perform targeted genome editing in cells and model organisms. Here, we describe targeted gene deletion and replacement in human cells via the CRISPR/Cas9 system using two guide RNAs. The system effectively generated targeted deletions of varied length, regardless of the transcriptional status of the target gene. It is notable that targeted gene deletions generated via CRISPR/Cas9 and two guide RNAs resulted in the formation of correct junctions at high efficiency. Moreover, in the presence of a homology repair donor, the CRISPR/Cas9 system could guide precise gene replacement. Our results illustrate that the CRISPR/Cas9 system can be used to precisely and effectively generate targeted deletions or gene replacement in human cells, which will facilitate characterization of functional domains in protein-coding genes as well as noncoding regulatory sequences in animal genomes.

AIM:To investigate the protective mechanism of Gingko Biloba extract (EGb761) on the ability of retinal pigment epithelial (RPE) cells to resist light-induced damage in a comparative proteomics study.METHODS:Human RPE cells (ARPE-19) were randomly distributed to one of three groups:normal control (NC group) and light-damaged model without or with EGb761 group (M and ME groups, respectively). The light-damaged model was formed by exposing to white light (2 200±300)lx for 6h. The RPE cells in ME group were conducted with EGb 761 (100μg/mL) before light exposure. The soluble cellular proteins extracting from each groups were separated by two-dimensional electrophoresis and stained by silver staining. Different proteins in the profiles of the gels were analyzed by Image Master Software. Two-fold expressing protein spots were identified by Matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) mass spectrometry.RESULTS: NC, M and ME groups displayed 1 892±71, 2 145±23 and 2 216±85 protein spots, respectively. We identified 33 proteins with different expression levels between the NC and M groups, 25 proteins between the M and ME groups, and 11 proteins between the NC and ME groups. MALDI-TOF/TOF mass spectrometry successfully identified 16 proteins, including metabolic enzymes, cytoskeletal proteins, anti-oxidation proteins, and others.CONCLUSION:Differences in some important proteins, such as cathepsin B, heat shock protein, and cytochrome creductase, indicated that multiple pathways may be induced in light-damaged RPE cells and the protective effect of EGb761.

AIM:To investigate the efficacy and safety of needle revision combined with subconjunctival injection of 5-Fluorouracil(5-FU)for the treatment of early non-functioning blebs after Ex-PRESS glaucoma drainage device implantation.METHODS:The medical records of 18 cases(23 eyes)with non-functional blebs within postoperative 3mo treated with needle revision combined with subconjunctival injection of 5-FU after Ex-PRESS glaucoma drainage device implantation in our hospital were retrospectively analyzed. All cases were followed up for at least 6mo.The IOP, the changes of filtering blebs morphology before and after treatments and complications were analyzed. RESULTS:The IOP before and immediately, 1, 3, 6mo after treatments were 24.13±2.94, 15.13±4.93, 14.98±5.12, 15.18±3.77 and 15.54±5.07mmHg(1mmHg=0.133kPa)respectively. The IOP at every time point after treatments was significantly decreased compared with that before treatments(all PCONCLUSION:It is safe, convenient and effective to treat early non-functional blebs after Ex-PRESS glaucoma drainage device implantation by needle revision combined with subconjunctival injection of 5-FU around the filtering bleb.

AIM: To evaluate the clinical efficacy of intravitreous injection of Lucentis combined with argon laser photocoagulation on retinal macroaneurysm.METHODS: A retrospective observation about intravitreous injection of Lucentis combined with argon laser photocoagulation was performed on 9 patients(9 eyes)with retinal macroaneurysms with macular edema between January 2011 and July 2013. Through the collection of clinical data in patients best-corrected visual acuity, change of the retinal macroaneurysm, optical coherence tomography and fluoresce in fundus angiography before therapy and 1 mouth,3 mouths after therapy, comparative analysis the changes in best-corrected visual acuity and central macular retinal thickness(CMT)between before and after treatment.RESULTS: Followed for more than 3 months, all patients' best-corrected visual acuity were improved obviously, the difference was significant(PPCONCLUSION:Intravitreous injection of Lucentis combined with argon laser photocoagulation is effective and security to improving visual acuity of retinal macroaneurysms with macular edema.

The development and homeostasis of multicellular organisms relies on gene regulation within individual constituent cells. Gene regulatory circuits that increase the robustness of gene expression frequently incorporate microRNAs as post-transcriptional regulators. Computational approaches, synthetic gene circuits and observations in model organisms predict that the co-regulation of microRNAs and their target mRNAs can reduce cell-to-cell variability in the expression of target genes. However, whether microRNAs directly regulate variability of endogenous gene expression remains to be tested in mammalian cells. Here we use quantitative flow cytometry to show that microRNAs impact on cell-to-cell variability of protein expression in developing mouse thymocytes. We find two distinct mechanisms that control variation in the activation-induced expression of the microRNA target CD69. First, the expression of miR-17 and miR-20a, two members of the miR-17-92 cluster, is co-regulated with the target mRNA Cd69 to form an activation-induced incoherent feed-forward loop. Another microRNA, miR-181a, acts at least in part upstream of the target mRNA Cd69 to modulate cellular responses to activation. The ability of microRNAs to render gene expression more uniform across mammalian cell populations may be important for normal development and for disease.

Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR) signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.

Mature miRNAs can often be classified into large families, consisting of members with identical seeds (nucleotides 2 through 7 of the mature miRNAs) and highly homologous approximately 21-nucleotide (nt) mature miRNA sequences. However, it is unclear whether members of a miRNA gene family, which encode identical or nearly identical mature miRNAs, are functionally interchangeable in vivo.We show that mir-181a-1, but not mir-181c, can promote CD4 and CD8 double-positive (DP) T cell development when ectopically expressed in thymic progenitor cells. The distinct activities of mir-181a-1 and mir-181c are largely determined by their unique pre-miRNA loop nucleotides-not by the one-nucleotide difference in their mature miRNA sequences. Moreover, the activity of mir-181a-1 on DP cell development can be quantitatively influenced by nucleotide changes in its pre-miRNA loop region. We find that both the strength and the functional specificity of miRNA genes can be controlled by the pre-miRNA loop nucleotides. Intriguingly, we note that mutations in the pre-miRNA loop regions affect pre-miRNA and mature miRNA processing, but find no consistent correlation between the effects of pre-miRNA loop mutations on the levels of mature miRNAs and the activities of the mir-181a-1/c genes.These results demonstrate that pre-miRNA loop nucleotides play a critical role in controlling the activity of miRNA genes and that members of the same miRNA gene families could have evolved to achieve different activities via alterations in their pre-miRNA loop sequences, while maintaining identical or nearly identical mature miRNA sequences.

AIM: To study the efficacy of a single intravitreal injection of perfluoropropane(C3F8)in releasing vitreomacular traction. METHODS: Twelve eyes of 12 consecutive patients with vitreomacular traction received a single intravitreal injection of 0.3mL 100%(C3F8)were retrospectively analyzed. The best corrected vision acuity and the neural epithelium thickness of central macular were observed. RESULTS: One month following treatment, vitreomacular traction was released in 5 eyes(42%), mean final visual acuity(VA)improved 0.04 and mean central foveal thickness decreased by 69μm. The vision acuity before and after treatment were 0.20±0.07, 0.25±0.04 respectively.CONCLUSION: Intravitreal C3F8 injection could offer a minimally invasive alternative to pars plana vitrectomy in patients with vitreomacular traction.

Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR) signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1. [ABSTRACT FROM AUTHOR]

Major RNA products of a microRNA (miRNA) gene-the long primary transcript (pri-miRNA), the ∼70-nucleotide (nt) precursor miRNA (pre-miRNA), and the ∼21-nt mature miRNA-all contain the same sequence required for target gene recognition. Thus, it is intrinsically difficult to discern the contribution of individual RNA species or to rule out a function of miRNA precursor species in target repression. Here, we describe a novel approach to dissect the functional contribution of pri-miRNA without compromising important cellular pathways. We show that pri-let-7 has a direct function in target repression in the absence of properly processed mature let-7. Moreover, we show that loop nucleotides provide regulatory controls of the activity of pri-let-7 by modulating interactions between pri-let-7 and target RNAs in vitro and in vivo. Finally, we show that human let-7a-3 pri-miRNA can directly interact with target mRNAs. These findings illustrate that the regulatory information encoded in structured pri-miRNAs may be translated into function through direct interactions with target mRNAs. [ABSTRACT FROM AUTHOR]

A series of Al-Li-Cu alloys with copper content of 0 to 6 wt pct and lithium content of 2.5 wt pct were studied. The results showed that copper plays an important role in grain refining, homogenization, and aging, and significantly influences the mechanical properties and fracture behaviors of the alloys. With the addition of copper, the hardness and peak-aging time increase, and the tensile strength gradually increases to a maximum value with copper content of about 3 wt pct and decreases after that. However, elongation decreases constantly, and the crack roots increase and lead to early crack. The mechanism of mechanical properties and fracture behaviors of Al-Li-Cu alloy is also discussed. [ABSTRACT FROM AUTHOR]

We describe a strategy to obtain highly enriched long-term repopulating (LTR) hematopoietic stem cells (HSCs) from bone marrow side-population (SP) cells by using a transgenic reporter gene driven by a stem cell enhancer. To analyze the gene-expression profile of the rare HSC population, we developed an amplification protocol termed "constant-ratio PCR," in which sample and control cDNAs are amplified in the same PCR. This protocol allowed us to identify genes differentially expressed in the enriched LTR-HSC population by oligonucleotide microarray analysis using as little as 1 ng of total RNA. Endoglin, an ancillary transforming growth factor β receptor, was differentially expressed by the enriched HSCs. Importantly, endoglin-positive cells, which account for 20% of total SP cells, contain all the LTR-HSC activity within bone marrow SP. Our results demonstrate that endoglin, which plays important roles in angiogenesis and hematopoiesis, is a functional marker that defines LTR HSCs. Our overall strategy may be applicable for the identification of markers for other tissue-specific stem cells. [ABSTRACT FROM AUTHOR]

Investigates hot spot mutations common in protein-protein complexes within the interfaces of placental ribonuclease inhibitor with angiogenin and RNase A. Kinetic characterization of complexes; Binding energy; Structural analysis of the complexes.

Intronic microRNAs have been proposed to complicate the design and interpretation of mouse knockout studies. The endothelial-expressed Egfl7/miR-126 locus contains miR-126 within Egfl7 intron 7, and angiogenesis deficits have been previously ascribed to Egfl7 gene-trap and lacZ knock-in mice. Surprisingly, selectively floxed Egfl7Δ and miR-126Δ alleles revealed that Egfl7Δ/Δ mice were phenotypically normal, whereas miR-126Δ/Δ mice bearing a 289-nt microdeletion recapitulated previously described Egfl7 embryonic and postnatal retinal vascular phenotypes. Regulation of angiogenesis by miR-126 was confirmed by endothelial-specific deletion and in the adult cornea micropocket assay. Furthermore, miR-126 deletion inhibited VEGF-dependent Akt and Erk signaling by derepression of the p85β subunit of PI3 kinase and of Spred1, respectively. These studies demonstrate the regulation of angiogenesis by an endothelial miRNA, attribute previously described Egfl7 vascular phenotypes to miR-126, and document inadvertent miRNA dysregulation as a complication of mouse knockout strategies. [ABSTRACT FROM AUTHOR]

An abstract of the article "Dissecting MicroRNA-Mediated Gene Regulation and Function in T-Cell Development," by Tin Ky Mao and Chang-Zheng Chen is presented.

Understanding the consequences of tuning TCR signaling on selection, peripheral T cell function, and tolerance in the context of native TCR repertoires may provide insight into the physiological control of tolerance. In this study, we show that genetic ablation of a natural tuner of TCR signaling, mir-181a-1/b-1, in double-positive thymocytes dampened TCR and Erk signaling and increased the threshold of positive selection. Whereas mir-181a-1/b-1 deletion in mice resulted in an increase in the intrinsic reactivity of naive T cells to self-antigens, it did not cause spontaneous autoimmunity. Loss of mir-181a-1/b-1 dampened the induction of experimental autoimmune encephalomyelitis and reduced basal TCR signaling in peripheral T cells and their migration from lymph nodes to pathogenic sites. Taken together, these results demonstrate that tolerance can be modulated by microRNA gene products through the control of opposing activities in T cell selection and peripheral T cell function. [ABSTRACT FROM AUTHOR]