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Papers by rachel li

Georgetown Journal of International Affairs

HIV positive adolescents are becoming a progressively more sizeable and prominent sub-group in th... more HIV positive adolescents are becoming a progressively more sizeable and prominent sub-group in the South African HIV/AIDS epidemic. As HAART becomes increasingly available, vertically infected children can be expected to survive into adolescence and adulthood. Additionally, sexual transmission of HIV remains a problem, and incidence and prevalence rates among South African youth are high. Experience from the developed world indicates that providing effective care and treatment for youth can be a challenging task. In light of the antiretroviral rollout in South Africa, this exploratory study aimed to identify the experiences and needs of adolescents growing up in care or on treatment for HIV in the Western Cape

OTA International: The Open Access Journal of Orthopaedic Trauma

This is a test release of the core of the Quantal Synaptic Optical Reconstruction (QuaSOR) Matlab... more This is a test release of the core of the Quantal Synaptic Optical Reconstruction (QuaSOR) Matlab pipeline for analysis of synaptic transmission and corresponding Matlab scripts for the analysis of synaptic nanostructures at the Drosophila neuromuscular junction. Includes scripts largely authored by Zachary Newman in the Isacoff Lab at UC Berkeley and used in submitted manuscript Newman et al., (2021) Determinants of synapse diversity revealed by super-resolution quantal transmission and active zone imaging. Please contact newmanza@gmail.com with any issues.

Cancers

Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroen... more Gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) are rare cancers consisting of neuroendocrine carcinomas (NECs) and neuroendocrine tumors (NETs), which have been increasing in incidence in recent years. Few cell lines and pre-clinical models exist for studying GEP NECs and NETs, limiting the ability to discover novel imaging and treatment modalities. To address this gap, we isolated tumor cells from cryopreserved patient GEP NECs and NETs and injected them into the flanks of immunocompromised mice to establish patient-derived xenograft (PDX) models. Two of six mice developed tumors (NEC913 and NEC1452). Over 80% of NEC913 and NEC1452 tumor cells stained positive for Ki67. NEC913 PDX tumors expressed neuroendocrine markers such as chromogranin A (CgA), synaptophysin (SYP), and somatostatin receptor-2 (SSTR2), whereas NEC1452 PDX tumors did not express SSTR2. Exome sequencing revealed loss of TP53 and RB1 in both NEC tumors. To demonstrate an application of these novel NEC ...

Natural Products and Drug Discovery, 2018

Abstract In this chapter, common inflammation processes and mediators are presented briefly befor... more Abstract In this chapter, common inflammation processes and mediators are presented briefly before a detailed study of potential natural product lead compounds on targeting the inflammation processes and mediators for the discovery and development of antiinflammatory agents with two approaches: traditional “one molecule one target one disease” and currently emerging “one molecule multiple targets several diseases.” The inflammatory processes outline the cellular and molecular changes of inflammatory responses, whereas the inflammatory mediators include those involved in arachidonic acid pathways, nuclear transcription factor κB (NF-κB) pathways, inducible nitric oxide, and proinflammatory cytokines. Natural products targeting the inflammation processes and mediators are surveyed in groups of phenolics, terpenes, and alkaloids. Finally, antiinflammatory natural products with multiple targets are highlighted by citing examples of curcumin, (−)-epigallocatechin-3-gallate, trans -resveratrol, quercetin, and racemosic acid. Mother nature has created these unique molecules, each possessing bioactivities against multiple molecular targets, including cyclooxygenases, lipoxygenases, microsomal PGE 2 synthase-1, NF-κB signaling, and inducible nitric oxide.

Nature Communications, 2022

Neural circuit function depends on the pattern of synaptic connections between neurons and the st... more Neural circuit function depends on the pattern of synaptic connections between neurons and the strength of those connections. Synaptic strength is determined by both postsynaptic sensitivity to neurotransmitter and the presynaptic probability of action potential evoked transmitter release (Pr). Whereas morphology and neurotransmitter receptor number indicate postsynaptic sensitivity, presynaptic indicators and the mechanism that sets Pr remain to be defined. To address this, we developed QuaSOR, a super-resolution method for determining Pr from quantal synaptic transmission imaging at hundreds of glutamatergic synapses at a time. We mapped the Pr onto super-resolution 3D molecular reconstructions of the presynaptic active zones (AZs) of the same synapses at the Drosophila larval neuromuscular junction (NMJ). We find that Pr varies greatly between synapses made by a single axon, quantify the contribution of key AZ proteins to Pr diversity and find that one of these, Complexin, suppre...

Evidence Based Validation of Traditional Medicines, 2021

The emergence of omics technologies has revolutionised modern biology and also offers promise to ... more The emergence of omics technologies has revolutionised modern biology and also offers promise to addressing epidemic chronic diseases including type 2 diabetes mellitus (T2DM). Sustained peripheral insulin resistance and an irreversible systemic alteration and progressive decline of physiological functions in T2DM patients are borne of modern unhealthy lifestyle and contribute to disability and mortality worldwide. Earlier-onset and prolonged disease state underscore the need for both prophylactic and ameliorating therapeutics to impact the chronicity of T2DM and progressive comorbidities. This complexity has not been solved with prolonged use of tissue-target screens for synthetic drug discovery. The modern disease of T2DM can be impacted with recognised antidiabetic agents derived from traditional medicines and phytochemicals. Exploit of phytochemicals employed in medicinal practices can now be validated with omics technologies. Constructive omics testing offers new and meaningful insights to improving drug discovery and implementation. This chapter reviews the application of genomics, transcriptomics, proteomics, metabolomics and network analysis to ascertain candidature of anti-diabetic agents arising from green tea, citrus, and garlic isolates including (À)-epigallocatechin gallate, tangeretin, and allicin. The restoration of the old natural products and new technologies will progress pharmacological and pathological insights into T2DM beyond current allopathic measures.

Fracture healing continues to pose challenges for researchers and clinicians in the field of trau... more Fracture healing continues to pose challenges for researchers and clinicians in the field of trauma and orthopaedic surgery. The future treatment strategies for fracture healing will most likely focus on the use of biologic and biochemical methods in combination with established fixation and mechanical methods. In this study, heparanase (HPSE), a mammalian endo-glycuronidase that promotes angiogenesis through cleavage of the extra cellular matrix (ECM)-heparan sulphate and mobilization of ECM resident growth factors, was investigated for its osteoblasts-stimulating effect. Osteoblast cells, originated from osteoporotic and healthy human subjects who underwent total knee replacement, were cultured and exposed to HPSE at a series of final concentrations of 1, 3, and 6μg/mL. The cell density, proliferation, alkaline phosphatase (ALP) production and specific activity, and expression of osteogenic genes were examined. A marked stimulating effect of HPSE in cell density and proliferation ...

SSRN Electronic Journal, 2021

Device-associated bacterial infections remain a clinical challenge. Present strategies to prevent... more Device-associated bacterial infections remain a clinical challenge. Present strategies to prevent bacterial infection are either toxic to healthy mammalian cells and tissue or involve high doses of antibiotics that can prompt long-term negative consequences in terms of side effects or drug resistance. An antibiotic-free coating strategy to prevent bacterial attachment and biofilm formation is presented, which promotes bone cell growth and moderates the dissolution kinetics of resorbable magnesium (Mg) biomaterials. Herein pure Mg substrates were coated with gallium doped strontium-phosphate through a chemical conversion process. Gallium was distributed in a graduated manner throughout the strontium-phosphate coating, with a compact structure and a gallium-rich surface. It was demonstrated that the coating protected the underlying Mg from significant degradation in minimal essential media at physiological conditions over 9 days. In terms of bacteria culture, the liberated gallium ions from the coatings upon Mg specimens, even though minute quantities, reduced the viability and biofilm formation of Gram-negative P. aeruginosa and E. coli – two important clinical strains causing infections. More importantly, the gallium dopants displayed minimal interference with the strontium-phosphate based coating which boosted osteoblasts and undermined osteoclasts, in in vitro co-cultures. This work provides a new biocompatible strategy to prevent bacterial infection and control the degradation behaviour of Mg-based orthopaedic implants, while preserving osteogenic features of the devices.

Molecular Genetics and Metabolism, 2021

ANZ Journal of Surgery, 2021

Renal ischemia–reperfusion injury (IRI) can lead to significant morbidity and mortality. It remai... more Renal ischemia–reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically. Riluzole, Lidocaine and Lamotrigine have been demonstrated to show anti‐ischaemic properties in other organs; however, their use has not been tested in the kidneys. We investigated Riluzole, Lidocaine and Lamotrigine for their preventive effects of renal IRI using a rat model.

In Taiwan, there are veterinary departments in each of the four national universities, yet no cen... more In Taiwan, there are veterinary departments in each of the four national universities, yet no central accrediting body similar to the American Veterinary Medical Association (AVMA) in the U.S. for all the 28 colleges. Disparities are also evident between both countries in the amount of tuition and fees a veterinary student is charged. In the U.S. tuition and fees amount to 9-10 times greater than that of Taiwan Bachelor of Veterinary Medicine (BVM) students. Furthermore, the ratio of new graduates to the U.S. population is around 1:115,000 whereas in Taiwan the ratio is about 1:92,000. Faculty size in Taiwan collegiate programs is smaller and salaries for collegiate faculty amount to only one-third to one-fourth those in the U.S. Paralleling the U.S. veterinary medical education system to Taiwan serves a method to foster a better understanding of the strengths and weaknesses in Taiwan. In the future, adopting a more in international viewpoint as well as hospital management regarding...

Investigative Ophthalmology & Visual Science, 2019

Reactive Oxygen Species, 2018

Our early work suggested that graphene quantum dots (GQDs) block Cu(II)/Cu(I) redox cycle in biol... more Our early work suggested that graphene quantum dots (GQDs) block Cu(II)/Cu(I) redox cycle in biological systems. Here we report that GQDs could also potently protect against copper redoxmediated oxidative DNA damage. Using Cu(II)/hydrogen peroxide, Cu(II)/hydroquinone, and Cu(II)/ascorbic acid as three biologically relevant systems for inducing oxidative DNA damage, we demonstrated that GQDs protected against the above system-induced DNA strand breaks in ϕx-174 plasmid DNA in a concentration-dependent manner. Notably, a significant protection was observed with GQDs at 1 μg/ml, and a nearly complete protection was shown with 10 and 100 μg/ml of GQDs. Using electron paramagnetic resonance (EPR) spectrometry in conjunction with α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN)-spin trapping, we showed that the above three systems generated hydroxyl radicals, as evidenced by the formation of a POBN-CH 3 radical adduct in the presence of 0.5 M dimethyl sulfoxide (DMSO). Consistent with the protective effects of GQDs on DNA damage, the hydroxyl radical formation was markedly reduced in the presence of GQDs in a concentration dependent manner. A nearly complete blockage of the hydroxyl radical generation was seen with GQDs at 10 and 100 μg/ml. Taken together, our results showed that GQDs potently protected against oxidative DNA damage. Considering the critical role of copper in cancer development, our findings might have important implications for cancer intervention with GQD-based nanotech modality.

Ophthalmic Genetics, 2021

ABSTRACT Background MED12-related disorders are a rare group of intellectual disability syndromes... more ABSTRACT Background MED12-related disorders are a rare group of intellectual disability syndromes with a broad range of phenotypic characteristics. The phenotypic spectrum of MED12-related disorders currently includes X-Linked Ohdo Syndrome, Lujan-Fryns Syndrome (LS), and FG syndrome type 1 (FG), also known as Opitz-Kaveggia Syndrome. The MED12 gene encodes the largest component of the mediator complex of RNA polymerase II, which is critical for recruiting activators and repressors to regulate the transcription of genes critical to growth, development, and differentiation. Methods We performed a systematic literature review of previously published cases to highlight the key ocular features in individuals with MED12-related disorders. In addition, we present a new case of a female patient with a de novo pathogenic c. 3866A>G, p.Q1289R variant. Ocular manifestations are not uncommon in MED12-related disorders, but have not been characterized in literature reports. Commonly reoccurring reported eye and ocular adnexa features within the spectrum include ptosis, downslanting palpebral fissures, and hypertelorism. Other less common findings include strabismus, astigmatism, and optic nerve hypoplasia. Results Our patient presented with developmental delay, mild hypotonia and dysmorphic features including frontal bossing, high arched palate, and syndactyly of the 2nd and 3rd toes bilaterally. Discussion Ocular manifestations identified in this patient included intermittent esotropia, hyperopic astigmatism, epicanthal folds and ptosis bilaterally.

SN Applied Sciences, 2020

Patient-specific surgical guides are increasingly demanded. Material Extrusion (ME) is a popular ... more Patient-specific surgical guides are increasingly demanded. Material Extrusion (ME) is a popular 3D printing technique to fabricate personalized surgical guides. However, the ME process usually generates deleterious surface topography which is not suitable for orthopaedic emergencies. We designed and optimized parametric combinations of a laser polishing approach as post process to improve the surface quality of ME-made poly-lactic acid (PLA) objects. In this study, we investigated the contribution of processing variables to the mechanical properties and the biocompatibilities in vitro of the ME-made PLA objects. Conventional surface grinding was conducted as comparison. The results demonstrate that the ME-made PLA samples exhibit good mechanical properties and favourable biocompatibility after being post processed using laser polishing. The post laser polishing, as a powerful tool in manufacture of ME-made PLA objects, will open a new approach with a great promise in its applicatio...

Journal of American Association for Pediatric Ophthalmology and Strabismus, 2021

Case Reports in Genetics, 2021