TBD

ABCA1 activity in the RPE is unnecessary for RPE reverse cholesterol transport (RCT) and AMD pathophysiology

METHODS : Gene expression of ABCA1 and ApoA1 on human donor tissue and iPSC-RPE were examined by qPCR (n=3). Bulk RNAseq examined transcript changes in key RCT genes on donor retinas across different stages of disease progression. RNAscope probes (ACDBio) were designed against abca1 transcripts with appropriate mismatch controls. Neutral lipid stain with oil-red O on 10um cryo-sections of abca1 KO and wild type (WT) eyes (N= 5). Two siRNAs knocked down abca1 in iPSC-RPE cells to assess abca1 contribution to cholesterol efflux (n=3).

Expression profiles of potentially angio-modulative microRNAs in the mouse model of oxygen-induced retinopathy (OIR)

METHODS : To induce OIR, C57BL/6J mice were exposed to 75% oxygen from postnatal day (p) 7 to p12 and then maintained under normal room air conditions. Control mice were kept under room air conditions throughout. At p12, p17, and p25, one eye of each mouse was harvested to prepare retinal flatmounts to analyze retinal vascular changes. From the contralateral eye, total RNA was isolated and reverse transcribed into cDNA for relative quantification of miRNA expression using qRT-PCR.

[Not Available]

Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied.

Optimizing Precision Medicine for Breast Cancer Brain Metastases with Functional Drug Response Assessment

The development of novel therapies for brain metastases is an unmet need. Brain metastases may have unique molecular features that could be explored as therapeutic targets. A better understanding of the drug sensitivity of live cells coupled to molecular analyses will lead to a rational prioritization of therapeutic candidates. We evaluated the molecular profiles of 12 breast cancer brain metastases (BCBM) and matched primary breast tumors to identify potential therapeutic targets.

Comparative pathology of VIC01 isolate and Omicron variant of SARS-CoV-2 infection, including a rechallenge model, in the Golden Syrian hamster

Introduction: The emergence of variants such as Omicron has raised questions regarding their comparative pathogenicity, infectivity and ability to circumvent naturally acquired and vaccine-induced immunity. The Golden Syrian hamster (Mesocricetus auratus) has become the established model for studying SARS-CoV-2 infection, with endpoints providing discriminatory power for countermeasure efficacy. The Omicron variant was compared with ancestral SARS-CoV-2 (VIC01) to evaluate comparative disease severity and to investigate protection against rechallenge.

UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis

Hepatocyte apoptosis plays an essential role in the progression of nonalcoholic steatohepatitis (NASH). However, the molecular mechanisms underlying hepatocyte apoptosis remain unclear. Here, we identify UDP-glucose 6-dehydrogenase (UGDH) as a suppressor of NASH-associated liver damage by inhibiting RIPK1 kinase-dependent hepatocyte apoptosis. UGDH is progressively reduced in proportion to NASH severity. UGDH absence from hepatocytes hastens the development of liver damage in male mice with NASH, which is suppressed by RIPK1 kinase-dead knockin mutation.

Sustained remission of type 2 diabetes in rodents by centrally administered fibroblast growth factor 4

Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite the availability of multiple drugs for short-term management, sustained remission of T2D is currently not achievable pharmacologically. Intracerebroventricular administration of fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents, propelling intense research efforts to understand its mechanism of action. Whether other FGFs possess similar therapeutic benefits is currently unknown.

Neural mechanisms of comforting: Prosocial touch and stress buffering

Comforting is a crucial form of prosocial behavior that is important for maintaining social unity and improving the physical and emotional well-being of social species. It is often expressed through affiliative social touch toward someone in distress, providing relief for their distressed state. In the face of increasing global distress, these actions are paramount to the continued improvement of individual welfare and the collective good. Understanding the neural mechanisms responsible for promoting actions focused on benefitting others is particularly important and timely.

Isoflurane rapidly modifies synaptic and cytoskeletal phosphoproteomes of the supraoptic nucleus of the hypothalamus and the cortex

Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia and natural sleep.

Cytomembrane Trafficking Pathways of Connexin 26, 30, and 43

The connexin gene family is the most prevalent gene that contributes to hearing loss. Connexins 26 and 30, encoded by GJB2 and GJB6, respectively, are the most abundantly expressed connexins in the inner ear. Connexin 43, which is encoded by GJA1, appears to be widely expressed in various organs, including the heart, skin, the brain, and the inner ear. The mutations that arise in GJB2, GJB6, and GJA1 can all result in comprehensive or non-comprehensive genetic deafness in newborns.

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