Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat

Transformation of somatic cells with a set of embryonic transcription factors produces cells with the pluripotent properties of embryonic stem cells (ESCs). These induced pluripotent stem (iPS) cells have the potential to differentiate into any cell type, making them a potential source from which to produce cells as a therapeutic platform for the treatment of a wide range of diseases. In many forms of human retinal disease, including age-related macular degeneration (AMD), the underlying pathogenesis resides within the support cells of the retina, the retinal pigment epithelium (RPE). As a monolayer of cells critical to photoreceptor function and survival, the RPE is an ideally accessible target for cellular therapy. Here we report the differentiation of human iPS cells into RPE. We found that differentiated iPS-RPE cells were morphologically similar to, and expressed numerous markers of developing and mature RPE cells. iPS-RPE are capable of phagocytosing photoreceptor material, in vitro and in vivo following transplantation into the Royal College of Surgeons (RCS) dystrophic rat. Our results demonstrate that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis of photoreceptor outer segments. Long-term visual function is maintained in this model of retinal disease even though the xenografted cells are eventually lost, suggesting a secondary protective host cellular response. These findings have identified an alternative source of replacement tissue for use in human retinal cellular therapies, and provide a new in vitro cellular model system in which to study RPE diseases affecting human patients

Pengembangan Potensi TOGA di Desa Pucang Anom sebagai Wirausaha Minuman Herbal Celup dan Jelly Milkshake

Pucang Anom is one of the villages in Bondowoso which is known to have potential in agriculture. This can be proven by the breadth of land in Pucang Anom village, which almost 60% of the total is dominated by agricultural lands. This village has an abudant potential of famili medicinal plants (TOGA), but still underutilized and underestimated by the community. Even though TOGA can be processed into a product that has a high sale valus addition to the great benefits at the time of of the corona virus outbreak that is spreading through out the world. Therefore, KKN 04 Pucang Anom University of Jember on 6th of January until 19th of February 2020 had explored the potential in the village through the entepreneurship development of  TOGA as herbal beverage that rich in benefits. TOGA as a variety of its preparations that could be consumed by people invarious circles. The target of the program was to raise the enthusiasm of the community for enterpreneurship that was focused on processing technology and manufacturing products that did not yet exist in Pucang Anom village. Based on public response, it was known that 57% stated that they “really like” herbaldyed products and prossesed Herbal Jelly Milkshake, 100% said they werw “attracted” to the products, 95% said the were “innovative” products, and 100% stated thet the continuation of business potential was “needs to be continued”. Finally, the products won 1st place in the Product Expo of KKN Students of the University of Jember at 1st period in 2019/2020 academic year which was held on February 26, 2020

Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein

The Beclin 1 gene is a haplo-insufficient tumor suppressor and plays an essential role in autophagy. However, the molecular mechanism by which Beclin 1 functions remains largely unknown. Here we report the crystal structure of the evolutionarily conserved domain (ECD) of Beclin 1 at 1.6 Å resolution. Beclin 1 ECD exhibits a previously unreported fold, with three structural repeats arranged symmetrically around a central axis. Beclin 1 ECD defines a novel class of membrane-binding domain, with a strong preference for lipid membrane enriched with cardiolipin. The tip of a surface loop in Beclin 1 ECD, comprising three aromatic amino acids, acts as a hydrophobic finger to associate with lipid membrane, consequently resulting in the deformation of membrane and liposomes. Mutation of these aromatic residues rendered Beclin 1 unable to stably associate with lipid membrane in vitro and unable to fully rescue autophagy in Beclin 1-knockdown cells in vivo. These observations form an important framework for deciphering the biological functions of Beclin 1

Dendritic Slow Dynamics Enables Localized Cortical Activity to Switch between Mobile and Immobile Modes with Noisy Background Input

Mounting lines of evidence suggest the significant computational ability of a single neuron empowered by active dendritic dynamics. This motivates us to study what functionality can be acquired by a network of such neurons. The present paper studies how such rich single-neuron dendritic dynamics affects the network dynamics, a question which has scarcely been specifically studied to date. We simulate neurons with active dendrites networked locally like cortical pyramidal neurons, and find that naturally arising localized activity – called a bump – can be in two distinct modes, mobile or immobile. The mode can be switched back and forth by transient input to the cortical network. Interestingly, this functionality arises only if each neuron is equipped with the observed slow dendritic dynamics and with in vivo-like noisy background input. If the bump activity is considered to indicate a point of attention in the sensory areas or to indicate a representation of memory in the storage areas of the cortex, this would imply that the flexible mode switching would be of great potential use for the brain as an information processing device. We derive these conclusions using a natural extension of the conventional field model, which is defined by combining two distinct fields, one representing the somatic population and the other representing the dendritic population. With this tool, we analyze the spatial distribution of the degree of after-spike adaptation and explain how we can understand the presence of the two distinct modes and switching between the modes. We also discuss the possible functional impact of this mode-switching ability

Draft genome sequence of a New Zealand rickettsia-like organism isolated from farmed Chinook salmon

We report here the draft genome sequence of a rickettsia-like organism, isolated from a New Zealand Chinook salmon farm experiencing high mortality. The genome is approximately 3 Mb in size, has a G+C content of approximately 39.2%, and is predicted to contain 2,870 coding sequences

Developing high throughput quantitative PCR assays for diagnosing Ikeda and other Theileria orientalis types common to New Zealand in bovine blood samples

<div><p></p><p>AIMS: To develop rapid, quantitative PCR (qPCR) assays using high resolution melt (HRM) analysis and type-specific TaqMan assays for identifying the prevalent types of <i>Theileria orientalis</i> found in New Zealand cattle; and to evaluate their analytical and diagnostic characteristics compared with other assays for <i>T. orientalis</i>.</p><p>METHODS: Nucleotide sequences aligned with <i>T. orientalis</i> Buffeli, Chitose and Ikeda types, obtained from DNA extracted from blood samples from infected cattle, were used to design HRM and type-specific probe-based qPCR assays. The three type-specific assays were also incorporated into a single-tube multiplex qPCR assay. These assays were validated using DNA extracted from blood samples from cattle in herds with or without clinical signs of <i>T. orientalis</i> infection, other veterinary laboratory samples, as well as plasmids containing <i>T. orientalis</i> type-specific sequences. Diagnostic specificity (DSp) and sensitivity (DSe) estimates for the qPCR assays were compared to blood smear piroplasm results, and other PCR assays for <i>T. orientalis</i>. Copy number estimates of Ikeda DNA in blood were determined from cattle exhibiting anaemia using the Ikeda-specific qPCR assay.</p><p>RESULTS: The <i>T. orientalis</i> type-specific and the HRM qPCR assays displayed 100% analytical specificity. The Ikeda-specific qPCR assay exhibited linearity (R²=0.997) with an efficiency of 94.3%. Intra-assay CV were ≤0.08 and inter-assay CV were ≤0.095. For blood samples from cows with signs of infection with <i>T. orientalis</i>, the DSp and DSe of the multiplex probe qPCR assay were 93 and 96%, respectively compared with blood smears, and 97 and 100%, respectively, compared with conventional PCR assays. For the Ikeda-specific qPCR assay, the number of positive samples (n=66) was slightly higher than a conventional PCR assay (n=64). The concentration of Ikeda genomes in blood samples from 41 dairy cows with signs of infection with <i>T. orientalis</i> ranged between 5.6×10⁴ and 3.3×10⁶ genomes per µL of blood.</p><p>CONCLUSIONS: All qPCR assays had improved specificity and sensitivity over existing conventional PCR assays for diagnosis of <i>T. orientalis</i> Ikeda. The burden of Ikeda DNA in blood was demonstrated using an Ikeda-specific qPCR assay with titrated synthetic gene target.</p><p>CLINICAL RELEVANCE: Adoption of high-throughput DNA extraction and qPCR reduced <i>T. orientalis</i> and Ikeda diagnosis times. The Ikeda-specific qPCR assay provides a specific diagnosis for Ikeda in animals with signs of infection with <i>T. orientalis</i> and can be used to monitor the parasite load of Ikeda in blood.</p></div

In vivo growth and genomic characterization of rickettsia-like organisms isolated from farmed Chinook salmon (Oncorhynchus tshawytscha ) in New Zealand

A rickettsia‐like organism, designated NZ‐RLO2, was isolated from Chinook salmon (Oncorhynchus tshawytscha) farmed in the South Island, New Zealand. In vivo growth showed NZ‐RLO2 was able to grow in CHSE‐214, EPC, BHK‐21, C6/36 and Sf21 cell lines, while Piscirickettsia salmonis LF‐89T grew in all but BHK‐21 and Sf21. NZ‐RLO2 grew optimally in EPC at 15°C, CHSE‐214 and EPC at 18°C. The growth of LF‐89 T was optimal at 15°C, 18°C and 22°C in CHSE‐24, but appeared less efficient in EPC cells at all temperatures. Pan‐genome comparison of predicted proteomes shows that available Chilean strains of P. salmonis grouped into two clusters (p‐value = 94%). NZ‐RLO2 was genetically different from previously described NZ‐RLO1, and both strains grouped separately from the Chilean strains in one of the two clusters (p‐value = 88%), but were closely related to each other. TaqMan and Sybr Green real‐time PCR targeting RNA polymerase (rpoB) and DNA primase (dnaG), respectively, were developed to detect NZ‐RLO2. This study indicates that the New Zealand strains showed a closer genetic relationship to one of the Chilean P. salmonis clusters; however, more Piscirickettsia genomes from wider geographical regions and diverse hosts are needed to better understand the classification within this genus