Comprehensive Monosynaptic Rabies Virus Mapping of Host Connectivity with Neural Progenitor Grafts after Spinal Cord Injury.

Neural progenitor cells grafted to sites of spinal cord injury have supported electrophysiological and functional recovery in several studies. Mechanisms associated with graft-related improvements in outcome appear dependent on functional synaptic integration of graft and host systems, although the extent and diversity of synaptic integration of grafts with hosts are unknown. Using transgenic mouse spinal neural progenitor cell grafts expressing the TVA and G-protein components of the modified rabies virus system, we initiated monosynaptic tracing strictly from graft neurons placed in sites of cervical spinal cord injury. We find that graft neurons receive synaptic inputs from virtually every known host system that normally innervates the spinal cord, including numerous cortical, brainstem, spinal cord, and dorsal root ganglia inputs. Thus, implanted neural progenitor cells receive an extensive range of host neural inputs to the injury site, potentially enabling functional restoration across multiple systems

Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC

On the Limits of Analogy Between Self-Avoidance and Topology-Driven Swelling of Polymer Loops

The work addresses the analogy between trivial knotting and excluded volume in looped polymer chains of moderate length, $N<N_0$, where the effects of knotting are small. A simple expression for the swelling seen in trivially knotted loops is described and shown to agree with simulation data. Contrast between this expression and the well known expression for excluded volume polymers leads to a graphical mapping of excluded volume to trivial knots, which may be useful for understanding where the analogy between the two physical forms is valid. The work also includes description of a new method for the computational generation of polymer loops via conditional probability. Although computationally intensive, this method generates loops without statistical bias, and thus is preferable to other loop generation routines in the region $N<N_0$.Comment: 10 pages, 5 figures, supplementary tex file and datafil

Pengukuran Resistivitas Bahan Organik Superkonduktor β'-(BEDT-TTF)2ICl2 Dengan Metode Four Point Probe

Telah dilakukan pembuatan kristal β'-(BEDT-TTF)2ICl2 dengan proses elektro sintesis kimia selama 8 hari. Proses elektrolisis ini dilakukan di dalam incubator dengan arus 1.5 μA. Kristal yang dihasilkan berwarana hitam memanjang . Kristal ini bersifat bahan organik metal dimana BEDT-TTF sebagai kation dan ICl2 sebagai anion. Selanjutnya kristal ini dilakukan pengukuran resistivitas dengan menggunakan metode four point probe. Metode ini menggunakan kawat emas (Au) sebagai probe, dua probe sebagai sumber arus dan 2 probe lainya sebagai pengukur beda potensial. Hasil karakterisasi menunjukan penambahan resistivitas sesuai dengan penurunan temperatur. Hal ini dikibatkan pengaruh dari β', sehingga kristal ini memiliki bentuk satu dimensi. Oleh sebab itu kristal β'-(BEDT-TTF)2ICl2 ini bersifat antiferromagnetik insulator (Mott Insulator)

Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.

Neural progenitor cell (NPC) transplantation has high therapeutic potential in neurological disorders. Functional restoration may depend on the formation of reciprocal connections between host and graft. While it has been reported that axons extending out of neural grafts in the brain form contacts onto phenotypically appropriate host target regions, it is not known whether adult, injured host axons regenerating into NPC grafts also form appropriate connections. We report that spinal cord NPCs grafted into the injured adult rat spinal cord self-assemble organotypic, dorsal horn-like domains. These clusters are extensively innervated by regenerating adult host sensory axons and are avoided by corticospinal axons. Moreover, host axon regeneration into grafts increases significantly after enrichment with appropriate neuronal targets. Together, these findings demonstrate that injured adult axons retain the ability to recognize appropriate targets and avoid inappropriate targets within neural progenitor grafts, suggesting that restoration of complex circuitry after SCI may be achievable

Expanding the Repertoire of Optogenetically Targeted Cells with an Enhanced Gene Expression System

Optogenetics has been enthusiastically pursued in recent neuroscience research, and the causal relationship between neural activity and behavior is becoming ever more accessible. Here, we established knockin-mediated enhanced gene expression by improved tetracycline-controlled gene induction (KENGE-tet) and succeeded in generating transgenic mice expressing a highly light-sensitive channelrhodopsin-2 mutant at levels sufficient to drive the activities of multiple cell types. This method requires two lines of mice: one that controls the pattern of expression and another that determines the protein to be produced. The generation of new lines of either type readily expands the repertoire to choose from. In addition to neurons, we were able to manipulate the activity of nonexcitable glial cells in vivo. This shows that our system is applicable not only to neuroscience but also to any biomedical study that requires understanding of how the activity of a selected population of cells propagates through the intricate organic systems