Differential Neurotoxicity Related to Tetracycline Transactivator and TDP-43 Expression in Conditional TDP-43 Mouse Model of Frontotemporal Lobar Degeneration.

Frontotemporal lobar degeneration (FTLD) is among the most prevalent dementias of early-onset. Pathologically, FTLD presents with tauopathy or TAR DNA-binding protein 43 (TDP-43) proteinopathy. A biallelic mouse model of FTLD was produced on a mix FVB/129SVE background overexpressing wild-type human TDP-43 (hTDP-43) using tetracycline transactivator (tTA), a system widely used in mouse models of neurological disorders. tTA activates hTDP-43, which is placed downstream of the tetracycline response element. The original study on this transgenic mouse found hippocampal degeneration following hTDP-43 expression, but did not account for independent effects of tTA protein. Here, we initially analyzed the neurotoxic effects of tTA in postweaning age mice of either sex using immunostaining and area measurements of select brain regions. We observed tTA-dependent toxicity selectively in the hippocampus affecting the dentate gyrus significantly more than CA fields, whereas hTDP-43-dependent toxicity in bigenic mice occurred in most other cortical regions. Atrophy was associated with inflammation, activation of caspase-3, and loss of neurons. The atrophy associated with tTA expression was rescuable by the tetracycline analog, doxycycline, in the diet. MRI studies corroborated the patterns of atrophy. tTA-induced degeneration was strain-dependent and was rescued by moving the transgene onto a congenic C57BL/6 background. Despite significant hippocampal atrophy, behavioral tests in bigenic mice revealed no hippocampally mediated memory impairment. Significant atrophy in most cortical areas due solely to TDP-43 expression indicates that this mouse model remains useful for providing critical insight into co-occurrence of TDP-43 pathology, neurodegeneration, and behavioral deficits in FTLD.SIGNIFICANCE STATEMENT The tTA expression system has been widely used in mice to model neurological disorders. The technique allows investigators to reversibly turn on or off disease causing genes. Here, we report on a mouse model that overexpresses human TDP-43 using tTA and attempt to recapitulate features of TDP-43 pathology present in human FTLD. The tTA expression system is problematic, resulting in dramatic degeneration of the hippocampus. Thus, our study adds a note of caution for the use of the tTA system. However, because FTLD is primarily characterized by cortical degeneration and our mouse model shows significant atrophy in most cortical areas due to human TDP-43 overexpression, our animal model remains useful for providing critical insight on this human disease.

Investigating the Influence of Alkyl Chain Length in Poly(3-alkylthiophene)s Over the Thin Film Morphology by Optical and Electrical Characterization.

This paper studies the influence of alkyl-chain length in poly(3-alkylthiophene)s over the morphology of thin films and electrical parameters of the devices based on it. Regioregular poly(3-hexylthiophene) and poly(3-octylthiophene) were chosen as the semiconducting materials for the study. The morphological variations were studied by absorption spectroscopy, photoluminescence spectroscopy and X-ray diffraction study. The absorption and photoluminescence showed decreased coplanarity of main chain in poly(3-octylthiophene) over poly(3-hexylthiophene) and which was later confirmed using X-ray diffraction studies which clearly showed increased interchain spacing in case of poly(3-octylthiophene). The schottky diodes fabricated using these materials showed decreased mobility in poly(3-octylthiophene) based diodes as measured by space-charge limiting current method and photo-induced charge carrier extraction by linearly increasing voltage technique. Moreover, we observed a negative field dependence of mobility at room temperature in both the devices and attributed this to the presence of dominant positional disorder in poly(3-alkylthiophene)s. Furthermore, the photocurrent dependence on electric field too showed inferior mobility of poly(3-octylthiophene) based diodes.

Observation of Room Temperature Photoluminescence from Asymmetric CuGaO2/ZnO/ZnMgO Multiple Quantum Well Structures.

Asymmetric (CuGaO2/ZnO/ZnMgO) and symmetric (ZnMgO/ZnO/ZnMgO) multiple quantum well (MQW) structures were successfully fabricated using pulsed laser deposition (PLD) and their comparison were made. Efficient room temperature photoluminescent (PL) emission was observed from these MQWs and temperature dependent luminescence of asymmetric and symmetric MQWs can be explained using the existing theories. A systematic blue shift was observed in both MQWs with decrease in the confinement layer thickness which could be attributed to the quantum confinement effects. The PL emission from asymmetric and symmetric MQW structures were blue shifted compared to 150 nm thick ZnO thin film grown by PLD due to quantum confinement effects.

A double output pulsed high current thyratron driver.

The design and development of a double output pulsed high current driver for high power multi-grid thyratron is reported. The driver generates a 100 A current pulse of 2 µs duration with a compliance voltage of 1000 V for driving grid-1. A voltage pulse of 1200 V and 1.2 µs duration, superimposed with -150 V bias has been generated for driving grid-2. A delay of 1 µs between the two drive pulses is achieved with the use of a simple circuit. The rate of rise of voltage better than 10 kV/µs and jitter of ±3 ns is achieved for grid-2 pulse. This driver module has been successfully used in a 50 kV, CX1575C thyratron switched pulsed power supply to drive a multi-joule transversely excited atmospheric CO(2) laser at 100 Hz. The grid driver module can also be used for driving any high current thyratrons with minor external changes.

Nano-engineering by implanting Al2O3 nano particle as sandwiched scattering centers in between the Lao.5Pr0.2Sr0.3MnO3 thin film layers.

We report the use of non-magnetic Al2O3 nano particles deposited between two ferromagnetic La0.5Pr0.2Sr0.3MnO3 (LPSMO) manganite layers with an aim to improve the electronic and magnetotransport properties of the layered supper lattice grown on single crystal STO(100) substrate using Pulsed Laser Deposition (PLD) technique. We studied the electronic-transport and magnetotransport properties of this system wherein Al2O3 particles are expected to act as insulating scattering centers between two ferromagnetic LPSMO layers. The scattering due to additional scattering centers (insulating Al2O3 nano particles) could be controlled by application of external field, resulting in high magnetoresistance (MR) approximately 72% as compared to pristine LPSMO film (MR approximately 51%) at temperature close to their T(M) values. In addition, incorporation of nanostructured Al2O3 barrier between the two ferromagnetic LPSMO layers results in a 2-3 fold increase in the values of temperature coefficient of resistance (TCR) and the field coefficient of resistance (FCR) as compared to pristine LPSMO film, suggesting the use of such nanoengineered manganite layered structure for better device application.

In vitro occlusion of human fallopian tubes with Nd:YAG laser.

BACKGROUND: There is a need for an atraumatic, fast, reliable, inexpensive, reversible-on-demand method for female sterilization which is also free from side-effects. The use of an Nd:YAG laser for occlusion of human fallopian tubes in vitro was assessed for achieving these aims. METHODS: An in vitro study was performed on coagulation of fallopian tube tissue using continuous wave Nd:YAG laser. Posthysterectomy human uteri were exposed to laser radiation either directly through an optical fibre or through a sapphire contact probe at the ostia at different laser powers and inter-action times. RESULTS: Laser-induced tissue coagulation plugged the ostia in a clean, controlled and predictable manner. Microscopic examination of the coagulated tissue showed about 50 microns wide blind holes without any continuous channel; thus eliminating the possibility of passage of sperms through such a plug. The depth of coagulation along the lumen of the fallopian tubes increased linearly with the interaction time of the laser beam at a constant power, either by direct irradiation or through a contact probe. The maximum depth of coagulation was found to be about 3 mm in case of direct irradiation at a laser power of about 6.5 W and interaction time of 50 seconds. Beyond these values, charring occurred at the surface of the tissue. CONCLUSION: Nd:YAG laser might be a suitable means for female sterilization. Further studies in experimental and clinical settings would be required to confirm its utility.

Laparoscopic surgery in the developing world. An overview of the Indian scene.

We present experience of laparoscopic surgery commencing in 1972 with diagnostic laparoscopy in a Surgical Unit in Bombay. By 1990 we had completed 2800 diagnostic laparoscopies with no mortality, 0.08% complication rate, 85% positive diagnosis and an instrument cost of about Rs. 35 (US $ 1.2) per patient. We have over the past 5 years performed 890 laparoscopic cholecystectomies (LC) with no mortality, no blood transfusion, and one CBD injury. With reusable equipment, monopolar diathermy and selective cholangiography, LC is cost-efficient in a developing country. Over this period over 60 laparoscopic appendectomies were performed, with the use of catgut ligatures and self-made endo-loops. laparoscopic appendectomy is cost-effective under our conditions. We have done 46 hernia repairs, and by contrast find it far more expensive and with inferior results to standard hernia repair. Advanced laparoscopy for ulcer and reflux disease, bowel resection, retroperitoneal and thoracic laparoscopy are being given a trial in several centres in the developing world.

Occlusion of human fallopian tubes using a carbon dioxide laser-in vitro investigations.

The fallopian tube ostium can be occluded by laser coagulation. The penetration depth of an Nd:YAG laser of wavelength 1.06 µm is about three times more than that of a CO2 laser of wavelength 10.6 µm in the fallopian tube tissue but for deep coagulation, diffusion of the heat through the tissue plays a more Important role. Using a cw-CO2 Iaser, a coagulation depth of more than 1 mm is achieved in the interstitial fallopian tube near the uterine-oviduct junction at the laser power of 1 W and interaction time of 20 sec. Thermal analysis of the fallopian tube tissue revealed that the maximum temperature attained during coagulation was 105°C. The coagulated tissue was free from microholes. This in vitro experimental investigation indicates that it may be possible to perform female sterilization quickly and atraumatically using lasers via a hysteroscope.