Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution

Optimization and application of kilohertz electrical stimulation nerve block to autonomic neural circuits

Kilohertz Electrical Stimulation (KES) enables a rapid, reversible, and localized inhibition of peripheral nerve activity. Discovered in the early 1900’s, the utility and application of KES nerve block to treat symptoms of various disease states is nearly non-existent. Although a handful of clinical products utilize KES, it is highly debated and unknown if these products provide therapeutic benefit or, if they do, whether they do it by achieving a true conduction block of nerve activity or through other unknown mechanisms of action. Furthermore, many critical questions still re- main about the optimal electrodes, waveforms, and approaches necessary for clinical utility of KES nerve conduction block. In this thesis, I investigate multiple facets of KES nerve conduction block. In Part I, I present electrode optimizations that reduce energy requirements and ensure optimal KES nerve conduction block. I de- scribe critical geometry and materials considerations for electrode design, quantify charge characteristics of KES waveforms, and discuss how electrode characteristics can impact clinical device design. In Part II, I demonstrate the utility of KES in a variety of somatosensory and autonomic neural circuits to treat symptoms arising from immune and metabolic disorders. I show that KES nerve block can selectively block conduction in different fiber-types for selective inhibition of motor and sensory information. I then demonstrate the ability of KES nerve block to provide direction- specific stimulation of the vagus nerve for modulation of the innate immune system. Finally, I demonstrate the utility of KES nerve block for modulation of glucose metabolism. Collectively, the methods, tools, and results presented in this thesis significantly impact the design and clinical translation of KES therapies.Ph.D

RECENT METHOD DEVELOPMENT BY ANALYTICAL TECHNIQUES OF NEW FDA APPROVED RUGS IN 2021

In this present situation increase in the number of diseases has been observed and several new medications are invented and have been developed to treat various disorders, which are approved by FDA. But before these drugs come to market it must undergo several procedures. The validation and analytical process of a new drug development helps in ensuring its purity and reliability. This process involves the use of various analytical techniques to collect data about the drug. This review includes various types of analytical techniques such as ultraviolet-visible spectrophotometric and some chromatography methods (High-performance thin-layer chromatography, High-performance liquid chromatography, gas chromatography), hyphenation techniques such as LC-MS of the newly approved drug in the year of 2021 have been discussed

Open Ephys: An open-source, plugin-based platform for multichannel electrophysiology

[Objective] Closed-loop experiments, in which causal interventions are conditioned on the state of the system under investigation, have become increasingly common in neuroscience. Such experiments can have a high degree of explanatory power, but they require a precise implementation that can be difficult to replicate across laboratories. We sought to overcome this limitation by building open-source software that makes it easier to develop and share algorithms for closed-loop control.[Approach] We created the Open Ephys GUI, an open-source platform for multichannel electrophysiology experiments. In addition to the standard 'open-loop' visualization and recording functionality, the GUI also includes modules for delivering feedback in response to events detected in the incoming data stream. Importantly, these modules can be built and shared as plugins, which makes it possible for users to extend the functionality of the GUI through a simple API, without having to understand the inner workings of the entire application.[Main results] In combination with low-cost, open-source hardware for amplifying and digitizing neural signals, the GUI has been used for closed-loop experiments that perturb the hippocampal theta rhythm in a phase-specific manner.[Significance] The Open Ephys GUI is the first widely used application for multichannel electrophysiology that leverages a plugin-based workflow. We hope that it will lower the barrier to entry for electrophysiologists who wish to incorporate real-time feedback into their research.Peer reviewe

Pincer-Ligated Nickel Hydridoborate Complexes: the Dormant Species in Catalytic Reduction of Carbon Dioxide with Boranes

Nickel pincer complexes of the type [2,6-(R₂PO)₂C₆H₃]­NiH (R = ^tBu, <b>1a</b>; R = ⁱPr, <b>1b</b>; R = ^cPe, <b>1c</b>) react with BH₃·THF to produce borohydride complexes [2,6-(R₂PO)₂C₆H₃]­Ni­(η²-BH₄) (<b>2a</b>–<b>c</b>), as confirmed by NMR and IR spectroscopy, X-ray crystallography, and elemental analysis. The reactions are irreversible at room temperature but reversible at 60 °C. Compound <b>1a</b> exchanges its hydrogen on the nickel with the borane hydrogen of 9-BBN or HBcat, but does not form any observable adduct. The less bulky hydride complexes <b>1b</b> and <b>1c</b>, however, yield nickel dihydridoborate complexes reversibly at room temperature when mixed with 9-BBN and HBcat. The dihydridoborate ligand in these complexes adopts an η²-coordination mode, as suggested by IR spectroscopy and X-ray crystallography. Under the catalytic influence of <b>1a</b>–<b>c</b>, reduction of CO₂ leads to the methoxide level when 9-BBN or HBcat is employed as the reducing agent. The best catalyst, <b>1a</b>, involves bulky substituents on the phosphorus donor atoms. Catalytic reactions involving <b>1b</b> and <b>1c</b> are less efficient because of the formation of dihydridoborate complexes as the dormant species as well as partial decomposition of the catalysts by the boranes

Optimization of therapeutic benefit of tACS via closed-loop EEG feedback-controlled tACS.

<p>(A) Hard real-time closed-loop protocol used for feedback-controlled delivery of tACS. EEG are measured and amplified prior to sampling with RTXI while the subject opens and closes their eyes every 30 seconds. EEG data from international 10–20 system sites O2, A1, and A2 are processed in hard RT using a custom module written to measure the alpha band power within a one second window. The computed power is validated against a threshold criteria, which determines the tACS amplitude to be delivered. The output from RTXI is connected to an external current-controlled stimulation and isolation unit. Sample alpha-filtered EEG traces with and without feedback-controlled tACS are shown in (B). Feedback-controlled tACS (C) almost completely suppressed alpha band power in a targeted way (Ratio EC_<i>α</i> to EO_<i>α</i> = 1.03, <i>p</i> = 0.041). Dose-matched random tACS (D) also suppressed alpha band power (normalized random-No Stim = −0.31, <i>p</i> = 0.0183), but was less effective than feedback-controlled tACS (normalized feedback_<i>α</i>—random_<i>α</i> = −0.10, <i>p</i> = 0.0145). All figures obtained and modified with permission from [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005430#pcbi.1005430.ref014" target="_blank">14</a>].</p

Hard RT distorted auditory feedback system.

<p>(A) Simplified diagram of the acoustic feedback system. When not triggered (top), the system computes the root mean square (RMS) of the input signal. When the RMS exceeds the threshold, the system is triggered. When triggered (bottom), the system computes the spectrogram of the most recent 20ms of signal and computes the correlation coefficient of this spectrogram with the spectrogram of the template sound (e.g., song syllable). The template sound is detected when the correlation coefficient exceeds a threshold value; in this case, acoustic feedback can be generated. Both the input and the acoustic output are saved to the computer hard drive. (B) Spectrogram of the song of a Bengalese finch and the times of occurrence of one of the song syllables. The system was programmed to only detect the occurrences of the target syllable in real time, no acoustic feedback was generated. The detection times are shown as vertical red lines. Bottom: the system is detecting the target syllables (vertical red lines) and is generating acoustic feedback after detection. The acoustic feedback waveform is shown below. The feedback signal is one of the birdsong syllables; the acoustic feedback pickup by the microphone is visible on the spectrogram. The zoomed-in spectrogram of the template is shown on the right. (C) DAF increases the duration of the time interval between Bengalese finch song syllables. Histogram depicts the time intervals between two subsequent syllables in the song in the presence of DAF (blue) and without DAF (red). The means are: Δ<i>t</i>_<i>mean</i> = 74.8ms (control, <i>N</i> = 637 syllables) and Δ<i>t</i>_<i>mean</i> = 75.7ms (feedback, <i>N</i> = 97 syllables), the difference is statistically significant (<i>p</i> = 0.001, two-way Kolmogorov—Smirnov test). All figures obtained and modified with permission from [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005430#pcbi.1005430.ref038" target="_blank">38</a>].</p