The Plasmodium NOT1-G paralogue is an essential regulator of sexual stage maturation and parasite transmission

Productive transmission of malaria parasites hinges upon the execution of key transcriptional and posttranscriptional regulatory events. While much is now known about how specific transcription factors activate or repress sexual commitment programs, far less is known about the production of a preferred mRNA homeostasis following commitment and through the host-to-vector transmission event. Here, we show that in Plasmodium parasites, the NOT1 scaffold protein of the CAF1/CCR4/Not complex is duplicated, and one paralogue is dedicated for essential transmission functions. Moreover, this NOT1-G paralogue is central to the sex-specific functions previously associated with its interacting partners, as deletion of not1-g in Plasmodium yoelii leads to a comparable or complete arrest phenotype for both male and female parasites. We show that, consistent with its role in other eukaryotes, PyNOT1-G localizes to cytosolic puncta throughout much of the Plasmodium life cycle. PyNOT1-G is essential to both the complete maturation of male gametes and to the continued development of the fertilized zygote originating from female parasites. Comparative transcriptomics of wild-type and pynot1-g− parasites shows that loss of PyNOT1-G leads to transcript dysregulation preceding and during gametocytogenesis and shows that PyNOT1-G acts to preserve mRNAs that are critical to sexual and early mosquito stage development. Finally, we demonstrate that the tristetraprolin (TTP)-binding domain, which acts as the typical organization platform for RNA decay (TTP) and RNA preservation (ELAV/HuR) factors is dispensable for PyNOT1-G’s essential blood stage functions but impacts host-to-vector transmission. Together, we conclude that a NOT1-G paralogue in Plasmodium fulfills the complex transmission requirements of both male and female parasites.

Prospective genomic surveillance reveals cryptic MRSA outbreaks with local to international origins among NICU patients.

MRSA infections cause significant morbidity and mortality in neonates. Clinical testing and routine surveillance screening identified an increase in neonates with MRSA colonization and infection which triggered prospective genomic surveillance. Here we show the complex transmission dynamics of MRSA in a NICU setting. Analyses revealed concurrent transmission chains affecting 16 of 22 MRSA-colonized patients (68%), and 3.1% of all NICU patients (n=517). Prematurity and longer lengths of stay increased risks for colonization. Intervals of up to 7 months occurred among some cluster-related isolates. 3 of 22 MRSA-colonized patients developed invasive infections with the colonizing strain. Comparisons with 21,521 isolates in the NCBI Pathogen Detection Resource revealed NICU strains to be distinct from MRSA seen locally and internationally. Integration of international strain datasets in analyses increased the resolution of strain clusters and helped rule-out suspected transmission events. Analyses also identified sequence type 1535 isolates, emergent in the Middle East, carrying a unique SCCmec with fusC and aac(6)-Ie/aph(2)-1a that provided a multi-drug resistant phenotype. NICU genomic surveillance identified cryptic MRSA colonization events, including NICU-endemic strains not linked with local hospital or international clusters, and has rich potential to guide improvements in infection prevention for this vulnerable patient population.

The Plasmodium NOT1-G Paralogue Acts as an Essential Nexus for Sexual Stage Maturation and Parasite Transmission

Productive transmission of malaria parasites hinges upon the execution of key transcriptional and post-transcriptional regulatory events. While much is now known about how specific transcription factors activate or repress sexual commitment programs, far less is known about the production of a preferred mRNA homeostasis following commitment and through the host-to-vector transmission event. Here we show that Plasmodium parasites have taken the unique approach to duplicate the NOT1 scaffold protein of the CAF1/CCR4/Not complex in order to dedicate one paralogue for essential transmission functions. Moreover, this NOT1-G paralogue is central to the sex-specific functions previously associated with its interacting partners, as deletion of not1-g in Plasmodium yoelii leads to a comparable or complete arrest phenotype for both male and female parasites. We show that, consistent with its role in other eukaryotes, PyNOT1-G localizes to cytosolic puncta throughout much of the Plasmodium life cycle. PyNOT1-G is essential to both the complete maturation of male gametes and to the continued development of the fertilized zygote originating from female parasites. Comparative transcriptomics of wild-type and pynot1-g- parasites shows that loss of PyNOT1-G leads to transcript dysregulation preceding and during gametocytogenesis, and shows that PyNOT1-G acts to preserve mRNAs that are critical to sexual and early mosquito stage development. Finally, we demonstrate that the tristetraprolin-binding domain, which acts as the typical organization platform for RNA decay (TTP) and RNA preservation (ELAV/HuR) factors is dispensable for PyNOT1-Gs essential blood stage functions but impacts host-to-vector transmission. Together, we conclude that Plasmodium has created and adapted a NOT1-G paralogue to fulfill the complex transmission requirements of both male and female parasites.

Development of a direct penetrating signal compensator in a distributed reception channel of a surveillance radar

General structure of a compensator of a direct penetrating signal in the diversed reception channel was developed. It is advisable to use the antenna and the receiver of the auxiliary diverted reception channel as an auxiliary antenna and an auxiliary channel. To be able to suppress the penetrating signal in the band of the receiving device of the surveillance radar, distance between the antennas should be up to 6 m. In general, the compensator of the penetrating signals should contain an adder in which the signals received by the main channel are added with the signals received by the auxiliary channel and sent through the amplifier with a corresponding complex transmission coefficient. The direct penetration signal compensator features the obligatory condition of adjusting the value of the complex transmission coefficient of the auxiliary channel signal amplifier. The direct penetration signal compensator is digital and uses the direct method of forming weighting coefficients without the use of feedback. To reduce the time of formation of weighting coefficients when using direct methods of calculation of the correlation matrix, the technology of parallel computational processes was used. The quality of operation of the direct penetrating signal suppression system in the diverted reception channel was evaluated. It was established that without the use of suppression of direct penetrating signals, their powerful response at the output of the matched filter mask weak echo signals. When using a direct penetrating signal in the main channel of the compensator, its response at the output of the matched filter is significantly reduced. This makes it possible to observe weak echoes against the background of a strong penetrating signal. The use of the developed direct penetrating signal compensator provides suppression of the direct penetrating signal from 57 dB to 70 dB

Synthesis of matched filters.

Methods for approximating the impulse response of a matched, physically realizable filter with the minimum required number of functional nodes are in thei focus of the paper. Methods for approximating the pulse characteristics of a matched filter are proposed, namely: approximation by causal physically realizable functions, which are the correlation functions of the pulse characteristics of low-pass filters (LPF) Butterworth; using the Fourier series to describe the complex transmission coefficient of the filter; direct use of the Fourier series to approximate the impulse response of a matched filter. As a result, the number of elements of the matched filter is significantly reduced.

Photonic generation of broadband RF phase shift with unbounded phase trajectory

<p>A means of applying an adjustable RF phase shift over a broad band of frequencies is a requirement of diverse application. Photonic solutions to the generation of RF phase shifts have receive significant attention for reasons of reduced cost, compactness and simplicity, yet the achievement of a phase shift extending beyond 360˚ range remains a challenge. The circuit architecture of a compact and broadband RF phase shifter with unbounded range based on two parallel DP-MZM architecture is presented and verified by simulation verification and emulated using off the shelf low frequency electronic components. Results demonstrate that the complex transmission of the phase shifter follows a trajectory that may encircle the origin an arbitrary number of times in either direction. The proposed architecture can be implemented using commercially available DP-QPSK modulator or can be integrated in any material platform that offers linear electro-optic phase modulators. </p><p><br></p><p><br></p>

Photonic generation of broadband RF phase shift with unbounded phase trajectory

<p>A means of applying an adjustable RF phase shift over a broad band of frequencies is a requirement of diverse application. Photonic solutions to the generation of RF phase shifts have receive significant attention for reasons of reduced cost, compactness and simplicity, yet the achievement of a phase shift extending beyond 360˚ range remains a challenge. The circuit architecture of a compact and broadband RF phase shifter with unbounded range based on two parallel DP-MZM architecture is presented and verified by simulation verification and emulated using off the shelf low frequency electronic components. Results demonstrate that the complex transmission of the phase shifter follows a trajectory that may encircle the origin an arbitrary number of times in either direction. The proposed architecture can be implemented using commercially available DP-QPSK modulator or can be integrated in any material platform that offers linear electro-optic phase modulators. </p><p><br></p><p><br></p>