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Approximately 10%–15% of couples worldwide are infertile, and male factors account for approximately half of these cases. Teratozoospermia is a major cause of male infertility. Although various mutations have been identified in teratozoospermia, these can vary among ethnic groups. In this study, we performed whole‐exome sequencing to identify genetic changes potentially causative of teratozoospermia. Out of seven genes identified, one, ATP/GTP Binding Protein 1 (AGTPBP1), was characterized, and three missense changes were identified in two patients (Affected A: p.Glu423Asp and p.Pro631Leu; Affected B: p.Arg811His). In those two cases, severe sperm head and tail defects were observed. Moreover, AGTPBP1 localization showed a fragmented pattern compared to control participants, with specific localization in the neck and annulus regions. Using murine models, we found that AGTPBP1 is localized in the manchette structure, which is essential for sperm structure formation. Additionally, in Agtpbp1‐null mice, we observed sperm head and tail defects similar to those in sperm from AGTPBP1‐mutated cases, along with abnormal polyglutamylation tubulin and decreasing △−2 tubulin levels. In this study, we established a link between genetic changes in AGTPBP1 and human teratozoospermia for the first time and identified the role of AGTPBP1 in deglutamination, which is crucial for sperm formation. [ABSTRACT FROM AUTHOR]

Borneol dehydrogenase (BDH) catalyses the last step of the camphor biosynthetic pathway in plants and the first reaction in the borneol degradation pathway in soil microorganisms. Native or engineered BDH can be used to produce optically pure borneol and camphor. The recently reported apo-form crystal structure of BDH (PDB ID: 6M5N) from Pseudomonas sp. TCU-HL1 superimposes well with that of 3-quinuclidinone reductase (QR) (PDB ID: 3AK4) from Agrobacterium tumefaciens. QR catalyses the conversion of 3-quinuclidinone into (R)-3-(−)-quinuclidinol, an important chiral synthone for several drugs. However, the kinetic parameter, kcat, of QR was not determined in the previous reports even though both BDH and QR have various potential industrial applications. Here, we aimed to further characterise their structural and functional relationship. Recombinant QR with the native sequence was cloned, expressed in E. coli, and purified. We found that 3-quinuclidinone can be used as an alternative substrate for BDH. Only (R)-3-(−)-quinuclidinol was detected in this BDH-catalysed reaction. The results of 3 D molecular docking simulation show that 3-quinuclidinone and (+)-/(-)- borneol were docked to two different parts of the QR active site. In contrast, all three compounds are docked uniformly to the alpha-1 helix of BDH. There results explain why BDH can turnover 3-quinuclidinone, while QR can not act on (+)-/(-)-borneol. [ABSTRACT FROM AUTHOR]

A commercial three-detector single-photon emission computed tomography (SPECT) system that enables simultaneous acquisition of transmission and emission data without increasing patient scanning time has been designed and manufactured. This system produces a reconstructed attenuation coefficient distribution that can be used to correct for photon attenuation in the emission reconstruction. The three detectors with fan-beam collimators are mounted to the gantry in a triangular arrangement. A transmission line source assembly was mounted at the focal line of one of the detectors and controlled to move in synchrony with the opposing fan-beam collimator. Data from transmission and emission sources at different energies were acquired in one detector, while the other two simultaneously acquired emission data. A transmission source of 153Gd was used with 99mTc-labeled radiopharmaceuticals, and 57Co was used with 201Tl. Algorithms were developed to subtract crosstalk between transmission and emission energy windows in all three detectors. A transmission maximum-likelihood iterative algorithm was used to reconstruct the attenuation distribution, which was used in combination with an iterative maximum-likelihood expectation-maximization algorithm to compensate for the attenuation of the projection of the emission distribution. The results in phantom studies displayed greater uniformity of activity with attenuation-corrected reconstruction. This was demonstrated visually and quantitatively by using anterior-to-inferior ratios close to one and low spatial %rms error as a measure of improved uniformity. Index Terms - Anger gamma camera, attenuation correction, brain SPECT, cardiac SPECT, clinical imaging hardware, clinical imaging software, emission computed tomography, fan-beam tomography, iterative reconstruction, simultaneous transmission and emission imaging, single-photon emission computed tomography, SPECT, transmission computed tomography.

Transmission scans are an important part of the process of obtaining patient attenuation maps for accurate SPECT (single photon emission computed tomography) imaging. In order to avoid truncation of the projection data, asymmetric cone-beam imaging geometries were investigated. By using the Beacon[TM] SPECT system, it was shown that in the acquisition process transmission and emission imaging geometries can be different. Utilizing this new system, cone-beam transmission scans can be performed while the parallel collimators are attached for emission data acquisition. Patient and phantom studies were performed and compared with x-ray CT. A whole-body helical scan to obtain a whole-body attenuation map is also proposed. For helical asymmetric cone-beam geometries, at least two detectors are required in order to provide sufficient cone-beam data. If two detectors are used, they must have opposite geometries. Computer simulations were performed to demonstrate the feasibility of the proposed asymmetric helical cone-beam scanning geometry.

Objective: We investigate an optimization-based approach to image reconstruction from list-mode data in digital time-of-flight (TOF) positron emission tomography (PET) imaging. Method: In the study, the image to be reconstructed is designed as a solution to a convex, non-smooth optimization program, and a primal-dual algorithm is developed for image reconstruction by solving the optimization program. The algorithm is first applied to list-mode TOF-PET data of a typical count level from physical phantoms and a human subject. Subsequently, we explore the algorithm’s potential for image reconstruction in low-dose and/or fast TOF-PET imaging of practical interest by applying the algorithm to list-mode TOF-PET data of different, low-count levels from the same physical phantoms and human subject. Results: Visual inspection and quantitative-metric analysis reveal that the optimization reconstruction approach investigated can yield images with enhanced spatial and contrast resolution, suppressed image noise, and increased axial volume coverage over the reference images obtained with a standard clinical reconstruction algorithm especially for low-dose TOF-PET data. Significance: The optimization-based reconstruction approach can be exploited for yielding insights into potential quality upper bound of reconstructed images in, and design of scanning protocols of, TOF-PET imaging of practical significance. [ABSTRACT FROM PUBLISHER]