Although the role of the epididymis, a male accessory sex organ, in sperm maturation has been established for nearly four decades, the maturation process itself has not been linked to a specific molecule of epididymal origin. Here we show that Bin1b, a rat epididymis-specific beta-defensin with antimicrobial activity, can bind to the sperm head in different regions of the epididymis with varied binding patterns. In addition, Bin1b-expressing cells, either of epididymal origin or from a Bin1b-transfected cell line, can induce progressive sperm motility in immotile immature sperm. This induction of motility is mediated by the Bin1b-induced uptake of Ca(2+), a mechanism that has a less prominent role in maintaining motility in mature sperm. In vivo antisense experiments show that suppressed expression of Bin1b results in reduced binding of Bin1b to caput sperm and in considerable attenuation of sperm motility and progressive movement. Thus, beta-defensin is important for the acquisition of sperm motility and the initiation of sperm maturation.

Herpesvirus lytic DNA replication requires both the cis-acting element, the origin, and trans-acting factors such as virally encoded origin-binding protein and DNA replication enzymes. Recently, the origins of lytic DNA replication (ori-Lyt) in Kaposi's sarcoma-associated herpesvirus (KSHV) have been identified and a virally encoded bZip protein, K8, has been shown to specifically bind to the origin. To map cis-acting elements within KSHV ori-Lyt that are required for DNA replication function and to define the nature of K8 bZip protein binding to the origin, we constructed consecutive internal deletion mutations across the core domain of a KSHV ori-Lyt and tested them for DNA replication function in a transient replication assay. This mutagenesis study allowed the identification of four components within the ori-Lyt, and all were indispensable for ori-Lyt function. The first component contains eight CCAAT/enhancer binding protein (C/EBP) binding motifs that organize as four spaced C/EBP palindromes. Each palindrome contains two head-to-head CCAAT consensus motifs that are separated by a 13-or 12-bp space sequence. Substitution mutagenesis of these C/EBP motifs showed that these C/EBP palindromes are required for both K8 binding and ori-Lyt-dependent DNA replication. The second component is an 18-bp AT palindrome, which is essential for ori-Lyt function. The third component was determined to be a 32-bp previously unidentified sequence and is required for DNA replication. The last component consists of an open reading frame 50 (ORF50)/Rta responsive element (RRE) and a TATA box. We showed that the binding of an ORF50/Rta protein to the RRE was essential for ori-Lyt-dependent DNA replication. The presence of a functional RRE and a downstream TATA box suggested that this region serves as an ORF50/Rta-dependent promoter and a transcription event may be necessary for ori-Lyt-dependent DNA replication. Using a luciferase reporter system, we demonstrated that the region of the RRE and TATA box constitutes an ORF50/Rta-dependent promoter. Furthermore, a polyadenylated RNA of 1.4 kb was identified downstream of the promoter.As a gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV) has two alternative life cycles, namely latent and lytic replication cycles (14, 16). During latency, only a limited number of viral genes are expressed and no infectious virus is produced. In latently infected cells, multiple copies of the viral genome are maintained as extrachromosomal episomes (plasmids) and are replicated in synchrony with cell division (3). The terminal repeat sequence in the KSHV genome is necessary and sufficient for episome persistence and likely serves as the origin of latent plasmid replication (ori-P) (2). Virally encoded latency-associated nuclear antigen specifically binds to cis-acting terminal repeat DNA and acts in trans on the ori-P to mediate episome persistence (2). When latency is disrupted, KSHV switches to a lytic life cycle (14, 16). In the lytic phase, the virus expresses most or all of its ge...

Ketamine abusers frequently presented with upper GI symptoms, the commonest of which is epigastric pain (73% of abusers). Abstinence from ketamine abuse can lead to the relief of symptoms, which is an important message for ketamine abusers.

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The Hong Kong Link Road (HKLR) is part of the prominent structure, Hong Kong-Zuhai-Macao Bridge (HZMB), connecting 3 vibrant cities in Southern China. The works which are administered under Highways Department of HKSAR comprises design and construction of approximately 9km of viaducts. About 7km of the viaducts are marine structures with three navigation channels. The basic structural form of the viaducts is precast segmental prestressed concrete box girder. The span length of the viaducts ranges from 35m to 180m. Balanced cantilever method is selected due to the variability of the span lengths and flexibility in construction. The piers consist of both castinsitu and precast concrete structures. The viaducts are supported on bored piles with diameters ranging from 2.2m to 2.8m. Foundation in areas with complex geology such as fault zones has posed a major challenge to the job. Some piles are over 100m long due to complex geology. This paper presents the challenges and solutions employed in the design and construction of the viaducts. It describes the prestressed schemes employed in both the decks and piers with special details used in the formation of monolithic deck-column connections. The three main Challenges on the project were the erection in open sea, the vicinity of the Airport and enverinmental constraints.