Dry swing training with a light bat increases bat speed

Baseball training usually includes dry swing training to improve batting ability. However, no consensus has been reached on the relationship between bat weight and the increase in post-dry swing training bat speed. We hypothesized that dry swing training with a light bat would increase post dry swing training bat speed. Therefore, the purpose of this study was to examine the effect of dry swing training with a light bat on post dry swing training bat speed by comparing a light bat group with a heavy bat group. A total of 34 healthy male students from a university baseball team were randomly divided into a light bat group (n = 17) and a heavy bat group (n = 17). Subjects performed 100 dry swings per day, twice a week for eight weeks. The light bat group performed dry swing training with a 10.6 oz bat and the heavy bat group with a 38.8 oz bat. Bat speed and muscle power were measured before and after the intervention. There was no interaction between the intervention and post dry swing training bat speed, knee extension strength, shoulder horizontal flexion, or hand grip strength. There was a main effect of the intervention on post dry swing training bat speed and shoulder horizontal flexion. Bat speed increased in both groups, but without significant group differences in intervention effects. Since light bat loads in this study were very low, dry swing training with a light bat may be more effective and less strenuous

Investigating Factors Related to Criminal Trips of Residential Burglars Using Spatial Interaction Modeling

This study used spatial interaction modeling to examine whether origin-specific and destination-specific factors, distance decay effects, and spatial structures explain the criminal trips of residential burglars. In total, 4041 criminal trips committed by 892 individual offenders who lived and committed residential burglary in Tokyo were analyzed. Each criminal trip was allocated to an origin–destination pair created from the combination of potential departure and arrival zones. The following explanatory variables were created from an external dataset and used: residential population, density of residential burglaries, and mobility patterns of the general population. The origin-specific factors served as indices of not only the production of criminal trips, but also the opportunity to commit crimes in the origin zones. Moreover, the criminal trips were related to the mobility patterns of the general population representing daily leisure (noncriminal) trips, and relatively large origin- and destination-based spatial spillover effects were estimated. It was shown that considering not only destination-specific but also origin-specific factors, spatial structures are important for investigating the criminal trips of residential burglars. The current findings could be applicable to future research on geographical profiling by incorporating neighborhood-level factors into existing models

Double C(sp³)–H Bond Functionalization Mediated by Sequential Hydride Shift/Cyclization Process: Diastereoselective Construction of Polyheterocycles

Described herein are two novel types of double C­(sp³)–H bond functionalizations triggered by a sequential hydride shift/cyclization process: (1) construction of a bicyclo[3.2.2]­nonane skeleton by a [1,6]- and [1,5]-hydride shift sequence and (2) sequential [1,4]- and [1,5]-hydride shift mediated construction of a linear tricyclic skeleton

Expression of mutant mRNA and protein in pancreatic cells derived from MODY3- iPS cells.

Maturity-onset diabetes of the young (MODY) is a heterozygous monogenic diabetes; more than 14 disease genes have been identified. However, the pathogenesis of MODY is not fully understood because the patients' pancreatic beta cells are inaccessible. To elucidate the pathology of MODY, we established MODY3 patient-derived iPS (MODY3-iPS) cells using non-integrating Sendai virus (SeV) vector and examined the mutant mRNA and protein of HNF1A (Hepatocyte Nuclear factor 1A) after pancreatic lineage differentiation. Our patient had a cytosine insertion in the HNF1A gene (P291fsinsC) causing frameshift and making a premature termination codon (PTC). We confirmed these MODY3-iPS cells possessed the characteristics of pluripotent stem cells. After we differentiated them into pancreatic beta cells, transcripts of HNF1A gene were cloned and sequenced. We found that P291fsinsC mutant transcripts were much less frequent than wild ones, but they increased after adding cycloheximide (CHX) to the medium. These results suggested that mutant mRNA was destroyed by nonsense-mediated mRNA decay (NMD). Moreover, we were not able to detect any band of mutant proteins in pancreatic lineage cells which were differentiated from MODY3-iPSCs by western blot (WB) analysis. A scarcity of the truncated form of mutant protein may indicate that MODY3 might be caused by a haplo-insufficiency effect rather than a dominant negative manner

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY

The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria. MraY is a membrane enzyme required for bacterial cell wall synthesis. Here, the authors modify sphaerimicins as antibacterials targeting it via structure-based design and synthesis through two key reactions, showing a platform for further development of MraY inhibitors as antibacterials

Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month- old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS IVA was treated with HSCT at 15 years of age and followed up for 10 years. Radiographs showed that the figures of major and minor trochanter appeared. Loud snoring and apnea disappeared. In all, 1 year after bone marrow transplantation, bone mineral density at L2-L4 was increased from 0.372 g/cm(2) to 0.548 g/cm(2) and was maintained at a level of 0.48 +/- 0.054 for the following 9 years. Pulmonary vital capacity increased approximately 20% from a baseline of 1.08 L to around 1.31 L over the first 2 years and was maintained thereafter. Activity of daily living was improved similar to the normal control group. After bilateral osteotomies, a patient can walk over 400 m using hip-knee-ankle-foot orthoses. This long-term observation of a patient shows that this treatment can produce clinical improvements although bone deformity remained unchanged. In conclusion, ERT is a therapeutic option for MPS IVA patients, and there are some indications that HSCT may be an alternative to treat this disease. However, as neither seems to be a curative therapy, at least for the skeletal dysplasia in MPS IVA patients, new approaches are investigated to enhance efficacy and reduce costs to benefit MPS IVA patients