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Purpose: To investigate the effects of 4 weeks high-intensity interval training in hypoxia on aerobic and anaerobic performance of 3-on-3 basketball players. Methods: In a randomised controlled trial, 15 female basketballers completed eight 1-h high-intensity training sessions in either normobaric hypoxia (hypoxic group n= 8, altitude 3052 m) or normoxia (normoxic group n= 7, sea-level). Results: After training, the hypoxic group increased their 1-min all-out shuttle run distance by 2.5% ± 2.3% (mean ± 95% CI, d= 0.83, P= 0.04), compared to the normoxic group 0.2% ± 2.3% (d= 0.06, P= 0.8), with the difference between groups being clinically worthwhile but not statistically significant (d= 0.77, P= 0.1). Distance covered in the Yo-Yo intermittent recovery test tended to increase in the hypoxic (32.5% ± 39.3%, d= 1.0, P= 0.1) but not normoxic group (0.3% ± 24.5%, d= 0.08, P= 0.9), with a non-significant change between groups (d= 0.9, P= 0.2). Compared to normoxia, the hypoxic group significantly increased subjective markers of stress (d= 0.53, P= 0.005), fatigue (d= 0.43, P= 0.005), and muscle soreness (d= 0.46, P= 0.01), which resulted in a lower perceived training performance in the hypoxic compared to the normoxic group (d= 0.68, P= 0.001). Conclusion: High-intensity interval training under hypoxic conditions likely improved 1-min all-out shuttle run ability in female basketball 3-on-3 players but also increased subjective markers of stress and fatigue which must be taken into consideration when prescribing such training.

Females as well as males can influence the outcome of sperm competition, and may do so through the anatomy of their reproductive tracts. Female Drosophila melanogasterstore sperm in two morphologically distinct organs: a single seminal receptacle and, normally, two spermathecae. These organs have different temporal roles in sperm storage. To examine the association between sperm storage organ morphology and sperm competition, we used a mutant type of female with three spermathecae. Although the common measure of sperm competition, P2, did not differ between females with two and three spermathecae, the pattern of sperm use over time indicated that female morphology did affect male reproductive success. The rate of offspring production by females with three spermathecae rose and fell more rapidly than by females with two spermathecae. If females remate or die before using up second male sperm, then second male reproductive success will be higher when they mate with females with three spermathecae. The results indicate that temporal patterns of sperm use as well as P2should be taken into account when measuring the outcome of sperm competition.

The platelet-derived growth factor alpha-receptor (PDGFRalpha) plays a vital role in the development of vertebrate embryos, since mice lacking PDGFRalpha die in mid-gestation. PDGFRalpha is expressed in several types of migratory progenitor cells in the embryo including cranial neural crest cells, lung smooth muscle progenitors and oligodendrocyte progenitors. To study PDGFRalpha gene regulation and function during development, we generated transgenic mice by pronuclear injection of a 380 kb yeast artificial chromosome (YAC) containing the human PDGFRalpha gene. The YAC transgene was expressed in neural crest cells, rescued the profound craniofacial abnormalities and spina bifida observed in PDGFRalpha knockout mice and prolonged survival until birth. The ultimate cause of death was respiratory failure due to a defect in lung growth, stemming from failure of the transgene to be expressed correctly in lung smooth muscle progenitors. However, the YAC transgene was expressed faithfully in oligodendrocyte progenitors, which was not previously observed with plasmid-based transgenes containing only upstream PDGFRalpha control sequences. Our data illustrate the complexity of PDGFRalpha genetic control, provide clues to the location of critical regulatory elements and reveal a requirement for PDGF signalling in prenatal lung growth, which is distinct from the known requirement in postnatal alveogenesis. In addition, we found that the YAC transgene did not prolong survival of Patch mutant mice, indicating that genetic defects outside the PDGFRalpha locus contribute to the early embryonic lethality of Patch mice.

The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10)?g] were either assigned as non-exercised controls or subjected to 30?min of treadmill exercise (grade, -16°; speed, 15?m?·?min -1), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery ( n?=?5–6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd +) were seldom detected in the TA. In the VI and S, higher proportions of MHCd + fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P?=?0.01). In S, MHCd + fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd + fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd + fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd + fibres were smaller (<2500?µm 2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd + fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.

Two identical polyamine peptide conjugate libraries were screened against the parasitic enzyme trypanothione reductase. One of these libraries was in a solution format, while the other was resin-based and was used in two resin-based screens (a diminution assay and a direct bead screening). Potent inhibitors (100 nM) of trypanothione reductase were identified both in the solution screen and in the resin-based screens when using the PEGA resin of Meldal. Resin screening of both types failed to work with TentaGel resin. Importantly there was excellent agreement between the solution and resin-based assays, suggesting both methods are reliable for the screening of combinatorial libraries.

Highly cross-linked azlactone functional supports were prepared by dispersion polymerization of 2-vinyl-4,4-dimethylazlactone (VDM), 2-hydroxyethyl methacrylate (HEMA), and trimethylolpropane trimethacrylate (TMPTMA). The supports were recovered in high yield and possessed high surface areas. Individual particles, which ranged from 10 to 300 μm in diameter, were irregularly shaped and comprised of filamentous strands. Support polarity was tailored through increases in the HEMA level in the polymer formulations and was quantified by a lipophilicity index derived from solvent partition data collected on the constituent monomers. Support reactivity, as determined by azlactone aminolysis and measured by IR, was found to increase linearly with increasing support polarity. This effect was shown to be independent of the support cross-link density.

We have developed a system for temperature-inducible killing of specific cells in the fruitfly Drosophila melanogaster. The system overcomes many of the limitations of existing cell ablation methods and is in principle applicable to any non-homeothermic eukaryote. Temperature-sensitive and cold-sensitive mutations in the ricin toxin A chain (RTA) of castor bean were generated in yeast. One cold-sensitive mutation, RAcs2, produced temperature-dependent ablation of eye cells in Drosophila when expressed under control of the eye-specific sev enhancer. At 29 degrees C, cell death was observed within 7 hours in the developing eye and no obvious toxic effects were observed elsewhere; at 18 degrees C, extremely low toxicity was observed. DNA sequencing of RAcs2 revealed a single amino acid substitution in the RTA active site cleft.

Abstract:  In Drosophila, P-GAL4 enhancer trap lines can target expression of a cloned gene, under control of a UASGAL element, to any cells of interest. However, additional expression of GAL4 in other cells can produce unwanted lethality or side-effects, particularly when it drives expression of a toxic gene product. To target the toxic gene product ricin A chain specifically to adult neurons, we have superimposed a second layer of regulation on the GAL4 control. We have constructed flies in which an effector gene is separated from UASGAL by a polyadenylation site flanked by two FRT sites in the same orientation. A recombination event between the two FRT sites, catalysed by yeast FLP recombinase, brings the effector gene under control of UASGAL. Consequently, expression of the effector gene is turned on in that cell and its descendants, if they also express GAL4. Recombinase is supplied by heat shock induction of a FLP transgene, allowing both timing and frequency of recombination events to be regulated. Using a lacZ effector (reporter) to test the system, we have generated labelled clones in the embryonic mesoderm and shown that most recombination events occur soon after FLP recombinase is supplied. By substituting the ricin A chain gene for lacZ, we have performed mosaic cell ablations in one GAL4 line that marks the adult giant descending neurons, and in a second which marks mushroom body neurons. In a number of cases we observed loss of one or both the adult giant descending neurons, or of subsets of mushroom body neurons. In association with the mushroom body ablations, we also observed misrouting of surviving axons.

The carbonyl compounds (I) are converted to the α‐amino nitriles (III) which are directly coupled with the acryloyl chlorides (IV) to produce the acrylamido nitriles (V).