Antibiotics limit adaptation of drug-resistant Staphylococcus aureus to hypoxia

Bacterial pathogens are confronted with a range of challenges at the site of infection, including exposure to antibiotic treatment and harsh physiological conditions, that can alter the fitness benefits and costs of acquiring antibiotic resistance. Here, we develop an experimental system to recapitulate resistance gene acquisition by Staphylococcus aureus and test how the subsequent evolution of the resistant bacterium is modulated by antibiotic treatment and oxygen levels, both of which are known to vary extensively at sites of infection. We show that acquiring tetracycline resistance was costly, reducing competitive growth against the isogenic strain without the resistance gene in the absence of the antibiotic, for S. aureus under hypoxic but not normoxic conditions. Treatment with tetracycline or doxycycline drove the emergence of enhanced resistance through mutations in an RluD-like protein-encoding gene and duplications of tetL, encoding the acquired tetracycline-specific efflux pump. In contrast, evolutionary adaptation by S. aureus to hypoxic conditions, which evolved in the absence of antibiotics through mutations affecting gyrB, was impeded by antibiotic treatment. Together, these data suggest that the horizontal acquisition of a new resistance mechanism is merely a starting point for the emergence of high-level resistance under antibiotic selection but that antibiotic treatment constrains pathogen adaptation to other important environmental selective forces such as hypoxia, which in turn could limit the survival of these highly resistant but poorly adapted genotypes after antibiotic treatment is ended

Repeating the Errors of Our Parents? Family-of-Origin Spouse Violence and Observed Conflict Management in Engaged Couples

Based on a developmental social learning analysis, it was hypothesized that observing parental violence predisposes partners to difficulties in managing couple conflict. Seventy-one engaged couples were assessed on their observation of parental violence in their family of origin. All couples were videotaped discussing two areas of current relationship conflict, and their cognitions during the interactions were assessed using a video-mediated recall procedure. Couples in which the male partner reported observing parental violence (male-exposed couples) showed more negative affect and communication during conflict discussions than couples in which neither partner reported observing parental violence (unexposed couples). Couples in which only the female partner reported observing parental violence (female- exposed couples) did not differ from unexposed couples in their affect or behavior. Female-exposed couples reported more negative cognitions than unexposed couples, but male-exposed couples did not differ from unexposed couples in their reported cognitions

X-RAY ABSORPTION STUDIES OF AMORPHOUS SEMICONDUCTORS

Two families of amorphous (a-) semiconductors are chosen to demonstrate current state-of-the-art techniques in x-ray absorption spectros copy (XAS). We first briefly review recent developments in XAS methods before limiting the discussion to tetrahedrally co-ordinated films (a-Si, a-Ge, and a-SixGe1-x:H with 0 < x < 1) and arsenic trisulfide (a-As2S3). The phenomenon of crystallization of a-Si and a-Ge as well as the ordering of these elemental a-semiconductors prior to the nucleation of microcrystallites is discussed in terms of XAS experiments. We review XAS studies of the role of H in determining the structure of a-SixGe1-x:H. Investigations of XAS on a-As2S3 are shown to result in : (1) an ability to use XAS to measure bond strengths ; (2) a better understanding of reversible photodarkening ; and, (3) development of a technique for crystallizing pure bulk As2S3 glass

ANALYSIS OF BOND STRENGTHS OF ARSENIC AND ARSENIC CHALCOGEN COMPOUNDS USING THE TEMPERATURE DEPENDENCE OF THE EXAFS

We present a study of the temperature dependence of the EXAFS of crystalline (c-) As. As2S3 and As4S4, amorphous (a-) As and glassy (g-) As2S3. Based on an Einstein mode, we find that for the first shell of these materials, the mean square relative displacement (MSRD) is related to the bond-stretching force constant. Our result indicates that As-As bonds in c- As are about 17% softer than those in a- As. The stretching forces of the As-S bonds in c- and g- As2S3 are quite similar. The calculation of bond strengths in c- As4S4 shows that As-S bonds are about 30% stronger than As-As bonds. This work underscores the fact that temperature dependent EXAFS data may be used to provide information about the nature and, in particular, the strength of local bonding

EXAFS STUDIES OF THERMOSTRUCTURAL AND PHOTOSTRUCTURAL CHANGES OF VAPOR-DEPOSITED AMORPHOUS As2S3 FILMS

We report the effects of thermal-annealing and light-soaking on the structure of amorphous (a-) As2S3 films. The EXAFS of near-stochiometric films were examined for as-deposited, thermally-annealed and light-soaked samples. The principle As-S feature increases slowly for spectra of all films, while a weak homopolar As-As feature decreases with both thermal-annealing and subsequent light-soaking. Slight changes are also seen in the higher shells. Our results imply that structural changes in a- As2S3 brought about by thermal-annealing and by light-soaking involve breaking, rearranging and remaking a significant fraction of the material's bonds

The continued value of central histopathological review of testicular tumours

Aims: Central histopathological review of testicular tumours prior to definitive treatment can have an important impact on patient management. This study was designed to assess the continued value of central review in the light of increasing subspecialization and increased numbers of consultant histopathologists.Materials and results: The original and review reports of 291 testicular cancer specimens from 1998 to 2002 were analysed, looking particularly at major diagnosis, vascular invasion and the tumour elements within non-seminomatous germ cell tumours (NSGCT). When a diagnosis was altered any effect on subsequent patient management was assessed. There was a discrepancy in tumour type in 11 cases (4%) compared with 6% in 1992–1997. The commonest change was from seminoma to NSGCT or combined germ cell tumour (5/11). There was also diagnostic difficulty with spermatocytic seminoma (3/11). The clinical management of all 11 cases was influenced as a result of the review diagnosis. Discrepancies in vascular invasion were noted in 13 of the 126 NSGCTs (10%) compared with 20% in 1992–1997. Differences in NSGCT tumour elements, though clinically less important, were frequent in both groups.Conclusions: There continues to be a small number of significant and clinically important errors identified following central histopathological review of testicular tumours. This study highlights the value of central review and supports its continued practice in the management of testicular tumours