In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70

To determine the role of interleukin-12 (IL-12) in primary and secondary immunity to a model intracellular bacterium, we have comprehensively evaluated infection with Francisella tularensis LVS in three murine models of IL-12 deficiency. Mice lacking the p40 protein of IL-12 (p40 knockout [KO] mice) and mice treated in vivo with neutralizing anti-IL-12 antibodies survived large doses of primary and secondary LVS infection but never cleared bacteria and exhibited a chronic infection. In dramatic contrast, mice lacking the p35 protein (p35 KO mice) of heterodimeric IL-12 readily survived large doses of primary sublethal LVS infection as well as maximal secondary lethal challenge, with only a slight delay in clearance of bacteria. LVS-immune wild-type (WT) lymphocytes produced large amounts of gamma interferon (IFN-gamma), but p35 KO and p40 KO lymphocytes produced much less; nonetheless, similar amounts of NO were found in all cultures containing immune lymphocytes, and all immune lymphocytes were equally capable of controlling intracellular growth of LVS in vitro. Purified CD4(+) and CD8(+) T cells from both WT and p40 KO mice controlled intracellular growth, even though T cells from WT mice produced much more IFN-gamma than those from p40 KO mice, and p40 KO T cells did not adopt a Th2 phenotype. Thus, while IL-12 p70 stimulation of IFN-gamma production may be important for bacteriostasis, IL-12 p70 is not necessary for appropriate development of LVS-immune T cells that are capable of controlling intracellular bacterial growth and for clearance of primary or secondary LVS infection. Instead, an additional mechanism dependent on the IL-12 p40 protein, either alone or in another complex such as the newly discovered heterodimer IL-23, appears to be responsible for actual clearance of this intracellular bacterium.     

Worker turnover because of spinal pathologies in the wards and outpatient clinics of the hospitals of Leno and Manerbo, Brescia]

A total of 306 employees of the hospitals of the Leno/Manerbio health area underwent clinical and anamnestic examination in order to ascertain the existence of degenerative diseases of the spine associated with "manual handling of loads" risk. The prevalences obtained for positive anamnestic threshold concerning the lumbosacral spine, the trend of total acute low back pain and of low back pain in the last year showed lower values compared to the entire national group and in any case lower or only slightly above the values for the reference group of non-exposed subjects. Therefore, in order to assess the real prevalences of disorders due to incorrect load handling in hospital environments, it is important to assess the presence of associated disorders of the spine also and especially in outpatients departments. In fact, unsuitable or unfit staff had recently been transferred from the wards to outpatients departments. 56 workers from outpatients departments underwent physical-anamnestic examination: 16 workers (4.5% of the entire group under study) from average-to-high risk wards were identified as suffering from degenerative disorders of the lumbosacral spine. Therefore the prevalence of unfit subjects from hospital wards, cancelling the effect of the turnover factor on outpatients departments, led to an almost twofold total frequency, which rose from 6.9% to 11.4%.     

Mapping of residues forming the voltage sensor of the voltage-dependent anion-selective channel.

Voltage-gated ion-channel proteins contain "voltage-sensing" domains that drive the conformational transitions between open and closed states in response to changes in transmembrane voltage. We have used site-directed mutagenesis to identify residues affecting the voltage sensitivity of a mitochondrial channel, the voltage-dependent anion-selective channel (VDAC). Although charge changes at many sites had no effect, at other sites substitutions that increased positive charge also increased the steepness of voltage dependence and substitutions that decreased positive charge decreased voltage dependence by an appropriate amount. In contrast to the plasma membrane K+ and Na+ channels, these residues are distributed over large parts of the VDAC protein. These results have been used to define the conformational transitions that accompany voltage gating of an ion channel. This gating mechanism requires the movement of large portions of the VDAC protein through the membrane.     

Proposal and preliminary validation of a check-list for the assessment of occupational exposure to repetitive movements of the upper lims

Over the last few years the Authors developed and implemented, a specific check-list for a "rapid" assessment of occupational exposure to repetitive movements and exertion of the upper limbs, after verifying the lack of such a tool which also had to be coherent with the latest data in the specialized literature. The check-list model and the relevant application procedures are presented and discussed. The check-list was applied by trained factory technicians in 46 different working tasks where the OCRA method previously proposed by the Authors was also applied by independent observers. Since 46 pairs of observation data were available (OCRA index and check-list score) it was possible to verify, via parametric and nonparametric statistical tests, the level of association between the two variables and to find the best simple regression function (exponential in this case) of the OCRA index from the check-list score. By means of this function, which was highly significant (R2 = 0.98, p < 0.0000), the values of the check-list score which better corresponded to the critical values (for exposure assessment) of the OCRA index looked for. The following correspondance values between OCRA Index and check-list were then established with a view to classifying exposure levels. The check-list "critical" scores were established considering the need for obtaining, in borderline cases, a potential effect of overestimation of the exposure level. On the basis of practical application experience and the preliminary validation results, recommendations are made and the caution needed in the use of the check-list is suggested.     

Gas exchange and metabolic transients in heart transplant recipients

In human heart transplant recipients (HTR) an impairment of the cardiac function was expected to reduce peak oxygen consumption and the kinetics of the adjustment of respiratory gas exchange at the onset of rectangular work loads. In nine patients (males, 23-59 yr) 1 to 8 months after cardiac transplantation average peak VO2 (VO2p) was 1.1 L.min-1 +/- 0.3 (SD), i.e. 45% of that of the controls, the corresponding VCO2p value being 1.4 L.min-1 +/- 0.3 (SD). Mean VEp was 62.9 L.min-1 +/- 20.3 (SD), mean HRp was 136 beats.min-1 +/- 11 (SD), i.e. 45 beats.min-1 higher than preexercise values. Mean [Lab]p was 7.7 mM +/- 1.7 (SD), indicating that at the heaviest load the HTR were performing work at or above their maximum aerobic power. During the initial 60-90 sec of the transition from rest to graded rectangular exercise HR did not change from the resting value, increasing thereafter almost linearly with time. The half time (t1/2) of the VE on-response was 112 sec +/- 30 (SD) (controls values: 59 sec +/- 16), that of the VCO2 on- was 95 sec +/- 18 (SD) (58 sec +/- 11), and that of the VO2 on- was 78 sec +/- 24 (SD) (38 sec +/- 6). In spite of the slow kinetics of the VO2 on- response, no massive accumulation of lactate was found in the early phase of exercise. The limitation of the peak exercise in HTR appears to be imposed by a reduced maximal cardiac performance. The slow readjustment of the latter, as expected from the sluggish heart rate response, however, does not impair substantially the work load transients nor reduce the anaerobic threshold.     

Border Cave and the beginning of the Later Stone Age in South Africa

The transition from the Middle Stone Age (MSA) to the Later Stone Age (LSA) in South Africa was not associated with the appearance of anatomically modern humans and the extinction of Neandertals, as in the Middle to Upper Paleolithic transition in Western Europe. It has therefore attracted less attention, yet it provides insights into patterns of technological evolution not associated with a new hominin. Data from Border Cave (KwaZulu-Natal) show a strong pattern of technological change at approximately 44-42 ka cal BP, marked by adoption of techniques and materials that were present but scarcely used in the previous MSA, and some novelties. The agent of change was neither a revolution nor the advent of a new species of human. Although most evident in personal ornaments and symbolic markings, the change from one way of living to another was not restricted to aesthetics. Our analysis shows that: (i) at Border Cave two assemblages, dated to 45-49 and >49 ka, show a gradual abandonment of the technology and tool types of the post-Howiesons Poort period and can be considered transitional industries; (ii) the 44-42 ka cal BP assemblages are based on an expedient technology dominated by bipolar knapping, with microliths hafted with pitch from Podocarpus bark, worked suid tusks, ostrich eggshell beads, bone arrowheads, engraved bones, bored stones, and digging sticks; (iii) these assemblages mark the beginning of the LSA in South Africa; (iv) the LSA emerged by internal evolution; and (v) the process of change began sometime after 56 ka.