Functional and idling rotatory motion within F1-ATPase

ATP synthase mediates proton flow through its membrane portion, F₀, which drives the synthesis of ATP in its headpiece, F₁. The F₁-portion contains a hexagonal array of three subunits α and three β encircling a central subunit γ, that in turn interacts with a smaller and with F₀. Recently we reported that the application of polarized absorption recovery after photobleaching showed the ATP-driven rotation of γ over at least two, if not three, β. Here we extend probes of such rotation aided by a new theory for assessing continuous versus stepped, Brownian versus unidirectional molecular motion. The observed relaxation of the absorption anisotropy is fully compatible with a unidirectional and stepping rotation of γ over three equidistantly spaced angular positions in the hexagon formed by the alternating subunits α and β. The results strongly support a rotational catalysis with equal participation of all three catalytic sites. In addition we report a limited rotation of γ without added nucleotides, perhaps idling and of Brownian nature, that covers only a narrow angular domain.     

The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia

The serine proteases tissue plasminogen activator, plasmin, and thrombin and their receptors have previously been suggested to contribute to neuronal damage in certain pathological situations. Here we demonstrate that mice lacking protease-activated receptor 1 (PAR1) have a 3.1-fold reduction in infarct volume after transient focal cerebral ischemia. Intracerebroventricular injection of PAR1 antagonist BMS-200261 reduced infarct volume 2.7-fold. There are no detectable differences between PAR1-/- and WT mice in cerebrovascular anatomy, capillary density, or capillary diameter, demonstrating that the neuroprotective phenotype is not likely related to congenital abnormalities in vascular development. We also show that the exogenously applied serine proteases thrombin, plasmin, and tissue plasminogen activator can activate PAR1 signaling in brain tissue. These data together suggest that if blood-derived serine proteases that enter brain tissue in ischemic situations can activate PAR1, this sequence of events may contribute to the harmful effects observed. Furthermore, PAR1 immunoreactivity is present in human brain, suggesting that inhibition of PAR1 may provide a novel potential therapeutic strategy for decreasing neuronal damage associated with ischemia and blood-brain barrier breakdown.     

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children

CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.     

Skin as marker for collagen type I/III ratio in abdominal wall fascia

Purpose

An altered collagen metabolism could play an important role in hernia development. This study compared collagen type I/III ratio and organisation between hernia and control patients, and analysed the correlation in collagen type I/III ratio between skin and abdominal wall fascia.

Methods

Collagen organisation was analysed in Haematoxylin–Eosin sections of anterior rectus sheath fascia, and collagen type I/III ratio, by crosspolarisation microscopy, in Sirius-Red sections of skin and anterior rectus sheath fascia, of 19 control, 10 primary inguinal, 10 recurrent inguinal, 13 primary incisional and 8 recurrent incisional hernia patients.

Results

Compared to control patients [7.2 (IQR = 6.8–7.7) and 7.2 (IQR = 5.8–7.9)], collagen type I/III ratio was significantly lower in skin and anterior rectus sheath fascia of primary inguinal [5.2 (IQR = 3.8–6.3) and 4.2 (IQR = 3.8–4.7)], recurrent inguinal [3.2 (IQR = 3.1–3.6) and 3.3 (IQR = 3–3.7)], primary incisional [3.5 (IQR = 3–3.9) and 3.4 (IQR = 3.3–3.6)] and recurrent incisional hernia [3.2 (IQR = 3.1–3.9) and 3.2 (IQR = 2.9–3.2)] patients; also incisional and recurrent inguinal hernia had lower ratio than primary inguinal hernia patients. Furthermore, collagen type I/III ratio was significantly correlated (r = 0.81; P < 0.001) between skin and anterior rectus sheath fascia. Finally, collagen organisation was comparable between hernia and control patients.

Conclusions

Furthermore, in both skin and abdominal wall fascia of hernia patients, collagen type I/III ratio was lower compared to control patients, with more pronounced abnormalities in incisional and recurrent inguinal hernia patients. Importantly, collagen type I/III ratio in skin was representative for that in abdominal wall fascia.     

Effects of Dietary Exposure to Zearalenone (ZEN) on Carp (Cyprinus carpio L.)

The mycotoxin zearalenone (ZEN) is frequently contaminating animal feeds including feed used in aquaculture. In the present study, the effects of dietary exposure to ZEN on carp (Cyprinus carpio L.) were investigated. ZEN at three different concentrations (low dose: 332 µg kg⁻¹, medium dose: 621 µg kg⁻¹ and high dose: 797 µg kg⁻¹ final feed, respectively) was administered to juvenile carp for four weeks. Additional groups received the mycotoxin for the same time period but were fed with the uncontaminated diet for two more weeks to examine the reversibility of the ZEN effects. No effects on growth were observed during the feeding trial, but effects on haematological parameters occurred. In addition, an influence on white blood cell counts was noted whereby granulocytes and monocytes were affected in fish treated with the medium and high dose ZEN diet. In muscle samples, marginal ZEN and α-zearalenol (α-ZEL) concentrations were detected. Furthermore, the genotoxic potential of ZEN was confirmed by analysing formation of micronuclei in erythrocytes. In contrast to previous reports on other fish species, estrogenic effects measured as vitellogenin concentrations in serum samples were not increased by dietary exposure to ZEN. This is probably due to the fact that ZEN is rapidly metabolized in carp.     

Perforation of a stomach ulcer into the left heart ventricle. Case report and review of the literature

We present a case of peptic-ulcer perforation from the stomach into the left ventricle. The patient who had no prior cardiac or abdominal symptoms was admitted with gastrointestinal bleeding and the electrocardiographic signs of myocardial infarction of the posterior wall. After the bleeding had subsided for 5 hours the patient died suddenly from massive upper gastrointestinal bleeding. At autopsy a peptic ulcer was found 3 cm beneath the cardia in the anterior wall on the lesser curvature which had perforated dorsal from the papillar muscle into the left ventricle. In the literature 19 such ulcer perforations have been reported which are compared with the present case.     

Epidemiology of injuries during the Wheelchair Basketball World Championships 2018: A prospective cohort study

Several international sports federations have implemented a standardized injury reporting system during their championships. However, very few studies have investigated athletes with disabilities during major championships apart from the Paralympic Games. Therefore, the aim of this study was to assess the rate and characteristics of injuries during the Wheelchair Basketball World Championships 2018 (WBWC). This prospective cohort study was conducted during the WBWC held in Hamburg, Germany, from August 16 to August 26, 2018. Physicians or physiotherapists of all 28 participating teams (total 336 players) were asked to report all newly incurred injuries (with location, diagnosis, cause, and estimated duration of absence) daily on a standardized injury report form. Prevalence and incidence rates were calculated. Medical staff of 11 teams (132 players) reported 100 injuries, equivalent to 75.8 per 100 players (95% CI: 60.9-90.7) or 68.9 per 1000 player-days (55.4-82.4). Eight time-loss injuries were reported (6.1 injuries per 100 players [95% CI: 1.9-10.3] or 5.5 injuries per 1000 player-days [1.7-9.3]). More injuries were incurred during matches (n = 68) than during training. Most injuries affected the neck/cervical spine (16%), thoracic spine/upper back (15%), and shoulder (14%). The most frequent diagnosis was muscle spasms (25%), the most frequent cause was overuse (52%). A high rate of non–time-loss injuries compared to Paralympic Games was reported. Future studies should focus on the etiology of muscle spasms and further identify injury mechanisms of traumatic and overuse injuries in wheelchair basketball players to develop adequate preventive measures.