X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle

Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called "troponin bridges," by analyzing real-time X-ray diffraction "movies" from sinusoidally stretch-activated Lethocerus muscles. Observed changes in X-ray reflections arising from myosin heads, actin filaments, troponin, and tropomyosin were consistent with the hypothesis that troponin bridges are the key agent of mechanical signal transduction. The time-resolved sequence of molecular changes suggests a mechanism for stretch activation, in which troponin bridges mechanically tug tropomyosin aside to relieve tropomyosin's steric blocking of myosin-actin binding. This enables subsequent force production, with cross-bridge targeting further enhanced by stretch-induced lattice compression and thick-filament twisting. Similar linkages may operate in other muscle systems, such as mammalian cardiac muscle, where stretch activation is thought to aid in cardiac ejection.     

Massive right-sided colon diverticular bleeding complicated by the transfusion related acute lung injury (TRALI)

Colonic diverticulosis is a condition which causes extensive bleeding of the lower gastrointestine in 40?C50% of cases. In particular, right-sided diverticulosis, although uncommon requires lifesaving colectomy. Transfusion related acute lung injury (TRALI) is a transfusion reaction, which can occur after administration of various blood products. Although life threatening, it can be completely reversed usually within 72 to 96 hours. Here, we report a case of a young Caucasian male hospitalized due to severe anemia, hematochezia and extensive blood loss, all due to lower gastrointestinal hemorrhage from right-sided diverticulosis. These conditions were overlooked endoscopically and diagnosed then treated surgically with the right-sided hemicolectomy. During postoperative course, four hours after the last transfusion, patient developed fever, hypoxia and noncardiogenic pulmonary oedema, but made complete recovery through aggressive oxygen support within 96 hours. The aim of this case was to review current literature, to draw attention to a serious and under-diagnosed transfusion reaction, as well as discuss possible explanations for the diagnostic difficulties that occurred in this case.     

Clinical characteristics of infections caused by <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> P1 genotypes in children

Mycoplasma pneumoniae (M. pneumoniae) isolates can be classified into two major genetic groups, P1 type 1 (MP1) and P1 type 2 (MP2), based on the DNA sequence of the P1 adhesion protein gene. The aim of our study was to determine if M. pneumoniae P1 genotype is associated with disease manifestation and severity of acute M. pneumoniae infection. We compared epidemiological and clinical data of children infected with either MP1 or MP2. In addition, we separately analysed data of patients presenting with individual manifestations of M. pneumoniae infection. Data of 356 patients infected with MP1 were compared with those of 126 patients infected with MP2. MP2-infected children presented with higher median baseline C-reactive protein levels and were admitted to the hospital more often. The distribution of P1 genotype varied among groups of patients with different manifestations of M. pneumoniae infection. MP2 was more common than MP1 among patients with neurological and cardiovascular manifestations, whereas MP1 was more prevalent in other manifestations. The results from our large cohort indicate that the two P1 subtypes may have different pathogenic potential and that infections with MP2 strains could be more virulent than those with MP1 strains.     

Longitudinal changes in cognition in young adult cannabis users

Introduction: Adolescent cannabis use (CU) is associated with impaired attention, executive function, and verbal learning/memory. These associations are generally observed in cross-sectional studies. Longitudinal studies of cannabis users are lacking.

Method: The present study examines associations between CU and cognition over time in chronic daily adolescent-onset CUs, as compared to nonusing controls. Both groups completed a neuropsychological battery at study intake and again 2 years later.

Results: Baseline group differences have been published and indicated deficits in verbal learning and memory, motivated decision-making, planning, and working memory in CUs. In this follow-up report, the longitudinal performance of users is compared to that of sustained nonusers using the same battery. At follow-up, the majority of CUs continued to report regular and heavy cannabis use. Relative impairments in the domains of working memory, planning and verbal memory remained stable, suggesting that these are enduring vulnerabilities associated with continued CU during young adulthood. Improvements in motivated decision-making were evident in both groups. In addition, CUs demonstrated relatively better performance on short-duration speeded tasks. An earlier age of CU onset was associated with poorer verbal learning and memory and planning performance over time.

Conclusions: Verbal learning and memory and planning processes, as well as their neural correlates, merit further scrutiny within etiological models of cannabis-induced cognitive impairments.     

Effects of reward sensitivity and regional brain volumes on substance use initiation in adolescence

This longitudinal study examines associations between baseline individual differences and developmental changes in reward [i.e. behavioral approach system (BAS)] sensitivity and relevant brain structures’ volumes to prospective substance use initiation during adolescence. A community sample of adolescents ages 15–18 with no prior substance use was assessed for substance use initiation (i.e. initiation of regular alcohol use and/or any use of other substances) during a 2-year follow-up period and for alcohol use frequency in the last year of the follow-up. Longitudinal ‘increases’ in BAS sensitivity were associated with substance use initiation and increased alcohol use frequency during the follow-up. Moreover, adolescents with smaller left nucleus accumbens at baseline were more likely to initiate substance use during the follow-up period. This study provides support for the link between developmental increases in reward sensitivity and substance use initiation in adolescence. The study also emphasizes the potential importance of individual differences in volumes of subcortical regions and their structural development for substance use initiation during adolescence.     

The effect of mitochondrial complex I inhibitor on longevity of short-lived and long-lived seed beetles and its mitonuclear hybrids

Mitochondria are suggested to play a central role in ageing and evolution of longevity. Gradual decline in mitochondrial function during ageing and concomitant increase in production of reactive oxygen species (ROS) leads to oxidative damage of macromolecules and impairment of ATP synthesis. To assess relationship between ageing and oxidative stress resistance we exposed different longevity lines of the seed beetle (Acanthoscelides obtectus) to four concentrations of tebufenpyrad, mitochondrial complex I inhibitor. Complex I is one of main sites of ROS production during normal respiration and its inhibition elevates oxidative stress. Our results showed that 24 h of exposure to tebufenpyrad decreased survival and post-stress longevity due to increased baseline mortality. Higher resistance was recorded in beetles from lines selected for late reproduction and extended longevity (L) than in early reproducing beetles (E). Also, females were more resistant than males. Since complex I is under dual genetic control, our second aim was to disentangle relative contribution of nuclear and mitochondrial genes to the variation in longevity. We used crossed combinations of distinct mitochondrial and nuclear genotypes (E × L, L × E) and compared them to control hybrids where mitochondrial genome was “transplanted” onto the original background (E × E, L × L). Our study revealed significant effect of nucleus, i.e. higher survival and post-stress longevity in beetles harbouring L nucleus. Mitochondrion effect was significant only within L nuclear background where E mitochondrion gave advantage.