Response to treatment in hereditary metabolic disease: 1993 survey and 10-year comparison.

Knowledge about cause, pathogenesis, and manifestations of hereditary metabolic diseases puts them among the best known of all human diseases. On the other hand, outcomes of treatment are cause for uncertainty and concern. In 1985, Hayes et al. analyzed efficacy of treatment up to 1983 in 65 of these diseases selected randomly from the McKusick catalogs. Disease scores were calculated for seven parameters: longevity; reproductive capability; somatic and cognitive development; and handicaps affecting schooling, work, and cosmetic appearance. Scores of the untreated and treated phenotypes were then compared. We have now measured progress over the past decade by calculating scores on the same 65 diseases from data in several hundred new reports published since 1983. All seven parameters in the 1993 survey reflect improved efficacy of treatment in the 10-year interval. However, the percent of diseases for which all manifestations of the disease were removed by treatment has not changed (12% in 1983; 12% in 1993). The group in which manifestations were untouched by treatment has become smaller (48% in 1983; 31% in 1993), and the group partially ameliorated by treatment had increased reciprocally (40% in 1983; 57% in 1993). Progress in the treatment of hereditary metabolic disease is thus better than it was, but it is still only a partial success. The advances are attributable to greater success with organ and tissue transplantation, better pharmacotherapy, and better support systems. Restoration of normal homeostasis, the key to successful treatment, remains an elusive challenge and is a logical, major focus for research in human genetics.     

Evidence that the nigrotegmental GABAergic projection mediates stereotypy induced by apomorphine and intranigral muscimol

The substantia nigra plays a pivotal role in the relay of output from the striatum. One neural pathway from substantia nigra projects GABAergic fibers to the caudal mesencephalic tegmentum, terminating in the vicinity of the pedunculopontine nucleus (PPN). To evaluate the functional importance of this projection in the mediation of stereotyped behaviors of striatal and nigral origin, we microinjected low doses of the GABA agonist, muscimol, bilaterally into the vicinity of the PPN. This muscimol treatment resulted in a total blockade of all stereotyped behaviors normally elicited by systemic apomorphine or by intranigral muscimol. Blockade was not observed in animals microinjected with muscimol into the dorsal reticular formation, 1 mm above the level of the PPN. Our results indicate that the nigrotegmental projection may play a crucial role in the expression of stereotyped and dyskinetic behaviors of basal ganglia origin.     

Mechanism of mda-5 Inhibition by Paramyxovirus V Proteins

The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible gene I (RIG-I) detect foreign cytoplasmic RNA molecules generated during the course of a virus infection, and their activation leads to induction of type I interferon synthesis. Paramyxoviruses limit the amount of interferon produced by infected cells through the action of their V protein, which binds to and inhibits mda-5. Here we show that activation of both mda-5 and RIG-I by double-stranded RNA (dsRNA) leads to the formation of homo-oligomers through self-association of the helicase domains. We identify a region within the helicase domain of mda-5 that is targeted by all paramyxovirus V proteins and demonstrate that they inhibit activation of mda-5 by blocking dsRNA binding and consequent self-association. In addition to this commonly targeted domain, some paramyxovirus V proteins target additional regions of mda-5. In contrast, V proteins cannot bind to RIG-I and consequently have no effect on the ability of RIG-I to bind dsRNA or to form oligomers.     

华南丘陵地区农林复合生态系统晚稻田甲烷和氧化亚氮排放

采用静态箱-气相色谱法对晚稻田甲烷(CH4)和氧化亚氮(N2O)排放进行田间原位测定。结果表明,有植株参与的稻田CH4排放通量季节变化与地下5cm温度呈显著正相关关系。稻田CH4和N2O季节平均排放通量在有植株参与时分别为1.16±0.38mgm-2h-1和42.33±20.00μgm-2h-1,而无植株参与的分别为0.15±0.11mgm-2h-1和51.69±15.87μgm-2h-1。水稻种植对CH4的排放影响较大,对N2O的排放影响较小,有植株参与的稻田CH4平均排放量显著高于无植株参与的稻田,N2O的平均排放量无显著差异。     

The epidemiology underlying age‐related avian malaria infection in a long‐lived host: the mute swan Cygnus olor

Quantifying the factors that predict parasite outbreak and persistence is a major challenge for both applied and fundamental biology. Key to understanding parasite prevalence and disease outbreaks is determining at what age individuals show signs of infection, and whether or not they recover. Age‐dependent patterns of the infection of a host population by parasites can indicate among‐individual heterogeneities in their susceptibility to, or rate of recovery from, parasite infections. Here, we present a cross‐sectional study of avian malaria in a long‐lived bird species, the mute swan Cygnus olor, examining age‐related patterns of parasite prevalence and modelling patterns of infection and recovery. One‐hundred and fifteen swans, ranging from one to nineteen years old, were screened for infection with Plasmodium, Haemoproteus and Leucocytozoon parasites. Infections with three cytochrome‐b lineages of Haemoproteus were found (pooled prevalence 67%), namely WW1 (26%), which is common in passerine birds, and two new lineages closely related to WW1: MUTSW1 (25%) and MUTSW2 (16%). We found evidence for age‐related infection in one lineage, MUTSW1. Catalytic models examining patterns of infection and recovery in the population suggested that infections in this population were not life‐long – recovery of individuals was included in the best fitting models. These findings support the results of recent studies that suggest hosts can clear infections, although patterns of infection‐related mortality in older birds remain to be studied in more detail.